CAR-T cells (Chimeric Antigen Receptor- T cells) are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy. Chimeric antigen receptors are receptor proteins that have been engineered to give T cells the new ability to target a specific protein.
This therapy use to treat several type of cancer but significantly treat leukemia. And this therapy is very effective than other.
Allogeneic hematopoietic stem cell transplantation (allo HSCT) from an HLA-matched related donor provides the most potent anti-leukemic effect of any post-remission therapy in AML, as demonstrated by the lowest rates of relapse.
Graft vs leukemia plays and important role here.
Provides the best chance of long-term survival
This document provides an overview of principles of cancer immunotherapy. It discusses anti-cancer immunity mechanisms like antigen presentation and T cell activation. It also examines how cancers can evade the immune system through strategies like low MHC expression and immunosuppressive factors. The document then reviews clinical applications of immunotherapy including cytokines, monoclonal antibodies, adoptive cell transfer, vaccines, and checkpoint inhibitors. Combination therapies are showing promise for enhancing anti-tumor responses.
Seminar on acute lymphoblastic leukemia by Dr. Prachi KalraMAMC,Delhi
This document provides information about acute lymphoblastic leukemia (ALL):
- ALL is a cancer of the white blood cells that starts from immature lymphocytes in the bone marrow. It causes a buildup of abnormal lymphocytes that crowds out normal blood cell production.
- Symptoms include fever, bleeding, bone pain, swollen lymph nodes and organs, and neurological issues. Diagnosis involves blood tests, bone marrow biopsy, immunophenotyping and cytogenetic analysis.
- Treatment involves supportive care, induction chemotherapy to achieve remission, consolidation therapy to further reduce cancer cells, and long-term maintenance therapy to prevent relapse. Prognosis depends on risk factors like age and specific genetic abnormalities.
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
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Primary cutaneous lymphoma is a type of non-Hodgkin lymphoma that presents in the skin without evidence of extracutaneous disease. Mycosis fungoides is the most common type of cutaneous T-cell lymphoma, presenting as patches and plaques on the skin that can progress to tumors. Treatment depends on the stage of disease and includes skin-directed therapies like radiation and phototherapy for early stages and systemic therapies for advanced disease. Prognosis is generally good for early stage mycosis fungoides but worsens with increasing stage and extracutaneous spread.
CAR-T cells (Chimeric Antigen Receptor- T cells) are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy. Chimeric antigen receptors are receptor proteins that have been engineered to give T cells the new ability to target a specific protein.
This therapy use to treat several type of cancer but significantly treat leukemia. And this therapy is very effective than other.
Allogeneic hematopoietic stem cell transplantation (allo HSCT) from an HLA-matched related donor provides the most potent anti-leukemic effect of any post-remission therapy in AML, as demonstrated by the lowest rates of relapse.
Graft vs leukemia plays and important role here.
Provides the best chance of long-term survival
This document provides an overview of principles of cancer immunotherapy. It discusses anti-cancer immunity mechanisms like antigen presentation and T cell activation. It also examines how cancers can evade the immune system through strategies like low MHC expression and immunosuppressive factors. The document then reviews clinical applications of immunotherapy including cytokines, monoclonal antibodies, adoptive cell transfer, vaccines, and checkpoint inhibitors. Combination therapies are showing promise for enhancing anti-tumor responses.
Seminar on acute lymphoblastic leukemia by Dr. Prachi KalraMAMC,Delhi
This document provides information about acute lymphoblastic leukemia (ALL):
- ALL is a cancer of the white blood cells that starts from immature lymphocytes in the bone marrow. It causes a buildup of abnormal lymphocytes that crowds out normal blood cell production.
- Symptoms include fever, bleeding, bone pain, swollen lymph nodes and organs, and neurological issues. Diagnosis involves blood tests, bone marrow biopsy, immunophenotyping and cytogenetic analysis.
- Treatment involves supportive care, induction chemotherapy to achieve remission, consolidation therapy to further reduce cancer cells, and long-term maintenance therapy to prevent relapse. Prognosis depends on risk factors like age and specific genetic abnormalities.
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
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Primary cutaneous lymphoma is a type of non-Hodgkin lymphoma that presents in the skin without evidence of extracutaneous disease. Mycosis fungoides is the most common type of cutaneous T-cell lymphoma, presenting as patches and plaques on the skin that can progress to tumors. Treatment depends on the stage of disease and includes skin-directed therapies like radiation and phototherapy for early stages and systemic therapies for advanced disease. Prognosis is generally good for early stage mycosis fungoides but worsens with increasing stage and extracutaneous spread.
Opportunities for Immune Therapy and Preventionbkling
This document summarizes a presentation on opportunities for immunotherapy in breast cancer. It discusses how the immune system fights cancer, types of immunotherapy including checkpoint inhibitors and CAR T-cell therapy. Experience with immunotherapy in breast cancer has been underwhelming due to breast cancer typically having low numbers of immune cells, but responses have been seen in triple negative and HER2+ breast cancers. Future opportunities include increasing immune cells prior to standard treatments and engaging the immune system in the adjuvant setting to reduce recurrence risks.
Principles of medical_oncology dr. varunVarun Goel
- The document discusses several key principles of medical oncology including that cancer treatment is multidisciplinary, early stage cancers are more curable than late stage, and the best treatment is often found in clinical trials.
- It describes the basic tenets of chemotherapy including that it can be used for induction treatment of advanced cancers or as adjuvant treatment after local therapy to treat high risk of recurrence. The intent of chemotherapy can be curative or palliative.
- Several models of tumor growth and response to chemotherapy are explained including the Skipper-Wilcox model, concepts of combination chemotherapy, and the Goldie-Coldman model regarding emergence of drug resistance with increased tumor size.
Proteasome inhibitors in treatment of multiple myelomaAlok Gupta
This document summarizes the development of the proteasome inhibitor bortezomib, including its mechanism of action, clinical trials, safety profile, and peripheral neuropathy issues. Key findings include:
- Bortezomib is a reversible inhibitor of the proteasome's chymotrypsin-like activity and was found to induce apoptosis in cancer cells.
- Phase I and II clinical trials demonstrated efficacy in hematological malignancies like multiple myeloma with a tolerable safety profile.
- Peripheral neuropathy is a common side effect that can often improve after stopping treatment.
- Further research aimed to improve response rates, overcome resistance, expand use to solid tumors, and address neuropathy issues.
1) Tumors exist within a complex microenvironment consisting of various cell types that influence tumor growth, progression, and metastasis.
2) Chronic inflammation can promote tumor development by increasing genetic mutations while also stimulating angiogenesis and tumor cell proliferation.
3) The tumor microenvironment interacts bidirectionally with cancer cells to encourage processes like angiogenesis, immune suppression, invasion, and metastasis through factors such as TGF-β, VEGF, and cytokines.
4) Therapies targeting the tumor microenvironment can impact its composition and make cancer cells more invasive, highlighting the need for combination treatments.
This phase 3 trial investigated adding abemaciclib to standard adjuvant endocrine therapy in patients with hormone receptor-positive, HER2-negative, lymph node-positive, high-risk early breast cancer. At the interim analysis, the addition of abemaciclib resulted in a statistically significant improvement in invasive disease-free survival compared to endocrine therapy alone. The most common adverse events with abemaciclib were diarrhea, neutropenia, and fatigue. Additional follow-up is still needed to determine if the benefit persists for later recurrences and overall survival.
Cancer immunotherapy shows promise for treating cancer. Recent advances include checkpoint inhibitors that help the immune system attack cancer cells. Over 200 types of cancer vaccines currently in clinical trials aim to strengthen the immune response against cancers. Dendritic cell vaccines have shown some success by extracting a patient's dendritic cells, exposing them to tumor antigens, and reintroducing them to induce an immune response. Combining immunotherapies with other treatments continues to be a promising area of research, as over 6,000 clinical trials are studying various immunotherapy combinations. With over 240 new immunotherapies in development, cancer experts are optimistic that immunotherapy can significantly improve cancer outcomes.
Introduction to Targeted Therapies in OncologyMohamed Abdulla
Describes the molecular background which represents the core for developing targeted therapies against specific biological events in malignant cellular clones.
Follicular lymphoma is the most common indolent non-Hodgkin lymphoma, accounting for about 45% of NHL cases. It involves B cells that are found in the germinal centers of lymph nodes. Key characteristics include a median age of 59 years at presentation, a male to female ratio of 1:1.7, and involvement of lymph nodes in the neck, underarms, or groin. The t(14;18) translocation results in overexpression of the BCL2 gene and inhibition of apoptosis. Treatment depends on the stage and grade of disease, and may include watchful waiting, chemotherapy, radiation therapy, immunotherapy, or stem cell transplantation.
This document discusses microsatellite instability (MSI), which refers to changes in repeated sequences of DNA called microsatellites during DNA replication due to defects in the DNA mismatch repair system. The key mechanisms, detection methods, clinical significance and applications of MSI in various cancers are described. MSI is an important factor in tumor development and progression. Detection of MSI using techniques such as PCR and immunohistochemistry can aid in cancer diagnosis and predict response to immunotherapy. Cancers with high MSI (MSI-H) often respond well to immune checkpoint inhibitors.
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.
chimeric antigen receptor, its structure and role in killing tumor cells,mechanism of antitumor killing, car's in clinic,evolution of cars and new chimeric antigen models
The passage summarizes key changes in the 2016 revision of the World Health Organization classification of lymphoid neoplasms compared to the 2008 classification. Some notable changes include new entities recognized based on next-generation sequencing and other molecular data, as well as splits or merges of some subtypes. The revised classification includes updated categories for mature B-cell, mature T-cell and NK-cell neoplasms, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and histiocytic and dendritic cell neoplasms. New provisional entities are also included to reflect evolving clinical and biological understanding.
This presentation is part of MIU CE Pharmacy Program and is designed primarily for pharmacists with the following learning objectives:
1- Explain the mechanisms of action behind immune response to cancer and the application of immunotherapy in cancer treatment
2- Distinguish new and emerging immunotherapy classes and individual agents efficacy, safety to therapy in cancer treatment
3-Strategies to counsel and assist patients to overcome barriers to therapy, including Treatment side effects to improve adherence to therapy
This document discusses a clinical trial evaluating the combination of ribociclib and endocrine therapy for pre/perimenopausal women with HR+, HER2- advanced breast cancer. The trial aimed to assess whether ribociclib plus an aromatase inhibitor and goserelin improved progression-free survival compared to placebo plus the same endocrine therapies. Key findings were that the combination led to a statistically significant improvement in progression-free survival. Overall survival data were also collected as a secondary outcome.
Immune check point inhibitors and adverse effectsSCGH ED CME
Immune checkpoint inhibitors can cause immune-related adverse events by removing inhibitory checkpoints and excessively activating the immune system. Common adverse effects include dermatitis in over 50% of patients, enterocolitis in under 20%, hepatitis in under 10%, and endocrinopathies. Symptoms usually onset several months after treatment. Management involves stopping the immune checkpoint inhibitor and administering corticosteroids in most cases. Life-threatening hyperimmunity is possible so consulting the oncologist and other specialists is important.
this slide contain information about antibody mediated anti-cancer therapy like antibody drug conjugates (ADC), Bispecific monoclonal antibody, Immuno-checkpoint therapy, biomarkers, mechanism of action of all 3 therapies, approved drugs of each category
How can immunotherapy be used to treat metastatic breast cancer? Ian Krop, MD, PhD, discusses the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 and hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
This document discusses recent advances in cancer immunotherapy. It describes how improved understanding of immunology has led to new immunotherapies using toll-like receptor agonists, T cells, NK cells, dendritic cells, and monoclonal antibodies. Major cellular immunotherapies discussed include using T cells activated outside the body with cytokines like IL-2, and engineering T cells to express tumor-targeting receptors.
This document discusses multiple myeloma, a plasma cell disorder. It begins with an overview of plasma cell disorders and defines multiple myeloma. It then covers the epidemiology, etiology, pathophysiology, clinical features, diagnostic tests including serum protein electrophoresis and immunofixation, bone marrow examination, skeletal survey, staging, prognostic factors. It also discusses related conditions like monoclonal gammopathy of undetermined significance, smoldering myeloma, non-secretory myeloma, solitary plasmacytoma, extramedullary plasmacytoma. It concludes with discussing criteria for diagnosing multiple myeloma and initial treatment approaches.
Update 2014: Hämatologie - A. Wacker, ReutlingenKlin-RT
Vortrag im Rahmen des Reutlinger Update Innere Medizin 2014 - 28. & 29. November 2014. Eine jährliche Fortbildungsveranstaltung der Bezirksärztekammer Südwürttemberg, der Kreisärzteschaft Reutlingen und der Kreiskliniken Reutlingen GmbH für Ärztinnen und Ärzte.
Opportunities for Immune Therapy and Preventionbkling
This document summarizes a presentation on opportunities for immunotherapy in breast cancer. It discusses how the immune system fights cancer, types of immunotherapy including checkpoint inhibitors and CAR T-cell therapy. Experience with immunotherapy in breast cancer has been underwhelming due to breast cancer typically having low numbers of immune cells, but responses have been seen in triple negative and HER2+ breast cancers. Future opportunities include increasing immune cells prior to standard treatments and engaging the immune system in the adjuvant setting to reduce recurrence risks.
Principles of medical_oncology dr. varunVarun Goel
- The document discusses several key principles of medical oncology including that cancer treatment is multidisciplinary, early stage cancers are more curable than late stage, and the best treatment is often found in clinical trials.
- It describes the basic tenets of chemotherapy including that it can be used for induction treatment of advanced cancers or as adjuvant treatment after local therapy to treat high risk of recurrence. The intent of chemotherapy can be curative or palliative.
- Several models of tumor growth and response to chemotherapy are explained including the Skipper-Wilcox model, concepts of combination chemotherapy, and the Goldie-Coldman model regarding emergence of drug resistance with increased tumor size.
Proteasome inhibitors in treatment of multiple myelomaAlok Gupta
This document summarizes the development of the proteasome inhibitor bortezomib, including its mechanism of action, clinical trials, safety profile, and peripheral neuropathy issues. Key findings include:
- Bortezomib is a reversible inhibitor of the proteasome's chymotrypsin-like activity and was found to induce apoptosis in cancer cells.
- Phase I and II clinical trials demonstrated efficacy in hematological malignancies like multiple myeloma with a tolerable safety profile.
- Peripheral neuropathy is a common side effect that can often improve after stopping treatment.
- Further research aimed to improve response rates, overcome resistance, expand use to solid tumors, and address neuropathy issues.
1) Tumors exist within a complex microenvironment consisting of various cell types that influence tumor growth, progression, and metastasis.
2) Chronic inflammation can promote tumor development by increasing genetic mutations while also stimulating angiogenesis and tumor cell proliferation.
3) The tumor microenvironment interacts bidirectionally with cancer cells to encourage processes like angiogenesis, immune suppression, invasion, and metastasis through factors such as TGF-β, VEGF, and cytokines.
4) Therapies targeting the tumor microenvironment can impact its composition and make cancer cells more invasive, highlighting the need for combination treatments.
This phase 3 trial investigated adding abemaciclib to standard adjuvant endocrine therapy in patients with hormone receptor-positive, HER2-negative, lymph node-positive, high-risk early breast cancer. At the interim analysis, the addition of abemaciclib resulted in a statistically significant improvement in invasive disease-free survival compared to endocrine therapy alone. The most common adverse events with abemaciclib were diarrhea, neutropenia, and fatigue. Additional follow-up is still needed to determine if the benefit persists for later recurrences and overall survival.
Cancer immunotherapy shows promise for treating cancer. Recent advances include checkpoint inhibitors that help the immune system attack cancer cells. Over 200 types of cancer vaccines currently in clinical trials aim to strengthen the immune response against cancers. Dendritic cell vaccines have shown some success by extracting a patient's dendritic cells, exposing them to tumor antigens, and reintroducing them to induce an immune response. Combining immunotherapies with other treatments continues to be a promising area of research, as over 6,000 clinical trials are studying various immunotherapy combinations. With over 240 new immunotherapies in development, cancer experts are optimistic that immunotherapy can significantly improve cancer outcomes.
Introduction to Targeted Therapies in OncologyMohamed Abdulla
Describes the molecular background which represents the core for developing targeted therapies against specific biological events in malignant cellular clones.
Follicular lymphoma is the most common indolent non-Hodgkin lymphoma, accounting for about 45% of NHL cases. It involves B cells that are found in the germinal centers of lymph nodes. Key characteristics include a median age of 59 years at presentation, a male to female ratio of 1:1.7, and involvement of lymph nodes in the neck, underarms, or groin. The t(14;18) translocation results in overexpression of the BCL2 gene and inhibition of apoptosis. Treatment depends on the stage and grade of disease, and may include watchful waiting, chemotherapy, radiation therapy, immunotherapy, or stem cell transplantation.
This document discusses microsatellite instability (MSI), which refers to changes in repeated sequences of DNA called microsatellites during DNA replication due to defects in the DNA mismatch repair system. The key mechanisms, detection methods, clinical significance and applications of MSI in various cancers are described. MSI is an important factor in tumor development and progression. Detection of MSI using techniques such as PCR and immunohistochemistry can aid in cancer diagnosis and predict response to immunotherapy. Cancers with high MSI (MSI-H) often respond well to immune checkpoint inhibitors.
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.
chimeric antigen receptor, its structure and role in killing tumor cells,mechanism of antitumor killing, car's in clinic,evolution of cars and new chimeric antigen models
The passage summarizes key changes in the 2016 revision of the World Health Organization classification of lymphoid neoplasms compared to the 2008 classification. Some notable changes include new entities recognized based on next-generation sequencing and other molecular data, as well as splits or merges of some subtypes. The revised classification includes updated categories for mature B-cell, mature T-cell and NK-cell neoplasms, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and histiocytic and dendritic cell neoplasms. New provisional entities are also included to reflect evolving clinical and biological understanding.
This presentation is part of MIU CE Pharmacy Program and is designed primarily for pharmacists with the following learning objectives:
1- Explain the mechanisms of action behind immune response to cancer and the application of immunotherapy in cancer treatment
2- Distinguish new and emerging immunotherapy classes and individual agents efficacy, safety to therapy in cancer treatment
3-Strategies to counsel and assist patients to overcome barriers to therapy, including Treatment side effects to improve adherence to therapy
This document discusses a clinical trial evaluating the combination of ribociclib and endocrine therapy for pre/perimenopausal women with HR+, HER2- advanced breast cancer. The trial aimed to assess whether ribociclib plus an aromatase inhibitor and goserelin improved progression-free survival compared to placebo plus the same endocrine therapies. Key findings were that the combination led to a statistically significant improvement in progression-free survival. Overall survival data were also collected as a secondary outcome.
Immune check point inhibitors and adverse effectsSCGH ED CME
Immune checkpoint inhibitors can cause immune-related adverse events by removing inhibitory checkpoints and excessively activating the immune system. Common adverse effects include dermatitis in over 50% of patients, enterocolitis in under 20%, hepatitis in under 10%, and endocrinopathies. Symptoms usually onset several months after treatment. Management involves stopping the immune checkpoint inhibitor and administering corticosteroids in most cases. Life-threatening hyperimmunity is possible so consulting the oncologist and other specialists is important.
this slide contain information about antibody mediated anti-cancer therapy like antibody drug conjugates (ADC), Bispecific monoclonal antibody, Immuno-checkpoint therapy, biomarkers, mechanism of action of all 3 therapies, approved drugs of each category
How can immunotherapy be used to treat metastatic breast cancer? Ian Krop, MD, PhD, discusses the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 and hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
This document discusses recent advances in cancer immunotherapy. It describes how improved understanding of immunology has led to new immunotherapies using toll-like receptor agonists, T cells, NK cells, dendritic cells, and monoclonal antibodies. Major cellular immunotherapies discussed include using T cells activated outside the body with cytokines like IL-2, and engineering T cells to express tumor-targeting receptors.
This document discusses multiple myeloma, a plasma cell disorder. It begins with an overview of plasma cell disorders and defines multiple myeloma. It then covers the epidemiology, etiology, pathophysiology, clinical features, diagnostic tests including serum protein electrophoresis and immunofixation, bone marrow examination, skeletal survey, staging, prognostic factors. It also discusses related conditions like monoclonal gammopathy of undetermined significance, smoldering myeloma, non-secretory myeloma, solitary plasmacytoma, extramedullary plasmacytoma. It concludes with discussing criteria for diagnosing multiple myeloma and initial treatment approaches.
Update 2014: Hämatologie - A. Wacker, ReutlingenKlin-RT
Vortrag im Rahmen des Reutlinger Update Innere Medizin 2014 - 28. & 29. November 2014. Eine jährliche Fortbildungsveranstaltung der Bezirksärztekammer Südwürttemberg, der Kreisärzteschaft Reutlingen und der Kreiskliniken Reutlingen GmbH für Ärztinnen und Ärzte.
This document summarizes a phase 3 clinical trial evaluating the efficacy and safety of lenalidomide plus low-dose dexamethasone (Rd) treatment versus observation alone in patients with high-risk smoldering multiple myeloma (SMM). The study found that early Rd treatment significantly prolonged the time to progression to symptomatic multiple myeloma compared to observation, with median times not reached versus 21 months. Early Rd treatment also significantly improved overall survival rates at 3 and 5 years. Long-term follow-up results at a median of 64 months further confirmed the efficacy and safety of early Rd intervention in high-risk SMM patients.
An overview of the John Theurer Cancer Center at Hackensack University Medical Center - a top-50 U.S. News & World Report Best Hospitals for Cancer – the only cancer center in New Jersey with this prestigious designation.
To request printed copies of this brochure, please contact aleahing@p4strategy.com.
This document discusses white foods and their nutritional value. It summarizes that while colorful foods contain many nutrients, white foods should not be avoided and contain important nutrition as well. Examples of healthy white foods provided are potatoes, cauliflower, beans, mushrooms, and onions. The document then provides recipes for a potato soup, white bean spread, and kasha pilaf with mushrooms to showcase nutritious white food options.
This presentation discusses common mistakes in PowerPoint presentations and provides tips for effective presentations. It emphasizes telling a story, engaging the audience, and using humor. The document also includes summaries of burn treatment including initial fluid resuscitation, medications, nutrition, and complications in the ICU. Overall it promotes practicing presentations and focusing on the audience experience over excessive words or bullet points.
This document summarizes recent developments in the treatment of immune thrombocytopenia (ITP). It discusses new evidence on treatments for refractory ITP including rituximab, thrombopoietin receptor agonists (TPO-RAs), and long-term use of eltrombopag. A randomized controlled trial found that rituximab did not significantly reduce long-term treatment failure compared to placebo in previously steroid-treated ITP patients. Long-term use of eltrombopag for up to 3 years was found to be generally safe and effective at maintaining platelet counts. The document concludes that large, randomized studies are still needed to better understand new ITP treatment options and balancing risks versus benefits requires consideration
Robert Orlowski is a professor of myeloma/lymphoma at MD Anderson Cancer Center who has published extensively on cancer therapy. His research focuses on translating promising laboratory findings into clinical trials for hematologic malignancies. The document summarizes several of his presentations and studies on new treatments for multiple myeloma and other plasma cell dyscrasias, including studies on carfilzomib, lenalidomide, and other novel agents alone and in combination for newly diagnosed, relapsed/refractory, and amyloidosis patients. It discusses efficacy and safety results and the changing treatment landscape in these diseases.
Jean-Luc Harousseau, M.D., Professor of Hematology, Head, Dept. of Clinical Hematology, Director of the Cancer Center Rene Gauducheau, University of Nantes, France - Impact of Novel Therapies in the Management of Multiple Myeloma
Presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center. jtcancercenter.org/CME
Multiple myeloma is a cancer of plasma cells that remains largely incurable. While initial treatments can achieve remission, patients will typically relapse with fewer treatment options available. Current therapies for relapsed and refractory multiple myeloma have limited efficacy and serious side effects. There remains an unmet need for additional effective and tolerable treatments. Carfilzomib is a novel proteasome inhibitor that has shown clinical activity with durable responses and an acceptable safety profile in patients with relapsed and refractory multiple myeloma who have limited treatment options.
This document provides an overview of multiple myeloma, including its definition, clinical presentation, workup, staging, management, and treatment regimens. Key points include:
- Multiple myeloma is a malignant neoplasm of plasma cells that accumulate in the bone marrow, leading to bone destruction.
- Workup involves blood and urine tests, bone marrow biopsy, skeletal survey, and imaging to determine disease severity and stage according to the Durie-Salmon or ISS staging systems.
- Treatment may include chemotherapy, steroids, immunomodulators, stem cell transplantation, and supportive care. The goal of initial therapy is to achieve remission prior to stem cell transplantation in eligible patients.
Carfilzomib: new standard of care for myelomaspa718
Carfilzomib is a second-generation proteasome inhibitor that is highly selective and irreversible. Studies show it has minimal off-target effects and less neurotoxicity compared to other proteasome inhibitors like bortezomib. Single agent and combination studies demonstrated high response rates in relapsed multiple myeloma patients, including those with high-risk cytogenetics or renal impairment. Phase 3 trials showed carfilzomib combinations had improved progression-free and overall survival compared to standards of care. Ongoing studies are exploring carfilzomib in frontline multiple myeloma treatment.
Multiple myeloma is a cancer of plasma cells that results in overproduction of abnormal antibodies in the bone marrow. It commonly causes bone pain, fractures, anemia, and kidney problems. Risk factors include age over 60 and exposure to chemicals like pesticides, radiation, or certain industrial chemicals. Treatment may include chemotherapy, steroids, stem cell transplantation, radiation, surgery, and newer drugs like thalidomide, lenalidomide, and bortezomib to improve outcomes. Despite recent advances, multiple myeloma remains incurable and patients often relapse, highlighting the need for additional therapeutic options.
Multiple myeloma is a cancer of plasma cells that results in excessive numbers of abnormal plasma cells in the bone marrow. It is characterized by overproduction of monoclonal proteins, known as M proteins, and can cause symptoms such as anemia, kidney damage, and bone fractures. Diagnosis involves blood and urine tests to detect M proteins, bone marrow biopsy to identify plasma cell percentage, and imaging tests to check for bone lesions. Treatment may include chemotherapy, steroids, stem cell transplantation, and other newer drugs depending on the stage of disease and patient health. The goals of treatment are to eliminate the myeloma, control disease activity, and relieve symptoms in order to prolong survival and quality of life.
Multiple myeloma is a malignant disease of plasma cells in the bone marrow. It commonly affects elderly individuals and presents with bone destruction, renal failure, and bone marrow infiltration. While incurable, treatments include chemotherapy, stem cell transplantation, and supportive care to manage symptoms and complications. Hyperdiploidy is associated with a better prognosis compared to hypodiploidy.
Multiple myeloma is a cancer of plasma cells that is characterized by malignant proliferation of a single clone of plasma cells in the bone marrow. It most commonly affects bones and can cause bone pain, fractures, anemia, renal failure and recurrent infections. Diagnosis involves blood and urine tests showing monoclonal proteins and bone marrow biopsy with over 30% plasma cells. Treatment involves chemotherapy, stem cell transplantation, radiation, steroids and supportive care. Newer targeted therapies are improving outcomes for patients.
Thank you for the detailed case presentation. Based on the investigations:
- Serum monoclonal protein >2g/dL
- Clonal BM plasma cells >20%
- FLC ratio >20
The patient meets criteria for high risk smoldering myeloma as per Mayo 2018 criteria.
Diagnosis is high risk smoldering myeloma.
Treatment options would include enrollment in a clinical trial or treatment with a proteasome inhibitor like bortezomib or immunomodulatory drug like lenalidomide. Close monitoring at 3 monthly intervals would also be recommended.
Lenalidomide maintenance compared with placebo in responding elderlyravi jaiswal
This randomized phase III trial compared lenalidomide maintenance therapy versus placebo in elderly patients with diffuse large B-cell lymphoma (DLBCL) who achieved a response to first-line R-CHOP induction therapy. The trial found that lenalidomide maintenance led to a statistically significant improvement in progression-free survival compared to placebo, with a median PFS not reached in the lenalidomide arm versus 58.9 months in the placebo arm. There was no significant difference in overall survival between the arms. Lenalidomide maintenance was associated with more grade 3-4 adverse events compared to placebo. The benefit of lenalidomide maintenance was seen across patient subgroups.
POST TRANSPLANT THERAPY FOR AML: Marcos Delimaspa718
1. The document discusses strategies for preventing relapse after allogeneic stem cell transplantation (SCT), including pre-emptive treatment of minimal residual disease and maintenance of remission.
2. It describes a phase II trial where patients with AML/MDS received azacitidine treatment after SCT if they had less than 80% donor chimerism, in order to pre-emptively treat minimal residual disease and prevent hematological relapse.
3. The ideal properties of a maintenance agent after SCT are discussed, including being active against the disease without too much toxicity, not causing myelosuppression, able to be given early after transplant, and increasing the immunogenicity of malignant cells.
Luciano J. Costa, MD, PhD, prepared useful Practice Aids pertaining to multiple myeloma for this CME activity titled "Exploring Clinical Decisions in the New Era of Myeloma Management: The Impact of Novel Platforms and Agent Classes Across the Spectrum of Care." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2Dypn7b. CME credit will be available until March 12, 2020.
This document summarizes the results of a clinical trial investigating the efficacy and safety of pembrolizumab (anti-PD-1 antibody) in patients with advanced melanoma that progressed after treatment with ipilimumab. The overall response rate was 26% in the 2 mg/kg group and 10% in the 10 mg/kg group, with responses ongoing after 1 year. Pembrolizumab demonstrated a manageable safety profile, with grade 3-4 drug-related adverse events occurring in 12% of patients. This trial provides evidence that pembrolizumab is an effective treatment option for patients with advanced melanoma who have progressed on ipilimumab.
A phase I/II trial to evaluate the safety, feasibility and activity of salvag...Enrique Moreno Gonzalez
The current standard treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma (DLBCL) primarily consists of intensified salvage therapy and, if the disease is chemo-sensitive, high dose therapy followed with autologous stem cell transplantation. In the rituximab era however, this treatment approach has shown only limited benefit. In particular, patients relapsing after rituximab-containing primary treatment have an adverse prognosis, especially if this occurs within the first year after therapy or if the disease is primarily refractory. Therefore there is an ultimate need for improved salvage treatment approaches.
- The patient presented with obstructive jaundice and was diagnosed with plasmacytoma and multiple myeloma based on tests. She received 2 cycles of chemotherapy but was then transferred due to a storm and taken off treatment.
- Multiple myeloma is a cancer of plasma cells characterized by proliferation of malignant plasma cells in the bone marrow. It accounts for 1% of cancers and treatment may include stem cell transplantation, thalidomide, lenalidomide, and bortezomib to extend survival.
- The document discusses diagnostic criteria, risk stratification, treatment including primary therapy and surveillance, stem cell transplantation criteria, and approaches to relapsed or refractory disease.
This case study examines the use of cetuximab-based chemotherapy for the re-treatment of patients with metastatic colorectal cancer who had previously responded to cetuximab treatment but experienced disease progression after stopping treatment. The study aims to evaluate the overall response and safety of re-treating these patients with cetuximab-containing chemotherapy. It describes the study design, inclusion/exclusion criteria, experimental and control treatments, and primary/secondary outcome measures that will be assessed over a 2-year period.
This document discusses anti-neoplastic drugs used to treat cancer. It begins by describing the characteristics of normal and cancerous cells, and how cancer is categorized. It then explains that anti-neoplastic drugs, also called chemotherapy, work by inhibiting or killing rapidly dividing cancer cells. The document classifies chemotherapy drugs and discusses their mechanisms of action, characteristics, administration as adjuvant or neoadjuvant therapy, and potential side effects like bone marrow suppression and hair loss. It emphasizes the nursing care needed for patients undergoing chemotherapy.
This document provides an overview of the management of plasma cell neoplasms including multiple myeloma and plasmacytoma. It discusses the clinical spectrum, epidemiology, etiology, pathogenesis, clinical features, evaluation, staging systems, imaging, and management approaches including treatment regimens for newly diagnosed, relapsed, and transplant eligible or ineligible patients. It also reviews treatment of complications such as bone disease, anemia, renal failure, and infections. Management involves risk-stratified chemotherapy, stem cell transplantation, radiation, surgery, bisphosphonates, and palliative care.
Inotuzumab ozogamicin is an antibody-drug conjugate being studied for the treatment of acute lymphoblastic leukemia (ALL) in adults. The INO-VATE ALL study compared inotuzumab ozogamicin to standard chemotherapy for adults with relapsed or refractory ALL. The primary objectives were to demonstrate higher rates of complete remission and longer overall survival with inotuzumab ozogamicin. Complete remission, safety, and overall survival were evaluated. If shown to be effective, inotuzumab ozogamicin could provide a new treatment option for adults with relapsed/refractory ALL.
The document discusses a clinical trial comparing the monoclonal antibodies obinutuzumab and rituximab for treating diffuse large B-cell lymphoma. Obinutuzumab is a glycoengineered, humanized antibody that clusters the CD20 antigen more effectively than rituximab. In a phase III trial, obinutuzumab plus chemotherapy did not significantly improve progression-free survival over rituximab plus chemotherapy. However, obinutuzumab's glycoengineering may enhance its antibody-dependent cellular cytotoxicity and direct cell death mechanisms relative to rituximab.
Larry W. Kwak discusses ongoing research for targeted therapy of Hodgkin's lymphoma. The goals are to [1] improve remission rates and decrease risk of death, [2] minimize side effects and maintain or prolong remissions, and [3] develop additional options for relapsed or refractory disease. Research is exploring targeted agents like HDAC inhibitors, OX40 receptor ligation, and oral panobinostat to alter the tumor microenvironment and induce apoptosis. Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, has shown durable responses in refractory Hodgkin's lymphoma with manageable toxicity. Introduction of targeted therapies into frontline treatment, such as brentuxim
Larry W. Kwak discusses ongoing research goals and therapeutic options for Hodgkin's lymphoma, including improving remission rates and minimizing side effects. He describes targeted therapies under investigation, such as deacetylase inhibitors that induce cell cycle arrest and apoptosis as well as alter the tumor microenvironment. Kwak also discusses the use of oral HDAC inhibitors like mocetinostat, which have shown clinical activity in Hodgkin's lymphoma. Finally, he examines the efficacy of the antibody-drug conjugate brentuximab vedotin in treating relapsed and refractory Hodgkin's lymphoma.
El futuro del tratamiento del cáncer renal metastásico: inmunoterapia y terap...Mauricio Lema
Ponencia en el primer simposio de la Asociación Colombiana de Hematología y Oncología (ACHO) de cáncer genitourinario, Bogotá, septiembre 23 y 24 de 2016.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...Donc Test
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Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
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The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
1. Journal presentation
Daratumumab monotherapy in patients with
treatment-refractory multiple myeloma
(SIRIUS): an open-label, randomised, phase 2
trial
Published on January 6, 2016
in
by–Dr. Shubham Prasad, Department of General Medicine, Institute
Of Medical Sciences, Banaras Hindu Uiversity [B.H.U.],
Varanasi, India
3. Clonal bone marrow plasma cells ≥10% or
biopsy-proven bony or extramedullary plasmacytoma
AND
any one or more of the following CRAB features or myeloma-defining events:
Evidence of end organ damage that can be attributed to the underlying
plasma cell proliferative disorder, specifically:
Calcium-Hypercalcemia
Renal insufficiency
Anemia
Bone lesions
Any one or more of the following biomarkers of malignancy (MDEs):
60% or greater clonal plasma cells on bone marrow examination
Serum involved / uninvolved free light chain ratio of 100 or greater,
provided the absolute level of the involved light chain is at least 100mg/L
(a patient’s “involved” free light chain—either kappa or lambda—is the
one that is above the normal reference range; the “uninvolved” free light
chain is the one that is typically in, or below the normal range)
More than one focal lesion on MRI that is at least 5mm or greater in size.
Lancet Oncol 2014; 15: e538–48
5. 5 YEAR
OVERALL SURVIVAL PROGRESSION FREE
SURVIVAL
82% 55%
62% 36%
40% 24%
2015 American Society of Clinical Oncology
R
E
V
I
S
E
D
ISS
S
T
A
G
I
N
G
14. TWO NEWER CR
Palumbo et al 2015 American Society of Clinical Oncology
Immunophenotypic CR sCR as defined plus absence of
phenotypically aberrant plasma cells
(clonal) in bone marrow with minimum of 1
million total bone marrow cells analyzed by
multiparametric flow cytometry (with four
colors)
Molecular CR CR as defined plus negative allele-specific
oligonucleotide polymerase chain reaction
(sensitivity 105) –PCR
15. When to label as refractory/relapse
Multiple Myeloma
16. • Refractory - when a patient's disease is resistant to
treatment or the disease progresses within 60 days of
their last therapy. Richardson, et al. “The Treatment of Relapsed and Refractory
Multiple Myeloma.” ASH Education Book January 1, 2007 vol. 2007 no. 1 317-323.
• Relapsed - means the disease has returned after a period
of initial, partial or complete remission. National Cancer Institute.
“NCI Dictionary of Cancer Terms: Relapsed multiple myeloma.” November 2015.
• Double-refractory disease – definition is evolving over
time, and can vary from country to country. The classical
definition refers to patients refractory to bortezomib and
thalidomide and/or lenalidomide—the first generation
proteasome inhibitors and immunomodulatory agents
(IMiDs). Maria-Victoria Mateos, MD, PhD, University Hospital of Salamanca-IBSAL; Jatin J.
Shah, MD, The University of Texas MD Anderson Cancer Center; Andrew Spencer, MD, Monash
University
Published Online: Thursday, December 17, 2015 http://global.onclive.com/insights/Global-
Relapsed-Refractory-MM/treating-double-refractory-multiple-myeloma#sthash.
19. UNDERSTANDING RELAPSE
6 unique clones at diagnosis
Variable chemotherapy response
Minor drug-resistant clone lethal
Multiple clones with variable
drug sensitivity
(Combination chemotherapy a
necessity
and
Continuous therapy logical)
Re-emergence of drug-sensitive clones
(Once resistant not always resistant)
Minor clone is lethal (CR is a goal)
IMPLICATIONS
22. Evidence before this study
• Although survival has improved substantially with
new drug classes (eg, proteasome inhibitors and
immunomodulatory drugs), along with autologous
stem cell transplantation, most patients will die
from refractory disease AND MULTIPLE MYELOMA
REMAINS INCURABLE.
Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple
myeloma and the impact of novel therapies. Blood 2008; 111: 2516–20.
Turesson I, Velez R, Kristinsson SY, Landgren O. Patterns of improved survival
in patients with multiple myeloma in the twenty-fi rst century: a population-
based study. J Clin Oncol 2010; 28: 830–34.
23. • Outcomes for patients who are resistant to proteasome
inhibitors (bortezomib and carfilzomib) and
immunomodulatory drugs (lenalidomide, thalidomide, and
pomalidomide) are especially poor.
• Additional treatment can be complicated by cytopenias,
secondary to poor haematological reserves, and comorbidities
such as renal insufficiency.
• Therefore, effective treatments that target novel pathways
with little toxicity and favourable tolerability are needed.
• Monoclonal antibodies are a novel class of agents in
myeloma, targeting cell surface markers, such as SLAMF7 (CS-
1) and CD38, with few off-target effects.
Kuroda J, Nagoshi H, Shimura Y, Taniwaki M. Elotuzumab and daratumumab: emerging new
monoclonal antibodies for multiple myeloma. Expert Rev Anticancer Ther 2013; 13: 1081–88
24. Daratumumab
• is a first-in-class human IgG1 monoclonal
antibody
• that binds CD38-expressing malignant cells with
high affinity
• induces tumour cell death through diverse
mechanisms of action:
1. complement-dependent cytotoxicity
2. antibody-dependent cell-mediated
cytotoxicity
3. antibody-dependent cellular phagocytosis
4. induction of apoptosis
26. • Daratumumab had gained US Food and Drug
Administration breakthrough therapy
designation based on phase 1 data from a
first-in-human study in patients with multiple
myeloma who relapsed or were refractory to
at least two previous therapies. The first-in-
human study was expanded and Concurrently
this study was initiated to further investigate
the selected dose schedule.
27. Added value of this study
• The current study is the largest study so far of the
single-agent activity of daratumumab 16 mg/kg in
heavily pretreated patients with multiple myeloma
who were refractory to both a proteasome inhibitor
and an immunomodulatory drug.
• As a result of this study, daratumumab was approved
by the FDA for the treatment of refractory myeloma.
• Daratumumab is indicated for patients who have
received at least three previous lines of therapy,
including a proteasome inhibitor and an
immunomodulatory drug, or who are double refractory
to a proteasome inhibitor and an immunomodulatory
drug.
28. Lines Of Therapy
• A line of therapy is defined as one or more cycles of a planned
treatment program.
• This may consist of one or more planned cycles of single-
agent therapy or combination therapy, as well as a sequence
of treatments administered in a planned manner.
• For example, a planned treatment approach of induction
therapy followed by autologous stem cell transplantation,
followed by maintenance is considered one line of therapy.
• A new line of therapy starts when a planned course of
therapy is modified to include other treatment agents (alone
or in combination) as a result of disease progression, relapse,
or toxicity.
• A new line of therapy also starts when a planned period of
observation off therapy is interrupted by a need for additional
treatment for the disease.
Consensus recommendations for the uniform
reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1
30. Inclusion criteria
1. Age at least 18 years old
2. Documented secretory multiple myeloma
3. Evidence of disease progression on or within 60
days of the last dose of the most recent previous
treatment regimen, based on the International
Myeloma Working Group criteria.
4. Eastern Cooperative Oncology Group
performance status score of 0, 1, or 2.
31. Exclusion criteria
1. Any antimyeloma treatment within 2 weeks
2. Autologous stem cell transplantation within 12
weeks, of day 1 of cycle 1
3. Meningeal involvement of multiple myeloma
and other malignancies within 5 years.
4. Absolute neutrophil counts of 1 × 109 per L or
lower, haemoglobin concentration of 75 g/L or
lower, platelet counts of less than 50 × 109 per L,
and creatinine clearance of 20 mL/min per 1·73
mm2 or lower.
32. Other exclusion criteria were:
4. Myocardial infarction within 1 year,
uncontrolled or unstable angina, congestive
heart failure (New York Heart Association
Class III or IV)
5. Arrhythmia (grade 2 or higher), QTcF interval
that was longer than 470 ms
6. Chronic obstructive pulmonary disease,
persistent asthma, or a history of asthma
within 5 years.
34. Outcomes Measures
The primary endpoint = overall response rate
(ORR = partial response [PR] + very good
PR + complete response [CR] + stringent CR).
Secondary endpoints = included duration of
response, progression-free survival (PFS),
overall survival, and clinical benefit rate
(minimal response + ORR).
35. Safety assessments = were the monitoring of
adverse events, physical examinations,
electrocardiogram monitoring, clinical
laboratory measurements, vital sign
measurements, and ECOG performance
status. Severity of adverse events was
assessed with the National Cancer Institute
Common Terminology Criteria for Adverse
Events (version 4.03).
36. Statistical analysis
Response assessments were done by an
independent review committee using the
International Myeloma Working Group
response criteria.
ORRs were reported with two-sided 95%
exact CI.
All patients who received at least one dose of
daratumumab were used for efficacy and
safety analyses.
37. RESULTS
• 124 patients received at least one dose of
daratumumab
(18 received 8 mg/kg and 106 received 16 mg/kg).
• At the first interim analysis, the daratumumab
8 mg/kg group did not meet the criteria for expansion
because of an ORR of 11·1% (95% CI 1·4–34·7).
• At the second interim analysis, after an additional 25
patients were treated in the 16 mg/kg group, the
cumulative ORR justified expansion of the study into
part 2 and an additional 65 patients were enrolled.
38. Concurrent pharmacokinetic analyses of the 8 mg/kg
dose in the first-in-human study indicated that drug
concentrations were probably less than the trough
threshold for target saturation.
The results of these analyses also suggested that,
although 24 mg/kg daratumumab would have been
well tolerated, the gain in clinical benefit would have
been small with this dose compared with 16 mg/kg.
45. • The median duration of follow-up of patients was 9·3
months
• Median duration of response was 7·4 months
• Median PFS was 3·7 months
• The 12-month overall survival was 64·8%
• Median overall survival was not reached in responders
and was 13·7 months in non-responders .
• 29 (94%) of 31 responders treated with daratumumab
16 mg/kg were still alive, compared with 45 (60%) of
75 non-responders.
• A subsequent clinical cutoff for a safety update to meet
regulatory requirements was June 30, 2015. With this
update, the median overall survival was 17·5 months
(13·7–NE).
49. • Daratumumab was well tolerated, and no patients
discontinued because of drug-related adverse events,
infusion-related reactions, or death.
• The safety profile in the 8 mg/kg group was similar to
that in the 16 mg/kg group.
• Grade 3 or higher anaemia and thrombocytopenia
occurred more frequently in non-responders than in
responders . Grade 3 or higher neutropenia rates were
similar in non-responders and responders.
50. • Few patients required additional supportive care: 40
(38%) of 106 received red blood cell transfusions, 14
(13%) had platelet transfusions, and eight (8%)
needed granulocyte colony-stimulating factor.
• The most common infusion-related reactions
included nasal congestion [12%] f/b throat irritation
[7%].
• No patient discontinued daratumumab because of an
infusion-related reaction. No immunogenicity was
reported.
51. • WITH TIME….90 (85%) of 106 patients
SUBSEQUENTLY discontinued daratumumab 16
mg/kg: 82 (77%) because of progressive disease, five
(5%) because of treatment-unrelated adverse events,
and three (3%) as a result of consent withdrawal
because of symptoms related to disease progression.
• Five (5%) patients discontinued treatment -two with
general physical health deterioration and one each
with H1N1 influenza, hypercalcaemia, and spinal
cord compression).
52. • 31 (29%) patients died after treatment with
daratumumab 16 mg/kg: 29 (27%) because of
progressive disease and two (2%) because of adverse
events (cardiorespiratory failure secondary to H1N1
influenza complications, and general health
deterioration secondary to complications of
aspiration pneumonia).
• 29 (94%) of 31 responders treated with
daratumumab 16 mg/kg were still alive, compared
with 45 (60%) of 75 non-responders.
53. DISCUSSION
• Daratumumab monotherapy showed substantial clinical
activity, with an ORR of 29%, and was well tolerated in
patients with multiple myeloma who had been heavily
treated; most patients were double refractory to bortezomib
and lenalidomide, and many were refractory to pomalidomide
or carfilzomib.
• Resistance to any previous therapy had no effect on the
activity of daratumumab, lending support to a novel
mechanism of action, but these findings need to be confirmed
in larger studies.
54. • Similar response rates were also noted in patients with
moderate renal impairment, older than 75 years of age, and
with extramedullary disease or high-risk baseline cytogenetic
characteristics.
• Although this study did not have a control arm, patients with
the degree of treatment refractoriness in our study
historically have poor outcomes.
• The results of our study corroborate the previously reported
efficacy of daratumumab 16 mg/kg monotherapy in relapsed
or refractory patients with multiple myeloma.
Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with
daratumumab monotherapy in multiple myeloma. N Engl J Med 2015; 373: 1207–19.
55. • Elotuzumab, a monoclonal antibody, that targets
SLAMF7, lacks single-agent activity, increased
median PFS by 4·5 months compared with the
control arm in combination with lenalidomide and
dexamethasone in a population of patients who were
less heavily pretreated than those in the this study.
Zonder JA, Mohrbacher AF, Singhal S, et al. A phase 1,
multicenter, open-label, dose escalation study of elotuzumab in patients with advanced
multiple myeloma. Blood 2012; 120: 552–59
56. • Deep responses of very good PR or better, particularly
stringent CR, are associated with improved long-term
outcomes in patients with newly diagnosed multiple
myeloma.
Kapoor P, Kumar SK, Dispenzieri A, et al. Importance of achieving stringent complete
response after autologous stem-cell transplantation in multiple myeloma.
J Clin Oncol 2013; 31: 4529–35.
• Whether the same trend occurs in patients with relapsed and
refractory multiple myeloma remains to be seen, although
many patients treated in this study had responses to
daratumumab that improved over time and might contribute
to prolonged overall survival.
57. • These high-quality responses (9% very good PR, 3% stringent
CR) are notable in treatment-refractory patients with multiple
myeloma.
• The rate of high-quality responses with single-agent
daratumumab were higher than those with pomalidomide
monotherapy in the mm-002 clinical trial (2% of patients with
a very good PR). Richardson PG, Siegel DS, Vij R, et al. Pomalidomide alone or in
combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a
randomized phase 2 study. Blood 2014; 123: 1826–32.
• In the PX-171-003-A1 studyof carfilzomib monotherapy in 266
patients, responses of very good PR or better were noted in
6% of patients. Siegel DS, Martin T, Wang M, et al. A phase 2 study of single-agent
carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma.
Blood 2012; 120: 2817–25.
58. • When considering daratumumab monotherapy for treatment of refractory
multiple myeloma, it should be placed in the context of other
combination regimens that are in use in these patients.
• In the POMALIDOMIDE alone versus pomalidomide plus low-dose
dexamethasone treatment groups of the mm-002 phase 2 study, 61% and
62% of 108 and 113 patients, respectively, were refractory to both
bortezomib and lenalidomide, and in these double-refractory patients the
ORR was 21% and 31%, median PFS was 2·0 and 3·8 months, median
duration of response was 11·4 and 6·5 months, and median overall
survival was 12·5 and 13·4 months, respectively.
• In the PX-171-003-A1 study, in those treated with CARFILZOMIB
monotherapy who were refractory to both bortezomib and lenalidomide,
the ORR was 15%, median PFS was 3.6 months, median duration of
response was 7·8 months, and median overall survival was 11·9 months.
• Thus, the ORR of 29%, median PFS of 3·7 months, median duration of
response of 7·4 months , and median overall survival of more than 16
months in this study of DARATUMUMAB monotherapy compare
favourably with these agents, particularly because most of the patients
were refractory to both proteasome inhibitors and immunomodulatory
drugs (95%), and many were refractory to pomalidomide (63%) or
carfilzomib (48%).
59. • Daratumumab has a favourable safety profile
compared with other available agents, and results in
clinically manageable side-effects. No patient treated
with 16 mg/kg discontinued daratumumab
treatment because of a treatment-related adverse
event.
• This result compares favourably with the substantial
risk of neutropenia, febrile neutropenia, and
infections with pomalidomide and dexamethasone
reported in other studies.
60. • Additionally, non-haematological toxicities, such as
cardiopulmonary and renal side-effects, are an
important consideration with carfilzomib,
particularly in patients with advanced disease.
• The overall favourable toxicity profile of
daratumumab makes it an attractive drug for use in
combination regimens, and it has shown early
promising activity in combination with lenalidomide
and dexamethasone.
61. CONCLUSION
• Based on deep and durable response and a
favourable safety profile, daratumumab 16
mg/kg seems to be an effective option for
patients with relapsed and refractory multiple
myeloma for whom available treatments have
been exhausted.
62. Darzalex (Daratumumab)
• Approved By FDA ; has world wide commercialisation rights.
• Originally developed by Genmab pharmaceuticals; but now
being jointly developed by Genmab and Johnson & Johnson
biotech.
• Darzalex is an infused therapy, and it will be available in vials
that come in two sizes: A smaller vial that contains 100 mg of
the drug, and a larger vial that contains 400 mg.
• The recommended dose of the drug is based on a patient’s
weight expressed in kilograms: 16 mg per kilogram. Infusions
should be given once a week for the first 8 weeks of
treatment, once every two weeks during weeks 9 through 24,
and once every four weeks thereafter.
• the wholesale price per vial of Darzalex will be $450 for the
100 mg vial and $1800 for the 400 mg vial.
These changes are based on the identifi cation of biomarkers associated with near inevitable development of CRAB features in patients who would otherwise be regarded as having smouldering multiple myeloma. A delay in application of the label of multiple myeloma and postponement of therapy could be detrimental to these patients.