Efficacy of Autologous Stem Cell Transplantation for Myeloma Patients with Suboptimal Response: A Multicenter Retrospective Analysis

Abstract

Autologous stem cell transplantation (ASCT) is the standard of care for myeloma patients when partial response (PR) or better is achieved after induction therapy. However, its clinical significance in patients with suboptimal response (SR), including stable disease (SD) and progressive disease (PD) before ASCT, has not been established. Additionally, functional high-risk (FHR), including RS and early PD within 12 months, was a poor prognostic factor up to now. This study aimed to evaluate the efficacy of ASCT in myeloma patients having SR in novel agent era. This multicenter, retrospective study was conducted using the Transplant Registry Unified Management Program (TRUMP) database of the Japanese Society of Transplantation and Cellular Therapy (JSTCT) and included 3898 patients with transplant-eligible patients with newly diagnosed multiple myeloma who underwent ASCT between 2007 and 2020 and were followed up until 2021. The SR rate was 4.7% including 1.7% of PD. In survival time analysis for overall cases, The significant difference of PFS between the VGPR and PR groups were observed while there was no significant difference of OS between the VGPR and PR groups. Additionally, there was no significant difference of OS and PFS between the PR and SD groups. Therefore, we focused on the PR, SD, and PD groups as the purpose of this retrospective study was to investigate the clinical significance of ASCT in patients with SR compared with those with PR. The median age of the patients was 60 years (range, 30-77 years). In total, 1605 (97.4%), 561 (38.2%), and 512 (34.9%) patients received bortezomib, immunomodulatory drug (IMiD), and both bortezomib and IMiD, respectively. A total of 558 (38.0%) patients received reinduction therapy. There were 229 (37.7 %) patients with high-risk cytogenetic risk (HRCA). In a median follow-up period of 31.7 months, a significant difference was observed in 30-month overall survival (OS) rates between the PR, SD, and PD groups (86.3%, 78.5%, and 39.4%, respectively; p <0.001). In a comparison between the PR and SD groups, the OS in the SD group was significantly shorter than that in the PR among the patients with HRCA (p <0.001) and in the patients treated with reinduction therapy (p = 0.013). Concerning the PD group, the 30-month OS and PFS rates in the PD group were 39.4% and 17.9%. Finally, early PD within 12 months after ASCT predicted short OS, whereas OS without early PD even in the PD group was similar to that in the SD and PR groups. In conclusion, the OS in the SR was not always short, but the SR in the HRCA and the reinduction therapy groups predicted to short OS so that alternative therapeutic options to ASCT are needed. OS in the PD group was significantly short, but ASCT improved clinical outcome when early PD was not occurred even in the PD group.