Outcomes of Standard-Risk Multiple Myeloma Patients Who Undergo Upfront Autologous Hematopoietic Stem Cell Transplantation

Background: Patients with multiple myeloma without high-risk cytogenetic abnormalities are classified as having standard-risk MM (SRMM), and data focusing on their outcomes after autologous stem-cell transplantation (autoHCT) are limited.

Objective: To evaluate survival outcomes for patients with SRMM receiving autoHCT, and to elucidate factors that impact these outcomes.

Study design: Single-center retrospective analysis that included consecutive MM patients who received upfront autoHCT between 2013-2021, had available cytogenetic information and had no high-risk chromosomal abnormalities on fluorescence in situ hybridization (FISH), defined as t(4;14), t(14;16), del(17p) or 1q21 gain or amplification.

Results: A total of 1000 SRMM patients were included, with a median age of 61 years (range 25-83), and 61% were male (n=612). The most common induction regimens were bortezomib/lenalidomide/dexamethasone (VRD; n=398, 40%) and carfilzomib/ lenalidomide/dexamethasone (KRD; n=212, 21%), and the majority (87%) received single-agent melphalan as conditioning. After induction and before autoHCT, 16% and 57% achieved ≥ complete response (CR) and ≥ very good partial response (VGPR), respectively. At day 100 post autoHCT, 37% and 77% achieved ≥CR and ≥VGPR, respectively. Sixty-two percent and 89% of patients achieved ≥CR and ≥VGPR as best response post-transplant. A measurable residual disease (MRD) negative response pre- and post-transplantation was achieved in 43% (401/936) and 64% (199/311) of patients, respectively. After a median follow-up of 42.1 months, the median PFS for the entire cohort was 68.3 months (95% CI 60.1-72.1), and the median OS was not reached (95% CI 102.3-not reached). The 5-year PFS and OS rates were 55% and 83%, respectively. In multivariable analysis, achieving MRD-negative CR prior to autoHCT (HR 0.65 [95% CI 0.44 - 0.97], p=0.033) or as best response (0.52 [0.34 - 0.78], p=0.002), and use of post-transplant maintenance (0.69 [0.52 - 0.93], p=0.013) and lenalidomide-based combination maintenance (0.68 [0.48 - 0.96], p=0.030) were associated with improved PFS, whereas use of an induction regimen other than KRD was associated with worse PFS (1.50 [1.04 - 2.17], p=0.031). For OS, post-transplant maintenance (0.48 [0.32 - 0.70], p<0.001) was associated with better survival in multivariable analysis, whereas R-ISS stage III, compared with stage I, (2.34 [1.01 - 5.43], p=0.047) was associated with worse OS.

Conclusions: Patients with SRMM who received upfront autoHCT had a median PFS of >5.5 years, and median OS was not reached. These results highlight the favorable outcomes with upfront autoHCT for patients with SRMM, serving as a benchmark for future therapeutic approaches in this subgroup of MM patients.