i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This live or zoom broadcasted hematology/oncology fellowship program will bring an expert faculty member to your institution to discuss the latest developments and expert perspectives in the treatment of follicular lymphoma.
Optimizing Treatment Sequencing for Patients With Relapsed/ Refractory Multi...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Shaji Kumar, MD, Professor of Hematological Malignancies
Mayo Clinic Cancer Center, offers expert insight on the assessment of MM, emerging and current therapies, cutting edge approaches to personalized treatments plans, and much more.
Expert Guidance on Current Standards and New Directions in Newly Diagnosed Mu...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
Presented by leading expert Urvi Shah, MD, Assistant Attending in the Myeloma Service at Memorial Sloan Kettering Cancer Center, this slide deck will explore guidance on current standards and new directions in newly diagnosed multiple myeloma.
STATEMENT OF NEED
An estimated 35,730 new cases of multiple myeloma are diagnosed in the United States annually, and 12,590 people die of the disease (Siegel et al, 2023). Characterized by clonal proliferation of malignant plasma cells in the bone marrow, multiple myeloma is associated with anemia, renal insufficiency, bone destruction, and hypercalcemia, all of which significantly impact patients’ quality of life. The development of novel therapies and combinations in recent years, including anti-CD38 antibodies, has provided numerous therapeutic options for newly diagnosed multiple myeloma. However, the optimal selection of induction therapy and subsequent treatment sequencing for individual patients remains a challenge. Additionally, factors including age, frailty, comorbidities, transplant eligibility, treatment-related toxicities, and supportive care needs complicate treatment decisions (Costello et al, 2022). This hematology/oncology fellows lecture series will explore expert guidance on current standards and new directions in newly diagnosed multiple myeloma.
TARGET AUDIENCE
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with multiple myeloma.
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Assess guideline-recommended treatment combination and sequencing strategies in NDMM
Evaluate the role of minimal residual disease (MRD) assessment in NDMM treatment
Review the mechanism of action, efficacy, and safety of anti-CD38 monoclonal antibodies in the treatment of NDMM
Discuss strategies to monitor and manage treatment-related toxicities and optimize survivorship care
Optimizing Treatment Sequencing for Patients With Relapsed/ Refractory Multi...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Shaji Kumar, MD, Professor of Hematological Malignancies
Mayo Clinic Cancer Center, offers expert insight on the assessment of MM, emerging and current therapies, cutting edge approaches to personalized treatments plans, and much more.
Expert Guidance on Current Standards and New Directions in Newly Diagnosed Mu...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
Presented by leading expert Urvi Shah, MD, Assistant Attending in the Myeloma Service at Memorial Sloan Kettering Cancer Center, this slide deck will explore guidance on current standards and new directions in newly diagnosed multiple myeloma.
STATEMENT OF NEED
An estimated 35,730 new cases of multiple myeloma are diagnosed in the United States annually, and 12,590 people die of the disease (Siegel et al, 2023). Characterized by clonal proliferation of malignant plasma cells in the bone marrow, multiple myeloma is associated with anemia, renal insufficiency, bone destruction, and hypercalcemia, all of which significantly impact patients’ quality of life. The development of novel therapies and combinations in recent years, including anti-CD38 antibodies, has provided numerous therapeutic options for newly diagnosed multiple myeloma. However, the optimal selection of induction therapy and subsequent treatment sequencing for individual patients remains a challenge. Additionally, factors including age, frailty, comorbidities, transplant eligibility, treatment-related toxicities, and supportive care needs complicate treatment decisions (Costello et al, 2022). This hematology/oncology fellows lecture series will explore expert guidance on current standards and new directions in newly diagnosed multiple myeloma.
TARGET AUDIENCE
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with multiple myeloma.
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Assess guideline-recommended treatment combination and sequencing strategies in NDMM
Evaluate the role of minimal residual disease (MRD) assessment in NDMM treatment
Review the mechanism of action, efficacy, and safety of anti-CD38 monoclonal antibodies in the treatment of NDMM
Discuss strategies to monitor and manage treatment-related toxicities and optimize survivorship care
Immunotherapy for Metastatic Triple Negative Breast Cancerbkling
Sylvia Adams, MD, medical oncologist, and associate professor at the NYU School of Medicine, discusses the latest research including the role of immunology in the treatment of triple negative metastatic breast cancer. This webinar was hosted on October 19, 2016.
Mutations in Chronic myeloid leukaemia and Imatinib resistanceDr Sandeep Kumar
some corrections over previous presentation on CML. Covers topics like - pathophysiology of CML, Mutations discussed in detail, TKI resistance in various mutations and treatment options. Also Imatinib resistance has been discussed in detail.
Audio and slides for this presentation are available on YouTube: http://youtu.be/ozNSEND5PbE
Erica Mayer, MD, MPH, of the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, discusses triple-negative breast cancer and what makes it different from other forms of breast cancer. Mayer also talks about treatment options for triple-negative breast cancer and what you need to know about clinical trials for the disease.
Immunotherapy for Metastatic Triple Negative Breast Cancerbkling
Sylvia Adams, MD, medical oncologist, and associate professor at the NYU School of Medicine, discusses the latest research including the role of immunology in the treatment of triple negative metastatic breast cancer. This webinar was hosted on October 19, 2016.
Mutations in Chronic myeloid leukaemia and Imatinib resistanceDr Sandeep Kumar
some corrections over previous presentation on CML. Covers topics like - pathophysiology of CML, Mutations discussed in detail, TKI resistance in various mutations and treatment options. Also Imatinib resistance has been discussed in detail.
Audio and slides for this presentation are available on YouTube: http://youtu.be/ozNSEND5PbE
Erica Mayer, MD, MPH, of the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, discusses triple-negative breast cancer and what makes it different from other forms of breast cancer. Mayer also talks about treatment options for triple-negative breast cancer and what you need to know about clinical trials for the disease.
Managing Immune-Related Adverse Events to Ensure Optimal Cancer Immunotherapy...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck, presented by Blanca Ledezma, MSN, NP, AOCNP® Nurse Practitioner
Hematology/Oncology
University of California, Los Angeles (UCLA) Health, will provide insight into the nurse’s view on managing immune-related adverse events to ensure optimal cancer immunotherapy outcomes.
Immune checkpoint inhibitors, which alter immune regulatory pathways and promote cell-mediated destruction of tumor cells, have revolutionized the treatment of cancer in recent years, with numerous therapeutic agents approved and several targets under investigation (Chennamadhavuni et al, 2022). However, up to 90% of patients receiving immune checkpoint inhibitors experience immune-related adverse events, which can affect a wide variety of organ systems and can occur at any time during treatment or even after treatment completion (NCCN, 2023). Immune-related adverse events are associated with significant morbidity as well as the risk of therapy discontinuation, which can have an unpredictable impact on patients’ disease course. Therefore, it is critical for nurses to understand the mechanism, identification, and timely management of immune-related adverse events (Shankar et al, 2022). In this activity presented by Blanca Ledezma, MSN, NP, AOCNP®, Nurse Practitioner at the University of California, Los Angeles (UCLA) Health, will provide insight into the nurse’s view on managing immune-related adverse events to ensure optimal cancer immunotherapy outcomes.
TARGET AUDIENCE
Oncology nurses, nurse practitioners, clinical nurse specialists, and other health care professionals involved in the management of patients with immune-related adverse events (IRAEs).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Discuss how the mechanisms of action of immunotherapies influence their safety profile
Identify risk factors predisposing patients to IRAEs
Distinguish IRAEs from chemotherapy- and targeted therapy-related adverse events
Coordinate with the interdisciplinary health care team to apply evidence-based guidelines and best practices in personalized nursing management plans for patients with IRAEs
Develop patient counseling strategies promoting awareness, self-monitoring, and escalated reporting of IRAEs
Stem Cell Transplantation in Hodgkin’s Lymphoma Past, Present and FutureAmir Abbas Hedayati Asl
Treatment for HL has improved significantly since the ABVD chemotherapeutic combination was invented over 30 years ago .
Despite using the same ABVD regimen in most patients treated in the first line, we now have a much better understanding of disease biology and the late side effects of therapy, and we have moved toward a personalized, risk-adapted approach.
This approach promises to deliver low toxicities and high cure rates for lower risk patients while reserving aggressive regimens for those high risk patients who really need them.
For the minority of patients who fail first-line therapy, novel drugs like the antibody-drug conjugate BV and immunotherapies with nivolumab and pembrolizumab have produced high response rates and durability of benefit.
Further research is needed to determine whether these novel drugs could make life better for both patients with HL who are undergoing treatment and for the growing cohort of HL survivors.
One of my best friends (when I was a teenager) died of leukemia. Several advances have been made in the ensuing decades (see attached document). Watch this space for additional notes.
Naval Daver, MD, and Joseph D. Khoury, MD, FCAP, prepared useful practice aids pertaining to acute myeloid leukemia for this CME/MOC/CC activity titled "The Pathology–Oncology Partnership in AML: Identifying and Treating the Diversity of Disease Subtypes." For the full presentation, complete CME/MOC/CC information, and to apply for credit, please visit us at https://bit.ly/32hvh7Z. CME/MOC/CC credit will be available until October 14, 2022.
Molecular mechanisms of action and potential biomarkers of growth inhibition ...Enrique Moreno Gonzalez
Molecular targeted therapy has emerged as a promising treatment of Hepatocellular carcinoma (HCC). One potential target is the Src family Kinase (SFK). C-Src, a non-receptor tyrosine kinase is a critical link of multiple signal pathways that regulate proliferation, invasion, survival, metastasis, and angiogenesis. In this study, we evaluated the effects of a novel SFK inhibitor, dasatinib (BMS-354825), on SFK/FAK/p130CAS, PI3K/PTEN/Akt/mTOR, Ras/Raf/MAPK and Stats pathways in 9 HCC cell lines.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Exploring Novel Treatments for Rett Syndromei3 Health
This slide deck, led by Timothy John Feyma, MD, Pediatric Neurologist at Gilette Children’s Hospital, will explore novel treatments and quality-of-life improvement strategies for children and adults with Rett syndrome.
STATEMENT OF NEED
Rett syndrome is a rare, debilitating neurodevelopmental disorder almost always associated with a spontaneous mutation in the methyl-CpG-binding protein 2 (MECP2) gene on the X-chromosome. Affected individuals experience loss of purposeful hand skills, abnormalities in gait, loss of spoken language, and stereotypic hand movements, with more severe manifestations including seizures, autistic features, autonomic nervous system dysfunction, breathing abnormalities, sleep disturbances, and cardiac abnormalities. While therapies for Rett syndrome are being investigated in clinical trials and have demonstrated modest benefit, no curative or effective disease-modifying treatments currently exist (Petriti et al, 2023). Therefore, the multidisciplinary team is challenged with the optimal management of complex comorbidities that persist throughout patients’ lives. This activity chaired by Timothy John Feyma, MD, Pediatric Neurologist at Gilette Children’s Hospital, will explore novel treatments and quality-of-life improvement strategies for children and adults with Rett syndrome.
TARGET AUDIENCE
Pediatric and adult neurologists, pediatricians, internists, family physicians, child and adult psychiatrists, nurse practitioners, physician assistants, nurses, and other health care professionals involved in the treatment of children and adults with Rett syndrome.
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Identify distinguishing features of Rett syndrome that can inform early and accurate diagnosis
Evaluate the safety, efficacy, and clinical utility of novel and emerging treatments for Rett syndrome in children and adults
Devise strategies to monitor and manage Rett syndrome symptoms in children and adults
Leveraging the Growing Arsenal of Adjuvant Therapies for Early-Stage NSCLCi3 Health
3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by, Dr. Helena A. Yu, Associate Attending Physician at Memorial Sloan Kettering Cancer Center, will provide insights into strategies for leveraging the growing arsenal of adjuvant therapies for early-stage non–small cell lung cancer (NSCLC), including treatment selection and adverse event management.
STATEMENT OF NEED
Lung cancer is the second most commonly diagnosed cancer and the leading cause of death for men and women worldwide. In the United States, non–small cell lung cancer (NSCLC) accounts for 81% of all lung cancer diagnoses (Cancer.net, 2023). Therapeutic options, survival rates, and outcomes for NSCLC are dramatically impacted by disease stage. For patients with early-stage disease, radical surgery is the mainstay of treatment; however, patients have a significant risk of relapse following surgery and local treatment. Numerous novel therapeutic approaches, including the use of molecular biomarkers and the development of targeted agents and immune checkpoint inhibitors, are under investigation for early-stage NSCLC, contributing to a growing arsenal of treatment options for this disease (Indini et al, 2020). In this visiting faculty meeting series chaired by Helena A. Yu, MD, Associate Attending Physician at Memorial Sloan Kettering Cancer Center, speakers will provide expert perspectives on diagnosis, identification of biomarkers, and efficacy and safety data of novel adjuvant therapies to improve survival outcomes for patients with early-stage NSCLC.
TARGET AUDIENCE
Medical oncologists, radiation oncologists, surgical oncologists, pulmonologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with non–small cell lung cancer (NSCLC).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Identify the correct tumor stage and appropriate management approach for NSCLC based on the latest evidence
Distinguish biomarkers for early-stage NSCLC that can inform individualized treatment strategies
Appraise efficacy and safety data of novel adjuvant therapies for patients with NSCLC as elucidated by recent clinical trials
Apply strategies to prevent and mitigate adverse events associated with novel adjuvant therapies for early-stage NSCLC
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Leveraging the Growing Arsenal of Adjuvant
Therapies for Early-Stage NSCLC
Helena A. Yu, MD
Associate Attending Physician
Memorial Sloan Kettering Cancer Center
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Disclosures
Advisory board/panel: AbbVie, AstraZeneca, Black Diamond,
Blueprint, C4 Therapeutics, Cullinan, Daiichi Sankyo, Janssen, Taiho,
Takeda
Grants/research support: AstraZeneca, Black Diamond, Blueprint,
Cullinan, Daiichi Sankyo, Erasca, Janssen, Novartis, Pfize
Exploring Advances in the Early Diagnosis and Treatment of Alzheimer Disease ...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
In this slide deck, discover new insights into early diagnosis, emerging treatment modalities, and supportive care services for Alzheimer disease. An expert faculty member will discuss biological and clinical distinctions between mild cognitive impairment, dementia, and Alzheimer disease; methods for timely diagnosis; clinical trial data on novel monoclonal antibody therapies; prevention and management of side effects associated with monoclonal antibody therapies, including ARIA, and interdisciplinary support services for improving quality of life.
STATEMENT OF NEED
Alzheimer disease, the most common form of dementia among older adults, is a slowly progressive neurogenerative disease that affects approximately 6 million Americans aged 65 and older (Rajan et al, 2021). Symptoms of Alzheimer disease include memory loss, confusion, impulsive behavior, difficulty with language, mood and personality changes, hallucinations, and increased anxiety or aggression, with severe symptoms such as physical decline, difficulty swallowing, and inability to communicate developing as the disease progresses into its final stages (NIA, 2023). While new therapeutic agents have recently emerged to slow the progression of Alzheimer disease by targeting its underlying causes, the disease remains incurable, and the demands of day-to-day care place significant strain on both patients and their families and caregivers. Therefore, it is critical that clinicians remain up to date on early diagnosis, emerging treatment modalities, and supportive care services in order to provide optimal care for their patients. In this live webinar chaired by Nathaniel Chin, MD, Associate Professor of Medicine in the Division of Geriatrics and Gerontology at the University of Wisconsin-Madison, speakers will explore advances in the diagnosis and treatment of Alzheimer disease.
TARGET AUDIENCE
Geriatricians, neurologists, primary care physicians, psychiatrists, psychogeriatricians, nurse practitioners, physician assistants, nurses, and other health care professionals (HCPs) involved in the treatment of patients with Alzheimer disease (AD).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Utilize diagnostic methods that enable the timely identification of early Alzheimer disease (AD)
Evaluate the clinical utility of novel and emerging DMTs for the treatment of individual patients with early AD
Apply strategies to enhance interdisciplinary care for patients with early AD
Enhancing MRD Testing in Hematologic Malignancies: When Negativity is a Posit...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This expert CME-approved slide deck, presented by Noopur Raje, MD, Director of the Center for Multiple Myeloma at Massachusetts General Cancer Center, will explore the current and emerging roles of MRD testing in hematologic malignancies. She presents the ongoing questions and latest data regarding the clinical utility of MRD testing in prognosis and treatment.
STATEMENT OF NEED
Measurable residual disease (MRD) is defined as the persistence of cancer cells at levels below morphologic detection after treatment. For patients with hematologic malignancies, MRD testing is increasingly being used to predict disease progression, monitor disease status, and evaluate treatment options (Dekker et al, 2023). Questions about current and future roles of MRD testing abound, including validation of assays, such as next-generation sequencing, machine learning, and flow cytometry; standardization of collection methods and modalities; considerations for clinical trial design and statistical analyses; and improved understanding of the roles of MRD status and depth of response across hematologic malignancies (Dekker et al, 2023; Baines et al, 2023). It is critical for members of the multidisciplinary cancer care team to stay up-to-date on the latest data regarding the clinical utility of MRD testing in prognosis and treatment. In this CME-approved activity, Noopur Raje, MD, Director of the Center for Multiple Myeloma at Massachusetts General Cancer Center, will explore the current and emerging roles of MRD testing in hematologic malignancies.
TARGET AUDIENCE
Medical oncologists, hematologists, pathologists, and other health care professionals involved in the treatment of patients with hematologic malignancies.
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Distinguish the advantages and limitations of current MRD detection methods
Evaluate consensus recommendations on indications for MRD testing in hematologic malignancies
Explain the current and potential roles of MRD status and depth of response as a biomarker in clinical trials
Describe mechanisms of drug resistance/loss of response to BCMA-directed therapies
Assess the clinical utility of MRD in prognosis and treatment of selected hematologic malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma
Recurrent/Metastatic HNSCC: Harnessing Immunotherapy in Comprehensive Carei3 Health
i3 Health is pleased to make this slide deck from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck, presented by Glenn J. Hanna, MD, Director, Center for Cancer Therapeutic Innovation (Early Drug Development Program)
Medical Oncologist, Center for Head & Neck Oncology
Dana-Farber Cancer Institute, and Deborah Wong, MD, PhD, Associate Clinical Professor of Medicine, Division of Hematology-Oncology, UCLA Medical Center, was presented at a live educational event at the 2024 Multidisciplinary Head and Neck Cancers Symposium. It will provide expert perspectives on harnessing immunotherapy in recurrent/metastatic HNSCC to provide comprehensive care.
Slowing Progression of Chronic Kidney Disease Through Value-Based Carei3 Health
i3 Health is pleased to make this infographic from this activity available for use as a non-accredited self-study or teaching resource.
This two module CPE activity brings two leading pharmacists together to discuss the slowing progression of Chronic Kidney disease through value-based care.
In Module 1 of this activity, Jeff Sperry, PharmD, BCPS, Clinical Pharmacist at UCHealth Memorial Hospital, will explore risk factors contributing to CKD, efficacy and safety of novel therapies for slowing kidney function decline, and evidence-based strategies for management of CKD complications.
In Module 2 Justin J. Bioc, PharmD, BCPS, BCGP, RPh, Head of Clinical Pharmacy at Devoted Health, will explore the cost-effectiveness of novel therapies indicated to slow kidney function decline and strategies that maximize collaboration between payers and providers to optimize the care of patients with CKD.
Putting the Freeze on Cold Agglutinin Diseasei3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by, Catherine M. Broome, MD, Associate Professor of Medicine at Georgetown University School of Medicine, will provide expert guidance on diagnostic features, current treatment standards, emerging therapies, and supportive care strategies for patients with cold agglutinin disease (CAD). Start the activity now!
STATEMENT OF NEED
Cold agglutinin disease (CAD) is a rare subtype of autoimmune hemolytic anemia (AIHA) in which antibodies cause hemolysis at cold temperatures, generally between 37º to 39º Fahrenheit. Approximately 1 in a million people are affected by CAD annually, with onset usually occurring between the ages of 40 and 80 years. Individuals commonly experience fatigue, dizziness, palpitations, and shortness of breath caused by the anemia; jaundice caused by degradation of hemoglobin into bilirubin; and sweating, coldness, or painful discoloration of their fingers, toes, ankles, and wrists triggered by exposure to cold (NORD, 2020). While progress has been made in recent years in understanding the pathogenesis of CAD, consensus recommendations based on randomized trials are needed for improving treatment outcomes and reducing symptom burden (Berentsen, 2021). In this Hematology/Oncology Fellows Lecture Series chaired by Catherine Broome, MD, Associate Professor of Medicine at Georgetown University School of Medicine, faculty will provide expert perspectives on optimizing the diagnosis, treatment, and supportive care of CAD.
TARGET AUDIENCE
Hematology fellows, attending faculty, and other health care professionals involved in the treatment of patients with cold agglutinin disease (CAD).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Evaluate the clinical and laboratory features of CAD that can inform timely and accurate diagnosis
Discuss the pathophysiology of CAD and the scientific rationale for targeting the classical complement pathway
Appraise the efficacy and safety of novel complement inhibitors for CAD as elucidated by recent studies
Assess strategies for managing anemia, cold-induced circulatory symptoms, and treatment-related adverse events to optimize the clinical outcomes of patients with CAD
Faculty
Catherine M. Broome, MD
Professor of Medicine
Georgetown University School of Medicine
Virtual Tumor Board: Multidisciplinary Management of Advanced Soft Tissue Sar...i3 Health
i3 Health is pleased to make the Clinical Decision Aid from this activity available for use as a non-accredited self-study or teaching resource.
Gain insights and perspectives from this multidisciplinary panel of experts as they discuss cases and explore strategies to optimize treatment outcomes for patients with advanced soft tissue sarcoma. This distinguished Virtual Tumor Board features Shreyaskumar R. Patel, MD, Medical Director of the Sarcoma Center at the University of Texas MD Anderson Cancer Center; Kathleen Polson, NP, Nurse Practitioner at Dana-Farber Cancer Institute; and Brian Rubin, MD, PhD, Professor of Pathology at Cleveland Clinic Cancer Center
STATEMENT OF NEED
Sarcomas, which represent 1% to 2% of adult cancers, are a rare, heterogeneous group of neoplasms originating in the connective tissue. Soft tissue sarcomas, which begin in the muscle, tendons, fat, lymph, blood vessels, and nerves, encompass more than 80 histological subtypes. Approximately 25% of patients develop metastatic disease after curative-intent surgery, and for these patients, treatment options are limited and prognosis is very poor. In recent decades, the identification of genetic alterations in soft tissue sarcoma has led to the rise of targeted therapy, significantly expanding the therapeutic landscape. Remaining up to date on pathological characteristics and emerging data on novel therapies is crucial (Riskjell et al, 2023; NCI, 2023). In this Virtual Tumor Board, Shreyaskumar R. Patel, MD, Medical Director of the Sarcoma Center at the University of Texas MD Anderson Cancer Center; Kathleen Polson, NP, Nurse Practitioner at Dana-Farber Cancer Institute; and Brian Rubin, MD, PhD, Professor of Pathology at Cleveland Clinic Cancer Center, will present cases and explore multidisciplinary strategies to optimize treatment outcomes for patients with advanced soft tissue sarcoma.
TARGET AUDIENCE
Medical/surgical/radiation oncologists, pathologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with soft tissue sarcoma.
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Distinguish patient and tumor characteristics that can inform personalized therapeutic approaches in soft tissue sarcoma
Evaluate emerging data on novel therapies for soft tissue sarcoma
Appraise multidisciplinary strategies to optimize treatment outcomes of patients with advanced soft tissue sarcoma
FACULTY
Shreyaskumar R. Patel, MD
Robert R. Herring Distinguished Professor of Medicine
Center Medical Director, Sarcoma Center
The University of Texas
MD Anderson Cancer Center
Kathleen Polson, NP
Nurse Practitioner
Dana-Farber Cancer Institute
Brian Rubin, MD, PhD
Professor of Pathology
Chairman, Robert J. Tomsich Pathology and Laboratory Medicine Institute
Cleveland Clinic Cancer Center
Pathology and Oncology Expert Perspectives in the Management of Triple-Negati...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck, presented by Dr. Ira Bleiweiss, Chief of Breast Pathology at the University of Pennsylvania, and Dr. Sara Tolaney, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, will feature expert pathology and oncology perspectives on the management of triple-negative breast cancer (TNBC), including case explorations and insights into frequently asked questions. Register today to hear these expert perspectives!
Statement of Need
Triple-negative breast cancer (TNBC) is an aggressive disease that accounts for approximately 10% to 15% of breast cancer diagnoses and is characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). TNBC is more common in Black women and in women under the age of 40 (ACS, 2023). Compared with other subtypes of invasive breast cancer, TNBC has high rates of metastasis and a poor prognosis. Due to the lack of hormone and receptor targets, therapeutic options are limited, and prognostication and treatment selection are complicated by the heterogeneity of the disease (Yang et al, 2022). In this live webinar, Dr. Sara Tolaney, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, and Dr. Ira Bleiweiss, Chief of Breast Pathology at the Hospital of the University of Pennsylvania, will provide expert oncology and pathology perspectives on evidence-based strategies for diagnosis, treatment, and adverse event management for patients with TNBC.
TARGET AUDIENCE
Medical oncologists, surgical oncologists, radiation oncologists, pathologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with triple-negative breast cancer (TNBC).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Evaluate receptor and expression status for prognostication and treatment selection in TNBC
Differentiate the pathological characteristics of the various types of TNBC
Select optimal therapy for TNBC based on shared goals, biomarker testing, and clinical data on novel therapies
Discuss strategies for timely recognition and mitigation of adverse events associated with novel TNBC therapies
Current Standards and New Directions in the Treatment of Acquired Thrombotic ...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
Gain insight and expertise in this presentation on acquired thrombotic thrombocytopenic purpura. Spero Cataland, MD, Professor of Clinical Internal Medicine and Director of Benign Hematology at The Ohio State University, will provide guidance on current treatment standards and will discuss emerging therapies with the potential to improve patient outcomes in aTTP.
STATEMENT OF NEED
Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening thrombotic microangiopathy with a rapid onset and progression and a mortality rate of 10% to 20% with prompt treatment. Onset of aTTP is characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, and a constellation of associated symptoms including hemorrhage, neurologic and renal manifestations, cardiac abnormalities, and mesenteric ischemia (Joly et al, 2017). Survivors of first aTTP events tend to have relapse events which need to be controlled. Rapid recognition and immediate appropriate treatment are critical for achieving optimized outcomes in aTTP. In this activity chaired by Spero Cataland, MD, Professor of Clinical Internal Medicine and Director of Benign Hematology at The Ohio State University, expert faculty will provide insightful guidance on current treatment standards and will discuss emerging therapies with the potential to improve patient outcomes in aTTP.
TARGET AUDIENCE
Hematology fellows, attending faculty, and other health care professionals involved in the treatment of patients with acquired thrombotic thrombocytopenic purpura (aTTP).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Evaluate the clinical and laboratory features of aTTP that can inform timely and accurate diagnosis
Discuss how ADAMTS13 activity can be used to guide the management of aTTP
Assess the mechanism of action, efficacy, and safety of novel anti-von Willebrand factor nanobodies in aTTP as elucidated by recent clinical trials
Evaluate novel treatment combinations and sequences with the potential to improve the outcomes of patients with aTTP
Hitting the Target in HER2-Positive Metastatic Colorectal Canceri3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck will share the latest data and strategies for hitting the target in HER2-positive metastatic colorectal cancer. Dr. Christopher Lieu, Associate Professor at the University of Colorado Cancer Center, explores actionable targets to inform personalized care plans, guideline-recommended combination and sequencing strategies, adverse event monitoring and management, and more.
STATEMENT OF NEED
An estimated 153,020 new cases of colorectal cancer (CRC) are diagnosed annually, and 52,550 people die of the disease (Siegel et al, 2023). Approximately 22% of patients present with metastatic disease, which is associated with a dismal 5-year survival rate of 15% (SEER, 2022). Targeting biomarkers is a key strategy for expanding therapeutic options and improving outcomes in metastatic CRC. Human epidermal growth factor receptor 2 (HER2) amplification status and treatments targeting HER2 are some of the most recent additions to the arsenal of targeted therapy for this disease. This activity chaired by Christopher Lieu, MD, Associate Director of Clinical Research at the University of Colorado Cancer Center, will provide expert perspectives and practical guidance on treating HER2-positive metastatic CRC.
TARGET AUDIENCE
Oncologists, gastroenterologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with colorectal cancer (CRC).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Distinguish actionable targets that can inform personalized care plans in metastatic CRC
Evaluate practice guidelines on treatment combinations and sequences for patients with metastatic CRC
Appraise emerging efficacy and safety data on novel targeted therapies for patients with HER2-positive metastatic CRC
Assess strategies for optimizing the safety and tolerability of novel targeted therapies for HER2-positive metastatic CRC
Leveraging BCMA-Directed Therapies for Improved Patient Outcomes in Relapsed/...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Rahul Banerjee, Assistant Professor at the University of Washington and Fred Hutchinson Cancer Center, will provide a case-based discussion on leveraging BCMA-directed antibody-drug conjugates, CAR T-cell therapies, and bispecific T-cell engagers to improve outcomes for patients with multiple myeloma in need of additional treatment options.
STATEMENT OF NEED
Multiple myeloma is a disease that remains incurable for most patients, many of whom become refractory to the majority of available treatments (Kumar et al, 2022). It is estimated that 35,730 new cases of multiple myeloma are diagnosed in the United States annually, and 12,590 people die of the disease (Siegel et al, 2023). Agents targeting B-cell maturation antigen (BCMA), including antibody-drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapies, and bispecific T-cell engagers, represent a promising therapy class for patients in need of additional treatment options, including those with higher genetic risk and heterogeneity (Kumar et al, 2022). This activity led by Rahul Banerjee, MD, FACP, Assistant Professor in the Division of Medical Oncology at the University of Washington and Fred Hutchinson Cancer Center, will provide strategies for leveraging BCMA-directed therapies for improved patient outcomes in relapsed/refractory multiple myeloma.
TARGET AUDIENCE
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with multiple myeloma (MM).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Evaluate the mechanisms of action, efficacy, and safety of BCMA-directed therapies in relapsed/refractory MM
Assess guideline-recommended combination and sequential treatment strategies for relapsed/refractory MM
Identify risk factors for the development of treatment-specific adverse events with different classes of BCMA-directed therapies
Describe mechanisms of drug resistance/loss of response to BCMA-directed therapies
Examine the roles of gene expression profiling, soluble BCMA, and measurable residual disease (MRD) in clinical practice.
Optimizing Therapeutic Strategies in Castration-Resistant Prostate Canceri3 Health
This activity will discuss emerging efficacy and safety data on novel therapies for nmCRPC and mCRPC, strategies to manage adverse events, and the role of imaging studies and PSA testing in evaluating treatment response.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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Evaluation of antidepressant activity of clitoris ternatea in animals
Tailoring Therapy for Follicular Lymphoma Based on the Latest Evidence
1. Tailoring Therapy for Follicular Lymphoma
Based on the Latest Evidence
Christopher Flowers, MD, MS, FASCO
Chair, Professor, Department of Lymphoma/Myeloma
MD Anderson Cancer Center
3. Learning Objectives
FL = follicular lymphoma.
Evaluate molecular profiling recommendations that can inform
personalized care plans for patients with FL
Differentiate the mechanisms of action, efficacy, and safety of
emerging agents for FL
Assess the clinical application of novel therapeutic strategies for
patients with newly diagnosed and relapsed/refractory FL
4. Case 1: Ms. SM
PET = positron emission tomography; CT = computed tomography; LN = lymph node;
R-CHOP = rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone.
61-year-old woman diagnosed with FL grade 1/2
Asymptomatic
Noted on exam and PET/CT to have the following:
2-cm LN left cervical chain; multiple mesenteric LN 1.7-2.3 cm; palpable right
inguinal LN ~2.5 cm
Bone marrow biopsy: negative
Which option is most suitable for this patient?
A. R-CHOP
B. Rituximab + lenalidomide (R2)
C. Watch and wait
D. Obinutuzumab + bendamustine
5. Case 1: Ms. SM (cont.)
62-year-old woman diagnosed with FL grade 1/2
Stage III low tumor burden
Now with fatigue/weight loss, all prior LN larger but all <5 cm
Which treatment option is most suitable for this patient?
A. Rituximab alone
B. R2
C. Watch and wait
D. Obinutuzumab + bendamustine
6. Case 1: Ms. SM (cont.)
SUV = standardized uptake value.
65-year-old woman originally diagnosed with FL grade 1/2
Stage III low tumor burden
Had a partial response to R x4 doses; no maintenance
Now with return of increased in prior areas (largest 4 cm) and new para-
aortic LN 6 cm
SUVmax = 5
7. Case 1: Ms. SM (cont.)
B-R = bendamustine/rituximab; axi-cel = axicabtagene ciloleucel.
Which treatment option is most suitable for this patient?
A. Rituximab alone
B. R2
C. Watch and wait
D. Tazemetostat
E. R-CHOP
F. B-R
G. Axi-cel
8. Case 1: Ms. SM (cont.)
LDH = lactate dehydrogenase.
66-year-old woman with relapsed FL grade 1/2 following rituximab x4 doses
No maintenance with 3-year disease control
Now with progression on B-R
LDH 520 units/L
Which treatment option is most suitable for this patient?
A. Rituximab alone
B. R2
C. Watch and wait
D. Tazemetostat
E. R-CHOP
F. B-R
G. Axi-cel
9. Case 2: Mr. TD
CR = complete response.
72-year-old man diagnosed with stage III FL high tumor burden
Treated with B-R x6 cycles and achieved a CR
2.5 years later, he had progression of disease
Biopsy confirmed relapsed FL grade 1-2
Which option is most suitable for this patient?
A. R-CHOP
B. R2
C. Tazemetostat
D. Obinutuzumab + bendamustine
10. Case 2: Mr. TD (cont.)
79-year-old man diagnosed with stage III FL high tumor burden
Treated with B-R x6 cycles and achieved a CR
2.5 years later, he had progression of disease
Then treated (at age 76) with R-CHOP x6 cycles with maintenance
and achieved a CR
Now has relapsed with bulky disease in the abdomen (largest LN 7 cm
in mesentery)
Which option is most suitable for this patient?
A. Axi-cel
B. R2
C. Tazemetostat
D. Obinutuzumab + bendamustine
11. Annual Incidence of Lymphoid Cancers in the US
Teras et al, 2016.
US Cancer Statistics for Lymphoid Malignancies by WHO Subtypes
Overall Survival
FL
WHO = World Health Organization; HL = Hodgkin lymphoma; MZL = marginal zone lymphoma; PTCL = peripheral T-cell lymphoma;
MCL = mantle cell lymphoma; BL = Burkitt lymphoma; MF = mycosis fungoides; HCL = hairy cell leukemia; LPL = lymphoplasmacytic lymphoma;
WM = Waldenstrom macroglobulinemia;DLBCL = diffuse large B-cell lymphoma; PCN = plasma cell neoplasms; CLL = chronic lymphocytic leukemia;
SLL = small lymphocytic lymphoma.
12. Follicular Lymphoma Pathogenesis
Huet, Sujobert & Salles, 2018.
VDJ = variable diversity joining; Ag = antigen; GC = germinal center; CSR = class-switch recombination; sIgM = switched but immunoglobulin M–expressing; SHM = somatic hypermutation;
ISFN = in situ follicular neoplasia; PFL = FL with partial involvement follicular lymphoma; BCL-2 = B cell lymphoma 2 protein; AID = activation-induced cytidine deaminase.
13. Pathway Gene Function Frequency Oncogenic Alteration
Epigenetic and
transcriptional
regulation
KMT2D Histone H3K4 methyltransferase 70%-90% Loss of function
CREBBP
Histone H3K27 and H3K17
acetyltransferase
50%-70% Loss of function
Histone-encoding genes Histone linkers and core histones 20%-30% Unknown
EZH2 Histone H3K27 methyltransferase 10%-30% Gain of function
EP300
Histone H3K27 and H3K18
acetyltransferase
10%-20% Loss of function
MEF2B Transcription factor 10%-20% Gain of function
BCR signaling
IGH and IGL variable domains Promotes N-glycosylation ~80% Gain of function
CARD11 BCR-NF-κB signaling pathway 10%-15% Gain of function
Survival
BCL-2 Anti-apoptosis
Translocations ~85%
~85%
Gain of function
Mutations ~50% Unknown
SOCS1, STAT6, and STAT3 JAK-STAT signaling 20% Gain of function
NOTCH1, NOTCH2, NOTCH3,
NOTCH4, DTX1, and SPEN
NOTCH pathway 18% Unknown
Immune escape
HVEM Receptor ~50% Loss of function
EPHA7 Ephrin receptor 70% Loss of function
Common Genetic Alterations in Follicular Lymphoma
KMT2D = histone-lysine N-methyltransferase 2D; CREBBP = cyclic AMP response element binding protein; EZH2 = enhancer of zeste homolog 2; MEF2B = myocyte enhancer binding factor 2B;
BCR = B-cell receptor; IGH = immunoglobulin heavy locus; IGL = immunoglobulin lamda locus; CARD11 = caspase recruitment domain family member 11; NF- κB = nuclear factor-κB;
SOCS1 = suppressor of cytokine signaling 1; STAT = signal transducer and activator of transcription; HVEM = herpesvirus entry mediator; EPHA7 = ephrin type-A receptor 7.
Huet, Sujobert & Salles, 2018.
14. Follicular Lymphoma International Prognostic Index (FLIPI)
OS = overall survival; Hgb = hemoglobin.
Solal-Céligny et al, 2004.
Survival of 1,795 Patients According to Risk Group
Number
factors
FLIPI risk
group
10-year
0-1 Low 70%
2
Intermediate
50%
≥3 High 35%
FLIPI risk factors
>4 lymph nodes
Age >60 years
Stage III/IV
High LDH
Hgb <12 g/dL
21. Unmet Needs in Personalizing Therapy for FL
Nastoupil et al, 2018.
Unmet Needs
Model to predict early relapse
Tools to inform treatment
selection
Predictive biomarkers
Novel therapies
Goals
Identify high-risk patients for
access to clinical trials and
novel therapies
Identify low-risk patients for
shorter duration and less toxic
therapy
Improve outcomes in later lines
22. Considerations in the Choice of Therapy for an FL Patient
Indications for therapy
Bulk of disease
Comorbidities
Toxicity concerns
Interest in and availability of clinical trials
Risk of transformation
Grade (typically, I treat FL grade 1, 2, and 3A similarly)
Nastoupil et al, 2012.
At Diagnosis or Relapse
23. Which Patients With FL Need Treatment?
GELF = Groupe d'Etude des Lymphomes Folliculaires; BNLI = British National Lymphoma Investigation.
Brice et al, 1997; Nastoupil et al, 2012; Ardeshna et al, 2003.
GELF Criteria
High tumor bulk defined by either
• Tumor >7 cm
• 3 nodes in 3 distinct areas, each >3 cm
• Symptomatic splenic enlargement
• Organ compression
• Ascites or pleural effusion
Presence of systemic symptoms
Serum LDH or ß2-macroglobulin above normal values
values
Leukemia or blood cytopenia
BNLI Criteria
Rapid disease progression in the preceding 3 months
months
Life-threatening organ involvement
Renal or liver infiltration
Bone lesions
Systemic symptoms or pruritus
Hb <10g/dL or WBC <3.0x109/L or platelet count
<100x109/L; related to marrow involvement
24. Criteria for Therapy Requirement
NCCN, 2022.
Follicular lymphoma
Requiring therapy Not requiring therapy
B symptoms
Cytopenia due to BM infiltration
Leukemic phase
Elevated LDH
Pleural effusion or ascites
Bulk: node >7 cm
≥3 nodes >3 cm
Discomfort due to tumor masses
Watch and wait
25. A General Framework for Initial Therapy for FL
Kahl & Yang, 2016; Nastoupil et al, 2012; NCCN, 2022.
Staging
evaluation
Localized
Advanced indolent
Advanced with
symptoms
Rituximab-chemo
(R-chemo)
Watch and wait
Rituximab (R)
Obinutuzumab-chemo
(G-chemo)
Watch and wait
Radiotherapy
No chemo?
26. Case 1: Ms. SM (cont.)
62-year-old woman diagnosed with FL grade 1/2
Stage III low tumor burden
Now with fatigue weight loss, all prior LN larger but all <5 cm
Which treatment option is most suitable for this patient?
A. Rituximab alone
B. R2
C. Watch and wait
D. Obinutuzumab + bendamustine
28. Initial Treatment for Advanced Disease
CIT = chemoimmunotherapy; PFS = progression free survival; CVP = cyclophosphamide/vincristine sulfate/prednisone; AE = adverse events; TTNT = time to next treatment.
Rummel et al, 2013; Flinn, van der Jagt, et al, 2019; Marcus et al, 2017; FDA, 2017; Morschhauser et al, 2018; Salles et all, 2011; Bachy et al, 2019; Drugs.com, 2011.
CIT is generally recommended for active therapy
StiL trial
phase 3
B-R vs R-CHOP
BRIGHT trial
phase 3
B-R vs
R-CHOP/R-CVP
GALLIUM trial
phase 3
G- vs R-chemo
• B-R superior to R-
R-CHOP
• Trend toward PFS
benefit with B-R vs
R-CHOP/R-CVP
• Superior PFS with G-
G- vs R-chemo, but
no difference in OS
• More grade 3-5 AEs
AEs with G
(75% vs 68%)
• Approval in 2017 for
for initial
chemotherapy and
maintenance G
R2 considered in certain
patients (eg, desiring
chemotherapy-free
regimens)
RELEVANCE trial
phase 3
R2 (lenalidomide + R) vs
R-chemo
• Similar efficacy with R2
compared with R-
R-chemotherapy
• Less hematologic toxicity
toxicity with R2, but more
more grade 3/4 cutaneous
cutaneous toxicity (7% vs
vs 1%)
R maintenance for
who respond to
therapy
PRIMA trial
phase 3
rituximab maintenance
• Superior PFS (and TTNT),
but not OS, with R
maintenance
• FDA approved in 2011 as
as maintenance therapy in
in patients with FL who
respond to induction
therapy
29. GALLIUM: G-Chemo vs R-Chemo
iNHL = indolent non-Hodgkin lymphoma; ECOG = Eastern Cooperative Oncology Group; PS = performance status; D = day; C = cycle;
Q3W = every 3 weeks; Q4W = every 4 weeks; CR = complete response; EOI = end of induction; IV = intravenous; Q2Mo = every 2 months;
PD = progressive disease; INV = investigator; IRC = independent review committee; EFS = event-free survival; DFS = disease-free survival;
DOR = duration of response; ORR = objective response rate; FDG-PET = fluorodeoxyglucose PET.
Marcus et al, 2017.
International, Open-Label, Randomized Phase 3 Study
Primary end point
• PFS (INV-assessed in FL)
Secondary and other end points
• PFS (IRC-assessed)
• CR/ORR at EOI (± FDG-PET)
• OS, EFS, DFS, DOR, TTNT
• Safety
Previously untreated CD20-positive iNHL
• Age ≥18 years
• FL grade 1-3a or
splenic/nodal/extranodal MZL
• Stage III/IV or stage II bulky disease (≥7
cm) requiring treatment
• ECOG PS 0-2
• Target FL enrollment: 1,200
1:1
R
A
N
D
O
M
I
Z
A
T
I
O
N
G-chemo
G 1,000 mg IV on D1, D8,
D15 of C1 and D1 of C2-8
(Q3W) or C2-6 (Q4W)
plus CHOP, CVP, or
bendamustine
R-chemo
R 375 mg/m2 IV on D1 of
C1-8 (Q3W) or C1-6
(Q4W) plus CHOP, CVP,
or bendamustine
CR or PR
at EOI visit
G
G 1,000 mg IV Q2Mo for 2
years or until PD
R
R 375 mg/m2 IV Q2Mo for
2 years or until PD
32. RELEVANCE: R2 vs R-chemo in Frontline FL
Morschhauser et al, 2018; Morschhauser et al, 2021.
Figure 2. Progression-Free Survival by IRC (A) and Overall Survival (B)
in the Intention-to-Treat Population
Figure 1. Consort Diagram
33. Rates of Anti–SARS-CoV-2 Spike Protein IgG Antibody Seroconversion
HM = hematological malignancies.
Ribas et al, 2021.
Patients With Different Histologies of HM Compared With Healthy
Subjects
34. Serologic Response SARS-CoV-2 Vaccinations: Patient Characteristics
Greenberger et al, 2021; LLS, 2021.
While many patients with HM fail to mount a full antibody response, the safety profiles of SARS-CoV-2 mRNA vaccines are similar compared
with age-matched healthy individuals
Therefore, patients with blood cancer are encouraged to get the SARS-CoV-2 vaccines as recommended by NCCN guidelines
Prospective national
registry (LLS National
Patient Registry):
https://www.ciitizen.com/lls/
NCT04794387
was used to assess the
serologic response to
vaccinations against
SARS-CoV-2
Cancer diagnosis Neg (n=357) Pos (n=1,088) All patients (n=1,445)
Acute lymphoblastic leukemia 2 (11.8%) 15 (88.2%) 17 (100.0%)
Acute myeloid leukemia 3 (8.8%) 31 (91.2%) 34 (100.0%)
Burkitt lymphoma 0 (0.0%) 1 (100.0%) 1 (100.0%)
Chronic lymphocytic leukemia 233 (35.8%) 417 (64.2%) 650 (100.0%)
Chronic myeloid leukemia 1 (2.9%) 33 (97.1%) 34 (100.0%)
Diffuse large B cell lymphoma 11 (21.2%) 41 (78.8%) 52 (100.0%)
Follicular lymphoma 22 (22.4%) 76 (77.6%) 98 (100.0%)
Hairy cell leukemia 0 (0.0%) 7 (100.0%) 7 (100.0%)
Hodgkin lymphoma 1 (1.5%) 64 (98.5%) 65 (100.0%)
Mantle cell lymphoma 15 (55.56%) 12 (44.4%) 27 (100.0%)
Marginal zone lymphoma 13 (38.2%) 21 (61.8%) 34 (100.0%)
Multiple myeloma 9 (4.9%) 175 (95.1%) 184 (100.0%)
Non-Hodgkin lymphoma not specified 10 (20.8%) 38 (79.2%) 48 (100.0%)
Primary mediastinal (thymic) large B cell lymphoma
lymphoma
0 (0.0%) 4 (100.0%) 4 (100.0%)
Smoldering multiple myeloma 0 (0.0%) 29 (100.0%) 29 (100.0%)
T-cell lymphoma 2 (15.4%) 11 (84.6%) 13 (100.0%)
Waldenstrom macroglobulinemia 25 (25.8%) 72 (74.2%) 97 (100.0%)
35. Patients %
Stay during COVID-19
Hospital 75 66.4%
COVID-19 ward 59/75 83.8%
ICU 16/75 14.2%
Of which, invasive mechanical ventilation 10/16 8.8%
Home 38 33.6%
Overall mortality at 30 days 14 12.4%
Attributable to COVID-19 9/14 64.3%
+ Hematological malignancy 3/14 21.4%
Mortality according to type of hematological malignancy
Acute lymphoid leukemia 0/3 0.0%
Chronic lymphoid leukemia 2/28 7.1%
Acute myeloid leukemia 0/5 0.0%
Chronic myeloid leukemia 0/1 0.0%
Myelodysplastic syndrome 2/7 28.6%
Hodgkin lymphoma 1/4 25.0%
Non-Hodgkin lymphoma 6/36 16.7%
Myelofibrosis 1/3 33.3%
Polycythemia vera 0/2 0.0%
Systemic mastocytosis 1/2 50.0%
Multiple myeloma 1/20 5.0%
Aplastic anemia 0/2 0.0%
Mortality for patients with active hematological malignancy
Yes 7/14 50.0%
No 7/14 50.0%
Mortality for patients with chemoimmunotherapy or radiotherapy
In the last 3 mos 10/14 71.4%
>3 mo/watch and wait 4/14 28.6%
Outcome of Vaccinated Patients That Developed COVID-19 Infection
Low serologic
response rate to anti–
SARS-CoV-2 vaccines
in patients with HM
may translate to
higher rates of
infections
This has previously
been described
following monoclonal
antibody treatment
Pagano et al, 2022.
37. Case 1: Ms. SM (cont.)
65-year-old woman originally diagnosed with FL grade 1/2
Stage III low tumor burden
Had a partial response to R x4 doses; no maintenance
Now with return of increased size in prior areas (largest 4 cm) and new para-
aortic LN 6 cm
SUVmax = 5
Which treatment option is most suitable for this patient?
A. Rituximab alone
B. Rituximab + lenalidomide
C. Watch and wait
D. Tazemetostat
E. R-CHOP
F. B-R
G. Axi-cel
38. Poorer Outcomes in the R/R Setting
R/R = relapsed/refractory.
Link et al, 2019; Casulo et al, 2015.
National LymphoCare Study
PFS by Treatment Line
First line: 79.4 months
Second line: 18.0 months
Third line: 10.0 months
Fourth line: 8.3 months
Fifth line: 8.2 months
Line of treatment, median PFS
39. Progression of Disease in 24 Months Predicts Poor Survival
POD24 = progression of disease within 24 months.
Casulo, Dixon et al, 2022; Casulo et al, 2017.
Analysis of >5000 patients on 13 clinical trials
POD24 independently associated with increased risk of death or progression
POD24 predicted by:
Male sex
Poor PS
High-risk FLIPI
Elevated ß2-macroglobulin
For patients with POD24,
death more likely in the
following:
Age >60
Male sex
PS ≥2
High-risk FLIPI
Hgb <12
Elevated ß2-macroglobulin
40. Relapsed/Refractory FL (LEO CReWE)
Casulo, Larson et al, 2022.
441 patients with R/R FL
Non-transformed grade 1-3a
≥2 prior lines of systemic therapy, including an alkylating agent and an anti-CD20
For lines of therapy 3 and later (any therapy):
5-year OS: 75% (95% CI: 70-79)
PFS: 17 months
ORR: 70% (95% CI: 65-74)
Patients refractory to an alkylating agent have lower ORR (68% vs 77%) and lower 5-
year OS (72% vs 81%; HR 1.60) than patients not refractory to an alkylating agent
Mortality at 5 years: 17% from lymphoma, 3% other causes, 9%
unknown
Treatment Patterns and Outcomes After 3+ Lines of Therapy
43. Novel Therapies in Relapsed/Refractory FL
Lymphoma Research Foundation, 2021; Gilead, 2022; Secura Bio, 2021; US Food and Drug Administration, 2022.
2017 2019 2020 2021
R2: Rituximab +
lenalidomide
Tazemetostat
Umbralisib
(withdrawn)
Lisocabtagene
maraleucel
Axicabtagene
ciloleucel
Obinutuzumab
Duvelisib
(withdrawn)
Copanlisib
2018
2014
Idelalisib
(withdrawn)
2022
Tisagenlecleucel
44. NHL Treatment: Relapsed/Refractory FL
HDT = high-dose therapy; SCT = stem cell transplantation.
NCCN, 2022.
Second-line and later therapy
Bendamustine + obinutuzumab or rituximab (except if
prior bendamustine)
CHOP + obinutuzumab or rituximab
CVP + obinutuzumab or rituximab
Lenalidomide ± rituximab
PI3K inhibitors
Copanlisib
Tazemetostat
EZH2 mutation positive
EZH2 wild type or unknown relapsed/refractory disease
with no satisfactory alternative options
CAR T-cell therapy
Axi-cel
Consolidation or extended dosing
(optional)
Rituximab maintenance
Obinutuzumab maintenance
(rituximab refractory)
HDT plus autologous SCT
Allogeneic SCT for selected
patients
47. Lenalidomide in Follicular Lymphoma
Flowers et al, 2020.
First-line treatment options Relapsed treatment options
Rituximab (R) Rituximab (R)
R-chemotherapy R-chemotherapy
R2 R2
Study Lenalidomide dosing Study Lenalidomide dosing
Zucca et al, 2019
15 mg/day with rituximab
for 18 weeks
Witzig et al, 2009
25 mg/day Days 1-21 (28-
day cycle) for up to 52
weeks
Fowler et al, 2014
20 mg/day Days 1-21 (28-
day cycle) with rituximab
for up to 12 cycles
Leonard et al, 2015
15-25 mg/day Days 1-21
(28-day cycle) ± rituximab
Martin et al, 2017
20-25 mg/day Days 1-21
(28-day cycle) with
rituximab for up to 12
cycles
Chong et al, 2015 10 mg daily with rituximab
Morschhauser et al, 2018
20 mg/day Days 1-21 (28-
day cycle) with rituximab
x6 cycles followed by 10
mg/day Days 1-21 (28-day
cycle) for 12 cycles in
patients with CR
Andorsky et al, 2019
20 mg/day Days 1-21 (28-
day cycle) with rituximab
for 12 cycles followed by
1:1 randomization for
patients with ≥SD to
maintenance lenalidomide
10 mg/day Days 1-21 with
rituximab versus rituximab
alone
48. AUGMENT (NHL-007): R/R FL or MZL
Leonard et al, 2019.
R2 vs Rituximab Monotherapy
12 months
R/R
FL or MZL
(n=358)
Placebo
Rituximab weekly x4 then every month x4
Lenalidomide 20 mg
Rituximab weekly x4 then every month x4
Primary end point: PFS
49. Case 1: Ms. SM (cont.)
66-year-old woman with relapsed FL grade 1/2 following R x4 doses
No maintenance with 3-year disease control
Now with progression on B-R
LDH 520 units/L
Which treatment option is most suitable for this patient?
A. Rituximab alone
B. R2
C. Watch and wait
D. Tazemetostat
E. R-CHOP
F. B-R
G. Axi-cel
50. Case 2: Mr. TD (cont.)
72-year-old man diagnosed with stage III FL with high tumor burden
Treated with B-R x6 cycles and achieved a CR
2.5 years later, he had progression of disease
Biopsy confirmed relapsed FL grade 1-2
Which option is most suitable for this patient?
A. R-CHOP
B. R2
C. Tazemetostat
D. Obinutuzumab + bendamustine
51. Case 2: Mr. TD (cont.)
79-year-old man diagnosed with stage III FL high tumor burden
Treated with B-R x6 cycles and achieved a CR
2.5 years later, he had progression of disease
Then treated (at age 76) with R-CHOP x6 cycles with maintenance and achieved a CR
Now has relapsed with bulky disease in the abdomen; largest LN 7 cm in mesentery
Which option is most suitable for this patient?
A. Axi-cel
B. R2
C. Tazemetostat
D. Obinutuzumab + bendamustine
52. AUGMENT: R2 vs Rituximab Monotherapy
a2 patients in each group had an ECOG PS of 2.
bBulky disease = at least 1 lesion that is ≥7 cm or at least 3 lesions with ≥3 cm in the longest diameter, by investigator review.
c2 patients in the R2 group and 1 patient in the R-placebo group did not have FLIPI scores recorded.
ULN = upper limit of normal.
Leonard et al, 2019.
Characteristic, n (%)
R2
(n=178)
Rituximab-placebo
(n=180)
Median age, years (range) 64 (26-86) 62 (35-88)
Age ≥60 years 108 (61%) 106 (59%)
Age ≥65 years 82 (46%) 73 (41%)
ECOG PS 1-2a 62 (35%) 52 (29%)
Positive BM involvement, n involved/performed (%) 33/106 (31%) 31/111 (28%)
Ann Arbor stage III or IV at study entry 137 (77%) 124 (69%)
Bulky diseaseb (≥7 cm or ≥3 cm x3) 45 (25%) 49 (27%)
High tumor burden per GELF criteria 97 (54%) 86 (48%)
Histology
FL 147 (83%) 148 (82%)
MZL 31 (17%) 32 (18%)
LDH > ULN 43 (24%) 39 (22%)
B-symptoms 16 (9%) 12 (7%)
FLIPI scorec
0 or 1 52 (29%) 67 (37%)
2 55 (31%) 58 (32%)
3 to 5 69 (39%) 54 (30%)
Baseline Characteristics (ITT)
53. AUGMENT: R2 vs Rituximab Monotherapy (cont.)
ITT = intent to treat; CI = confidence interval; NE = not estimable; NR = not reached.
Leonard et al, 2019.
Primary End Point: Progression-Free Survival (ITT, IRC)
Median PFS
R2
(n=178)
Rituximab-
placebo
(n=180)
HR
(95% CI)
P value
By IRC, mo
(95% CI)
39.4
(22.9-NE)
14.1
(11.4-16.7)
0.46
(0.34-0.62)
<0.001
By investigator,
mo (95% CI)
25.3
(21.2-NR)
14.3
(12.4-17.7)
0.51
(0.38-0.69)
<0.0001
54. AUGMENT: R2 vs Rituximab Monotherapy (cont.)
*Refractory = no response or progressive disease <6 months after the last dose.
Leonard et al, 2019.
Prespecified Subgroup PFS Analysis (IRC, ITT)
55. AUGMENT: R2 vs Rituximab Monotherapy (cont.)
Leonard et al, 2019.
Grade 3/4 neutropenia (50% vs 13%) and leukopenia (7% vs 2%) higher with R2
Efficacy and Safety
Progression-Free
Survival
Overall Survival
PFS
Probability
Months Since Randomization
R2
R-placebo
Months Since Randomization
OS
Probability
R2
R-placebo
Median PFS by IRC
• R2 = 39.4 months
• R-placebo = 14.1 months
HR=0.46
2-year OS
• R2 = 93%
• R-placebo = 87%
Median follow-up: 28.3 months
56. mPFS = median PFS; mOS = median OS; ALT = alanine transaminase; AST = aspartate aminotransferase.
Gopal et al, 2014; Dreyling et al, 2017; Flinn, Miller, et al, 2019; Dreyling et al, 2020; Fowler et al, 2021; Zydelig® prescribing information, 2020; Copiktra® prescribing information, 2019.
Idelalisib Copanlisib Duvelisib Umbralisib
Isoform
targeted
δ α, δ δ,γ δ,CK1ε
ORR in FL
patients
54% 59% 42% 45%
mPFS 11 months 12.5 months 9.5 months 10.6 months
mOS 20.3 months 42.6 months 28.9 months N/A
Serious AEs
of interest
Black box warnings:
Hepatotoxicity
Diarrhea/colitis
Pneumonitis
Infection
Intestinal perforation
perforation
Most common
grade 3/4 AEs:
Hyperglycemia
Hypertension
Neutropenia
Pneumonia
Black box warnings:
Diarrhea/colitis
Infection
Pneumonitis
Skin reaction
Most common grade 3/4
3/4 Aes:
Neutropenia
Diarrhea
ALT/AST elevation
PI3K Inhibitors Approved for R/R FL
57. EZH2, a Histone Methyltransferase, in FL
Morschhauser et al, 2017; Morschhauser et al, 2020; Makita & Tobinai, 2018.
In normal B-cell biology, EZH2 regulates
germinal center formation
EZH2 mutations can lead to oncogenic
transformation by locking B cells in
germinal state and preventing terminal
differentiation
EZH2-activating mutations found in
~20% of patients with FL
Tazemetostat: selective, oral, first-in-
class EZH2 inhibitor
Whether WT or mutant, EZH2 biology is
relevant to FL
58. Tazemetostat: EZH2 Inhibitor
COO = cell of origin; GCB = germinal center B-cell; Mt = mutant; WT = wild type; BID = twice a day; PK = pharmacokinetic.
Morschhauser et al, 2018.
PRESCREENING
COHORT
ALLOCATION
ELIGIBILTY,
ENROLLMENT
EOT
FOLLOW-UP
DLBCL, GCB
EZH2 Mt (n=60)
FL, EZH2 WT
(n=45)
FL, EZH2 Mt (n=45)
DLBCL, non-GCB
(n=60)
DLBCL, GCB
EZH2 WT (n=60)
Archival tissue
Central lab COO, EZH2
Tazemetostat 800 mg BID until
PD or withdrawal
ORR, PFS, DOR, safety, PK OS
Clinical Activity and Favorable Safety in a Phase 2 Multicenter Study
Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
59. Tazemetostat: Relapsed FL Activity by EZH Mutation Status
Morschhauser et al, 2020.
Best response, IRC assessed
FL EZH2 Mt
(n=45)
FL EZH2 WT
(n=54)
Objective response rate (CR + PR), n (%) 95% CI
31 (69%)
53-82
19 (35%)
23-49
Complete response 6 (13%) 2 (4%)
Partial response 25 (56%) 17 (31%)
Stable disease 13 (29%) 18 (33%)
Progressive disease 1 (2%) 12 (22%)
No data/unknown 0 5 (9%)
Final responses, IRC assessed n=31 n=19
Median duration of response, months 10.9 13.0
Median progression-free survival, months 13.8 11.1
Median overall survival, months NR NR
60. Tazemetostat Efficacy
Morschhauser et al, 2020.
EZH2 Mt EZH2 WT
Response ≥6 months 61% 53%
Response ≥12 months 23% 37%
Response ≥18 months 19% 21%
EZH2 Mt EZH2 WT
%
Patients
With
Response
Duration of Response (months) Duration of Response (months)
Durability of Response in Both Cohorts
62. CAR T-Cell Therapy: Axi-Cel
CAR = chimeric antigen receptor.
Yescarta® Prescribing Information, 2022; Neelapu et al, 2018; van der Stegen et al, 2015.
Axi-cel is an autologous anti-CD19 CAR T-cell therapy
Axi-cel is approved in the US and EU, for the treatment of adult patients with
relapsed or refractory large B-cell lymphoma after 2 or more lines of
systemic therapy
63. ZUMA-5 Study Design: Axi-Cel in R/R FL
mAb = monoclonal antibody.
Neelapu, 2021; Jacobson et al, 2022.
Key ZUMA-5 Eligibility Criteria
• R/R FL (grades 1-3a) or MZL (nodal
or extranodal)
• ≥2 prior lines of therapy that must have
included an anti-CD20 mAb combined
with alkylating agent
R/R NHL
(N=157) Leukapheresis
Conditioning
Chemotherapy
Fludarabine 30 mg/m2
IV and
cyclophosphamide 500
mg/m2 on Days -5, -4,
-3
Axi-Cel Infusion
2x106 CAR-positive cells/kg on
Day 0
Post-treatment assessment and
long-term follow-up periods
Primary End Point
• ORR (IRRC-assessed per the
Lugano classification)
Key Secondary End Points
• CR rate (IRRC-assessed)
• Investigator-assessed ORR
• DOR, PFS, OS
• AEs
• CAR T cell and cytokine levels
64. .
ZUMA-5: Axi-Cel in R/R FL
Among efficacy-eligible patients with iNHL (n=109), the ORR was 92% (95% CI: 85-96), with a
76% CR rate
Among all treated patients with iNHL (n=149), the ORR was 92% (95% CI: 86-96), with a 77%
CR rate
Neelapu, 2021; Jacobson et al, 2022.
ORR by Central Review
All Patients (n=109) Patients with FL (n=86)
65. ZUMA-5: Axi-Cel in R/R FL (cont.)
Neelapu, 2021; Jacobson et al, 2022.
Median OS was not yet reached in efficacy-eligible patients with FL or MZL
Among patients with FL, 3 deaths occurred after Month 24
No disease progression events occurred after Month 24
PFS and OS
66. ZUMA-5: Axi-Cel in R/R FL (cont.)
CRS = cytokine release syndrome; NEs = neurologic events.
Neelapu, 2021; Jacobson et al, 2022.
Consistent with prior reports, the most common grade ≥3 AEs in all treated
patients were neutropenia (33%), decreased neutrophil count (28%), and
anemia (24%)
Grade ≥3 CRS and NEs occurred in 7% of patients (6% FL; 8% MZL) and
19% of patients (15% FL; 36% MZL), respectively
Most CRS cases (120 of 121) and NEs (82 of 87) of any grade resolved by data cutoff
Nearly half of NEs (49%) resolved ≤2 weeks after onset; most NEs (76%) resolved ≤8
weeks after onset
Grade ≥3 cytopenias present ≥30 days post-infusion were reported in 34%
of patients (33% FL; 36% MZL), most commonly neutropenia in 29% of
patients (27% FL; 36% MZL)
Safety Results
67. TRANSCEND: Liso-Cel for R/R Follicular Lymphoma Grade 3b
Liso-cel = lisocabtagene maraleucel.
Abramson et al, 2020; FDA, 2021.
Median 3 (1-8) lines of prior therapy
ORR: 73% (95% CI: 66.8%-78.0%)
CR: 53% (95% CI: 46.8%-59.4%)
OS: 21.1 months
PFS: 6.8 months
Approved in February 2021 for R/R large B-cell
lymphoma after ≥2 lines of systemic therapy
Baseline characteristics Patients (n=269)
Diffuse large B-cell lymphoma, not
not otherwise specified
137 (51%)
Diffuse large B-cell lymphoma
transformed from indolent
lymphomas
• From follicular lymphoma
• From other indolent subtypes
78 (29%)
60 (22%)
18 (7%)
High-grade B-cell lymphoma with
with gene rearrangements in MYC
MYC and BCL-2 or BCL-6 or both
both
36 (13%)
Primary mediastinal B-cell
lymphoma
15 (6%)
Follicular lymphoma grade 3B 3 (1%)
CD-19–Directed CAR T-Cell Therapy
68. TRANSCEND : Liso-Cel (cont.)
Abramson et al, 2020.
Consistent with other CAR T
Most common grade ≥3:
Neutropenia 60%
Anemia 37%
Thrombocytopenia 27%
CRS in 42% of patients, grade ≥3: 2%
Neurologic toxicity in 30%, grade ≥3: 10%
Dose-limiting toxicity: 6% (9 patients)
Prolonged cytopenias, hypogammaglobulinemia, infections
Safety Results: Treatment-Emergent Adverse Events
69. ELARA: Tisagenlecleucel for R/R FL Grade 1, 2, and 3a
Fowler et al, 2022.
PFS at 12 months: 67%
Median PFS not reached
Safety Analysis Set (n=97)
Selected AEs Any grade Grade ≥3
Any TRAE 78.4% 46%
CRS 48.5% 0
Neutropenia 33.0% 32.0%
Anemia 24.7% 13.4%
Any neurological 37.1% 3.1%
Headache 23.7% 1%
Any gastrointestinal 41.2% 4.1%
Approved May 2022 for R/R
follicular lymphoma after ≥2 prior
lines of systemic therapy
Efficacy Analysis Set (n=94)
Complete response
(95% CI)
69.1%
(59%-78%)
Partial response 17.0%
Stable disease 3.2%
Progressive disease 9.6%
Grade 1, 2, and 3a Without Histologic Transformation
70. Structure of Selected BiTE and Bispecific Antibodies
BiTE = bispecific T-cell engager.
Schuster, 2021.
72. Mosunetuzumab: Anti-CD20xCD3 Bispecific Antibody for R/R FL
Budde et al, 2022.
Single-arm, phase 2 study
90 patients with R/R FL
Grade 1-3a
2 or more prior lines of therapy
Efficacy by Independent review committee assessment
Objective response rate 72 (80%)
Complete response rate 54 (60%)
Median duration of response 22.8 months
Safety and Efficacy
Accelerated approval
December 2022
Safety Analysis (n=90)
Selected AEs Any grade Grade ≥3
Any TRAE 83 (92%) 46 (51%)
CRS 40 (44%) 2 (2%)
Fatigue 33 (37%) 0
Headache 28 (31%) 1 (1%)
Neutropenia 26 (28%) 24 (27%)
Pyrexia 26 (28%) 1(1%)
Hypophosphatemia 24 (27%) 15 (17%)
73. Key Takeaways
In the modern era, the median OS of FL is approaching 20
years
Treatment options for newly diagnosed advanced-stage FL
include multiple immunochemotherapy regimens ± anti-
CD20 maintenance
Several approved options for relapsed/refractory FL
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Which option is most suitable for this patient?
R-CHOP
R2
Watch and wait
Obinutuzumab + bendamustine
Which treatment option is most suitable for this patient?
Rituximab alone
R2
Watch and wait
Obinutuzumab + bendamustine
Which treatment option is most suitable for this patient?
Rituximab alone
R2
Watch and wait
Tazemetostat
R-CHOP
B-R
Axi-cel
All are reasonable options. Bendamustine/rituximab (B-R) would be the most commonly used.
Which treatment option is most suitable for this patient?
Rituximab alone
R2
Watch and wait
Tazemetostat
R-CHOP
B-R
Axi-cel
Which option is most suitable for this patient?
R-CHOP
Rituximab + lenalidomide
Tazemetostat
Obinutuzumab + bendamustine
Which option is most suitable for this patient?
Axi-cel
R2
Tazemetostat
Obinutuzumab + bendamustine
A and C are also options.
Results in phase 1 were promising, prompting a large phase 2 in 5 cohorts of patients with relapsed/refractory non-Hodgkin lymphoma prospectively stratified by disease (FL or diffuse large B-cell lymphoma (DLBCL)), mutation status, and cell of origin of DLBCL
Patients were eligible if they had failed ≥2 prior systemic therapies, including an anti-CD20 for both and an alkylating agent for FL or an anthracycline for DLBCL
Best objective response rate as primary end point, according to Cheson (2007)
Target enrollment for all DLBCL cohorts is 60 and for all FL cohorts is 45
Recently, a sixth cohort was added, consisting of DLBCL wild-type patients treated with combination of tazemetostat and prednisolone based on compelling preclinical synergy data. Cohort is open for accrual