Safety and efficacy of a new high‐dose regimen of panobinostat, gemcitabine, busulfan, and melphalan for 1st or 2nd salvage ASCT for refractory/relapsed or high‐risk myeloma: Matched‐pair comparisons with concurrent control cohorts

Abstract

AbstractImprovement of autologous stem‐cell transplantation (ASCT) for myeloma is needed. Building on our prior work, we prospectively evaluated panobinostat and gemcitabine/busulfan/melphalan (GemBuMel) with ASCT in this population. Patients aged 18–65 years with relapsed/refractory or high‐risk myeloma and adequate end‐organ function were eligible. Treatment included panobinostat (20 mg/day, days −9 to −2) and GemBuMel (days −8 to −2). Patients were enrolled in 1st (ASCT‐1) or 2nd ASCT (ASCT‐2) cohorts. We compared their outcomes with all our other concurrent ASCT patients who met eligibility criteria but received melphalan or BuMel off study, matched for age, prior therapy lines, high‐risk cytogenetics, and response at ASCT. We enrolled 80 patients, 48 and 32 in the ASCT‐1 and ASCT‐2 cohorts, respectively; in these two cohorts, high‐risk cytogenetics were noted in 33 and 15 patients, respectively; unresponsive disease in 12 and 11 patients, respectively, after a median of 2 and 3 therapy lines, respectively. Transplant‐related mortality (TRM) occurred in two ASCT‐2 patients. One‐year PFS rates were 69% (ASCT‐1) and 72% (ASCT‐2); 1‐year OS rates were 79% (ASCT‐1) and 84% (ASCT‐2). Minimal residual disease negativity improved after ASCT‐1 (8.5%–23%, p < .0001) and ASCT‐2 (34%–55%, p = .02), which correlated with improved outcomes. Trial patients and controls (N = 371) had similar TRM and post‐ASCT maintenance. Trial patients had better PFS after either a 1st (p = .02) or a 2nd ASCT (p = .04) than matched‐paired control patients. In conclusion, panobinostat/GemBuMel is effective for relapsed/refractory or high‐risk myeloma patients, with better PFS than concurrent matched controls receiving melphalan or BuMel.