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Bendamustine and bendamustine/rituximab combinations have shown high efficacy in relapsed/refractory chronic lymphocytic leukemia (CLL) and indolent B-cell malignancies (non-Hodgkin lymphoma, NHL). No data exist about bendamustine retreatment after relapse, concerning efficacy and toxicity in this patient population. Eighty-eight outpatients (57 patients with CLL, 31 patients with NHL) who had previously been treated with bendamustine were retreated with a bendamustine regimen. Treatment consisted of bendamustine (B) or bendamustine + mitoxantrone (BM) or bendamustine + rituximab (BR) or bendamustine + mitoxantrone + rituximab (BMR). Median age was 72 years (50-88). A reversible grade 3 or 4 leukocytopenia or thrombocytopenia was observed in 24% and 13%, respectively. The overall response rate (ORR) was 76% (7% complete remission [CR], 69% partial remission [PR]) with 77% (6% CR, 71% PR) in CLL and 71% (8% CR, 63% PR) in NHL. ORR according to regimen was as follows: B: 57% (14% CR, 43% PR), BM: 70% (4% CR, 66% PR), BR: 55% (10% CR, 45% PR), BMR: 84% (7% CR, 78% PR). Bendamustine retreatment is feasible and achieves high response rates and some long lasting remissions.

We have evaluated all outpatients with relapsed or refractory chronic lymphocytic leukemia (CLL) who were treated with bendamustine/mitoxantrone/rituximab (BMR) between May 1999 and December 2008. Treatment consisted of bendamustine 90 mg/m2 on day 1 + 2, Mitoxantrone 6 mg/m2 on day 1, and Rituximab 375 mg/m2 on day 8, 15, 22 + 29. Thirty-nine patients (19 males, 20 females) received BMR with a median age of 69 years (46–81). Nineteen patients (49%) were above 70 years and 13 patients (33%) were 75 years or above. Performance score ranged between 0 and 2. The median number of previous therapies was 2 (1–4). Therapy was tolerated well with two observed therapy-associated hospitalizations. A reversible grade 3 or 4 hematotoxicity was seen in 30 patients (77%). Other reversible grade 3 or 4 toxicities were seen in two patients (5%). The overall response rate was 92% (10% complete remission, 82% partial remission). Median time to next CLL-therapy was 13 months (0–69). We conclude that BMR is a short and effective outpatient chemoimmunotherapy for patients with relapsed or refractory CLL, which can be used safely in elderly patients.

On the basis of a preceding phase I study, the current trial explored bendamustine in combination with mitoxantrone and rituximab (BMR) in patients with stage III/IV relapsed or refractory indolent lymphomas and mantle cell lymphoma (MCL) with or without prior rituximab containing chemo-immunotherapy (R-chemo) treatment. Therapy consisted of bendamustine 90 mg/m(2) days 1 + 2, mitoxantrone 10 mg/m(2) day 1, rituximab 375 mg/m(2) day 8. Treatment was repeated on day 29 for a total of four cycles. Between 3 April and 04 July, 57 patients were recruited from 24 participating institutions, 39% of whom had received prior R-chemo therapy. Median age was 66 years (40 - 83). Lymphoma subtypes were 29 follicular (FL), 18 MCL, and 10 other indolent lymphomas. The overall response rate (ORR) was 89% with 35% CR and 54% PR. ORR in R-chemo pretreated patients was 76% (38% CR, 38% PR). After a median observation time of 27 months (1 - 43), the estimated median progression free survival is 19 months. The 2 year overall survival is 60% for patients with FL and MCL. Treatment related toxicities of grade 3/4 comprised a reversible myelosuppression (10% anemia, 78% leukocytopenia, 46% granulocytopenia, 16% thrombocytopenia). However, unexpected hospitalisations were necessary after 4% of BMR-application only. BMR is a very effective new outpatient immuno-chemotherapy with low toxicity for patients with relapsed/refractory FL, MCL and other indolent lymphomas.