OA - 64: Belantamab Mafodotin in Combination with VRd for the Treatment of Newly Diagnosed Transplant Eligible Multiple Myeloma Patients: Results from the Phase II, Open Label, Multicenter, GEM-BELA-VRd Trial

Introduction: GEM-BELA-VRd is a phase II, open label, multicenter, non-randomized single arm clinical trial evaluating belantamab mafodotin (belamaf) plus bortezomib, lenalidomide, and dexamethasone (VRD) in transplant-eligible newly diagnosed multiple myeloma (TE NDMM) patients (pts). The preliminary analyses of safety and efficacy after 4 cycles (cy) of induction were encouraging (González-Calle V et al. ASH, 2022). Here we report the results after all pts have completed 1 year of maintenance (1 yr-maint).


Methods:
50 pts were recruited. Treatment consisted of 6 induction cy with VRd (Q4W) and belamaf 2.5 mg/kg iv (Q8W), followed by autologous stem cell transplant (ASCT). Patients also receive 2 consolidation cy with VRd (Q4W) and belamaf (at 2.5mg/kg Q8W) and maintenance with R until progression/toxicity and belamaf (Q8W) for 2 yrs (at 2.5 and 1.9 mg/kg after protocol amendment).


Primary endpoint was safety (incidence of adverse events (AEs) [CTCAE v. 4.0]). Main key secondary endpoints were overall response rate (ORR), complete response rate (CR) and minimal residual disease negativity (MRD neg) rate. Cut-off date: June 1, 2024.



Results:
Median age was 56 years (27-75). Most of pts had MM Ig G kappa (64%), ECOG 0 (66%) and ISS I (64%). Besides, 12% had high LDH and 15% paraskeletal plasmacytomas.


Ocular AEs were the most frequent. Among the patients with normal best correct visual acuity (BCVA) at baseline (20/25 or better), a decrease in the BCVA to 20/50 or worse occurred in 18/43 pts (41.9%) in induction; 8/43 (18.6%) in consolidation; and 11/43 (25.6%) in 1yr-maint. Blurred vision improved in all patients prior to ASCT (12 wks from last dose of belamaf). Only 1 pt had decrease of BCVA to 20/200 (2.3%), during 1yr-maint.


Most common non-ocular G≥3 AEs were hematological and infections. Incidence of G≥3 neutropenia and thrombocytopenia were 18 and 16%, during induction, and 28% and 8% during 1yr-maint, respectively. The incidence of G≥3 infections was 30% in induction, 16% in consolidation and 14% within 1yr-maint. The most common type was respiratory.


In the ITT population (n=50), best ORR was 96%, sCR/CR rate improved overtime: 36% after induction; 56% after ASCT; 70% after consolidation and 82% after 1yr-maint. For those evaluable patients, MRD neg rate was 28/46 (60.9%) after induction; 29/42 (69.0%) after ASCT; 32/38 (84.2%) after consolidation and 31/34 (91.2%) after 1-yr maint.


With a median follow-up of 28.5 m (18.8-37.6), 4 pts progressed, at 7, 26, 28 and 34 months with 2yr-TTP of 96% and 2yr-PFS of 78%. Eight pts died, 5 from infections (4 Covid and 1 sepsis), 1 early gastrointestinal toxicity, 1 disease progression and 1 unknown reason.



Conclusions: Belamaf-VRD resulted in manageable eye-related AEs, expected hematological toxicity and respiratory infections, also due to the impact of the COVID -19 pandemic during trial recruitment. Besides, this combination was effective with a deepening of the response over time in TE NDMM.