Frontline Treatment Patterns and Outcomes in Patients with Newly Diagnosed Multiple Myeloma Who Did Not Undergo Transplant: A US Electronic Health Records Database Analysis

Introduction: Despite considerable evolution in the treatment landscape, multiple myeloma remains incurable, and outcomes deteriorate once patients become relapsed or refractory. While introduction of novel therapies has improved outcomes especially among those who are not ineligible for stem cell transplant (SCT), up-to-date real-world data on treatment patterns and outcomes is lacking. The objective of this study was to assess treatment patterns and outcomes among newly diagnosed multiple myeloma (NDMM) patients ineligible for transplant using retrospective data from an EMR database. Methods: Adults diagnosed with MM between January 2016 and October 2023, who received systemic treatment after MM diagnosis, did not participate in randomized controlled trials, and did not receive SCT during 1L were followed until the earliest of death or the end of data availability. Lines of therapy (LOTs) and regimens were inferred from EMR records of MM-recommended antineoplastic agents (e.g., bortezomib [V], lenalidomide [R], cyclophosphamide [C], daratumumab [D]). Dexamethasone (d) was assumed to be included in all regimens. Time to event outcomes, including real-world progression-free survival (rwPFS), overall survival (rwOS), time to 1L discontinuation (TTD), and time to next LOT (TTNT), were analyzed using Kaplan-Meier method. Associations between patient characteristics and rwPFS were evaluated using multivariable Cox proportional hazards regression, from which we report hazard ratios (HR) and 95% confidence intervals (CIs). Results: A total of 6,627 patients with non-transplant NDMM who had received systemic treatment (median age: 72 years; aged 75+ years: 39.1%; male: 53.7%; White: 56.4%) were included in the analysis. Among patients with available data, 76.0% had Eastern Cooperative Oncology Group performance status (ECOG) score 0/1, 64.2% had International Staging System (ISS) stage I/II disease, and 29.9% had high-risk cytogenetics. Anemia was the most often recorded MM symptom (73.4%), followed by renal impairment (34.8%) and hypercalcemia (22.2%). VRd was the most used 1L regimen (43.1%; n=2853), followed by Rd (17.2%; n=1139), VCd (9.4%; n=624), and Vd (8.5%; n=566). Daratumumab was used in 13.8% (n=917) of 1L regimens (D-based regimens used by >50 patients: DVRd [n= 358], DRd [n=273], DVCd [n=92], DVd [n=89]). During a median follow-up of 20.9 months, 2,940 (44.4%) patients received second LOT (2L), 1,715 (25.9%) patients discontinued 1L but did not start 2L, and 560 (8.5%) patients died while undergoing 1L therapy. The Kaplan-Meier based median (95% CI) TTD of 1L was 7.1 (6.8-7.4) months and the median (95% CI) TTNT was 12.5 (11.8-13.1) months. The estimated Kaplan-Meier rwPFS rates at 1-, 3-, and 5-years were 68.8%, 42.9%, and 29.6%, respectively; the median (95% CI) rwPFS was 26.7 (25.3-28.3) months. The estimated rwOS rates at 1-, 3-, and 5-year were 81.3%, 61.5%, and 46.1%, respectively; the median (95% CI) rwOS was 54.3 (52.1-56.7) months. Higher risk of disease progression or death was seen in older patients [HR (95% CI) = 0.60 (0.45 - 0.81), 0.63 (0.58 - 0.69), 0.73 (0.68 - 0.79) for age groups 18-44, 45-64, and 65-74 versus age group 75+, respectively], patients having high-risk cytogenetics [HR (95% CI) = 1.44 (1.30 - 1.59) vs standard risk], having ISS disease stages II and III [HR (95% CI) = 1.33 (1.18 - 1.50) and 1.64 (1.46 - 1.85) versus stage I, respectively], and having worse ECOG PS score [HR (95% CI) = 1.60 (1.42 - 1.82), 2.22 (1.86 - 2.65), and 2.89 (1.66 - 5.05) for ECOG PS = 2, 3, and 4 versus ECOG PS=0, respectively]. Conclusions: During the study period, VRd remained the standard 1L regimen for non-transplant NDMM patients. Although median duration of treatment reported in clinical trials for non-transplant NDMM was over 2 years, median duration of 1L treatment in real-world practice was less than 1 year and a quarter of patients did not receive subsequent treatment. Half of the non-transplant NDMM patients experienced disease progression or death within 2 years and the 5-year survival rate was less than 50%. Higher risk of disease progression or death was associated with older age, having high-risk cytogenetics, worse disease stage, and worse ECOG score. Suboptimal outcomes of currently available treatments highlight the need for better regimen to achieve optimal disease control, delay disease progression, and improve survival among patients with non-transplant NDMM.