In a retrospective study reported in the Journal of Clinical Oncology, Iacoboni et al found that preapheresis bendamustine exposure was associated with poorer outcomes among patients with relapsed or refractory large B-cell lymphoma receiving CD19-targeted chimeric antigen receptor (CAR) T-cell therapy.
Study Details
The study involved data from 439 patients who received CD19-targeted commercial CAR T cells in the third or later line of treatment between January 2019 and October 2022 at seven European sites. Median follow-up was 20.6 months (95% confidence interval [CI] = 19.9–23.2 months) from CAR T-cell infusion.
Key Findings
Of the 439 patients included in the study, 80 had received bendamustine prior to apheresis. These patients had significantly lower levels of CD3-positive cells and platelets at apheresis.
For patients who received bendamustine before apheresis vs those who did not, objective response rates were 53% vs 72% (P < .01) and complete response rates were 39% vs 52% (P < .04); median progression-free survival was 3.1 months (95% CI = 2.0–8.5 months) vs 6.2 months (95% CI = 4.2–11.3 months), with a hazard ratio (HR) of 1.36 (95% CI = 1.01–1.83, P =.04); and median overall survival was 10.3 months (95% CI = 5.6–27.3 months) vs 23.5 months (95% CI = 16.0–32.8 months), with a hazard ratio of 1.53 (95% CI = 1.10–2.12, P = .01).
The differences tended to be less marked after adjustment with inverse probability treatment weighting analysis (HR for progression-free survival = 1.21, 95% CI = 0.83–1.75, P = .33; HR for overall survival = 1.56, 95% CI = 1.01–2.41, P = .05) and after adjustment with propensity score matching analysis (HR for progression-free survival = 1.34, 95% CI = 0.92–1.95, P = .13; HR for overall survival = 1.37, 95% CI = 0.90–2.08, P = .14).
Among 42 patients with bendamustine exposure at < 9 months before apheresis, objective response rate (40%, P < .01), median progression-free survival (1.3 months, P < .01), and median overall survival (4.6 months, P < .01) were significantly poorer vs those for bendamustine-naive patients. Cumulative dose of bendamustine before apheresis did not seem to affect CAR T-cell therapy efficacy outcomes.
The investigators concluded: “Recent bendamustine exposure before apheresis was associated with negative treatment outcomes after CD19-targeted CAR T-cell therapy and should be therefore avoided in CAR T-cell candidates.”
Pere Barba, MD, PhD, of the Department of Hematology, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Carlos III Health Institute, Asociacíon Española contra el Cáncer, and others. For full disclosures of the study authors, visit ascopubs.org.
