Nieto Yago, Yang Zixi, Valdez Benigno C, Kundu Suprateek, Bashir Qaiser, Ramdial Jeremy, Srour Samer, Qazilbash Muzaffar
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Am J Hematol. 2024 Feb;99(2):245-253. doi: 10.1002/ajh.27168. Epub 2023 Dec 15.
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.
骨髓瘤的自体干细胞移植（ASCT）需要改进。基于我们之前的工作，我们前瞻性地评估了帕比司他与吉西他滨/白消安/美法仑（GemBuMel）联合ASCT在该人群中的应用。年龄在18 - 65岁、患有复发/难治性或高危骨髓瘤且终末器官功能良好的患者符合条件。治疗包括帕比司他（20毫克/天，第 -9天至 -2天）和GemBuMel（第 -8天至 -2天）。患者被纳入第1组（ASCT - 1）或第2组ASCT（ASCT - 2）队列。我们将他们的结果与所有其他符合资格标准但在研究外接受美法仑或BuMel的同期ASCT患者进行比较，这些患者在年龄、既往治疗线数、高危细胞遗传学以及ASCT时的反应方面进行了匹配。我们纳入了80名患者，ASCT - 1队列48名，ASCT - 2队列32名；在这两个队列中，分别有33名和15名患者存在高危细胞遗传学；分别有12名和11名患者在中位2次和3次治疗线后疾病无反应。两名ASCT - 2患者发生了移植相关死亡率（TRM）。1年无进展生存率（PFS）分别为69%（ASCT - 1）和72%（ASCT - 2）；1年总生存率（OS）分别为79%（ASCT - 1）和84%（ASCT - 2）。ASCT - 1（8.5% - 23%，p <.0001）和ASCT - 2（34% - 55%，p = 0.02）后微小残留病阴性率有所改善，这与预后改善相关。试验患者和对照组（N = 371）的TRM和ASCT后维持治疗情况相似。试验患者在第1次（p = 0.02）或第2次ASCT（p = 0.04）后的PFS均优于配对的对照患者。总之，帕比司他/GemBuMel对复发/难治性或高危骨髓瘤患者有效，其PFS优于同期接受美法仑或BuMel的匹配对照患者。
