Safe in Treating Myeloma With Brain Involvement

TOPLINE:

B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapy demonstrated safety in patients with multiple myeloma (MM) and central nervous system (CNS) involvement, achieving an 80% overall response rate and 100% CNS response. Treatment showed no excess toxicities, with 80% experiencing only grade 1-2 cytokine release syndrome and no grade > 3 cases observed.

METHODOLOGY:

• A multicenter, retrospective analysis included 10 patients with MM and CNS involvement who received either idecabtagene vicleucel (n = 6) or ciltacabtagene autoleucel (n = 4) at five major United States academic cancer centers.
• Participants exhibited CNS involvement confirmed by positive findings on brain/cranial nerve and/or spinal cord imaging (100%) and/or cerebrospinal fluid studies (40%), with eight patients diagnosed before CAR T-cell therapy and two diagnosed within 14 days postinfusion.
• The analysis encompassed safety outcomes including cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome, along with efficacy measures such as overall response rate and CNS response.
• Seven patients received CNS-directed therapy during bridging before CAR T-cell therapy, including radiotherapy alone, radiotherapy plus intrathecal chemotherapy, or surgery plus radiotherapy.

TAKEAWAY:

• Overall response rate reached 80%, including 60% complete response/stringent complete response, with minimal residual disease negativity achieved in 40% of patients within 90 days postinfusion.
• Median progression-free survival (PFS) was 6.3 months (95% CI, 1.9-10.7), and median overall survival was 13.3 months, with 6-month overall survival at 87.5% and 1-year overall survival at 75% for patients diagnosed before CAR T-cell therapy.
• The safety profile showed 80% of patients experiencing grade 1-2 cytokine release syndrome, with no grade > 3 cases, while immune effector cell–associated neurotoxicity syndrome occurred in 30% of patients (grade 1, 20%; grade 3, 10%).
• Patients who responded to bridging therapy (n = 4) demonstrated better outcomes, with all achieving a complete response within 6 months and showing improved survival, suggesting the importance of optimizing pre-CAR T-cell therapy.

IN PRACTICE:

“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.

SOURCE:

This study was led by Mahmoud R. Gaballa, of The University of Texas MD Anderson Cancer Center in Houston. It was published online on March 11 in Blood Advances.

LIMITATIONS:

According to the authors, the study’s limitations include its retrospective nature, variability in data collection methods across different institutional guidelines, variation in minimal residual disease testing techniques, and lack of correlative laboratory data. While the sample size was small, the authors noted that given the rarity of patients with CNS myeloma involvement who successfully receive CAR T-cell therapy, the findings still provide valuable practice-informing insights.

DISCLOSURES:

Gaballa reported receiving consulting or advisory role fees from Bristol Myers Squibb, Boxer Capital LLC, and Arcellx. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.