Background: Managing patients (pts) with relapsed/refractory (RR) light chain (AL) amyloidosis is challenging, as there is no current standard treatment, many available options are associated with low efficacy and toxicity, and options for daratumumab (DARA)- and bortezomib-exposed patients are limited. Belantamab mafodotin (belamaf), a multi-modal antibody-drug conjugate targeting BCMA, has shown efficacy and tolerability in heavily pretreated pts with RR multiple myeloma, including those refractory to DARA. Since clonal plasma cells in AL amyloidosis and MM are phenotypically similar, belamaf could be a novel treatment option in AL amyloidosis.
Aims: To evaluate the efficacy and safety of belamaf monotherapy off-label in pts with RR AL amyloidosis.
Methods: The ongoing prospective, open-label, multinational, phase 2, EMN27 study (NCT04617925) aims to enroll 36 adult pretreated pts with AL amyloidosis who require therapy. Pts at Mayo cardiac stage 3b are excluded. Belamaf monotherapy at 2.5mg/kg is administered by intravenous infusion every 6 weeks for a maximum of 8 cycles; dosing can be reduced to 1.92mg/kg for toxicity. Per study design, a safety analysis (after 6 pts received ≥1 treatment cycle) and an efficacy analysis (after 13 pts are enrolled) were planned. The safety analysis revealed no new safety signals, and pt accrual continued to 13 pts. The efficacy analysis is currently conducted; however, already 3 pts achieved complete response, or very good partial response (VGPR), or low difference of involved to uninvolved serum free light chains (dFLC) response and enrollment is continuing to include all planned pts. This descriptive analysis included pts initiating study treatment ≥3 months before the cut-off date (15/01/2022).
Results: Of 11 pts included in the analysis, 4 (36.4%) continued treatment by the cut-off date, and 7 (63.6%) discontinued (disease progression: 5 [45.5%], death: 2 [18.2%]). The pts median age was 69.0 years (range 46.0–80.0), and most were males (7, 63.6%). At baseline, 3 (27.3%) and 8 (72.7%) pts had New York Heart Association class I and II symptoms, respectively; the median N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T, and dFLC were 1,979 pg/mL (range 190.0–4,135.0), 41.6 pg/mL (range 11.0–80.8), and 34.2mg/dl (range 4.4–279.1), respectively. Except for the heart, commonly involved organs were the nervous system (4 pts, 36.4%) and the soft tissue (2 pts, 18.2%). The median number of previous AL amyloidosis treatments was 3.0 (range 1.0–7.0), including DARA. The median duration of belamaf therapy was 3.1 months (range 1.4–5.7). At a median follow up of 9.4 months (range 3.1–10.0), the overall response rate was 72.7% (8 pts; VGPR: 27.3% [3 pts] and partial response: 45.5% [5 pts]). Median time to first hematological response was 8.5 days (range 1.0–28.0) and to VGPR or better 15.0 days (range 8.0–15.0). The 3-month organ (heart, kidney, or liver) response rate was 36.4% (4 pts). All pts had ≥1 non serious adverse event (SAE). Four (36.4%) pts had ≥1 SAE, including 2 (18.2%) pts with a belamaf-related grade 2 and 4 visual impairment (1 [9.1%] pt each). Eight (72.7%) pts had ≥1 adverse event of special interest. Two (18.2%) pts had a fatal SAE (pneumonia and intestinal perforation, 1 [9.1%] pt each), both unrelated to belamaf.
Summary/Conclusion: In this prospective study, belamaf monotherapy induced rapid, clinically meaningful responses with a manageable safety profile in heavily pretreated pts with RR AL amyloidosis. As the study progresses, additional data will be generated.