Idecabtagene Vicleucel for Relapsed/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium

Abstract

PURPOSE Idecabtagene vicleucel (ide-cel) is an autologous B-cell maturation antigen–directed chimeric antigen receptor T-cell therapy approved for relapsed/refractory multiple myeloma (RRMM) on the basis of the phase II pivotal KarMMa trial, which demonstrated best overall and ≥ complete response rates of 73% and 33%, respectively. We report clinical outcomes with standard-of-care (SOC) ide-cel under the commercial Food and Drug Administration label. METHODS Data were retrospectively collected from patients with RRMM who underwent leukapheresis as of February 28, 2022, at 11 US institutions with intent to receive SOC ide-cel. Toxicities were graded per American Society for Transplantation and Cellular Therapy guidelines and managed according to each institution's policies. Responses were graded on the basis of the International Myeloma Working Group response criteria. RESULTS One hundred fifty-nine of 196 leukapheresed patients received ide-cel by data cutoff. One hundred twenty (75%) infused patients would have been ineligible for participation in the KarMMa clinical trial because of comorbidities at the time of leukapheresis. Any grade and grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 82/3% and 18/6%, respectively. Best overall and ≥ complete response rates were 84% and 42%, respectively. At a median follow-up of 6.1 months from chimeric antigen receptor T infusion, the median progression-free survival was 8.5 months (95% CI, 6.5 to not reached) and the median overall survival was 12.5 months (95% CI, 11.3 to not reached). Patients with previous exposure to B-cell maturation antigen–targeted therapy, high-risk cytogenetics, Eastern Cooperative Oncology Group performance status ≥ 2 at lymphodepletion, and younger age had inferior progression-free survival on multivariable analysis. CONCLUSION The safety and efficacy of ide-cel in patients with RRMM in the SOC setting were comparable with those in the phase II pivotal KarMMa trial despite most patients (75%) not meeting trial eligibility criteria.

Management of Relapsed–Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice

“…Patients with previous exposure to anti-BCMA therapy, high-risk cytogenetics, Eastern Cooperative Oncology Group performance status ≥ 2 at lymphodepletion and young age had inferior PFS. Authors concluded that outcomes of ide-cel in a real-world setting were comparable to those reported by KarMMa, confirming its safety and efficacy [ 142 ].…”

Intent Matters: Real-World Applicability of Idecabtagene Vicleucel Usage in the United States

“…Second, an important point regarding baseline characteristics is that all patients in the pivotal KarMMA trial were required to be refractory to the last line of regimen before CAR T-cell therapy. 5 However, in this study by Hansen et al, 1 approximately two thirds of patients had refractory disease. Hence, further clarification on whether the remaining one third proceeded to CAR T without actively progressing myeloma is essential to contextualize the efficacy results.…”

Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN)

“…They may develop acute respiratory distress syndrome (ARDS) and thrombotic complications that can induce high in-hospital mortality [ 25 ]. This is due to MM patients’ advanced age, co-existing medical conditions, as well as to humoral and cellular immunity compromised by the disease itself and by concomitant, often prolonged-applied targeted and immunosuppressive therapies, including steroids, monoclonal antibodies [ 26 , 27 ], ASCT [ 28 ], and novel cellular therapies [ 29 , 30 ]. Furthermore, MM patients often show low/suboptimal rates (in terms of percentage of responders and magnitude of response) of both humoral and functional T-cell immune responses to anti-SARS-CoV-2 vaccines [ 31 – 34 ]; this further contributes to an increased risk of severe COVID-19, need of hospitalization and higher mortality rates [ 35 ].…”