Phase I/II study of bendamustine in combination with ofatumumab, carboplatin, etoposide (BOCE) for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma.

We developed an outpatient salvage chemotherapy regimen using bendamustine, ofatumumab, carboplatin and etoposide (BOCE) to treat relapsed/refractory non-Hodgkin lymphoma (RR NHL) in a single-center phase I/II study. Primary objectives were safety, tolerability and overall response rate (ORR). Thirty-five RR NHL patients (57% de novo large cell [DLBCL] or grade 3B follicular [FL], 26% transformed DLBCL, 9% grade 3A FL, 3% mantle cell; median age = 62, median prior therapies = 1) were treated. Median follow-up was 24.1 months. ORR was 69% (CR = 49%, PR = 20% [ORR = 70%, CR = 50%, PR = 20% in the de novo DLBCL/grade 3B FL subgroup]). Median progression-free survival was 5.1 months and overall-survival 26.2 months. Twelve patients subsequently underwent stem cell transplantation. The most common non-hematologic grade 3-4 toxicities were neutropenic fever and hypophosphatemia. There were no treatment-related deaths. In conclusion, BOCE is a safe and effective outpatient salvage regimen for patients with RR NHL and serves as an effective bridge to stem cell transplantation.

Final outcomes of escalated melphalan 280 mg/m2 with amifostine cytoprotection followed autologous hematopoietic stem cell transplantation for multiple myeloma: high CR and VGPR rates do not translate into improved survival.

The most common preparative regimen for autologous transplantation (ASCT) in myeloma (MM) consists of melphalan 200 mg/m2 (MEL 200). Higher doses of melphalan 220-260 mg/m2, although relatively well tolerated, have not shown significant improvement in clinical outcomes. Several approaches have been pursued in the past to improve CR rates, including poly-chemotherapy preparative regimens, tandem ASCT, consolidation, and/or maintenance therapy. Since there is a steep dose-response effect for intravenous melphalan, we evaluated an alternative single ASCT strategy using higher-dose melphalan at 280 mg/m2 (MEL 280) with amifostine as a cytoprotectant as the maximum tolerated dose determined in an earlier phase I dose escalation trial. We report the final long-term outcomes of MM patients who underwent conditioning with MEL 280 with amifostine cytoprotection followed by ASCT. Although the complete response rate was quite high in the era pre-dating the routine use of novel therapies (proteasome inhibitors, immunomodulatory agents) (49%), the progression-free survival was a disappointing 22 months. The implications of this dichotomy between the excellent depth of ASCT response and progression-free survival are discussed.