Efficacy and safety of carfilzomib regimens in multiple myeloma patients relapsing after autologous stem cell transplant: ASPIRE and ENDEAVOR outcomes

P Hari, M-V Mateos, R Abonour, S Knop, W Bensinger, H Ludwig, K Song, R Hajek, P Moreau, D S Siegel, S Feng, M Obreja, S K Aggarwal, K Iskander, H Goldschmidt, P Hari, M-V Mateos, R Abonour, S Knop, W Bensinger, H Ludwig, K Song, R Hajek, P Moreau, D S Siegel, S Feng, M Obreja, S K Aggarwal, K Iskander, H Goldschmidt

Abstract

Autologous stem cell transplantation (ASCT) is a standard treatment for eligible multiple myeloma (MM) patients, but many patients will relapse after ASCT and require subsequent therapy. The proteasome inhibitor carfilzomib is approved for relapsed or refractory MM (RRMM). In phase 3 trials, carfilzomib-based regimens (ASPIRE, carfilzomib-lenalidomide-dexamethasone; ENDEAVOR, carfilzomib-dexamethasone) demonstrated superior progression-free survival (PFS) compared with standard therapies for RRMM (ASPIRE: lenalidomide-dexamethasone; ENDEAVOR, bortezomib-dexamethasone). This subgroup analysis of ASPIRE and ENDEAVOR evaluated outcomes according to prior ASCT status. In total, 446 patients in ASPIRE and 538 in ENDEAVOR had prior ASCT. Median PFS was longer for carfilzomib-based regimens vs non-carfilzomib-based regimens for patients with prior ASCT (ASPIRE: 26.3 vs 17.8 months (hazard ratio (HR)=0.68); ENDEAVOR: not estimable vs 10.2 months (HR=0.61)), those with one prior line of therapy that included ASCT (ASPIRE: 29.7 vs 17.8 months (HR=0.70); ENDEAVOR: not estimable vs 11.2 months (HR=0.46)), and those without prior ASCT (ASPIRE: 26.4 vs 16.6 months (HR=0.76); ENDEAVOR: 17.7 vs 8.5 months (HR=0.43)). Overall response rates also favored the carfilzomib-based regimens. No new safety signals were detected. This analysis suggests that carfilzomib-based treatment may lead to improvement in PFS and response rates regardless of prior transplant status. Further evaluation is warranted.

Conflict of interest statement

MVM has received personal fees from Janssen, Celgene, BMS, Amgen and Takeda. PH has received grants and personal fees from Amgen, Celgene, Takeda, Spectrum and BMS. RA has no relationships to disclose. SK has received personal fees from Amgen, Celgene, Bristol-Myers Squibb and Onyx. WB has received grants and personal fees from Amgen and Celgene. HL has received grants from Takeda, Amgen and Janssen and personal fees from Takeda, Celgene, Amgen and Bristol-Myers Squibb. KS has received personal fees from Amgen, Celgene, Janssen and Takeda. RH has served as a consultant for and received honoraria from Janssen, Celgene and Amgen. PM has served as a consultant for and received honoraria from Celgene, Onyx, Janssen, Novartis and Millennium. DSS has served on the speakers’ bureau for and received honoraria from Celgene, Millennium and Onyx. SF, MO, SKA and KI are employees at Amgen. HG has served as a consultant for Amgen, Celgene, Janssen, Takeda, Novartis, Onyx and BMS and has received research funding and honoraria from Janssen, Celgene, Novartis, Chugai and Millennium.

Figures

Figure 1
Figure 1
Kaplan–Meier curves for PFS by ASCT status in the ASPIRE trial: (a) prior ASCT, (b) 1R1T, and (c) no prior ASCT. Vertical dashed line indicates the time point after which carfilzomib was discontinued according to study protocol.
Figure 2
Figure 2
Kaplan–Meier curves for PFS by ASCT status in the ENDEAVOR trial: (a) prior ASCT, (b) 1R1T, and (c) no prior ASCT. NE, not estimable.
Figure 3
Figure 3
Kaplan–Meier curves for PFS by time to relapse in the ASPIRE trial (1R1T group): (a) early relapsers and (b) late relapsers. Vertical dashed line indicates the time point after which carfilzomib was discontinued according to study protocol. Early relapsers refers to patients relapsing <12 months post-ASCT. Late relapsers refers to patients relapsing ⩾12 months post-ASCT.
Figure 4
Figure 4
Kaplan–Meier curves for PFS by time to relapse in the ENDEAVOR trial (1R1T group): (a) early relapsers and (b) late relapsers. Early relapsers refers to patients relapsing <12 months post-ASCT. Late relapsers refers to patients relapsing ⩾12 months post-ASCT. NE, not estimable.

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