Bendamustine and rituximab in elderly patients with low‐tumour burden follicular lymphoma. Results of the LYSA phase II BRIEF study

Abstract

The treatment of low-tumour burden follicular lymphoma (LTBFL) remains a challenge. Rituximab-based strategies may be improved by adding chemotherapy. This Lymphoma Study Association multicentre phase II study assessed rituximab and bendamustine in 63 patients with untreated LTBFL who were aged over 60 years old and had a follicular lymphoma International Prognostic Index (FLIPI) score ≥2. Induction comprised 4 weekly cycles of rituximab 375 mg/m intravenously combined with 2 cycles of bendamustine 90 mg/m days 1-2 with a 28-day interval, followed by twelve cycles of 375 mg/m rituximab maintenance therapy every 8 weeks. The primary endpoint was complete response (CR)/unconfirmed CR (CRu), at 12 weeks. Median age was 67·4 years and median FLIPI was 3. Ultimately, 18 patients (29%) had high tumour burden according to Groupe d'Etude des Lymphomes Folliculaires criteria. The 12-week CR/CRu rate was 54·0% and the overall response rate was 93·7%. Surprisingly, 3 patients died during maintenance (2 sepsis, 1 neoplasm). Progression-free survival was 85·4% at 24 months. In LTBFL patients with FLIPI ≥2, two cycles of rituximab and bendamustine result in a CR rate of 54·0%. However, the treatment-related deaths observed do not allow this regimen to be recommended for LTBFL patients aged over 60 years. EudraCT: 2010-020757-14; ClinicalTrials.gov: NCT01313611.

Follicular lymphoma: 2023 update on diagnosis and management

“…These studies provide support for BR as the primary therapy for FL. However a Medicare database review did demonstrate unacceptable treatment‐related mortality with bendamustine in low tumor burden patients over age 60 70 . Bendamustine should be used with caution in elderly patients, particularly those with co‐morbidities, and reduced doses should be used as necessary.…”

Follicular lymphoma: 2020 update on diagnosis and management

“…These studies provide support for BR as the primary therapy for FL. However a Medicare database review did demonstrate unacceptable treatment related mortality with bendamustine in low tumor burden patients over age 60 …”

A brief rituximab, bendamustine, mitoxantrone (R‐BM) induction followed by rituximab consolidation in elderly patients with advanced follicular lymphoma: a phase II study by the Fondazione Italiana Linfomi (FIL)

“…This trial showed that grade 3–5 infections occurred more frequently in patients treated with bendamustine, caused by a marked reduction in CD3+ and CD3+ CD4+ T cells during induction in both antibody arms, with prolonged recovery during and after maintenance. The uncertain safety of rituximab maintenance after bendamustine in elderly patients is also highlighted by the study of Gyant et al that was prematurely ended because of a high frequency of haematological toxicity and serious AEs during the maintenance phase and follow‐up 29 . In our study, the very low late infection rate may suggest a benefit of the reduction of the number of bendamustine courses and the absence of maintenance.…”

“…The uncertain safety of rituximab maintenance after bendamustine in elderly patients is also highlighted by the study of Gyant et al that was prematurely ended because of a high frequency of haematological toxicity and serious AEs during the maintenance phase and follow-up. 29 In our study, the very low late infection rate may suggest a benefit of the reduction of the number of bendamustine courses and the absence of maintenance.…”