P35 analysis of daratumumab clinical trials: characteristics and outcomes in patients with lenalidomide-refractory relapsed/refractory multiple myeloma treated with 1-3 prior lines of therapy

Introduction: Survival outcomes in patients with multiple myeloma (MM) have improved with new treatment combinations using proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies. However, for patients with multiple lines of therapy (LOT), especially those who are PI exposed and refractory to lenalidomide (len), selecting the next regimen can be challenging. Data that characterize treatments and outcomes in this difficult-to-treat population are limited. Methods: Individual patient-level data were derived from a pooled analysis of daratumumab clinical trials, which included the initial study, long-term follow-up, and all treatment arms and regimens with or without daratumumab (ALCYONE, APOLLO, CANDOR, CASSIOPEIA, CASTOR, EQUULEUS, GRIFFIN, MAIA and POLLUX). MM patients with 1-3 prior LOT (including a PI and IMiD) who were len-refractory and had an ECOG <2 were identified. Time zero (T0) was defined as the time when the subsequent LOT started after patient met inclusion criteria for each eligible index line. Patients with multiple therapies subsequent to meeting eligibility criteria contributed multiple observations. Treatment outcomes and patterns were analyzed by number of prior LOT. For all index lines, descriptive statistics for patient characteristics were assessed at T0. The Kaplan-Meier method was used to estimate time-to-event analyses starting at T0 for progression-free survival (PFS), time to next treatment (TTNT) and overall survival (OS). Results: Of 4764 patients, 915 with 1230 index lines (prior LOT, 1 [n=114]; 2 [n=516]; 3 [n=600]) met inclusion criteria. For all indexed lines, median age was 65.5 years (range 30-90), 57.5% were male, 76.4% were White, and 3.2% were Black. Median time from diagnosis was 3.6 years (range 0-23). At T0, 5.4% had baseline plasmacytoma, 16.1% had ISS stage III disease, and 14.3% had high-risk cytogenetics. 13.8% of all eligible index lines were triple-class refractory. 58.9% had stem cell transplant prior to T0. Most common treatment regimens subsequent to meeting eligibility criteria were DPd (13.3%), DKd (13.2%), Pd (11.4%), and Kd (8.9%). For all patient indices, the overall response rate was 50.1% (29.0% with very good partial response or better; 12.0% with complete response or better) (Figure 1A). Estimated median OS for all patient indices was 23.9 months (95% CI 21.8, 25.8), PFS was 12.2 months (95% CI 10.9, 13.5), and TTNT was 8.34 months (95% CI 7.7, 9.3). Estimated median OS, PFS, and TTNT by number of prior LOT are shown in Figure 1A. Response rates and PFS decreased as the number of prior LOT increased (Figure 1B). Conclusions: This analysis of patients from daratumumab randomized clinical trials demonstrates that response rates decrease with each additional prior LOT for PI-exposed, len-refractory patients with 1-3 prior LOTs. PFS is also poor in these patients, and they move quickly through available treatments, highlighting the need for a new effective and safe regimen for this patient population.