TY - JOUR
T1 - 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
T2 - Matched-pair comparisons with concurrent control cohorts
AU - Nieto, Yago
AU - Yang, Zixi
AU - Valdez, Benigno C.
AU - Kundu, Suprateek
AU - Bashir, Qaiser
AU - Ramdial, Jeremy
AU - Srour, Samer
AU - Qazilbash, Muzaffar
N1 - Publisher Copyright:
© 2023 Wiley Periodicals LLC.
PY - 2024/2
Y1 - 2024/2
N2 - Improvement 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.
AB - Improvement 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.
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U2 - 10.1002/ajh.27168
DO - 10.1002/ajh.27168
M3 - Article
C2 - 38100199
AN - SCOPUS:85179967277
SN - 0361-8609
VL - 99
SP - 245
EP - 253
JO - American journal of hematology
JF - American journal of hematology
IS - 2
ER -