Real-World Efficacy and Patient-Reported Quality of Life Outcomes with Daratumumab Regimens in Multiple Myeloma
Authors: Browning Sabrina L. , Li Fangyong , Theprungsirikul Poy , Parker Terri L. , Bar Noffar , Giri Smith , Anderson Tara , Stevens Erica , Gorshein Elan , Sabbath Kert D. , Wei Catherine , Ali Syed S. , Witt David H. , Persico Justin , Talsania Ashita , Rahmat Leena , Kidwai Wajih Zaheer , Legare Robert D. , LaSala Johanna , Austin Matthew , Neparidze Natalia 
Published: December 2024

Background: Based on superior clinical efficacy and tolerability observed in clinical trials, daratumumab, a monoclonal antibody targeting CD38 on plasma cells, is at the forefront of treatment for patients with newly diagnosed (NDMM) and relapsed/refractory multiple myeloma (RRMM). However, there is a paucity of prospective, real-world data on health-related quality of life (HRQoL) and patterns of use with daratumumab.
Methods: In this multi-center, prospective, observational study, patients with NDMM or RRMM were enrolled if they were started on a standard of care daratumumab-based regimen within 30 days prior to study enrollment. The EORTC core quality of life questionnaire (QLQ-C30), a 30-item instrument assessing different aspects of HRQoL in cancer patients, was completed at enrollment, 3 months, 6 months, and 12 months from start of daratumumab or end of treatment if this occurred prior to 12 months. Mixed effects model was used to analyze changes in HRQoL. We collected data on the line of therapy and combination in which daratumumab was used to describe patterns of care and International Myeloma Working Group (IMWG) clinical response assessment was documented at each time point. Adverse events (AEs), including AEs of special interest, were recorded. Herein, we report on the first 58 patients enrolled in this study.
Results: Between October 2020 and May 2024, 59 patients were enrolled in this ongoing prospective study with 58 patients evaluable. 43 (74.1%) had RRMM and 15 (25.9%) had NDMM at study entry. Median age was 67 (range, 47-97) and 69 years (range, 48-86) in NDMM and RRMM patients, respectively. Males represented 65% of the cohort. 13% were Black or African American and 7% were Hispanic or Latino. 13.8% of patients had an Eastern Cooperative Oncology Group performance status of 2-3. In the RRMM cohort, median lines of prior therapy was 1 (range, 1-5). Daratumumab was given as a part of a doublet regimen with dexamethasone in 6 (10.3%) patients, triplet in 38 (65.5%) patients, and as a quadruplet in 14 (24.1%) patients. In the NDMM cohort, 12 (80%) were treated with quadruplet and 3 (20%) with triplet therapy. 29 (50%) patients received daratumumab in combination with an immunomodulatory inhibitor (IMiD), 6 (10.3%) with a proteasome inhibitor (PI), and 10 (17.2%) with both an IMiD and a PI. 4 (6.9%) patients received a combination with an alkylator and a PI.
HRQoL questionnaire data were available in 49 patients, including 43 at 3 months, 32 at 6 months, and 24 at 12 months or end of treatment. There was a significant linear improvement in global health status (60.5±23.7, 68.8±21.3, 75.8±19.9 at baseline, 3 months, 6 months, respectively; p=0.001), exceeding a minimally important difference of 10 points. All function scales significantly improved at the 6-month time point except for emotional functioning scale. Cognitive functioning score also improved at 3 months (baseline 80.3±20.6 to 3 month 85.7±18.8; p=0.03). Multiple symptom scales improved over time including the mean fatigue score (baseline 42.6±26.5 to 3 month 31.9±22.8 (p=0.008) and 6 months 33.7±23.4 (p=0.03)). Pain significantly improved at 6 months. 31 (53.4%) patients achieved a very good partial response or better per IMWG response assessment criteria, 49 (84.5%) achieved a partial response or better. The median progression free survival in the RRMM subgroup was 33 months (95% CI: 8-35) with all 15 patients progressed or died on study having RRMM. There were no AEs of special interest during the study period, including no infusion-related reactions. The most common AEs observed were hematologic with ≥grade 2 cytopenias in 12 (20.7%) patients. There were no grade 3-4 infections.
Conclusions: With the introduction of novel therapies, overall survival has increased for MM and patients are receiving many lines of therapy during their disease course. It is imperative that we understand the impact on HRQoL with use of these anti-plasma cell regimens outside of clinical trials, including with daratumumab which serves as a common therapeutic backbone in NDMM and RRMM. In this interim analysis, we observed clinically meaningful improvement in global health status, as well as improvement in function scales, cognitive functioning, and multiple symptom scales. In a real-world clinical setting, daratumumab-based regimens were associated with notable efficacy and tolerability and improvement in HRQoL in patients with NDMM and RRMM.