Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma

Abstract

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Fair Allocation of Scarce CAR T-Cell Therapies for Relapsed/Refractory Multiple Myeloma

“…The least-efficient outcome is for a patient to die during the vein-to-vein delay. Both clinical trial and real-world data suggest that 10% of patients will never receive their CAR T-cell therapy, implying that a “sickest first” strategy will lead to unacceptable levels of wasted patient-specific therapies. Furthermore, there is mounting evidence that patients with disease characteristics that portend the highest risk of death without CAR T-cell therapy—those with higher disease stage, high-risk cytogenetic abnormalities, extramedullary disease, and prior BCMA-directed therapies—are the ones who also appear to benefit less from BCMA-directed CAR T-cell therapy even if they do not die during the vein-to-vein delay …”

“…Black individuals are at a higher risk for multiple myeloma and comprise approximately 20% of newly diagnosed multiple myeloma cases in the US; yet, only 4.5% of participants in trials included in new drug application submissions for multiple myeloma indications between 2003 and 2017 were Black . This underrepresentation of Black individuals extends to CAR T-cell therapy trials in multiple myeloma . This will likely apply to the clinical distribution of CAR T-cell therapy due to (1) lack of or delayed referral, (2) unconscious physician bias, (3) lack of social support and/or transportation, and (4) institutionalized barriers from under- or uninsurance.…”

“…The treatment landscape for relapsed/refractory multiple myeloma has undergone an immunotherapeutic breakthrough with the introduction of 2 commercial B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell therapies for patients with heavily pretreated relapsed/refractory multiple myeloma: idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (Carvykti) . These therapies have led to durable responses and significantly reduced the risk of progression or death compared with alternative chemotherapies.…”

“…A 2023 study of centers offering CAR T-cell therapy for multiple myeloma found that for every allocated slot per month per center, there were 20 patients on the waitlist; patients were waiting a median of 6 months prior to leukapheresis . Despite ongoing efforts to increase supply through expanding manufacturing capabilities, this severe shortage will likely increase as CAR T-cell therapy demonstrates superior efficacy over alternatives earlier in the course of multiple myeloma . Even if new therapies such as off-the-shelf bispecific antibodies reduce demand, there will not be enough CAR T-cell therapy slots for all eligible patients.…”

Long‐term survivorship care after CAR‐T cell therapy

“…been treated in real-world clinical practice, and this number is expected to increase substantially as randomized controlled trials establish a role for CAR-T cells in earlier lines of therapy. [11][12][13][14] Promising breakthroughs in the treatment of solid organ malignancies and autoimmune diseases raise hope that CAR-T cell therapy may play an even broader role in the future. 15,16 CAR-T cell therapy is associated with well-known early toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effectorcell associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), the assessment and management of which have been thoroughly described in consensus guidelines by the American Society for Transplantation and Cellular Therapy (ASTCT), European Society for Blood and Marrow Transplantation (EBMT), National Comprehensive Cancer Network (NCCN), and American Society of Clinical Oncology (ASCO).…”