Reduced-Dose Bendamustine as a First-Line Treatment of Follicular Lymphoma Is Associated With Poorer Prognosis

The dose of bendamustine used to treat previously untreated follicular lymphoma (FL) is sometimes reduced based on various clinical considerations, but the impact of such dose reductions on outcomes is unclear. We retrospectively analyzed 92 untreated FL patients treated with bendamustine at seven institutions in Japan. Dose reduction was defined as receiving less than 90% of the planned total dose of 1080 mg/m² over six cycles. Patients with disease progression observed at ≤ 180 days of treatment initiation were defined as primary bendamustine-refractory (PBR). The 3-year overall survival (OS) and progression-free survival (PFS) were 87.1% and 71.8%, respectively. Seven patients were classified as PBR, six of whom received bendamustine at full dose without dose reduction, and they had significantly worse OS with 3-year OS of 38.1%. We excluded the PBR cases from subsequent analyses of the dose intensity's prognostic significance. The dose-reduction group had a significantly lower CR rate (93.0% vs. 74.4%, p = 0.032). Similarly, the 3-year PFS was significantly worse in the dose-reduction group (86.8% vs. 68.1%, p = 0.005). In univariate and multivariate analyses, dose reduction was associated with inferior PFS. In an analysis limited to patients who completed all six courses, the CR rate was comparable between the two groups, but 3-year PFS was significantly worse in the dose-reduction group (86.8% vs. 68.7%, p = 0.041). Furthermore, even among patients who achieved CR, the 3-year PFS tended to be poorer in the dose-reduction group (85.7% vs. 72.7%, p = 0.062). These findings suggest that PBR cases are resistant to bendamustine itself regardless of the dose intensity. In contrast, among responders including those who achieved CR, dose reduction was associated with poorer PFS, indicating that maintaining treatment intensity is important for improving prognosis in the treatment of bendamustine-responsive FL patients.