Comparative Efficacy of Daratumumab, Pomalidomide and Dexamethasone Compared to Daratumumab, Carfilzomib and Dexamethasone in Patients with Relapsed-Refractory Multiple Myeloma (RRMM) Aged 70 and Above: A Multicenter Study

Introduction: Patients aged 70 years and older are often considered ineligible for intensive treatments, including autologous stem cell transplant (ASCT) due to relatively poor performance status and concomitant comorbidities. In this retrospective, multicenter study, we aimed to analyze real-world data on the efficacy of Daratumumab, Pomalidomide and Dexamethasone (DPd) Compared to Daratumumab, Carfilzomib and Dexamethasone (DKd) in a population of older RRMM patients (≥70) in real-world practice. Methods : We evaluated 399 RRMM patients, who had received either DPd or DKd for RRMM at three US centers in collaboration with the US Myeloma Innovations Research Collaborative (USMIRC) between January 2015 and April 2024. Using R Core Team (2024) software, a descriptive analysis was performed. Continuous variables were summarized and the mean (min, max) and median (IQR) were reported. Dichotomized factors were summarized by total numbers and frequency. Fisher's exact was used to analyze contingency tables. Wilcoxon rank-sum test was used to compare two independent samples. Doses and frequency of chemotherapy were adjusted for toxicities per the package insert and physician discretion. Responses were evaluated using IMWG criteria, including overall response rate (ORR) and complete response rate or better (≥ CR). Kaplan-Meier analyses were used to estimate progression-free (PFS) and overall survival (OS). A univariate/multivariate Cox proportional hazards analysis assessed the relationship between variables and a time-to-event outcome. The hazard ratios (HRs) and their associated confidence intervals (CIs) for each predictor variable were calculated, adjusting for censoring in survival data. Results: A total of 150 patients with RRMM ≥70 were included in the analysis; 119 (79%) patients received DPd, and 31 (21%) pts received DKd. The median age for the entire patient population was 79 years (range 70-93). Seventy-seven (51%) patients were female, 85 (57%) had IgG isotype, 28 (19%) had R-ISS stage III disease, and performance status was ECOG score 0/1 in 110 (73.3%) patients. High-risk cytogenetics were observed in 89 (60%) patients, and 27 (18%) had extramedullary disease (EMD), with no significant differences between the two groups (DPd vs. DKd). Both groups had a median of two lines of therapies. Patient and disease related characteristics in the two groups appeared equally balanced aisde from one factor. Patients in the DPd group with lenalidomide refractoriness vs DKd 107 (90%) vs 23 (74%), respectively (p = 0.035). A total of 29 (24%) vs three (9.7%) (p = 0.075) patients who had carfilzomib refractory disease while 13 (11%) vs five (16%) patients (p = 0.5) with pom refractory disease in DPd vs DKd, respectively. The overall response rate and very good partial response rate or better were 77% and 36% in the DPd group, compared to 74.5% and 64.5% in the DKd group, respectively (p < 0.01). With a median follow-up of 20 months (range: 1-77) for the entire patient population, the median progression-free survival (PFS) was 13 months (95% CI: 10-21) for the DKd group and 12 months (95% CI: 6.8-NA) for the DPd group (p = 0.6). Similarly, the median overall survival (OS) was 28 months (95% CI: 18-NA) for the DKd group and 50 months (95% CI: 38-NA) for the DPd group (p = 0.2). Conclusions: This multicenter study compared DPd versus DKd in patients aged 70 and above. The results demonstrated comparable efficacy, with no significant difference in PFS and OS. Our study suggests the potential to offer two therapeutic options for this patient population, considering efficacy and patient tolerance.