Recent Bendamustine Use Before CAR-T Therapy Linked to Worse Outcomes in LBCL

Recent exposure to bendamustine prior to undergoing apheresis was associated with worse outcomes in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) undergoing treatment with CD19-directed chimeric antigen receptor (CAR) T-cell therapy. Findings of this study were reported in the Journal of Clinical Oncology.

Researchers conducted a multicenter, retrospective analysis with patients treated across 7 European locations. Patients eligible for inclusion in the analysis had R/R LBCL and were being treated with CD19-directed CAR T-cell therapy as part of their third or later line of treatment. Patients were treated with lymphodepleting chemotherapy involving fludarabine and cyclophosphamide. 

The investigators assessed patient outcomes based on whether the patients had received bendamustine at least 1 cycle prior to apheresis. They evaluated efficacy outcomes of overall response rate (ORR), complete response rate (CRR), progression-free survival (PFS), and overall survival (OS). The investigators also performed additional analyses of the data using inverse probability of treatment weighting (IPTW) and with propensity score matching (PSM). 

A total of 439 patients in this analysis received commercial CD19-directed CAR T cells for R/R LBCL. Among these patients, 80 were considered exposed to bendamustine prior to apheresis. 

Platelet counts and CD3⁺ cell counts at apheresis were noted to be significantly decreased in patients with bendamustine exposure before apheresis. The median follow-up for survival analyses was 20.6 months (95% CI, 19.9-23.2) overall after CAR T-cell infusion.

The ORR for bendamustine-exposed patients was 53%, compared with a rate of 72% among bendamustine-naïve patients (P <.01), and CRRs were 39% and 52%, respectively (P <.04). 

The median PFS duration was significantly shorter (3.1 months) in bendamustine-exposed patients, compared with that of bendamustine-naïve patients (6.2 months; P =.04). The median OS time was also significantly shorter with prior bendamustine exposure (10.3 months) compared with absence of bendamustine before apheresis (23.5 months; P =.01). 

When these results were evaluated using IPTW and PSM adjustments, however, differences became less pronounced, with most differences no longer considered statistically significant.

However, when efficacy outcomes were considered with respect to the timing of prior bendamustine exposure, significant differences were seen between patients recently exposed to bendamustine (within 9 months prior to apheresis), compared with the bendamustine-naïve population, including in analyses conducted with IPTW and PSM adjustments. 

Across these analyses, outcomes of ORR, PFS, and OS were significantly improved for bendamustine-naïve patients than for the cohort recently exposed to bendamustine. 

Overall, 86% of the patients developed cytokine release syndrome, and at grade 3 or higher in 6%. Immune effector cell-associated neurotoxicity syndrome was reported in 38% of patients, and at grade 3 or higher in 15%. In multivariate analyses, bendamustine use prior to apheresis did not appear linked to increased risks of these outcomes, including with recent bendamustine use.

“In this comprehensive study on the role of previous bendamustine exposure before lymphocyte apheresis in a standard-of-care cohort of patients with R/R LBCL, we identified that recent bendamustine exposure has a deleterious effect on CAR T-cell therapy outcomes,” the investigators concluded in their report.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.

Reference

Iacobini G, Navarro V, Martin-López AA, et al. Recent bendamustine treatment before apheresis has a negative impact on outcomes in patients with large B-cell lymphoma receiving chimeric antigen receptor T-cell therapy. J Clin Oncol. Published online October 24, 2023. doi:10.1200/JCO.23.01097.

This article originally appeared on Hematology Advisor