Real World Evidence on Patient Reported Outcomes Among Newly Diagnosed Multiple Myeloma Patients Treated with Daratumumab-Based Regimens in Frontline (1L)

Background: Daratumumab (Dara; D) based regimens have demonstrated clinical efficacy as well as improvement in quality of life (QoL) in both transplant eligible (TE) and transplant ineligible (TIE) patients (pts) with newly diagnosed Multiple Myeloma (NDMM) in pivotal randomized clinical trials. However, the impact of these regimens as frontline-treatment (1L) for NDMM on the patient reported outcomes (PROs) in the real-world is not known. This study examined PROs among TE and TIE pts with NDMM initiating Dara-based regimens as 1L in the real-world.

Methods: PROs for MM pts treated at University of Alabama at Birmingham (UAB) are captured as part of the UAB Cancer and Aging Resilience Evaluation in Hematologic Malignancies (CARE-Heme) registry. In this study, we conducted a retrospective analysis of the PROs captured between Jan 2020-April 2024 among TE and TIE pts with NDMM initiating 1L Dara-based regimens. The PROs examined were QoL (using PROMIS® scale v1.2 Global Health which includes global physical health and global mental health), anxiety (using PROMIS® Anxiety Short Form (SF) 4a v1.0), and depression (using PROMIS® Depression SF 4a v1.0). PROs were captured at baseline (within 30 days of 1L initiation), and at 3, 6, and 12 months from 1L initiation, or at the end of treatment. Unadjusted longitudinal generalized linear mixed models were used to describe the mean change from baseline to 3, 6, and 12 months, among TE and TIE pts separately. A 3-point T-score difference was considered clinically meaningful for all measures consistent with the literature.

Results: Of the 81 eligible pts receiving Dara-based regimen in 1L, 37 (45.7%) were TE and 44 (54.3%) were TIE. The median age among TE pts was 62.8 years, with 49% ≥ 65 years old. The median age among TIE pts was 72.1 years, with 66.0% between ages 65-84 and 16.0% ≥85 years old. The proportion of Black pts in TE and TIE was 43.2% and 34.1%, respectively. Compared to TE pts, a greater proportion of TIE pts were frail (IMWG frailty index; 38.6% vs. 19.0%), had an ECOG score of 2 or 3 (38.6% vs. 16.0%), and a higher median Quan Charlson comorbidity index (3.0 vs. 0.0). In contrast, a greater proportion of TE pts had high cytogenetic risk (35.1% vs. 18.2%). The Dara-based regimens used among TE pts were D, bortezomib (V), lenalidomide (R), dexamethasone (d) (DVRd= 67.6%), D, carfilzomib (K), R, d (DKRd=16.2%), and D, V, Cyclophosphamide (C), d (DVCd= 16.2%), while those used among TIE pts were DVRd (50.0%), DRd (27.3%), and DVCd (22.7%).

Change from baseline to 12 months in global physical health was significant among TE (2.7; 95% CI: 0.3, 5.2) and significant as well as clinically meaningful among TIE pts (5.6; 95% CI: 2.8, 8.4). Non-significant improvements in global mental health scores were observed at 12 months in both TE (1.2; 95% CI: -1.1,3.5) and TIE pts (1.6; 95% CI: -1.0, 4.1).

Among TE pts, there was significant and clinically meaningful improvement in anxiety at each time point (-3.5; 95% CI: -6.1, -0.9 at 3 months, -4.8; 95% CI: -7.6, -2.1 at 6 months and -4.2; 95% CI: -6.9, -1.6 at 12 months) as compared to baseline, while significant and clinically meaningful improvements in anxiety was observed in TIE pts at 3 months (-4.1; 95% CI: -6.3, -1.8) and 12 months (-5.7; 95% CI: -8.1, -3.2) with non-significant improvement at 6 months. A significant improvement in depression was noted among TE pts at all time points (-2.8; 95% CI: -5.2, -0.4 at 3 months, -3.1; 95% CI: -5.6, -0.6 at 6 months, and -2.5; 95% CI: -4.9, -0.1 at 12 months), while significant and clinically meaningful improvement in depression was only observed at 12 months (-4.8; 95% CI: -7.4, -2.2) from baseline among TIE pts.

Conclusions: This real-world study observed improvements in PROs, consistent with the PRO outcomes observed in the clinical trials employing similar PRO instruments. TIE NDMM pts treated with Dara-based regimens as 1L demonstrated significant and clinically meaningful improvements in global physical health, anxiety, and depression at 12 months from 1L initiation, despite being older and frailer. TE NDMM pts treated with Dara-based regimens demonstrated significant improvement in global physical health at 12 months from 1L initiation. While improvements in PROs were seen within 3 months of 1L initiation, longer treatment with Dara led to significant improvements in PROs over time. These findings further support the use of daratumumab in 1L setting regardless of transplant eligibility, age, or frailty.

Giri:Sanofi: Honoraria, Research Funding, Speakers Bureau; Janssen Research & Development, LLC: Honoraria, Research Funding, Speakers Bureau. Rafalko:Johnson & Johnson: Current Employment. Gupta-Werner:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Ravi:Guidepoint: Consultancy. Bal:Janssen: Consultancy; AbbVie: Consultancy, Research Funding; AstraZeneca: Consultancy; MJH Life Sciences: Honoraria; Beigene: Research Funding; Fate Therapeutics: Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Armoon:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Medhekar:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Costa:BMS: Consultancy, Honoraria, Research Funding; Adaptive biotechnoligies: Honoraria; Caribou: Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria.