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
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
UAEU - CMHS - Hematology-Oncology Course - MMH 302 - HONC 320. Education material for medical students - It cover basic principles of hematology and oncology, including CAR-T and gene editing. It can be used for study and review. It illustrates main principles of hematology and oncology.
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
UAEU - CMHS - Hematology-Oncology Course - MMH 302 - HONC 320. Education material for medical students - It cover basic principles of hematology and oncology, including CAR-T and gene editing. It can be used for study and review. It illustrates main principles of hematology and oncology.
Tailoring Therapy for Follicular Lymphoma Based on the Latest Evidencei3 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 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.
Dr Abdullah Ansari
MBBS, MD Medicine
Aligarh Muslim University
Clinical case
Hemolytic Anemia
Intravascular vs extravascular hemolysis
Classification of hemolytic anemia
Approach to hemolysis
Patient history
Clinical features
Peripheral blood smear
Investigation
Treatment
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
Tailoring Therapy for Follicular Lymphoma Based on the Latest Evidencei3 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 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.
Dr Abdullah Ansari
MBBS, MD Medicine
Aligarh Muslim University
Clinical case
Hemolytic Anemia
Intravascular vs extravascular hemolysis
Classification of hemolytic anemia
Approach to hemolysis
Patient history
Clinical features
Peripheral blood smear
Investigation
Treatment
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
Trials in secondary progressive multiple sclerosis: design & efficiencyMS Trust
This presentation by Dr Jeremy Chataway looks at:
- What is MS progression?
- How would an anti-progressive drug be found?
- What outcome would be measured?
- What trial design could/would be used?
- Where are we now?
It was presented at the MS Trust Annual Conference in November 2013.
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.
Ohio State's ASH Review 2017 - Myeloproliferative DisordersOSUCCC - James
Katherine Walsh, MD
Assistant Professor of Clinical Internal Medicine
The Ohio State University Comprehensive Cancer Center -
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Similar to Current Standards and New Directions in the Treatment of Acquired Thrombotic Thrombocytopenic Purpura (20)
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
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.
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
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
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.
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.
Normal Labour/ Stages of Labour/ Mechanism of LabourWasim Ak
Normal labor is also termed spontaneous labor, defined as the natural physiological process through which the fetus, placenta, and membranes are expelled from the uterus through the birth canal at term (37 to 42 weeks
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
TESDA TM1 REVIEWER FOR NATIONAL ASSESSMENT WRITTEN AND ORAL QUESTIONS WITH A...
Current Standards and New Directions in the Treatment of Acquired Thrombotic Thrombocytopenic Purpura
1. Current Standards and New Directions in the
Treatment of Acquired Thrombotic
Thrombocytopenic Purpura
Spero R. Cataland, MD
Professor of Internal Medicine
Division of Hematology, Benign Hematology Section Head
Wexner Medical Center at The Ohio State University
3. Learning Objectives
aTTP = acquired thrombotic thrombocytopenic purpura; ADAMTS13 = a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13.
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
6. Pathophysiology of aTTP/iTTP
iTTP = immune-mediated TTP.
Moschowitz, 1925.
16-year-old female, high school
graduate, business school, now
employed for 8 months
Awoke with “weakness, pallor,
constipation”
Petechiae reported, no platelet count
Progressed to partial paresis of left
arm and leg, coma, irregular
respirations, and death
Immune-Mediated (Acquired) TTP
7. Types of Thrombotic Thrombocytopenic Purpura (TTP)
Arnold et al, 2017; Bae et al, 2022.
Thrombotic microangiopathy caused by severely reduced ADAMTS13
activity
ADAMTS13 protease cleaves ultra-large von Willebrand factor (VWF)
multimers on the endothelial surface
Acquired form of iTTP
Autoantibodies against ADAMTS13 protease
Incidence approximately 3 per million
Congenital form of TTP
<5% of all TTP cases
Biallelic pathogenic variants in ADAMTS13
Incidence approximately 1 per million
8. Immune-Mediated (Acquired) TTP
Survival now >90% with prompt recognition
Risk of future relapse
High prevalence of PTSD in TTP survivors
35% with positive screen for PTSD
Long-term complications from a prior iTTP diagnosis
Shortened life expectancy
Cardiovascular complications
Neurocognitive deficits
Short-term memory, new memory issues
PTSD = post-traumatic stress disorder.
Adeyemi et al, 2022; Chaturvedi et al, 2017; Deford et al, 2013; Sukumar et al, 2022; Cataland et al, 2011.
9. TTP: Evolution of the Clinical Syndromes
Slide courtesy of Dr. James George.
George, 2021.
1925-1964 1964-1980 1982-1989
Thrombocytopenia 96% 96% 100%
Hemolytic anemia 96% 98% 100%
Neurologic symptom
symptom
92% 84% 63%
Renal disease 88% 76% 59%
Fever 98% 59% 26%
Death 90% 54% 22%
10. Case Study 1: Ms. HB
ITP = immune thrombocytopenia.
22-year-old Caucasian female with a history of ITP as a child,
presenting with 7 days of nausea and headaches. She had epistaxis
that morning prior to her arrival
Past medical history: ITP
Family medical history: Hypertension
Social history: Smoker, social alcohol
11. Case Study 1: Ms. HB (cont.)
LDH = lactate dehydrogenase; Cr = creatinine.
George, 2006.
Laboratory Data at Presentation
10.4
1K
8.5
Serum Cr: 1.3 mg/dL
LDH: 1,200 U/L
ADAMTS13 activity: ?
13. Treatment of iTTP
CVA = cerebrovascular accident.
Arnold et al, 2017; Kremer Hovinga Strebel et al, 2022; Upreti et al, 2019.
Serves to confirm the clinical diagnosis of TTP
Defines those patients at greatest risk for exacerbations of iTTP
Predicts the risk of relapse during long-term follow-up
? Predicting the risk for long-term complications
CVA in patients with a history of iTTP in remission
What Is the Utility of ADAMTS13 Activity in Treatment?
14. ADAMTS13 Activity and TTP
Motto et al, 2005; Banno et al, 2006.
Deficient ADAMTS13 alone not sufficient
to lead to an acute TTP episode
ADAMTS13 -/- mice do not spontaneously
develop TMA findings
Shiga toxin, collagen/epinephrine required
to initiate the development of
thrombocytopenia
Congenital TTP
Delayed presentations at the time of
pregnancy
Second Hit Hypothesis
15. ISTH Guidelines for the Diagnosis of TTP
ISTH = International Society on Thrombosis and Hemostasis; IgG = immunoglobulin G.
Zheng et al, 2020b.
Stage 1
Acquire a plasma sample for ADAMTS13 testing (eg, ADAMTS13 activity and inhibitors or anti-ADAMTS13
IgG) before an initiation of therapeutic plasma exchange treatment (PEX) or use of any blood product
Stage 2
Start PEX and corticosteroids without waiting for the results of ADAMTS13 testing (see
Recommendation 1 in Management Guidelines)
Stage 3
Consider early administration of caplacizumab (see Recommendation 5 in Management Guidelines) before
receiving ADAMTS13 activity results
Stage 4
When the result of plasma ADAMTS13 activity is available, continue caplacizumab if ADAMTS13 activity is
<10 IU/dL or <10% of normal (a positive result) or stop caplacizumab and consider other diagnoses if
ADAMTS13 activity is >20 IU/dL or >20% of normal (a negative result)
Stage 5
For patients with a plasma ADAMTS13 activity <10 IU/dL or <10% of normal (a positive result), consider
adding rituximab as early as possible, as a majority of these patients (>95%) have autoantibodies against
ADAMTS13 (see Recommendation 2 in Management Guidelines)
Recommendation 1:
In settings with timely access to plasma ADAMTS13 activity
testing and for patients with a high clinical suspicion of
immune TTP, the panel suggests the following diagnostic
strategies (a conditional recommendation in the context of
low-certainty evidence)
16. Stage 1
Acquire a plasma sample for ADAMTS13 testing (eg, ADAMTS13 activity and inhibitor or anti-
anti-ADAMTS13 IgG) before an initiation of PEX or use of any blood product
Stage 2
Consider starting PEX and corticosteroids, depending on the clinician’s judgement and
assessment of the individual patient
Stage 3
Do not start caplacizumab until the result of plasma ADAMTS13 activity is available
Stage 4
When the result of plasma ADAMTS13 activity testing is available, consider adding
caplacizumab and rituximab (see Recommendation 2 in Management Guidelines) if
ADAMTS13 activity is <10 IU/dL or <10% of normal with an inhibitor or elevated anti-
ADAMTS13 IgG (a positive test result), but do not start caplacizumab and consider other
diagnoses if ADAMTS13 activity is >20 IU/dL or >20% of normal (a negative result)
ISTH Guidelines for the Diagnosis of TTP (cont.)
Recommendation 2:
In settings with timely access to plasma ADAMTS13 activity
testing and for patients with intermediate or low clinical
suspicion of iTTP, the panel suggests the following diagnostic
strategies (a conditional recommendation in the context of
low-certainty evidence)
Zheng et al, 2020b.
17. Prediction of ADAMTS13 Activity
Acquired Thrombotic Microangiopathies
Study
ADAMTS13
Threshold
ADAMTS13 Activity
Severely Deficient Non-Deficient
Platelets
(x 109/L)
Creatinine
(mg/dL)
Platelets
(x 109/L)
Creatinine
(mg/dL)
Raife et al, 2004 15% 13 1.2 44 2.7
Coppo et al, 2010 5% 17 1.3 67 5.1
Kremer Hovinga et al, 2010 10% 11 1.6 22 4.6
Bentley et al, 2010 15% 16 1.1 64 3.5
Cataland et al, 2012 10% 12 1.5 66 5.8
Raife et al, 2004; Coppo et al, 2010; Kremer Hovinga et al, 2010; Bentley et al, 2010; Cataland et al, 2012.
18. Predicting Severely Deficient (<10%) ADAMTS13 Activity
TTP
Derivation
(n=200)
Internal
cohort
(n=150)
External
validation
(n=146)
0-4 0/84 (0%) 0/89 (0%) 2/47 (4%)
5 2/44 (5%) 3/32 (9%) 6/25 (24%)
6 or 7 58/72 (81%) 18/29 (62%) 61/74 (82%)
Data are number of individuals with ADAMTS13 activity of ≤10%/total number of
number of individuals with that score (%)
Validation of PLASMIC score
PLASMIC score for prediction of microangiopathy
associated with severe ADAMTS13 deficiency
POINTS
Platelet count <30 x109/L 1
Hemolysis variable 1
No active cancer 1
No history of solid organ or stem-cell transplant 1
MCV <90 fL (<9.0 x10-14 L) 1
INR <1.5 1
Creatinine <2.0 mg/dL 1
Score of 0-4 denotes low risk for severe ADAMTS13 deficiency; score of 5
of 5 denotes intermediate risk; score of 6 or 7 denotes high risk
7-component score designed by the Harvard TMA Research
Collaborative Registry
PLASMIC
Score
MAT-GLB-2003153
MCV = mean corpuscular value; INR = international normalized ratio.
Bendapudi et al, 2017.
19. ADAMTS13 Activity After Starting PEX
PE = plasma exchange.
Wu et al, 2015.
Should I Still Order It?
14/18 (78%)
20. The Guideline Process
GRADE = Grading of Recommendations, Assessment, Development, and Evaluation.
Slide courtesy of Sara Vesely, PhD, University of Oklahoma.
Used the GRADE process (www.gradeworkinggroup.org)
Panel selection
Meeting 1: June 2018
PICO questions: use to frame and answer a clinical or health care
question
Population, Intervention, Comparison, Outcome
McMaster Team literature search and creation of Evidence Tables
Meeting 2: May 2019
Created Evidence to Decision Tables
Decided on a recommendation
Creating a Checklist for Guideline Developers
21. P = Population
I = Intervention
C = Comparison
O = Outcome
Example:
Should PEX plus corticosteroidsvs PEX alone be used for patients
with iTTP experiencing the first acute event?
Outcomes from most to least important, as follows:
1. All-cause mortality
2. All cardiovascular events
3. Stroke/TIA/clinically obvious neurologic deficit
4. Platelet count recovery
5. Relapse
6. Time to relapse
7. Acute kidney injury/dialysis
8. Days in hospital or days of therapeutic plasma exchange
9. Exacerbation
10. Normal ADAMTS13 level
PICO Questions
TIA = transient ischemic attack.
Slide courtesy of Sara Vesely, PhD, University of Oklahoma.
22. Conflict of Interest: During the Meetings
Slide courtesy of Sara Vesely, PhD, University of Oklahoma.
Individuals with major conflicts of interest (COI)
Were required to abstain from:
The formulation of individual PICO questions
Voting for the corresponding recommendations
Were allowed to:
Contribute to the discussion leading up to the final vote
23. Strength of Recommendations: Strong
Slide courtesy of Sara Vesely, PhD, University of Oklahoma.
Expressed as “the guideline panel recommends...”
The panel is confident that the desirable effects of following the
recommendation outweigh the undesirable effects
Most patients would accept the recommended course of action, while only a
small proportion would not
Most clinicians should follow the recommended course of action, and the
recommendation can be adopted as a policy in most situations
Recommendations are usually based on high-quality evidence in which we
have high confidence. However, in some cases, strong recommendations
are issued in the absence of high-certainty evidence
24. Strength of Recommendations: Conditional
Slide courtesy of Sara Vesely, PhD, University of Oklahoma.
Expressed as “the guideline panel suggests…”
Desirable effects of following the recommendation probably outweigh the
undesirable effects
Most patients would accept the suggested course of action, but many patients
would not
Decision aids might be useful in helping patients make this decision in a way that is
consistent with their values and preferences
Clinicians should note: different choices are appropriate for different patients
Policy making/standard setting around conditional recommendations should be
undertaken with caution; it requires substantial debate and engagement of a wide
range of stakeholders (eg, patients, treating physicians, and insurance
companies/payers)
25. Treatment of iTTP: Goals of Therapy
VWF = von Willebrand factor.
Slide courtesy of Spero R. Cataland, MD.
Zwicker et al, 2019.
Clinical response of disease:
PEX and immune suppressive therapy
Normalization of the platelet count
Surrogate for ongoing microvascular injury
End-organ recovery
Short- and long-term
Prevention of exacerbations of TTP
Need to restart PEX within the first 30
days after stopping PEX or anti-VWF
therapy (caplacizumab)
30%-40% of cases
Plasma
Platelet-rich
plasma leukocytes
Erythrocytes
Whole blood in
Component to be
removed out
26. Treatment of TTP: Immune Suppressive Therapy
Cataland et al, 2017; MayoClinic.org, 2022; Scully et al, 2011.
Corticosteroids:
Suppress anti-ADAMTS13
antibody production
Recovery of ADAMTS13
functional activity
Complications:
Mood issues, weight gain,
infection, osteoporosis
Rituximab:
Anti-CD20 antibody
Suppression of the production of
anti-ADAMTS13 antibodies
Responses begin in 1-2 weeks
27. Rituximab and Prevention of Relapse
Page et al, 2016.
Much clearer in the relapsed patient
Relapsing iTTP phenotype
What is the risk of relapse in my newly
diagnosed patient?
When is this risk determined?
Risk likely dynamic more that static
Rituximab and relapse prevention
If only the first episode, is the use of
rituximab potentially over-treating
patients?
Who then is at the greatest risk?
28. ISTH Guidelines for the Treatment of TTP (cont.)
Zheng et al, 2020b.
Rituximab has a beneficial effect in preventing relapse
Data are of low certainty (historical controls)
Risk of relapse may be higher in those with previous relapse
Conditional recommendation of rituximab in addition to PEX and
corticosteroids
More strongly consider if underlying autoimmune disorders
Recommendation 2/4: For patients with iTTP experiencing a first event/relapse,
the panel suggests the addition of rituximab to corticosteroids and PEX over
corticosteroids and PEX alone (a conditional recommendation in the context of
moderate-certainty evidence)
29. Clinical Issues in TTP: Exacerbations
Zwicker et al, 2019.
Definition:
Recurrent thrombocytopenia <30 days after last PEX or anti-VWF therapy
Differentiate continuation of prior event from “new” event
Need to restart PEX therapy
Occurs in 30%-40% of cases
Most common in first 2 weeks
Significant clinical issue
Readmission to hospital, line placement, PEX
Longer courses of PEX
30. Important TTP Clinical End Points
Med = median; BU = bethesda units; conc = concentration; AA = African American.
Cataland et al, 2009.
Exacerbation Rates and Risk Factors
Acute
(n=44)
Presenting Laboratory Data
(Median) Med.
Exchanges
Response
(Range)
Med. Days
Exacerbation
Platelet count
(150-
400x109/L)
LDH
(100-190)
Exacerbation 13 (30%)
16
(3-38)
900
(340-2,583)
7
(5-12)
7
(2-20)
Non-
exacerbation
31 (70%)
16
(5-93)
684
(370-3,077)
5
(3-23)
N/A
Samples Biomarkers (Median)
Comparison Groups
Exacerbation Non-Exacerbation
Pretreatment
ADAMTS13 activity
0.8%a
(<0.5-7.2)
1.4%a
(<0.5-57.5)
BU
2.2
(0.6-16.0)
4.0
(0.5-60.8)
Inhibitor conc. (µg/mL)
(µg/mL)
406
(94-4,040)
574
(59-3,397)
Response
ADAMTS13 activity %
1.2%
(<0.5-71.4)
22.5%
(<0.5-132.1)
BU
1.6
(0.5-89.6)
0.5
(0.5-44.8)
Inhibitor conc. (µg/mL)
(µg/mL)
534
(107-8,195)
259
(95-1,549)
aP=0.011; no longer statistically significant after
accounting for race, as covariate AA race
associated with an increased risk for
exacerbations P=0.014
31. Caplacizumab
Scully et al, 2019; Hanlon & Metjian, 2020.
A1 domain binding nanobody
Derived from heavy chain only
antibodies
Subcutaneous administration
Given concurrently with PEX
No significant clearance by PEX
Blocks microthrombotic disease
Does not alter/improve the
ADAMTS13 activity
32. Platelet string
formation inhibited by
anti-VWF nanobody
Anti-VWF
TITAN: Caplacizumab in iTTP
IV = intravenous; SC = subcutaneous.
Scully et al, 2019.
Phase 2 Study
Primary end point
• Time to a response, defined as confirmed
normalization of the platelet count
Key secondary end points
• Exacerbations
• Relapses
• Complete remission after PEX
• Safety
33. TITAN: Caplacizumab in iTTP (cont.)
Peyvandi et al, 2016.
Exacerbation, Relapse Status, and ADAMTS13 Activity
34. TITAN: Caplacizumab in iTTP
Peyvandi et al, 2016.
Adverse event Caplacizumab (n=35) Placebo (n=37)
Event related to study drug 57% 14%
Event leading to discontinuation
discontinuation
11% 5%
Bleeding-related event 54% 38%
Immune-related event 49% 32%
Drug-induced antidrug-antibody responses occurred in 3 (9%)
No neutralizing activity was detected
One patient treated with caplacizumab had moderate allergic dermatitis
Safety
35. HERCULES: Caplacizumab
Randomized, double-
blind, placebo-controlled, multi-
national study
Scully et al, 2019.
Phase 3 Study Design Recurrence
Daily PE & open-label caplacizumab
Key Eligibility Criteria:
• TTP episode
• First PEX
• Adults ≥18 (at some
sites, adults and
children 2-18 years)
1:1
PEX
Placebo n=73
PEX
Caplacizumab n=72 (10 mg IV, then 10 mg SC daily)
Treatment period Extension
Variable 30 days 4 x 7 days maximum 28 days
F
o
l
l
o
w
U
p
Extension based on
ADAMTS13 <10%
Primary end point
• Time to a response, defined as confirmed normalization of the platelet count (with
discontinuation of PEX within 5 days thereafter)
Secondary end points
• TTP-related death, recurrence of TTP, major thromboembolic event
• Recurrence of TTP
• Refractoriness to treatment
• Time to normalization of organ damage markers
36. HERCULES: Caplacizumab (cont.)
aPercentages are based on 71 subjects entering the study drug treatment period and 66 subjects in the follow-up period.
bRecurrence = recurrent thrombocytopenia after initial recovery of platelet count, requiring reinitiation of daily PEX.
cADAMTS13 activity levels were <10% at the end of the study drug treatment period in all of these patients.
dRefractory TTP = absence of platelet count doubling after 4 days of standard treatment and LDH >ULN.
Scully et al, 2019.
Key Secondary End Points
Number of subjects (%)
Placebo
n=73
Caplacizumab
n=72a
iTTP recurrenceb 28 (38.4%) 9 (12.7%)
During the study drug treatment period (exacerbations) 28 (38.4%) 3 (4.2%)
During the follow-up period (relapses) 0 6 (9.1%)c
P value <0.001
Percentage of Subjects With Refractory iTTP
Subjects With TTP Recurrence During Overall Study Period
Number of subjects (%)
Placebo
n=73
Caplacizumab
n=72
Refractory iTTPd 3 (4.2%) 0
P value 0.057
37. HERCULES: Caplacizumab (cont.)
aTreatment-emergent adverse events occurring in at least 2 subjects in either group.
bStandardized MedDRA Query “Hemorrhage.”
Slide adapted from Scully et al, 2019.
Safety: Bleeding-Related TEAEsa
Placebo
n (%)
Caplacizumab
n (%)
Bleeding-related TEAEs (by SMQ)b 17 (23.3%) 33 (45.6%)
Epistaxis 1 (1.4%) 17 (23.9%)
Gingival bleeding 0 8 (11.3%)
Bruising 3 (4.1%) 5 (7.0%)
Hematuria 1 (1.4%) 4 (5.6%)
Vaginal hemorrhage 1 (1.4%) 3 (4.2%)
Menorrhagia 1 (1.4%) 2 (2.8%)
Catheter site hemorrhage 3 (4.1%) 2 (2.8%)
Injection site bruising 2 (2.7%) 2 (2.8%)
Hematochezia 0 2 (2.8%)
Hematoma 0 2 (2.8%)
38. Caplacizumab and aTTP
Zheng et al, 2020b.
Based on data of moderate certainty
2 randomized, placebo-controlled studies
Data not available to differentiate newly diagnosed from relapsed TTP
Low mortality rates on both arms of studies (possible selection bias)
Caplacizumab-treated patients:
Significant reduction in exacerbations
Greater benefit if started early in an acute TTP event
Important caveats
FDA-approved drug not yet available worldwide
Only given under the guidance of an experienced clinician
Caplacizumab does not alter the underlying disease (ADAMTS13 deficiency)
Recommendation 5: For patients with iTTP experiencing an acute event
(first event or relapse) the panel suggests using caplacizumab over not
using caplacizumab (a conditional recommendation in the context of
moderate-certainty evidence)
39. ADAMTS13 in Remission and Relapse Risk
Peyvandi et al, 2008; Jin et al, 2008.
Peyvandi et al studied 109
patients with samples studied in
remission
>30 days after PEX
Prior to relapse
Majority with 1 sample
Risk of relapse (odds ratio):
ADAMTS13 <10%: 2.9
ADAMTS13 <10% +
antibody: 3.6
40. ADAMTS13 Activity and TTP
Motto et al, 2005; Banno et al, 2006.
Deficient ADAMTS13 alone not sufficient
to lead to an acute TTP episode
ADAMTS13 -/- mice do not spontaneously
develop TMA findings
Shiga toxin, collagen/epinephrine required
to initiate the development of
thrombocytopenia
Congenital TTP
Delayed presentations at the time of
pregnancy
Second Hit Hypothesis
41. ADAMTS13 Activity Monitoring in Remission
GPS = good practice statements.
Zheng et al, 2020a.
ADAMTS13 activity monitoring in remission:
Patients should be assessed regularly during follow-up
Literature on ADAMTS13 monitoring in remission not reviewed
Patients usually assessed:
Monthly for the first 3 months, every 3 months for the first year, then every 6-12
months if stable
More frequent measurements if declining ADAMTS13 activity
ADAMTS13 activity interpretation
Stable and durable ADAMTS13 activity near lower level of normal is
reassuring
Persistently low levels may be at risk for relapse
Supportive Care GPS: Statement 13
42. Zheng et al, 2020b.
Recommendation 6: For patients with iTTP who are in
remission but still have low plasma ADAMTS13 activity with
no clinical signs/symptoms, the panel suggests the use of
rituximab over non-use of rituximab for prophylaxis (a
conditional recommendation in the context of very low–
certainty evidence)
Preemptive Rituximab in iTTP in Remission
43. Preemptive Rituximab in iTTP in Remission
Jestin et al, 2018.
Data suggest that preemptive rituximab
has fewer relapses and requires longer
time for iTTP relapse
Non-randomized data
No clear effect on survival
Potential issue of expense
Patient commitment necessary:
Serial ADAMTS13 monitoring
Rituximab prophylaxis without
ADAMTS13 monitoring not an evidence-
based strategy
44. Chronic End-Organ Complications in aTTP
Figure 1. Sclerotic glomeruli and atrophic
tubules with petechial hemorrhage
Figure 2. Hypertrophic myocytes
Images courtesy of Spero R. Cataland, MD.
45. SLE = systemic lupus
erythematosus.
Deford et al, 2013.
70 enrolled patients with TTP and
ADAMTS13 activity <10%
57 survivors as of 2012 evaluated
Comparison to US norms
Mood disorders/depression
Hypertension
19% died
Greater than US and Oklahoma
norms (P<0.05)
Major Morbidities in Long-Term Follow-Up of iTTP Patients
47. Risk Factors For Early Mortality in iTTP Survivorsa
aAdjusted for AA race, HTN, CKD, and treatment site.
HTN = hypertension; CKD = chronic kidney disease; HR = hazard ratio; CI = confidence interval.
Sukumar et al, 2021.
Characteristic HR 95% CI P
Male sex 3.74 1.65-8.48 0.002
Increasing age 1.04 1.01-1.07 0.011
No. of iTTP episodes 1.10 1.01-1.20 0.022
48
Lack of association of mortality with traditional cardiovascular risk factors (HTN, CKD)
Possibly due to limited sample size, but raises question of iTTP specific factors which
may contribute to mortality ADAMTS13 activity??
49. -2.6
-2.4
-2.2
-2
-1.8
-1.6
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
DET IDN OBK OCL
magnitude
of
impairment
relative
.
to
matched
controls
(z)
.
Depression
in 35-55yrs
Dementia (AD)
in 65-75yrs
0.08%BAC
in 40-50yrs
TMA
DT: Detection Task
IDN: Identification Task
OBK: One Back Memory
OCL: One Card Learning
Neurocognitive Deficits in TTP
BAC = blood alcohol content; AD = Alzheimer disease.
Slide courtesy of Spero R. Cataland, MD.
Cataland et al, 2011.
Detection task:
“Has the card turned over?”
Identification task:
“Is the card red?”
One back memory:
“Does the face-up card exactly
match the one before?”
One card learning:
“Have you seen this card before in
this task?”
Comparison to Differing Disease States
50. Key Takeaways
iTTP is a rare, but very serious, hematologic disorder that requires
prompt recognition and treatment
Novel therapies including immune suppressive therapy (rituximab) and
caplacizumab have dramatic improved treatment outcomes for iTTP
patients
Challenges remain, however:
Greater number of survivors/patients at risk for complications
Shortened life expectancy from cardiovascular complications
Impact on quality of life
Mood disorders, neurocognitive complications, PTSD
52. References
Adeyemi A, Razakariasa F, Chiorean A & de Passos Sousa R (2022). Epidemiology, treatment patterns, clinical outcomes, and disease burden among patients with immune-mediated
thrombotic thrombocytopenic purpura in the United States. Res Pract Thromb and Haemost. 6(6):e12802. DOI:10.1002/rth2.12802
Arnold DM, Patriquin CJ & Nazy I (2017). Thrombotic microangiopathies: a general approach to diagnosis and management. CMAJ, 189(4):E153-E159 DOI:10.1503/cmaj.160142
Bae SH, Kim SH & Bang SM (2022). Recent advances in the management of immune-mediated thrombotic thrombocytopenic purpura. Blood Res, 57(suppl_1): 37-43.
DOI:10.5045/br.2022.2022005
Banno F, Kokame K, Okuda T, et al (2006). Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura. Blood, 107(8):3161-
3166. DOI:10.1182/blood-2005-07-2765
Bendapudi PK, Hurwitz S, Fry A, et al (2017). Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet
Haematol, 4(4):e157-e164. DOI:10.1016/S2352-3026(17)30026-1
Bentley MJ, Lehman CM, Blaylock RC, et al (2010). The utility of patient characteristics in predicting severe ADAMTS13 deficiency and response to plasma exchange. Transfusion, 50(8):1654-
1664. DOI:10.1111/j.1537-2995.2010.02653.x
Cataland SR, Kourlas PJ, Yang S, et al (2017). Cyclosporine or steroids as an adjunct to plasma exchange in the treatment of immune-mediated thrombotic thrombocytopenic purpura. Blood
Adv, 1(23):2075-2082. DOI:10.1182/bloodadvances.2017009308
Cataland SR, Scully MA, Paskavitz J, et al (2011). Evidence of persistent neurologic injury following thrombotic thrombocytopenic purpura. Am J Hematol 86(1):87-89. DOI:10.1002/ajh.21881
Cataland SR, Yang S & Wu HM (2012). The use of ADAMTS13 activity, platelet count, and serum creatinine to differentiate acquired thrombotic thrombocytopenic purpura from other thrombotic
microangiopathies. Br J Haematol, 157(4):501-503. DOI:10.1111/j.1365-2141.2012.09032.x
Cataland SR, Yang SB, Witkoff L, et al (2009). Demographic and ADAMTS13 biomarker data as predictors of early recurrences of idiopathic thrombotic thrombocytopenic purpura. Eur J
Haematol, 83(6):559-564. DOI:10.1111/j.1600-0609.2009.01331.x
Chaturvedi S, Oluwole O, Cataland S, et al (2017). Post-traumatic stress disorder and depression in survivors of thrombotic thrombocytopenic purpura. Thromb Res, 151:51-56.
DOI:10.1016/j.thromres.2017.01.003
Coppo P, Schwarzinger M, Buffet M, et al (2010). Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center
experience. PLoS One, 5(4):e10208. DOI:10.1371/journal.pone.0010208
Deford CC, Reese JA, Schwartz LH, et al (2013). Multiple major morbidities and increased mortality during long-term follow-up after recovery from thrombotic thrombocytopenic purpura. Blood,
122(12):2023-2029. DOI:10.1182/blood-2013-04-496752
George JN (2006). Thrombotic thrombocytopenic purpura, N Engl J Med, 354:1927-1935. DOI:10.1056/NEJMcp053024
George JN (2021). TTP: the evolution of clinical practice. Blood, 137(6):719-720. DOI:10.1182/blood.2020009654
53. References (cont.)
Hanlon A & Metjian A, et al (2020). Caplacizumab in adult patients with acquired thrombotic thrombocytopenic purpura. Ther Adv Hematol, 11:2040620720902904.
DOI:10.1177/2040620720902904
Jestin M, Benhamou Y, Schelpe AS, et al (2018). Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura. Blood, 132(20):2143-2153.
DOI:10.1182/blood-2018-04-840090
Jin M, Casper TC, Cataland SR, et al (2008). Relationship between ADAMTS13 activity in clinical remission and the risk of TTP relapse. BJR Hematol, 141(5):651-658. DOI:10.111/j.1365-
2141.2008.07107.x
Kremer Hovinga Strebel JA, de la Rubia J, Pavenski K, et al (2022). The role of ADAMTS13 activity levels on disease exacerbation or relapse in patients with immune-mediated thrombotic
thrombocytopenic purpura: post hoc analysis of the phase 3 HERCULES and post-HERCULES studies. Blood, 140(suppl_1):5651-5653. DOI:10.1182/blood-2022-156306
Kremer Hovinga JA, Vesely SK, Terrell DR, et al (2010). Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood, 115(8):1500-1511; quiz 1662. DOI:10.1182/blood-
2009-09-243790
MayoClinic.org (2022). Prednisone and other corticosteroids. Available at:https://www.mayoclinic.org/steroids/art-20045692
Moatti-Cohen M, Garrec C, Wolf M, et al (2012). Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytic purpura. Blood, 119(24):5888-5897.
DOI:10.1182/blood-2012-02-408914
Moschowitz E (1952). An acute febrile pleiochromic anemia with hyaline thrombosis of the terminal arterioles and capillaries; an undescribed disease. Am J Med, 13(5):567-569.
DOI:10.1016/0002-9343(52)90022-3
Motto DG, Chauhan AK, Zhu G, et al (2005). Shigatoxin triggers thrombotic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient mice. J Clin Invest, 115(10):2752-2761.
DOI:10.1172/JCI26007
Page EE, Kremer Hovinga JA, Terrell DR, et al (2016). Rituximab reduces risk for relapse in patients with thrombotic thrombocytopenic purpura. Blood, 127(24):3092-3094. DOI:10.1182/blood-
2016-03-703827
Peyvandi F, Lavoretano S, Palla R, et al (2008). DAMTS13 and anti-ADAMTS13 antibodies as markers for recurrence of acquired thrombotic thrombocytopenic purpura during remission.
Haematologica, 93(2):232-239. DOI:10.3324/haematol.11739
Peyvandi F, Scully M, Kremer Hovinga JA, et al (2016). Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med, 374(6):511-522. DOI:10.1056/NEJMoa1505533
Raife T, Atkinson B, Montgomery R, et al (2004). Severe deficiency of VWF-cleaving protease (ADAMTS13) activity defines a distinct population of thrombotic microangiopathy patients.
Transfusion Practice, 44(2):146-150. DOI:10.1111/j.1537-2995.2004.00626.x
54. References (cont.)
Sadler JE (2008). Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood, 112(1):11-18. DOI:10.1182/blood-2008-02-078170
Scully M, Cataland SR, Peyvandi F, et al (2019). Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura, N Engl J Med, 380(4):335-346. DOI:10.1056/NEJMoa1806311
Scully M, McDonald V, Cavenagh J, et al (2011). A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood,
118(7):1746-1753. DOI:10.1182/blood-2011-03-341131
Sukumar S, Brodsky M, Hussain S, et al (2022). Cardiovascular disease is a leading cause of mortality among TTP survivors in clinical remission. Blood Adv, 6(4): 1264–1270.
DOI:10.1182/bloodadvances.2020004169
Upreti H, Kasmani J, Dane K, et al (2019). Reduced ADAMTS13 activity during TTP remission is associated with stroke in TTP survivors. Blood, 134(13):1037-1045.
DOI:10.1182/blood.2019001056
Viswanathan S, Rovin BH, Shidham GB, et al (2010). Long-term, sub-clinical cardiac and renal complications in patients with multiple relapses of thrombotic thrombocytopenic purpura. Br J
Haematol, 149(4):623-625. DOI:10.1111/j.1365-2141.2010.08091.x
Wu N, Liu J, Yang S, et al (2015). Diagnostic and prognostic values of ADAMTS13 activity measured during daily plasma exchange therapy in patients with acquired thrombotic
thrombocytopenic purpura. Transfusion, 55(1):18-24. DOI:10.1111/trf.12762
Zheng XL, Vesely SK, Cataland SR, et al (2020a). Good practice statements (GPS) for the clinical care of patients with immune thrombotic thrombocytopenic purpura. J Thromb Haemostat,
18(10):2503-2512. DOI:10.111/jth.15009
Zheng XL, Vesely SK, Cataland SR, et al (2020b). ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost, 18(10):2486-2502. DOI:10.1111/jth.15006
Zwicker JI, Muia J, Dolatshahi L, et al (2019). Adjuvant low-dose rituximab and plasma exchange for acquired TTP. Blood, 134(13):1106-1109. DOI:10.1182/blood.2019000795