Combining bendamustine, bortezomib, and prednisone was previously shown to be active in the setting of relapsed multiple myeloma.1 Recently, however, the combination of bendamustine, bortezomib, and dexamethasone (BBD) was reported to be effective in achieving overall response rates of 91% and a complete response (CR) rate of 9% in the front-line treatment of patients who are not candidates for high-dose chemotherapy.2
The single-arm, open-label, multicenter, phase 2 study enrolled patients with active multiple myeloma who were ineligible for high-dose therapy and stem cell transplant. Patients were required to have adequate renal and hepatic function.
Treatment with BBD was based on 2 schedules: an initial schedule found to be effective, but relatively toxic, and an amended schedule found to be less toxic. The amended dosing changed the dosing schedule for bortezomib and lowered the dose and schedule for dexamethasone.
Maintenance therapy was not planned in the initial dosing schedule, though patients with stable disease or better were provided maintenance therapy with bortezomib and dexamethasone for 2 years. Herpes zoster prophylaxis was mandated on this modified regimen.
Of 59 patients in the study, 41 received the modified dosing schedule. Of 56 patients evaluable for responses, best objective response rate (ORR) was 91%, with 68% of patients achieving at least a very good partial response (VGPR), including CRs in 9% of patients.
For patients on the modified dosing schedule, best ORR was 92%, with 72% achieving at least a VGPR, including CRs in 13% of patients.
For patients older than 75 years, best ORR was 95%, with 77% achieving at least a VGPR, including CRs in 9% of patients.
Eighty percent of patients on the modified treatment schedule completed all 8 cycles of therapy, while only 28% of patients on the original dosing schedule completed all the 8 cycles. Twenty-eight patients on the modified schema received maintenance therapy, with 14 remaining on treatment at the time of data cut-off.
The authors indicated, however, that maintenance did not appear to deepen response in the modified treatment group.
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With a median follow up of 19.1 months, median progression-free survival (PFS) was 15.0 months; PFS was longer for patients on the modified dosing schema (18.9 vs 11.1 months, respectively). There was no significant difference in PFS for patients over 75 years of age compared with those 75 and younger (17.7 vs 15.0 months, respectively).