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Blood Cancer

CAR-T in multiple myeloma: cilta-cel & ide-cel [Video]

Nikhil Munshi, MD, Dana-Farber Cancer Institute, Boston, MA, shares his thoughts on how the addition of ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) to the treatment paradigm is adding value to the treatment of patients with multiple myeloma. This interview took place at the European Hematology Association (EHA) Congress 2022 held in Vienna, Austria.

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Blood Cancer

Latest Results from the CARTITUDE-2 Study Testing Cilta-cel in Multiple Myeloma Patients [Video]

Niels van de Donk, MD, PhD, Hematologist at the VU University Medical Center in Amsterdam, discusses new results from Cohort B of the phase 2 CARTITUDE-2 study evaluating the efficacy and safety of ciltacabtagene autoleucel (cilta-cel) in patients with multiple myeloma who had early relapse after initial therapy. These data were recently presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.Multiple myeloma is a rare blood cancer. While the disease is treatable, relapses are common and some patients are refractory to early therapies.As Dr. van de Donk explains, safety and efficacy were assessed in the CARTITUDE-2 study and the primary endpoint was minimal residual disease (MRD) negativity at 10-5. As of January 2022, 19 multiple myeloma patients who experienced early relapse after front-line therapy received cilta-cel as part of Cohort B. Overall response rate (ORR) was 100.0%, 90% achieved complete response (CR) or better, and 95% achieved Very Good Partial Response (VGPR) or better. Median time to first response and best response were 0.95 months and 5.1 months, respectively. Of patients who were MRD-evaluable (n = 15), 14 (93%) achieved MRD 10-5 negativity during this study. Median duration of response was not reached and 12-month event-free rate was 88.9%. The 12-month progression-free survival rate was 90%. Median time to onset of cytokine release syndrome (CRS) was 8 days and occurred in 16 (84.2%) patients. CRS resolved in all patients. ICANS (grade 1) occurred in one patient. Movement/neurocognitive adverse events (grade 3) occurred in one patient, which was previously reported. One patient died post cilta-cel due to Parkinson’s disease on day 158. Overall, these results indicate that a single cilta-cel infusion can lead to deep and durable responses in a functionally high-risk multiple myeloma patient population with a manageable safety profile.

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Blood Cancer

The impact of the approval of cilta-cel in multiple myeloma [Video]

Mohamad Mohty, MD, PhD, Saint-Antoine Hospital, Paris, France, talks on chimeric antigen receptor T-cell (CAR-T) therapies in multiple myeloma, commenting on the recent approval of ciltacabtagene autoleucel (cilta-cel). The first CAR-T product was approved in pediatric and young adult patients with acute lymphoblastic leukemia (ALL), and its use was later expanded to treat a larger number of indications. The first CAR-T product in multiple myeloma, idecabtagene vicleucel, was approved in 2021 based on the results of the KarMMa trial (NCT03361748). More recently, the highly promising results from the CARTITUDE-1 trial (NCT03548207) led to the approval of cilta-cel by the FDA. According to Prof. Mohty, the addition of cilta-cel to the treatment armamentarium in multiple myeloma will undoubtedly improve the outcomes of patients with R/R disease, and he believes that CAR-Ts will start being used in earlier lines of treatment. Several trials are already comparing CAR-T products versus existing standards of care (SOC) in myeloma. This interview took place at the 48th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) 2022, which was held virtually.

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Blood Cancer

Advances in CAR-T therapy for R/R multiple myeloma: ide-cel & cilta-cel [Video]

Mohamad Mohty, MD, PhD, Saint-Antoine Hospital, Paris, France, discusses the efficacy and promise of BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapies including idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) in relapsed/refractory (R/R) multiple myeloma. Ide-cel was approved in March 2021 for patients with R/R multiple myeloma based on the results of the Phase II KarMMA study (NCT03361748) which reported a median progression-free survival (PFS) of 8.8 months and overall survival (OS) of 19.4 months. The field of CAR-T therapies for multiple myeloma is rapidly evolving, notably with cilta-cel, which showed remarkable results in the Phase Ib/II CARTITUDE-1 trial (NCT03548207), with an overall response rate (ORR) of almost 98% and a 2-year PFS of 71%. In addition, the incidence of severe cytokine release syndrome (CRS) and neurotoxicity was low. These trials highlight the potency of BCMA-directed CAR-T therapies for R/R multiple myeloma and several clinical trials are now evaluating these approaches in earlier lines of treatment. This interview took place at the EBMT-EHA 4th European CAR T-cell Meeting which was held virtually in 2022.

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Blood Cancer

The future of CAR-T therapy for multiple myeloma [Video]

Niels van de Donk, MD, PhD, VU University Medical Center, Amsterdam, Netherlands, talks on the development of CAR T-cell therapy for multiple myeloma. Over recent years, substantial evidence has been gathered to support the use of CAR-T therapy in heavily pretreated patients. Most recently, these efforts led to the FDA approval of idecabtagene vicleucel (ide-cel) for people with multiple myeloma that has relapsed after or is refractory to at least four prior treatments. Ciltacabtagene autoleucel (cilta-cel), another BCMA-directed therapy with two BCMA-targeting single-domain antibodies designed to confer avidity, is also under FDA review and is expected to be approved in the coming months. Prof. van de Donk comments on continued investigations driving the field forwards, including the assessment of new constructs, and testing in earlier stages of disease. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.

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Blood Cancer

Meta-analysis of cilta-cel in patients with R/R multiple myeloma [Video]

Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor (CAR) T-cell therapy, is currently being investigated in patients with relapsed/refractory multiple myeloma in the CARTITUDE-1 trial (NCT03548207). Yi Lin, MD, PhD, Mayo Clinic, Rochester, MN, provides an overview of findings from a meta-analysis of cilta-cel verus the standard of care. Data from various real world registries and clinical trials such as POLLUX (NCT02076009) and CASTOR (NCT02136134), were analyzed and patients receiving cilta-cel had superior progression-free survival and overall survival. Despite cilta-cel causing more adverse events, patients overall reported a better quality of life. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.

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Blood Cancer

CAR-T therapy in multiple myeloma: research blind spots [Video]

CAR T-cell therapy has been shown to elicit high-quality responses in patients with multiple myeloma. Positive data from the pivotal Phase II KarMMa trial led to the approval of idecabtagene vicleucel, a BCMA-directed CAR T-cell therapy, in patients with heavily pretreated relapsed/refractory myeloma, and ongoing trials are investigating the utility of CAR-T versus standard of care regimens in earlier lines of treatment. Andrew Cowan, MD, University of Washington, Seattle, WA, discusses the blind spots in myeloma CAR-T research, highlighting key topics such as treatment sequencing, combination studies, and retreatment with BCMA-targeted therapies. This interview took place at during 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.

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Blood Cancer

Dr. Thomas Martin Discusses 18-Month Follow-up Data From the CARTITUDE-1 Study (Multiple Myeloma) [Video]

Thomas Martin, MD, UCSF Helen Diller Family Comprehensive Cancer Center, discusses 2-year results from the CARTITUDE-1 study evaluating cilta-cel in heavily pre-treated, relapsed/refractory multiple myeloma patients.Multiple myeloma is a blood cancer associated with uncontrolled growth of plasma cells. Abnormal plasma cells – also known as myeloma cells – interfere with the production of healthy blood cells in the bone marrow. Myeloma cells also produce inactive clones of abnormal antibodies that may negatively affect the bones and kidneys. Symptoms of multiple myeloma may include: bone pain (particularly in the chest and spine), frequent infections, weakness or numbness in the legs, fatigue, confusion, excessive thirst, and constipation. While the disease is treatable, relapses are common and some patients are refractory to first line treatment.As Dr. Martin explains, the CARTITUDE-1 study is an ongoing Phase 1b/2, open-label, multi-center study evaluating the safety and efficacy of cilta-cel in adults with relapsed and/or refractory multiple myeloma. Patients received a single cilta-cel infusion (target dose 0.75×106 CAR+ viable T cells/kg) 5–7 days after lymphodepletion. Primary objectives of the study were to characterize cilta-cel safety confirm the recommended dose, and to evaluate efficacy.Previous data was presented at the American Society of Hematology Meeting & Exposition in 2020 (ASH 2020) when the median length of follow-up was 12 months. More recently, additional follow-up data was presented at ASH 2021, when the median length of follow-up was 18 months. This 2-year follow-up data demonstrated that in the 97 patients reported on, the overall response rate was 98% and the stringent complete response was 83% (compared to 67% at 12-month follow-up). The median progression-free survival was not estimable but, according to Dr. Martin, was approximately 61%.Cilta-cel, as a treatment from relapsed and/or refractory multiple myeloma patients, is currently under review by the FDA. They are set to make a decision by February 28, 2022.

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Blood Cancer

The role of immunotherapy in multiple myeloma [Video]

Nina Shah, MD, University of California, San Francisco, CA, provides her insights on the future of multiple myeloma treatment. Multiple advancements have been made in recent years, especially with the development of immunotherapies. In addition to existing monoclonal antibodies such as daratumumab and isatuximab, chimeric antigen receptor (CAR) T-cell therapies including idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) represent alternative therapies for patients with relapsed/refractory multiple myeloma. Dr Shah additionally highlights the development of bispecific T-cell engagers (BiTEs), as well moving immunotherapies into the frontline setting. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.