Safety and clinical activity of belantamab mafodotin with pembrolizumab in patients with relapsed/refractory multiple myeloma (RRMM): DREAMM-4 Study.
Attaya Suvannasankha, Nizar J. Bahlis, Suzanne Trudel, Katja Weisel, Christian Koenecke, Albert Oriol Rocafiguera, Peter M. Voorhees, Aránzazu Alonso Alonso, Natalie S. Callander, María‐Victoria Mateos, Nishitha Reddy, Shawn Hakim, Nashita Patel, Danaè Williams, Roxanne C. Jewell, Xiangdong Zhou, Ira Gupta, Ajay K. Nooka
Abstract
8018 Background: Belantamab mafodotin (belamaf; BLENREP), a B-cell maturation antigen (BCMA) targeted antibody–drug conjugate approved for adult patients with RRMM, has a multimodal mechanism that eliminates myeloma cells via direct cytotoxicity and a systemic anti-tumor immune response, which may be augmented by an immune checkpoint inhibitor. DREAMM-4 (NCT03848845) assessed safety and clinical activity of belamaf with pembrolizumab (pembro) in RRMM. Methods: This was a Phase I/II, single-arm, open-label study of adults with RRMM after ≥3 lines of therapy (LOT, including anti-CD38 monoclonal antibody, proteasome inhibitor, and immunomodulator). Part 1 established the dose of belamaf 2.5 mg/kg with pembro 200 mg, both IV Q3W up to 35 cycles, for the Part 2 expansion. Primary efficacy endpoint was investigator-assessed overall response rate (ORR, ≥partial response [PR] per IMWG criteria by investigator). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), adverse events (AEs) per NCI-CTCAE v4.03, and pharmacokinetics (PK). Results: This primary analysis of all treated pts (as of Oct 18, 2021) included 34 pts (6 in Part 1 and 28 in Part 2). In both parts, median prior LOT was 5 (range 3–13); 10 pts (29%) had high-risk cytogenetics and 9 (26%) had extramedullary disease. ORR was 47%, with most responses (10/16 pts) ≥ very good PR (VGPR, Table). Median follow-up was 14.7 months (mo); median (95% CI) DoR was 8.0 (2.1–not reached) mo; median PFS was 3.4 (1.4–5.6) mo. Most pts had ≥1 AE (any grade [Gr]: 97%; Gr ≥3: 74%) and treatment-related AE (TRAE, any Gr: 97%; Gr ≥3: 65%). Most common (≥35%) AEs were keratopathy (any Gr: 76%; Gr ≥3: 38%), vision blurred (any Gr: 38%; Gr ≥3: 0%), and thrombocytopenia (any Gr: 35%; Gr ≥3: 29%). AEs led to dose delays (65%) and dose reductions (32%), but not discontinuation. Nine pts had a serious AE (SAE); 4 pts had ≥1 SAE related to study treatment. Two pts had immune-related AEs of Gr 1 (gout and autoimmune hypothyroidism). Preliminary PK and soluble BCMA data were consistent with single-agent belamaf therapy. Conclusions: Belamaf + pembro demonstrated a favorable ORR compared with single-agent belamaf in heavily pre-treated RRMM. No new TRAEs were identified; AE frequency and severity were similar to single-agent belamaf. Correlative biomarker studies are ongoing. Clinical trial information: NCT03848845. [Table: see text]