BCMA-Targeting CAR T-Cell Therapy Is Feasible in Patients With Multiple Myeloma and CNS Involvement

Chimeric antigen receptor (CAR) T-cell therapy is safe and feasible in patients with relapsed, refractory multiple myeloma (RRMM) with central nervous system (CNS) involvement, according to study results published in Blood Advances. The researchers reported a positive initial response to therapy, although a shorter progression-free survival (PFS) warrants consideration for post-CAR T-cell therapy maintenance and larger studies to confirm the findings.

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The development of CAR T-cell therapy has led to substantial improvements in treatment outcomes and overall survival (OS) in some patients with RRMM, which have been observed in both clinical trial and real-world settings. Despite numerous studies evaluating the efficacy and safety of CAR T-cell agents, there remains little investigation into their feasibility for patients with CNS involvement. Patients with MM and CNS interference have historically poor prognoses and have been largely excluded from clinical trials.

To determine the safety and efficacy of BCMA-targeted CAR T-cell therapy, researchers conducted a multicenter, retrospective analysis from 5 major US academic cancer centers, including patients with MM with CNS involvement who received BCMA-directed CAR T-cell therapy, either idecabtagene vicleucel (ide-cel, Abecma; Celgene Corporation) or ciltacabtagene autoleucel (cilta-cel, Carvykti; Janssen Biotech, Inc). The study involved 10 patients total—6 were treated with ide-cel and 4 were treated with cilta-cel—of which 8 had CNS diagnosis prior to CAR T-cell therapy and 2 were diagnosed 14 days post-infusion.

The primary end point was the incidence rates of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), with secondary end points including the best response rates and CNS response after CAR T-cell therapy. The researchers estimated OS and PFS using the Kaplan-Meier method.

In this study, there were no significant toxicities associated with the treatment. Specifically, no patients experienced CRS of grade 3 or higher. There was a 10% incidence of ICANS grade 3, but no cases of grade 4 ICANS. Two patients experienced delayed neurotoxicity, but both cases were treatable, and no parkinsonian side effects were reported.

The treatment yielded promising results, with an 80% overall response rate, including more than 70% achieving a very good partial response, and a 100% response rate for central CNS involvement. The median follow-up period was 381 days, during which patients who had CNS RRMM diagnosed prior to receiving CAR-T therapy (n = 8) had a median OS of 13.3 months and a median PFS of 6.3 months. The best outcomes were observed in 4 patients who responded to bridging therapy, indicating that optimizing pre-CAR-T therapy may enhance treatment outcomes.

“Our study suggests that CAR T-cell therapy in patients with CNS MM is safe and feasible, and screening for CNS involvement before CAR T-cell therapy could be warranted in high-risk patients. The excellent initial response but relatively short PFS suggests consideration for post-CAR-T maintenance,” the authors of the study wrote.

In conclusion, these findings suggest that CAR-T therapy can be a highly effective treatment option for patients with CNS myeloma, with promising response rates and manageable toxicity profiles. While some delayed neurotoxicities were observed, they were treatable and did not result in long-term neurological damage. The data also highlight the importance of optimizing bridging therapy before CAR-T treatment, as patients who responded to this pre-treatment demonstrated better overall outcomes.

REFERENCES

Gaballa M, Puglianini O, Cohen A, et al. BCMA-directed CAR T-cell therapy in patients with multiple myeloma and CNS involvement. Blood Adv. March 3, 2025. Doi:10.1182/bloodadvances.2024014345