P-318: A Real-World Comparison of First-Line Regimens in Transplant Ineligible Patients with Multiple Myeloma

Introduction: The management of transplant-ineligible (TI) patients with newly diagnosed multiple myeloma (MM) is challenging given wide variability in treatment tolerance. At this time, lenalidomide(R)/dexamethasone(Rd), bortezomib/Rd(VRd), and daratumumab/Rd(DRd) are used in TI patients. Data on treatment outcomes is derived from clinical trials which are not representative of the real-world population. In addition, real-world data on DRD is limited. We conducted a retrospective population-based study to compare outcomes between the 3 regimens in the first year of diagnosis.

Methods: We used data from the Institute for Clinical Evaluative Sciences (ICES), an administrative database capturing all health records in Ontario, Canada. We identified adult patients with MM from 2017-2023 who are TI, had 1st-line treatment with Rd, VRd, or DRd, and ≥1 year follow-up. We evaluated patient demographics, treatment details, health care utilization, early mortality, and 1-year overall survival (OS). We also captured patient-reported symptoms using the Edmonton Symptom Assessment System (ESAS) score which evaluates 9 common symptoms with a score of 7-10 considered to be severe.

Results: During the study period, 765, 547, and 73 patients received Rd, VRd, and DRd, respectively. This is consistent with approval dates: DRd was approved recently in September 2022. Median age at start was 80, 77, and 73 years, respectively. The most common dose for R was 10-15 mg both at treatment start (60%, 67%, and 56% for Rd, VRd, and DRd, respectively), and at 1 year (54%, 58%, and 49%, respectively); < 25% started at 20-25 mg. By 1 year, only 16%, 9%, and 14% of patients in the 3 groups, respectively, were using 20-25 mg. The 1-year mortality rate was 25% for Rd,19% for VRd, and 22% for DRd with 1-year OS being 75% (95%CI: 72-78), 81% (95%CI: 78-85), and 78% (95%CI: 69-88), respectively. Health care utilization was high across all 3 regimens, with >50% of patient experiencing at least one hospitalization within 1 year following regimen start. Post-treatment cytopenias were highest for the DRd group compared to other regimens with 42% experiencing at least one episode of grade 3+ anemia (Hb< 8g/dL), 23% thrombocytopenia (< 50 x 10^3/µL), and 52% neutropenia (< 1.0 x 10^3/µL) within year 1. For all regimens, there was a high symptom burden with 32%, 22%, and 25% of patients on Rd, VRd, and DRd, respectively reporting ≥1 severe ESAS score within the year 1 post treatment.

Conclusions: Our study is one of the first to highlight the ongoing high rate of early mortality, health care utilization, and symptom burden in TI MM patients with novel combinations including DRd, in the real-world. This highlights the need for better supportive care strategies. For all regimens, real world R dosing is lower compared to the clinical trial setting. Despite this, DRd is still associated with a high rates of neutropenia. One-year mortality appears similarly high for DRd and VRd, but further follow-up is needed for longer term outcomes.