Objective  To compare the efficacy and prognostic impact of distinct second-line treatment strategies in patients with first relapsed or refractory multiple myeloma (RRMM1). Methods  We conducted a retrospective cohort study of RRMM1 patients managed by the Myeloma Unit, Department of Hematology, West China Hospital, Sichuan University, between February 2014 and May 2024. Patients were categorized according to the backbone agent of their second-line regimen: daratumumab-based (D-based), bortezomib-based (B-based), pomalidomide-based (P-based), ixazomib-based (I-based), carfilzomib-based (K-based), and salvage autologous stem cell transplantation (ASCT). Pre-specified subgroup analyses were performed based on three key clinical variables: receipt of lenalidomide during initial maintenance therapy, pattern of first relapse (biochemical vs. clinical), and presence or absence of extramedullary disease at relapse. Primary endpoints were second-line progression-free survival (PFS2) and overall survival (OS). Results  A total of 257 patients with RRMM1 were included. As of March 31, 2025, with a median follow-up of 61 months, the median progression-free survival from initial treatment to the first relapse or being classified as refractory was 24.0 months [95% confidence interval (CI) (21.7, 26.9) months], and the median PFS2 (mPFS) was 22.0 months [95%CI (18.9, 25.0) months], with no statistically significant difference [hazard ratio (HR)=1.046, 95%CI (0.780, 1.403), P=0.764]; the median OS was 104.0 months [95%CI (93.5, 114.6) months]. Lenalidomide maintenance during frontline therapy conferred a significant OS advantage: median OS was not reached in the lenalidomide-maintained group (n=82) versus 75.0 months in the non-maintained group (n=47) (P=0.006). Although median OS was not reached in the salvage ASCT group (n=9), no statistically significant OS benefit was observed compared with the non-ASCT group (n=248, median OS=102.0 months, P=0.283). Notably, mPFS2 and mOS remained unreached in both the K-based and P-based groups—likely reflecting both superior outcomes and shorter median follow-up (40 months) for the K-based group due to later regulatory approval and real-world adoption. In multivariable Cox regression modeling, pomalidomide use emerged as an independent predictor of prolonged PFS2 [HR=0.421, 95%CI (0.214, 0.829), P=0.012] and demonstrated a strong trend toward improved OS [HR=0.382, 95%CI (0.142, 1.026), P=0.056). Biochemical relapse (n=130) was associated with significantly longer mPFS2 (31.0 vs. 13.0 months, P<0.001) and mOS (110.0 vs. 104.0 months, P=0.030) than clinical relapse (n=91). Similarly, absence of extramedullary disease (n=196) predicted markedly superior mOS compared with extramedullary involvement (n=25) (110.0 vs. 77.0 months, P=0.006). Conclusions  In this real-world cohort, second-line regimens incorporating novel agents, including pomalidomide, carfilzomib, and daratumumab, achieve depth and durability of response approaching that observed in newly diagnosed myeloma. Pomalidomide is a robust independent determinant of improved PFS2. Prior lenalidomide maintenance remains a key favorable prognostic factor for long-term mOS. Conversely, patients presenting with clinical relapse and/or extramedullary disease represent a high-risk population for whom current second-line approaches remain suboptimal, highlighting an urgent unmet need for biologically rational, intensified, or investigational strategies.

Citation： REN Zhigang, LI Yan, XIONG Yanqiu, ZHANG Li, PAN Ling. Analysis of real-world clinical characteristics and treatment outcomes in patients with first relapsed or refractory multiple myeloma. West China Medical Journal, 2026, 41(3): 435-441. doi: 10.7507/1002-0179.202508180 Copy

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