BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD

Abstract

Myelosuppression, graft-versus-host disease (GVHD), and relapse remain major causes of morbidity after stem cell transplantation for relapsed lymphoma. In this phase 1/2 study, we tested the safety and efficacy of escalating doses of bendamustine (70, 90, 110, and 130 mg/m2 per day for 3 days), coupled with our historical fixed doses of fludarabine and rituximab (BFR), as a nonmyeloablative allogeneic conditioning regimen for patients with relapsed lymphoma (n = 41) and chronic lymphocytic leukemia (CLL) (n = 15). Ten patients entered the phase 1 study; none experienced a dose-limiting toxicity. Forty-six additional patients were then treated in the phase 2 study at the maximum dose of 130 mg/m2 per day for 3 days. The proportions of transplants from matched siblings or unrelated donors were 54% and 46%. Remarkably, 55% of patients did not experience severe neutropenia. Forty-nine patients (88%) did not require platelet transfusion. The incidence of acute grade II-IV GVHD was 11%. The 2-year rate of extensive chronic GVHD was 26%. After a median follow-up duration of 26 months (range, 6-50 months), the 2-year overall and progression-free survival rates were 90% and 75%. In conclusion, our new BFR regimen is safe and effective for relapsed CLL and lymphoma patients.

Trial registration: ClinicalTrials.gov NCT00880815.

© 2014 by The American Society of Hematology.

Figures

Figure 1

Treatment schema of bendamustine, fludarabine, and rituximab (rituximab was omitted in patients with T-cell lymphoma).

Figure 2

Reduced risk of myelosuppression after BFR conditioning for alloSCT. (A) Proportion of patients with normal platelet counts at study entry and who maintained a platelet count >20 × 109/L after transplantation. (B) Proportion of patients with normal ANC at study entry who maintained counts of 0.5 × 109/L after transplantation.

Figure 3

Survival after BFR conditioning for alloSCT. (A) OS and PFS rates after nonmyeloablative allogeneic transplantation with bendamustine, fludarabine, and rituximab conditioning. (B) OS rates by histologic type. (C) OS rates by donor type. FL, follicular lymphoma; MCL, mantle cell lymphoma. DLBCL/TCL, diffuse large B-cell and T-cell lymphoma.

Figure 4

GVHD and TRM. (A) Incidence of acute II-IV GVHD. (B) Incidence of extensive chronic GVHD. (C) TRM rate.