B06 | BELANTAMAB MAFODOTIN PLUS LENALIDOMIDE/DEXAMETHASONE IN NEWLY DIAGNOSED INTERMEDIATE-FIT AND FRAIL MULTIPLE MYELOMA: LONG-TERM EFFICACY AND SAFETY FROM THE PHASE 1/2 BELARD CLINICAL TRIAL

Background. The aim of this study was to evaluate safety, tolerability, and clinical activity of belamaf plus lenalidomide and dexamethasone (Rd) (BelaRd) in transplant ineligible newly diagnosed myeloma (TI-NDMM) patients (pts).Methods. BelaRd trial (NCT04808037) was a phase 1/2, open label study in frail and intermediate-fit pts with NDMM In part 1 (n=36), we evaluated the safety/tolerability of belamaf 2.5/1.9/1.4 mg/kg every 8 weeks (Q8W) plus Rd and we established a recommended phase 2 dose (RP2D) of 1.9 mg/kg Q8W. In Part 2, pts (n=30) were treated at RP2D and randomized 1:1 to Group (Gr) A (dose modification guided by ophthalmologist-assessed KVA scale) or Gr B (hematologist-led Vision-Related Anamnestic (VRA) tool with ophthalmologist assessment focused on grade 3 ≥ ocular adverse events, OAEs). Results. To-date, 42 pts overall (part 1, n=12; part 2, n=30) received belamaf at the RP2D with Rd. Median follow up was 38.4 months (range 13.2-44.1) in part 1 and 19.7 months (range 3.9-26.4) in part 2. Median belamaf exposure was 12 doses in part 1, and 7 doses in part 2. Median dose intensity was 0.6 mg/kg/Q4W in both parts, with median relative dose intensity of 59.4% (range 44.0–89.7) and 51.3% (range 34.1–73.5), respectively. For pts treated at 1.9 mg/kg across both study parts, overall response rate (≥PR) was 97.6% (41/42 pts); 15 pts (35.7%) showed a sCR, 6 pts (14.3%) a CR, 16 pts (38.1%) a VGPR, 4 pts (9.5%) a PR. MRD negativity was achieved in 50% pts (6/12) in part 1, 40% pts (12/30) in part 2. The median time to first response was 1.0 month (range 0.9-3.8) and time to best response was 9.7 months (range 1.0-28.3). Median PFS & TTP were not reached. 18- and 24-month PFS were 82.9% (95%CI: 67.5-91.5) and 74.9% (95%CI: 56.3-86.5), respectively. TTP was 97.2% (95%CI: 81.9-99.6) for both 18- and 24 months. Belamaf administration frequently shifted beyond the normal Q8W schedule due to the OAE-guided holds: within the 1.9 mg/kg cohort (n=42) re-infusion intervals varied widely (8-19 weeks: coefficient of variation (CV) >20% in 32/42 pts) but stabilized beyond 12 months (CV<20% in 21/28 pts). Dose holds occurred in 32.0% in part 1 (OAEs) and in 26.5% in Gr A (OAEs) versus 16.9% in Gr B (VRA-guided); no VRA-enabled dosing was subsequently withheld by ophthalmologists for grade ≥3 OAEs. Grade ≥3 OAEs without VRA-reported “substantial time” (>50% of time) were detected in 10/300 (3.3%) ophthalmologist assessments in Gr A and 2/251 (0.8%) in Gr B. Stopping driving or reading due to eyesight issues occurred in 0.0%-0.6% of the monthly assessments in both groups. Eight pts experienced fatal TEAEs, most commonly pneumonia (3 pts; 7.1%). Grade ≥3 BCVA decline and keratopathy were observed in 54 (13.2%) and 1 (0.3%) of assessments in part 1, and 17 (3.4%) and 1 (0.2%) in part 2, respectively. Grade ≥3 ocular symptoms were observed in 7 pts (58.3%) in part 1 and 9 pts (30%) in part 2. No patient had to discontinue treatment. Conclusions. Belamaf 1.9 mg/kg Q8W with Rd produced rapid, deep responses and durable disease control with a high ORR and high PFS in TI intermediate-fit/frail NDMM patients. Efficacy was maintained with Q8W schedule having minimal impact on vision related daily activities. Overall, hematologist-led VRA strategy reduced dose holds without compromising ocular safety, supporting streamlined monitoring and warranting randomized phase 3 evaluation of Belamaf-Rd. Funding by GSK (NCT04808037); authors solely responsible for content.