Rituximab plus bendamustine as front-line treatment in frail elderly (>70 years) patients with diffuse large B-cell non-Hodgkin lymphoma: a phase II multicenter study of the Fondazione Italiana Linfomi

Abstract

We conducted a phase II study to assess activity and safety profile of bendamustine and rituximab in elderly patients with untreated diffuse large B-cell lymphoma (DLBCL) who were prospectively defined as frail using a simplified version of the Comprehensive Geriatric Assessment (CGA). Patients had to be over 70 years of age, with histologically confirmed DLBCL. Frail patients were those younger than 80 years with a frail profile at CGA or older than 80 years with an unfit profile. Treatment consisted of 4-6 courses of bendamustine [90 mg/m2 days (d)1-2] and rituximab (375 mg/m2 d1) administered every 28 days. Other main study end points were complete remission rate and the rate of extra-hematologic adverse events. Forty-nine patients were enrolled of whom 45 were confirmed eligible. Overall, 24 patients achieved a complete remission (53%; 95%CI: 38-68%) and the overall response rate was 62% (95%CI: 47-76%). The most frequent grade 3-4 adverse event was neutropenia (37.8%). Grade 3-4 extra-hematologic adverse events were observed in 7 patients (15.6%; 95%CI: 6.5-29.5%); the most frequent was grade 3 infection in 2 patients. With a median follow up of 33 months (range 1-52), the median progression-free survival was ten months (95%CI: 7-25). The study shows promising activity and manageable toxicity profile of BR combination as first-line therapy for patients with DLBCL who are prospectively defined as frail according to a simplified CGA, as adopted in this trial (clinicaltrials.gov identifier: 01990144).

Phase II Study of Bendamustine and Ofatumumab in Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy

“…Although the efficacy of ofatumumab plus bendamustine as first-line treatment for DLBCL in older patients was modest, elderly patients unable to tolerate R-CHOP treatment may still derive some benefit from this treatment regimen. The drug combination was safe in the study population, and both PFS and overall survival were similar to those seen in patients treated with rituximab and bendamustine [5][6][7]. There may also be some use for ofatumumab in treating rituximabrefractory patients.…”

“…At 33.3% (Table 1), the complete response rate was lower than the historic CRRs of approximately 50% in elderly patients treated with bendamustine plus rituximab [5][6][7]. However, it should be noted that the median PFS and median OS in this study, at 8.6 months and 12 months respectively, were generally consistent with those observed in similar populations treated with bendamustine plus rituximab [5][6][7]. The poor response rate seen here may have been due, in part, to patient age and general health.…”

“…Bendamustine is an alkylating agent that causes intra‐ and interstrand cross‐links between DNA bases . Studies of the combination of bendamustine and rituximab in elderly patients have demonstrated a complete response rate of approximately 50%, and the combination was associated with lower rates of grade ≥3 hematologic toxicities than R‐CHOP .…”

“…Over 50% of patients with diffuse large B‐cell lymphoma (DLBCL) are 65 years of age or older , and older patients with DLBCL have been shown to have a worse outcome than younger patients . In this study, we evaluated the safety and efficacy of bendamustine plus the anti‐CD20 monoclonal antibody ofatumumab for the treatment of DLBCL in older patients who were not good candidates for rituximab cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) therapy.…”

“…In addition, the common use of other treatment regimens such as rituximab plus bendamustine may have resulted in fewer patients entering the study. The combination of rituximab plus bendamustine treatment regimens has demonstrated some efficacy in older patients with DLBCL , but there remains a critical need for safer and more effective therapies.…”