Background: Belantamab mafodotin (belamaf), a multi-modal antibody-drug conjugate targeting BCMA, has shown efficacy and tolerability in pretreated patients (pts) with relapsed/refractory multiple myeloma. In pts refractory to immunomodulatory drugs, proteasome inhibitors, and antiCD38, belamaf plus pomalidomide and dexamethasone induced a very good partial response (VGPR) or better of 69.2% and a median progression-free survival of 16.2 months (Trudel S, ASH 2021). Preclinical evidence suggests that belamaf plus lenalidomide enhances antimyeloma activity, with no overlapping toxicities.
Aims: To evaluate the safety and efficacy of belamaf plus lenalidomide and dexamethasone (Rd) in transplant-ineligible (TI) pts with newly diagnosed multiple myeloma (NDMM).
Methods: The ongoing, prospective, open-label, 2-part, phase 1/2 BelaRd study (NCT04808037) aims to enroll 66 pts with TI NDMM from a Greek center. Eligible are adult pts with Eastern Cooperative Oncology Group status 0–2 and adequate organ function. Part 1 (dose selection) evaluates the safety/tolerability of 3 belamaf doses (2.5, 1.9, and 1.4 mg/kg on Day 1 of every other 28-day cycle) plus Rd (each dose regimen administered to a cohort of 6 pts) over ≥4 weeks of follow up; subsequently, an additional 6 pts are enrolled in each dose cohort to establish the recommended phase 2 dose (RP2D). Part 2 (dose expansion) evaluates the safety and clinical activity of belamaf RP2D plus Rd in 30 additional pts. This descriptive analysis presents the safety data for all Part 1 pts and the efficacy data for all Part 1 pts with ≥2 post-baseline efficacy assessments by the cut-off date (14/01/2022).
Results: Of 36 pts included, 35 (97.2%) continued study treatment by the cut-off date, and 1 (2.8%) had died due to a belamaf unrelated adverse event (AE). The pt median age was 72.5 years (range 64.0–86.0). Of pts with available data (30 [83.3%]), pts at revised International Staging System stages I, II, and III were 6 [20.0%], 21 [70.0%], and 3 [10.0%], respectively, and 3 (10.0%) had high-risk cytogenetics (i.e., del17p13, t(4;14), t[14;16]). Median duration of therapy was 4.2 months (range 0.5–11.9) and median number of cycles reached was 5.0 (range 1.0–11.0). Twenty-two (61.1%) pts experienced at least one grade (Gr) 3–4 AE. One (2.8%) pt experienced a Gr 5 AE (pneumonia), unrelated to belamaf. Most common (≥ 10.0% of pts) Gr 3–4 AE were fatigue (13 [36.1%] pts), visual acuity reduced (6 [16.7%] pts), and rash (5 [13.9%] pts). Gr 3–4 thrombocytopenias and infections were not reported, as were any Gr infusion-related reactions (Table). Pts with Gr 1–2 ocular symptoms, visual acuity reduced, and keratopathy, were 27 (75.0%), 21 (58.3%), and 18 (50.0%), respectively. Pts with Gr 3–4 ocular symptoms, visual acuity reduced, and keratopathy were 0 (0.0%), 5 (13.9%) and 0 (0.0%), respectively. Of all pts, 28 (77.8%) were evaluable for efficacy (Table). At a median follow up of 4.2 months (range 0.5–11.9), the overall response rate was 96.4% (27/28 pts; complete response [CR]: 14.3% [4/28 pts]; VGPR: 35.7% [10/28 pts]; partial response [PR]: 46.4% [13/28 pts]); no disease progression was reported. Of pts achieving VGPR, 6/10 (60.0%) had negative status serum/urine immunofixation electrophoresis. Median time to PR or better was 1.0 months (range 0.9–2.0).
Summary/Conclusion: In pts with TI NDMM, belamaf every 2 months plus Rd showed an improved safety profile, especially at lower doses. Rapid and deep hematological responses were recorded.