Outcomes of elderly patients with newly diagnosed multiple myeloma (NDMM): A retrospective comparison of daratumumab-based induction versus autologous stem cell transplant (autoSCT) Free

Introduction: AutoSCT is often considered for fit patients up to the age of 75. However, the MAIA trial showed that transplant-ineligible patients, who had a median age greater than 70, receiving Daratumumab-based triplet induction achieved a progression-free survival (PFS) of greater than 60 months. As autoSCT sees less utilization even in younger patients, analysis of preliminary data from the MIDAS trial implied there was no benefit to autoSCT when compared to quadruplet induction, although survival data is still maturing. These results bring into question the efficacy of autoSCT compared to anti-CD38 antibody-based induction, especially for patients of advanced age, where melphalan is often dose-reduced. Without impetus for a prospective study, we conducted a retrospective analysis to compare the outcomes of elderly patients with NDMM who have undergone Daratumumab-based induction versus autoSCT. A secondary aim is to compare the outcomes of elderly patients who underwent autoSCT and received melphalan at either 200mg/m² (Mel200) or 140mg/m² (Mel140).

Methods: Patients evaluated at the University of California, San Francisco between June 2019 to June 2023 who were age 70 or greater at the time of diagnosis of NDMM with measurable disease were considered for analysis. Patients in the nontransplant (noSCT) group must have received at least two cycles of triplet or quadruplet Daratumumab-based induction. Patients in the autoSCT group completed induction before proceeding to high-dose melphalan with autoSCT rescue as part of their first line of treatment. PFS was defined by the length of time between the first induction treatment and death or disease progression by International Myeloma Working Group (IMWG) criteria. High-risk cytogenetics were defined by the presence of t(14;16), t(4;14), t(14;20), or del(17p). Time-to-event variables were analyzed with the Kaplan-Meier method. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated based on the Cox proportional hazards model.

Results: A total of 117 consecutive patients were identified, 68 in the noSCT group and 49 in the autoSCT group. Median age of diagnosis was 75 (range 70-88) and 72 (range 70-76) years in the noSCT and autoSCT groups respectively. High-risk cytogenetic abnormalities were found in 19% (n=12) of the noSCT group compared to 48% (n=23) of the autoSCT group. ISS stage III disease was found in 37% (n=26) of the noSCT group and 20% (n=10) of the autoSCT group. Of the patients who received autoSCT, 24 (49%) patients received Mel140 and 25 (51%) patients received Mel200. Twenty-two patients (45%) underwent Daratumumab-based induction prior to autoSCT.

At median follow-up of 37 months, median PFS (mPFS) was not reached in either the noSCT group or the autoSCT group. 30-month PFS was 67% (95% CI, 56 to 80) in the noSCT group compared to 77% (95% CI, 66 to 91) in the autoSCT group. HR for progression or death in autoSCT compared to noSCT was 0.745 (95% CI, 0.4 to 1.4; p=0.4). Median overall survival (mOS) was also not reached for the noSCT and autoSCT groups. HR for death in autoSCT compared to noSCT was 0.30 (95% CI, 0.06 to 1.38; p=0.08). At best response prior to first progression, the rate of VGPR or better (≥VGPR) was 79% in the noSCT group compared to 94% in the autoSCT group (odds ratio 3.79; 95% CI, 1.13-18.06; p=0.03). When stratified based on melphalan dosing, Mel140 and Mel200 patients had similar rates of ≥VGPR (both at 95%). mPFS was 47 months for the Mel140 patients and was not reached in the Mel200 patients, though the hazard ratio for progression or death was not statistically significant (p=0.6). mOS was not reached in either the Mel140 or Mel200 patients.

Conclusion: Though a larger proportion of patients who underwent autoSCT achieved deeper responses, there was no difference identified in PFS or OS for autoSCT compared to noSCT. Patients who underwent Mel200 or Mel140 autoSCT had similar response rates and no difference in survival. With the CEPHEUS and IMROZ trials showing impressive rates of PFS for quadruplet induction through extended follow-ups of close to five years, the superiority of autoSCT will be difficult to uphold. We will update our analysis with propensity score matching to address confounders such as age, cytogenetics, ISS staging, and frailty for the national meeting.