(OA-48) Final Analysis of the GEM-BELA-VRd Phase II Trial: Belantamab Mafodotin Plus VRd in Newly Diagnosed Transplant-Eligible Myeloma After 2 Years of Maintenance with Belantamab and Lenalidomide

Initial results from the GEM-BELA-VRd trial showed that adding belantamab mafodotin (belamaf) to VRd in newly diagnosed transplant-eligible multiple myeloma (NDTE-MM) patients resulted in high rates of deep responses, including complete responses (CR) and minimal residual disease (MRD) negativity. Ocular events (OEs) were common but reversible and manageable. We report the final analysis after 2 years of belamaf-lenalidomide (len) maintenance.



Methods:

GEM-BELA-VRd is a phase II, open-label, multicenter trial evaluating belamaf (2.5 mg/kg IV Q8W) with VRd for 6 induction cycles, followed by autologous stem cell transplant (ASCT), 2 consolidation cycles with belamaf-VRd (2.5 mg/kg IV Q8W), and maintenance with continuous len plus belamaf (1.9 mg/kg Q8W) for up to 2 years. Primary endpoint: safety; secondary endpoints: ORR, CR, MRD negativity, TTP, PFS and OS. Data cutoff: April 28, 2025.



Results:

Fifty patients were enrolled; 9 discontinued prior maintenance, and 41 (82%) initiated it.

No new safety signals emerged during maintenance. OEs were less frequent than in previous phases. Among patients with normal best corrected visual acuity (BCVA) at baseline, 11 patients had a decrease to 20/50 or worse in the first year, and 5 in the second year. Only 1 patient reached 20/200, during the first year, recovering within one month. All OEs resolved, with median recovery time of 75 days and full resolution in 175 days (range, 35–476), except in 3 patients with ongoing follow-up and improved BCVA from 20/50.

Grade ≥3 neutropenia occurred in 36% in the first year, decreasing to 22% in the 2^nd year. Grade ≥3 thrombocytopenia was stable (14%–12%). Grade ≥3 infections occurred in 18% in the first year and 8% in the second one. Four patients discontinued maintenance due to toxicity (cytopenias or infections), occurring in both years.

Median follow-up (FU) was 40.0 months (range 36.2–49.0). In the ITT population (n=50), best ORR was 96%, CR 80%, and MRD negativity 88%. In a per-protocol analysis, MRD negativity was 87.8% at the end of consolidation (n=41), 91.9% after the first year of maintenance (n=37), and 93.9% after the second year (n=33).

At last FU, only 3 patients had progressed: one at 7 months (triple-hit), two at 26 and 33 months, with 3-year TTP: 93%. Ten patients died: 5 from infections (4 COVID-19, 1 sepsis), 2 from progression, 1 from inflammatory colitis during induction, 1 unknown and 1 unrelated, with 3-yr PFS: 78% and 3-yr OS: 82%.



Conclusions:

Final analysis of this pilot study of Belamaf-VRd followed by continuous len plus up to 2 years of belamaf confirms deep responses in NDTE-MM patients, with high rates of CR and MRD negativity. OEs and hematological AEs were manageable and belamaf appeared not to add toxicity to len maintenance. Infections, particularly COVID-19, had a notable impact on the trial, influencing outcomes and safety. These results support further evaluation of belamaf in the frontline setting.