P-358: Outcomes of Standard-Risk Multiple Myeloma Patients Who Undergo Upfront Autologous Hematopoietic Stem Cell Transplantation

Introduction: Autologous hematopoietic stem cell transplantation (autoHCT) is considered standard of care for eligible patients with multiple myeloma (MM). Patients without high-risk cytogenetic abnormalities are considered to have standard-risk MM (SRMM). There are limited data focusing specifically on the outcomes of SRMM patients after an upfront autoHCT.

Methods: We conducted a single-center retrospective analysis that included consecutive MM patients who received an upfront autoHCT between 2013 and 2021, had available cytogenetic information, and had no high-risk abnormalities on fluorescence in situ hybridization (FISH), defined as t(4;14), t(14;16), del(17p), or 1q21 gain or amplification. Primary endpoints were progression-free survival (PFS) and overall survival (OS).

Results: 1000 patients with SRMM were included in the study, with a median age of 61 years (range 25-83), and 61% were male (n=612). The most common induction regimen was bortezomib/lenalidomide/dexamethasone (n=398, 40%), and the majority of patients (87%) received single-agent melphalan as conditioning. Overall, 571 (57%) patients achieved ≥VGPR prior to autoHCT, with 401 (40%) patients achieving minimal residual disease (MRD) negative status prior to transplant. 873 (87%) patients received post-transplant maintenance, mostly with lenalidomide +/- dexamethasone (81%).

At day 100 post-autoHCT and at best post-transplant response, 772 (77%) and 885 (89%) patients achieved ≥VGPR, respectively; 367 (37%) and 624 (63%) achieved CR, respectively. After a median follow up of 42 months, the median PFS for the entire cohort was 68.3 months (95% CI 60.1-72.1), and median OS was not reached (95% CI 102.3-not reached). 5-year PFS and OS rates were 55% and 83%, respectively.

In multivariable analysis, achieving MRD-negative CR prior to autoHCT [hazard ratio (95% CI): 0.64 (0.44 – 0.95), p=0.027] and use of post-transplant maintenance [0.67 (0.50 – 0.90), p=0.008] were associated with better PFS. Use of post-transplant maintenance [0.48 (0.32 – 0.70), p< 0.001] was also associated with better OS in multivariable analysis. In contrast, R-ISS stage III was associated with worse OS [2.34 (1.01 – 5.43), p=0.047] and HCT-CI >3 exhibited a trend towards worse OS [1.40 (0.98 – 2.00), p=0.06].

Conclusions: Patients with SRMM who received upfront autoHCT had a median PFS of >5.5 years and a 5-year OS rate of 83%. Use of post-transplant maintenance was associated with significantly better outcomes. These results may further improve in the future with the use of quadruplet induction and MRD-guided maintenance.