Balancing safety and efficacy of Bendamustine plus anti CD20 regimens in elderly patients (> 70 y) with follicular lymphoma: a tertiary academic center experience

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL) in Western countries, with 65 beign the average age at diagnosis [1]. First-line treatment regimens combining Bendamustine (B) with Rituximab (R) or Obinutuzumab (G) have shown favorable outcomes in pivotal trials [2-4]. Their efficacy and safety in patients aged 70 or older, who often receive reduced doses, remain unclear. This retrospective study evaluated the impact of reduced Bendamustine Delivered Dose Intensity [DDI, calculated as the total amount of Bendamustine (mg/m²) administered divided by the time taken to complete the regimen, with imputation for missed cycles] on outcomes and toxicities in FL patients (grade 1-3a) aged 70 or older treated with B-R or B-G between January 2014 and December 2023 at our center. Patients were categorized in reduced intensity (Low-DDI) and full intensity (High-DDI), based on the median DDI of the cohort. Efficacy was evaluated in the low DDI vs. high DDI setting, while toxicity outcomes were evaluated in the elderly (age ≥ 70 < 75 years) vs. very elderly (age ≥ 75yrs) population. Primary outcomes included progression-free survival (PFS) and overall survival (OS). Secondary outcomes included response rates, Progression of disease at 24 months (POD24) and toxicities. Among 139 FL patients, 39 met inclusion criteria (median follow-up: 73 months). Median OS was 31.5 vs. 65.0 months (p 0.238) and median PFS was 20.5 vs. 28.0 months (p = 0.081) for low- (n = 20) and high-DDI (n = 19), respectively. ORR was 78.9% vs. 100% (p = 0.105); CRR was 36.8% vs. 72.2% (p = 0.067). POD24 rates were similar (29.4% vs. 22.2%, p = 0.711). Patients were significantly older in the low-DDI group; other baseline features were comparable. Toxicity analysis showed no significant difference in grade ≥ 3 hematologic (p = 0.399) or non-hematologic (p = 0.920) events, or rate of hospitalization (p = 0.378) between elderly and very elderly. Secondary primary malignancies (SPM) occurred in 13 patients (34.2%), with no difference between groups. These findings support the feasibility of bendamustine dose reduction in elderly FL patients, showing no significant compromise in efficacy or increased toxicity. However, larger prospective studies are needed to confirm optimal dosing strategies in this population.