The combination of bendamustine (Treanda), fludarabine, and rituximab (Rituxan), or BFR, was shown to be safe and effective conditioning for patients with relapsed chronic lymphocytic leukemia/lymphoma receiving allogeneic stem cell transplantation from related or unrelated donors. “Remarkably, this BFR regimen resulted in a low incidence of myelosuppression and severe acute graft-vs-host disease,” Issa F. Khouri, MD, and colleagues from The University of Texas MD Anderson Cancer Center in Houston stated in Blood.
The phase I/II study tested the safety and efficacy of escalating doses of bendamustine (70, 90, 110, and 130 mg/m2/d for 3 days), coupled with fixed doses of fludarabine and rituximab as a nonmyeloablative allogeneic conditioning regimen. Eligibility criteria included a diagnosis of resistant or relapsed CD20-positive chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL).
After none of the 10 patients in the phase I study experienced a dose-limiting toxicity, the other 46 patients were added for the phase II study and treated at the maximum dose of 130 mg/m2/d for 3 days. Among the total of 56 patients, 15 had CLL and 41 had lymphoma. “The CLL patients were generally considered to have high-risk disease,” the authors noted.
The median age of the patients was 59, and 63% were male. A total of 11 patients (20%) had bone marrow involvement, and 14 (25%) had more than one extranodal site of involvement with disease, the investigators reported. The median number of prior chemotherapies was three (range, 1–7).
“All patients received unmanipulated grafts from the peripheral blood (52 patients) or bone marrow (4 patients),” the researchers reported. Thirty patients (54%) received transplants from matched siblings and 26 patients (46%) from unrelated donors.
The clinical response included 50 patients (89%) with complete response and 3 (5%) with a partial response. In addition, two patients (10%) had stable disease and one patient was not evaluable because of early death. After a median follow-up of 26 months (range, 6–50 months), the 2-year overall survival rate was 90% and the progression-free survival rate was 75%.
“Recovery of neutrophils and platelets was prompt,” the researchers reported. “Remarkably, 55% of patients did not experience severe neutropenia,” the authors wrote, and 49 patients (88%) did not require platelet transfusion. The incidence of acute grade 2 to 4 graft-vs-host disease was 11% and grade 4 acute graft-vs-host disease occurred in only one patient. The 2-year rate of extensive chronic graft-vs-host disease was 26%.
Seven patients died, with two deaths related to disease progression, one to acute graft-vs-host disease, and 1 to chronic graft-vs-host disease. The other deaths were related to gastrointestinal bleeding, fungal infection, and West Nile virus infection.
“We were surprised by the low level of myelosuppression in this study,” the authors noted. “Through the course of the trial, it was noted that many patients with normal [absolute neutrophil counts (ANCs)] at study entry maintained an ANC of > 500 cells/μL throughout and did not need growth factor support. This observation prompted us to modify our administration of growth factors, which led to the full recovery of counts in 23% of patients with no growth factor support.”
The researchers concluded that the BFR regimen is safe and effective for relapsed CLL and lymphoma patients and “may be considered as a platform for outpatient allogeneic transplantation.”
This trial is registered at www.clinicaltrials.gov as NCT00880815. ■
Khouri IF, et al: Blood. August 21, 2014 (early release online).