TOPLINE:

Intensive cytotoxic bridging therapy before B-cell maturation antigen chimeric antigen receptor (CAR) T-cell therapy is associated with prolonged hematopoietic recovery and an increased risk for severe infections in patients with multiple myeloma (MM). The analysis of 158 patients revealed that intensive bridging predisposed to severe late cytopenias and reduced progression-free survival.

METHODOLOGY:

• Researchers analyzed 158 patients with relapsed or refractory MM treated with either cilta-cel (n = 22) or ide-cel (n = 136) at three university hospitals until May 2024.
• Analysis classified bridging regimens as noncytotoxic chemotherapy (CTX; n = 82), intermediate CTX (one to two CTX agents; n = 55), or intensive CTX (at least three CTX agents or high-dose therapy with stem cell transplantation; n = 21).
• Patients received lymphodepletion with fludarabine and cyclophosphamide (n = 153) or bendamustine (n = 5), with toxicities monitored from day 0 to day 90.

TAKEAWAY:

• Intensive CTX bridging was associated with prolonged time to neutrophil recovery (63 days vs 21 days for non-CTX group; hazard ratio [HR], 0.36; 95% CI, 0.17-0.78; P = .01).
• Patients receiving intensive CTX showed significantly higher risk for severe late thrombocytopenia (odds ratio [OR], 18.2; 95% CI, 4.04-132; P < .001) and increased infection susceptibility (HR, 2.32; 95% CI, 0.99-5.43; P = .05).
• Progression-free survival was significantly shorter in the intensive CTX group than in the non-CTX group (HR, 2.49; 95% CI, 1.27-4.87; P = .008).
• The researchers identified cytokine release syndrome grade > 2, preexisting grade > 3 cytopenias, and disease progression before lymphodepletion as relevant risk markers for post-CAR T cytopenias.

IN PRACTICE:

“Targeted and novel immunotherapies could provide alternatives for bridging, and high-risk patients may particularly benefit from enhanced monitoring, prophylaxis, and supportive care,” wrote the authors of the study.

SOURCE:

The study was led by Jan H. Frenking and Marc S. Raab, Heidelberg University Hospital in Heidelberg, Germany. It was published online in Blood Advances.

LIMITATIONS:

According to the authors, the major limitation was the retrospective design of the study. The cilta-cel cohort had limited patient numbers, a longer vein-to-vein time, and a shorter follow-up period. The researchers noted that bridging groups showed differences in baseline characteristics and outcomes, making it difficult to draw final conclusions regarding disease-, CAR T-, and bridging-related effects.

DISCLOSURES:

Frenking disclosed relationships with Bristol Myers Squibb, Janssen-Cilag, Pfizer, and Stemline Therapeutics. The study received funding from the International Myeloma Society, the Paula and Rodger Riney Foundation, the National Cancer Institute, the US Department of Defense, and the Dietmar Hopp Foundation. 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.