Impact of Prior Bendamustine Exposure on Chimeric Antigen Receptor T-Cell Therapy Outcomes in Follicular Lymphoma
Danielle DeCicco1, Sanjana Nethagani1, Shanawar Waris2
1Department of Medical Oncology, West Virginia University School of Medicine, Morgantown, West Virginia; West Virginia University Cancer Institute, Morgantown, West Virginia.
Abstract:
Prior bendamustine exposure impairs T-cell fitness and has been associated with inferior CAR T-cell therapy outcomes in large B-cell lymphoma, but follicular lymphoma (FL)-specific data are lacking. Using the TriNetX Research Network (107 healthcare organizations), we conducted a retrospective cohort study of adult patients with relapsed/refractory FL who received CD19-directed CAR T-cell therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, or tisagenlecleucel). Propensity score-matched comparisons evaluated overall survival (OS) stratified by bendamustine exposure timing. Any prior bendamustine exposure was associated with inferior 2-yr OS compared with bendamustine-naive patients (58.99% versus 76.73%; HR 1.855, 95% CI 1.003 to 3.432, P = .046, n = 89). Critically, bendamustine exposure within 1 yr of CAR T-cell infusion was associated with significantly worse 2-yr OS compared with exposure more than 1 yr prior (40% versus 68%; HR 2.277, 95% CI 1.117 to 4.644; P = .020, n = 46). In contrast, patients with bendamustine exposure more than 1 yr before CAR T-cell had the same OS as bendamustine-naive patients (71% versus 72%; HR 1.045; P = .914). A dose-response analysis demonstrated a consistent, statistically significant increase in mortality risk as bendamustine exposure approached the time of CAR T-cell infusion across all 3 measures of association (P < .05). Inpatient admission within 30, 60, and 90 days of CAR T-cell was significantly higher in patients with recent bendamustine exposure. These findings are hypothesis-generating and suggest a clinically actionable 12-mo washout interval and support preferential use of nonbendamustine-containing regimens over bendamustine-based regimens in patients with FL who may require future CAR T-cell therapy.
Insights
Recent bendamustine exposure significantly worsens survival outcomes for follicular lymphoma patients undergoing CAR T-cell therapy. A washout period of over 12 months may mitigate these negative effects, improving overall survival.
Area of Science:
- Hematology
- Immunotherapy
- Oncology
Background:
- Bendamustine-based chemoimmunotherapy is a common treatment for follicular lymphoma (FL).
- Bendamustine can cause prolonged T-cell suppression, potentially impacting CAR T-cell therapy efficacy.
- Limited FL-specific data exist on the impact of prior bendamustine exposure on CAR T-cell therapy outcomes.
Purpose of the Study:
- To evaluate the impact of prior bendamustine exposure timing on overall survival (OS) in adult patients with relapsed/refractory FL receiving CD19-directed CAR T-cell therapy.
- To determine if a specific washout period after bendamustine exposure can restore CAR T-cell therapy efficacy.
Main Methods:
- Retrospective cohort study using the TriNetX Research Network (107 healthcare organizations).
- Identified adult patients with relapsed/refractory FL who received axicabtagene ciloleucel, lisocabtagene maraleucel, or tisagenlecleucel.
- Used propensity score matching to compare OS stratified by bendamustine exposure timing (any, within 1 year, >1 year prior to CAR T-cell infusion).
Main Results:
- Any prior bendamustine exposure was associated with inferior 2-year OS (58.99% vs. 76.73%) compared to bendamustine-naive patients.
- Bendamustine exposure within 1 year of CAR T-cell infusion significantly worsened 2-year OS (40% vs. 68%) compared to exposure >1 year prior.
- Exposure >1 year prior to CAR T-cell therapy showed comparable OS to bendamustine-naive patients (71% vs. 72%).
- Recent bendamustine exposure increased inpatient admissions post-CAR T-cell therapy; CRS and neurotoxicity rates were similar.
Conclusions:
- Recent bendamustine exposure is linked to significantly worse OS after CD19-directed CAR T-cell therapy in FL.
- Bendamustine exposure beyond 12 months may not adversely affect CAR T-cell therapy outcomes.
- Consider avoiding bendamustine in FL patients anticipating CAR T-cell therapy or ensure a >12-month washout period.
