Real-world characteristics and outcomes of newly diagnosed multiple myeloma patients receiving autologous stem cell transplantation (2018–2024) from the honeur network

Abstract Introduction Eligibility for autologous stem cell transplantation (ASCT) in multiple myeloma clinical trials is primarily determined by age and comorbidities. Conversely, clinical practice often employs less stringent standards, leading to limited insight into the real-world baseline characteristics and outcomes for those with newly diagnosed multiple myeloma (NDMM) receiving ASCT. As new treatment options emerge, real-world data can uncover remaining unmet needs and foster ongoing improvements in the survival of these patients. This study outlines the baseline characteristics, treatment patterns, and outcomes of a cohort of patients with NDMM who underwent ASCT in clinical practice. MethodsData from patients starting frontline treatment followed by ASCT from 2018 to 2024 were selected in MyelomaToul - IUCT (France). Locally collected patient-level data were processed within the HONEUR network. Baseline characteristics (age, sex, International Staging System [ISS] stage, and cytogenetic profiles) and frontline treatment regimens were descriptively analyzed. Time to next treatment (TTNT), as a proxy for progression-free survival, and overall survival (OS) were assessed using Kaplan-Meier. A survival subgroup analysis was conducted based on age (<65 years and ≥65 years). A multivariate analysis was performed to identify the primary drivers of both TTNT and OS. Results A total of 2504 patients underwent ASCT, representing one-third of the newly diagnosed patients starting treatment between 2018 and 2024. Among the study population, 71.7% of patients were <65 years (n=1759), while 28.3% were ≥65 years (n=709), indicating that the real-world transplanted population often exceeds age-based clinical trial criteria. In this cohort, 40.9% of patients were classified as ISS stage II or III, and 12.9% were identified as having high-risk cytogenetics, defined as the presence of del(17p), and/or t(4;14), and/or t(14;16). Most transplanted patients received bortezomib, lenalidomide, and dexamethasone (VRD; n=1166; 46.6%) induction therapy. The second most frequent induction regimen was daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd; n=542; 21.6%). Other induction treatment options included daratumumab, bortezomib, thalidomide, and dexamethasone (DVTd; n=243; 9.7%) and other regimens (n=553; 22.1%). The median follow-up duration from the start of induction therapy was 31.7 months. Median TTNT from the start of induction was 57.0 months (95% CI, 52.4–60.1). While the median OS was not reached, 89.2% (95% CI, 87.2–90.9) of patients were alive at 4 years. The multivariate analysis results indicated that cytogenetics and ISS score were the primary factors influencing TTNT and OS. Compared with ISS stage I, TTNT was shorter for patients with stage II (hazard ratio [HR], 1.7; 95% CI, 1.3–2.2; P<0.001) and stage III disease (HR, 2.3; 95% CI, 1.7–3.1; P<0.001). Patients with standard-risk cytogenetics had longer TTNT and OS compared with high-risk cytogenetics (TTNT: HR, 0.5; 95% CI, 0.4–0.6; P<0.001; OS: HR, 0.3; 95% CI, 0.2–0.4; P<0.001). Median TTNT for patients <65 years was 57.0 months (95% CI, 52.1–60.6) compared with 54.3 months (95% CI, 51.1–not estimable) for patients ≥65 years. The median OS has not yet been reached for either patient group. Conclusions With nearly one-third of patients being ≥65 years, our study highlights how real-world practices extend beyond traditional clinical trial eligibility criteria for patients with NDMM receiving ASCT. The considerable proportion of high-risk profiles associated with reduced survival underscores the importance of prognostic assessments and personalized treatment strategies.