S198: Efficacy and Safety of Belantamab Mafodotin Monotherapy in Patients With Relapsed or Refractory Light Chain Amyloidosis: A Phase 2 Study by the European Myeloma Network

Topic: 13. Myeloma and other monoclonal gammopathies - Biology thus, belamaf could be a treatment option for patients with RRAL amyloidosis. Aims: To present an interim analysis of the prospective EMN27 study assessing the efficacy and safety of belamaf monotherapy in pts with RRAL amyloidosis. Methods: The ongoing prospective, open-label, multinational, phase 2 EMN27 study (NCT04617925) aims to enroll 36 pts with RRAL amyloidosis. Pts at Mayo cardiac stage 3B are excluded. Belamaf monotherapy at 2.5 mg/kg (or 1.92 mg/kg for toxicity) is administered every 6 weeks for up to 8 cycles. Pre-planned study analyses included an interim safety analysis (after 6 pts received ≥1 treatment cycle) and an efficacy analysis (after 13 pts were enrolled). The outcomes of both analyses were favorable and study enrollment is on-going. This descriptive analysis included pts initiating treatment ≥3 months before 31/12/2022 (cutoff date). Results: Twenty-five pts are included in this analysis (median age: 66 years 46–80; male: 15 60%). Heart was involved in 19 pts (76.0%), other commonly involved organs were the kidneys (16 pts, 64%), peripheral nerves (6 pts, 24%), and soft tissue (5 pts, 20%). At baseline, most pts (19, 76%) had New York Heart Association class II symptoms and median N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T, and dFLC were 1,197 ng/L (90–7,270), 35 ng/L (3–116), and 117 mg/L (38–2,791), respectively. The median number of prior treatment lines was 3 (1–10). Eighteen (72%) and 23 (92%) pts had previously received daratumumab and bortezomib. At cutoff, 6 (24%) pts were continuing study treatment, and 19 (76%) pts had discontinued mostly due to disease progression/inadequate response (9 pts, 36%) or adverse events (AE; 7 pts, 28%; 5 pts due to ocular AEs). Median belamaf administration in cycles was 2 (1–8). Eighty-two belamaf doses were given (2.5 mg/kg: 63, 1.92 mg/kg: 19). Nine (36%) pts had 15 belamaf dose holds, with median delay of 21 days from planned belamaf administration. At a median follow up of 11 months (4–22), the overall hematologic response rate (partial response or better) was 60%, VGPR was 36% (15 pts, 9 pts respectively; Table). Median time to first hematologic response was 15 days (1–148) and to VGPR 43 days (15–106; Table). At 1 and 3 months, the respective best hematologic response rate were 44% (11 pts) and 56% (14 pts) for all pts, while for pts with prior daratumumab exposure this was 33% (6 pts) and 50% (9 pts). For all pts, 3-month organ response rate was 20% (5 pts; Table). All pts experienced ≥1 AE, with 24 (96%) pts experiencing ocular AEs, 8 (32%) pts hematologic toxicity, and 4 (16%) pts cardiac disorders; no new cardiac or renal toxicity signals were observed. Three (12%) pts had a fatal AE, all considered unrelated to belamaf. Twenty-one (84%) pts had visual acuity reduced (grade Gr1: 3 (12%); Gr2: 7 28%; Gr3: 10 40%; Gr4: 1 4%), 19 (76%) keratopathy (Gr1: 8 32%; Gr2: 7 28%; Gr3: 4 16%; Gr4: 0 0%), and 5 (20%) visual impairment (Gr1: 1 4%; Gr2: 2 8%; Gr3: 1 4%; Gr4: 1 4%). Summary/Conclusion: In heavily pretreated pts with RRAL amyloidosis, belamaf monotherapy induced rapid responses without unexpected toxicity. Prolonged administration cycles could not prevent ocular toxicity. Results suggest belamaf could be a treatment option for patients with RRAL amyloidosis, a difficult to treat population.Keywords: AL amyloidosis