(PA-510) Delayed or Salvage Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

There are limited data on the outcomes of multiple myeloma (MM) patients who receive delayed/salvage autologous transplant (autoHCT) in the era of modern anti-myeloma agents.

Methods:

Single-center retrospective chart review of consecutive adult MM patients that received delayed (≥1 year from diagnosis) or salvage (≥1 year from 1^st transplant) autoHCT between 2006-2023.

Results:

650 patients were included: 335 (52%) received delayed autoHCT and 315 (48%), salvage autoHCT. Median age at autoHCT was 61 years, 23% of patients were Black, and 24% of patients had high-risk cytogenetic abnormalities (HRCA). 56% of patients received post-transplant maintenance, mostly lenalidomide (len) alone (44%). Within the salvage autoHCT cohort, 84% had achieved ≥VGPR at best response after 1^st autoHCT, and the median time from 1^st to 2^nd transplant was 4.6 years.

Median time to both neutrophil engraftment (ANC >500) and to platelet engraftment (Plt >20K) was 11 days. Prior to autoHCT, 26% of patients achieved ≥VGPR, which increased to 62% and 70% at day 100 and at best post-transplant response evaluation, respectively.

After a median follow up of 37 months, the median PFS and OS for the entire cohort were 17 (95% CI 16-19) months and 47 (95% CI 41-52) months, respectively. There was no significant difference in either PFS (hazard ratio (HR) 0.91, p=0.26) or OS (HR 0.89, p=0.23) between patients who got delayed or salvage transplant.

In multivariable analysis (MVA) for PFS, R-ISS (stage III HR 2.55, p< 0.001), HRCA (HR 1.47, p=0.002), >3 prior lines of treatment (HR 1.38, p=0.002), being len-refractory (HR 1.34, p=0.005), carfilzomib-refractory (HR 1.73, p=0.004) and not being exposed to an anti CD38 drug (HR 1.62, p=0.012) were associated with worse PFS. In MVA for OS, R-ISS (stage III HR 2.60, p< 0.001), >3 prior treatment lines (HR 1.47, p< 0.001) and being carfilzomib-refractory (HR 1.57, p=0.017) were associated with inferior survival. In contrast, achieving ≥CR at best post-transplant response (PFS: HR 0.53, OS: HR 0.37; p< 0.001 for both) and use of post-autoHCT maintenance (PFS: HR 0.80, p=0.021; OS: HR 0.54, p< 0.001) were associated with better survival outcomes.

Within the salvage autoHCT cohort, those transplanted >2 years after the first autoHCT had better PFS (HR 0.51, p=0.002) and OS (HR 0.53, p=0.004) in MVA.

56 patients developed a second primary malignancy (SPM), 21(6%) in the delayed group and 35 (11%) in the salvage group. Leading cause of death was MM progression (87%), followed by infection (4%). Rate of non-relapse mortality (NRM) was 3% at day100 and 4% at 1-year post autoHCT.

Conclusions: This is the largest study to date to evaluate outcomes of delayed/salvage autoHCT for MM, showing a median PFS of 17 months and OS of almost 4 years. NRM rates were higher than observed in the upfront setting, although SPM rates were similar. These results can serve as a benchmark for novel treatment modalities for patients with relapsed/refractory MM.