Belantamab Mafodotin Plus VRd Demonstrates Efficacy in Newly Diagnosed, Transplant-Eligible Myeloma

The combination of belantamab mafodotin-blmf (Blenrep), bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) showed efficacy signals and manageable toxicity in transplant-eligible patients with newly diagnosed multiple myeloma, according to data from the phase 2 GEM-BELA-VRD trial (NCT04802356) presented at the 21st Annual International Myeloma Society Meeting and Exposition.

Among the intent-to-treat (ITT) population, the objective response rate (ORR) with the belantamab mafodotin combination was 94% across all phases of treatment, which included induction therapy, autologous stem cell transplantation (ASCT), consolidation therapy, and 1-year maintenance therapy. The complete response (CR) rates were 36% in the induction phase, 56% after ASCT, 70% after consolidation, and 82% following a year of maintenance. Based on flow cytometry analysis, the quality of responses improved over time, as the minimal residual disease (MRD)-negative rates were 60.9%, 69.0%, 84.2%, and 91.2% during each respective treatment phase.

Similar response outcomes were reported among patients with high-risk cytogenetics and those with standard-risk cytogenetics. Additionally, all patients with high-risk cytogenetics achieved MRD-negative status after consolidation and maintenance therapy with the belantamab mafodotin combination. Other MRD-negative rates in this population included 64.3% following induction therapy and 83.3% after ASCT.

After a median follow-up of 28.5 months, progression-free survival (PFS) events occurred in 4 patients. At 12 months and 24 months, respectively, the PFS rates were 90% and 85%, and the time to progression (TTP) rates were 96% and 95%. Regarding overall survival (OS), data showed that 8 patients died, with causes including COVID-19 pneumonia (n = 4), sepsis (n = 1), inflammatory colitis (n = 1), disease progression (n = 1), and unknown reasons (n = 1). The 12-month and 24-month OS rates were 92% and 85%, respectively.

Among patients with high-risk cytogenetics, the PFS rates were 91% at 12 months and 91% at 24 months; the respective rates were 91% and 82% for those with standard-risk cytogenetics (P >.05). The 12-month and 18-month OS rates were 93% and 93% for those with high-risk cytogenetics. The respective rates were 91% and 82% in the standard-risk cytogenetics group (P>.05).

“The efficacy of the combination seems to be encouraging. Depth of response improved over [the course of] treatment, with 82% of patients with CR or better after 1 year of maintenance in the ITT population, and 91% of evaluable patients with negative MRD,” Verónica González-Calle, MD, MS, PhD, from the Hematology Department at the University Hospital of Salamanca, said in the presentation. “Maintenance is ongoing, and further analysis after completing 2 years of maintenance is planned.”

In the open-label, multi-center GEM-Bela-VRD trial, patients were assigned to receive induction therapy with bortezomib at 1.3 mg/m2 subcutaneously on days 1, 4, and 11 of each cycle; lenalidomide at 25 mg daily on days 1 to 21; dexamethasone at 40 mg on days 1 to 4 and 9 to 12; and belantamab mafodotin at 2.5 mg/kg intravenously every 8 weeks in 4-week intervals. Following ASCT, patients then received consolidation with belantamab mafodotin plus VRd for 2 cycles. During the maintenance phase, patients received belantamab mafodotin at 1.9 mg/kg intravenously every 8 weeks plus lenalidomide at 10 mg per day on days 1 to 28 of each cycle.

The trial’s primary end point was safety in terms of ocular events and other adverse effects (AEs). Key secondary end points included ORR; CR rate; MRD after induction, consolidation, and maintenance; PFS; and OS.

From June 2015 to June 2017, 50 patients enrolled on the trial. Additionally, 50 underwent induction therapy, 45 proceeded to ASCT, 44 received consolidation therapy, and 41 received maintenance therapy.

The median patient age was 56 years (range, 27-75), and 48.0% were male. Data also showed that most patients had an ECOG performance status of 0 (66.0%), IgG κ multiple myeloma (64.0%), κ light chain disease (64.0%), and stage I disease (65.3%). Of note, 30.4% of patients had high-risk cytogenetics, which included 17p deletions (10.9%), t(4;14) (17.0%), and t(14;16) (4.3%).

Following induction therapy, the most toxicities were ocular. Frequent any-grade and grade 3/4 ocular AEs, respectively, included blurred vision (89.6% vs 41.7%), foreign body sensation (62.5% vs 18.8%), dry eyes (58.3% vs 14.6%), and eye irritation (37.5% vs 8.3%). Regarding changes in best-corrected visual activity (BCVA), 40% (n = 17/43) of evaluable patients had blurred vision, which had a median onset of 49 days (range, 30-175) and a median time to resolution of 150 days (range, 49-566). Dose reductions, dose delays or interruptions, and dose discontinuations occurred for 30%, 48%, and 2%, respectively, due to ocular events. No patients experienced impaired vision following induction therapy.

In the induction phase, any grade and grade 3 or higher hematological AEs affected 62% and 40% of patients, respectively, with the most common including thrombocytopenia (28% vs 16%), neutropenia (22% vs 18%), and anemia (12% vs 6%). Additionally, patients experienced infections (80% vs 30%), peripheral neuropathy (42% vs 2%), and skin toxicity (38% vs 14%), among others.

During the consolidation phase, any grade and grade 3/4 ocular AEs included blurred vision (58.3% vs 14.6%), dry eye (37.5% vs 8.3%), foreign body sensation (31.3% vs 4.2%), and photophobia (18.8% vs 6.3%). No patients had impaired vision, although blurred vision occurred in 19% (n = 8/43) with a median duration of 73 days (range, 16-330). Additionally, 30% and 2% of patients had dose reductions and dose delays, respectively, due to ocular AEs; no patients discontinued therapy.

After 1 year of maintenance therapy, any grade and grade 3/4 ocular AEs included blurred vision (72.9% vs 33.3%), dry eye (56.3% vs 27.1%), foreign body sensation (47.9% vs 16.7%), and photophobia (43.8% vs 16.7%). Blurred vision was reported in 26% (n = 11/43) of patients at a median duration of 110 days (range, 35-476). Of note, 1 patient had impaired vision which was ongoing at the time of the analysis. Investigators facilitated dose reductions, dose delays, and dose discontinuations for 54%, 70%, and 4% of patients, respectively, due to ocular AEs.

Any grade and grade 3 or higher hematological AEs affected 56% and 38% of patients, respectively, at the time of the 1-year maintenance analysis. Other non-hematological AEs included infections (56% vs 14%), pneumonia (8% vs 6%), COVID-19 (12% vs 4%), and skin toxicity (14% vs 0%).

Reference

González-Calle V, Rey-Bua B, Puertas B, et al. 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. Presented at the 21st Annual International Myeloma Society Meeting and Exposition; September 25-28, 2024; Rio de Janeiro, Brazil. Abstract OA-64.