Purpose: Bendamustine is a new anti-lymphoma agent with promising activity. Based on a preceeding phase I study the current trial explored Bendamustine in combination with Mitoxantrone and Rituximab (BMR) in patients with relapsed or refractory indolent lymphomas.

Patients and Methods: Patients with relapsed or refractory symptomatic stage III/IV indolent lymphomas with or without prior treatment with Rituximab were eligible. Therapy consisted of Bendamustine 90 mg/m2 days 1+2, Mitoxantrone 10 mg/m2 day 1, Rituximab 375 mg/m2 day 8. Treatment was repeated on day 29 for a total of 4 cycles.

Results: Between 04/03 and 07/04 62 patients were recruited from 24 participating institutions, 40% of whom had received prior Rituximab therapy. Median age was 67 years (40–83). Lymphoma subtypes were 30 follicular (FL), 18 mantle cell (MCL), 4 B-CLL with plasmacytic differentiation, 3 lymphoplasmacytic (LPL), 3 marginal zone (MZL), 2 diffuse large B-cell (DLBCL), 1 high grade lymphoma not otherwise specified and 1 hairy cell leukemia. The overall response rate (ORR) was 88% with 36% CR and 53% PR. ORR in Rituximab pretreated patients was 75% (38% CR, 38% PR). After a median observation time of 17 months (1 – 33), the estimated median progression free survival is 19 months. Treatment related toxicities of grade 3/4 comprized a reversible myelosuppression (10 % anemia, 78 % leukocytopenia, 46 % granulocytopenia, 16 % thrombocytopenia). However, unexpected hospitalisations were necessary after 10 of 231 cycles (4%) only.

Conclusion: BMR is a very effective new outpatient immuno-chemotherapy with low toxicity for patients with relapsed/refractory indolent lymphoma.

Response rates

All patientsFLMCLpretreated with Rituximab
n 62 30 18 25 
end of therapy without staging 3 3 0 1 
evaluable patients 59 27 18 24 
CR 21 (36%) 13 (48%) 6 (33%) 9 (38%) 
PR 31 (53%) 12 (44%) 8 (44%) 9 (38%) 
MR 1 (2%) 0 (0%) 1 (6%) 1 (4%) 
SD 0 (0%) 0 (0%) 0 (0%) 0 (0%) 
PD 6 (10%) 2 (7%) 3 (17%) 5 (21%) 
EX 0 (0%) 0 (0%) 0 (0%) 0 (0%) 
CR+PR 52 (88%) 25 (93%) 14 (78%) 18 (75%) 
All patientsFLMCLpretreated with Rituximab
n 62 30 18 25 
end of therapy without staging 3 3 0 1 
evaluable patients 59 27 18 24 
CR 21 (36%) 13 (48%) 6 (33%) 9 (38%) 
PR 31 (53%) 12 (44%) 8 (44%) 9 (38%) 
MR 1 (2%) 0 (0%) 1 (6%) 1 (4%) 
SD 0 (0%) 0 (0%) 0 (0%) 0 (0%) 
PD 6 (10%) 2 (7%) 3 (17%) 5 (21%) 
EX 0 (0%) 0 (0%) 0 (0%) 0 (0%) 
CR+PR 52 (88%) 25 (93%) 14 (78%) 18 (75%) 
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Topics:
bendamustine, low-grade lymphomas, lymphoma, mitoxantrone, non-hodgkin's lymphoma, indolent, phase 2 clinical trials, rituximab, toxic effect, agranulocytosis, anemia

Disclosures: Restricted research grant for the conduction of the study from Hoffmann-La Roche and Ribosepharm.; Hoffmann-La Roche and Ribosepharm.

Author notes

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Corresponding author

2006, The American Society of Hematology
2006
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