Cilta-cel, a BCMA-targeting chimeric antigen receptor T-cell therapy for multiple myeloma, was approved in USA on 28 February 2022, for patients with relapsed or refractory disease who have received ≥4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Approval in the EU followed for patients with ≥3 prior therapies. At median 28-month follow-up, the pivotal CARTITUDE-1 trial showed a 98% response rate (83% stringent complete response); median progression-free survival had not been reached, and adverse events could be managed with supportive therapy. Cilta-cel efficacy and safety in earlier lines of therapy, and its optimal sequencing in a complex treatment landscape are important areas of investigation.

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http://dx.doi.org/10.2217/fon-2022-1317DOI Listing

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Article Synopsis
  • - This study analyzed adverse events (AEs) from CAR T-cell therapies using data from the FDA Adverse Event Reporting System (FAERS) between 2017 and 2024, revealing both common and unique AEs associated with different CAR T-cell products.
  • - Findings showed that the most frequently reported AEs were nervous system, immune system, and general disorders, with specific AEs like parkinsonism and cerebrovascular accidents linked to certain products (e.g., Ide-cel and Cilta-cel) but not others.
  • - The study highlights the importance of careful patient assessments and monitoring during treatment, particularly for cardiopulmonary toxicity and severe nervous system conditions, as the risks vary significantly among the different CAR T-cell
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Review of CAR T-Cell Therapy in Multiple Myeloma: A Canadian Perspective.

Curr Oncol

July 2024

Department of Medical Oncology and Haematology, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.

Multiple myeloma (MM) is an incurable plasma cell malignancy. In the context of the current standard of care therapies in Canada, outcomes among patients with relapsed/refractory multiple myeloma (RRMM), particularly those with triple-class (or more) refractory disease remain poor. Immunotherapies have significantly changed the treatment landscape of MM.

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Introduction: Ciltacabtagene autoleucel (cilta-cel), a BCMA-targeting CAR-T therapy, is approved in the United States and Europe for patients with relapsed/refractory multiple myeloma (RRMM) and ≥1 prior line of therapy (LOT), including a proteasome inhibitor and an immunomodulatory drug, and are lenalidomide refractory.

Areas Covered: We examine recent long-term data in heavily pretreated RRMM (LEGEND-2, CARTITUDE-1) and earlier LOTs (CARTITUDE-4) compared with standard therapy and discuss the rationale for investigating cilta-cel as frontline therapy for transplant-eligible and transplant-ineligible patients (CARTITUDE-5, CARTITUDE-6).

Expert Opinion: CAR-T therapies can improve outcomes for patients with MM across different LOTs.

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Recently, many new therapies have improved the outcomes of patients with relapsed and/or refractory multiple myeloma (RRMM). Nevertheless, recurrence is still unavoidable, and better treatment choices for RRMM are urgently needed. The clinical success of Chimera antigen receptor (CAR) T cell therapy in many hematological diseases, including leukemia and lymphoma, has drawn considerable attention to RRMM.

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Cilta-cel, a BCMA-targeting chimeric antigen receptor T-cell therapy for multiple myeloma, was approved in USA on 28 February 2022, for patients with relapsed or refractory disease who have received ≥4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Approval in the EU followed for patients with ≥3 prior therapies. At median 28-month follow-up, the pivotal CARTITUDE-1 trial showed a 98% response rate (83% stringent complete response); median progression-free survival had not been reached, and adverse events could be managed with supportive therapy.

View Article and Find Full Text PDF

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