Belantamab mafodotin plus lenalidomide maintenance was active and had an expected safety profile in transplant-eligible, newly diagnosed myeloma.
Treatment with 2 years of belantamab mafodotin-blmf (Blenrep) plus lenalidomide (Revlimid) maintenance therapy demonstrated an expected safety profile and generated high response rates in transplant-eligible patients with newly diagnosed multiple myeloma, according to findings from the updated analysis of the phase 2 GEM-Bela-VRd trial (NCT04802356) of belantamab mafodotin plus bortezomib (Velcade), lenalidomide, and dexamethasone (VRd), which were presented at the
Ocular toxicities that arose among patients in the intention-to-treat (ITT) population with normal baseline visual acuity (n = 43) during belantamab mafodotin/lenalidomide maintenance therapy were blurred vision (51.2%) and vision impairment (9.3%). Onset of blurred vision occurred during the first and second years of maintenance therapy in 86.3% and 13.6% of patients with this adverse effect (AE), respectively. The median time to improvement of blurred vision to grade 2 or lower was 91 days (range, 23-394). In total, 27.2% of patients with blurred vision were lost to follow-up. Blurred vision events resolved in all evaluable patients, and the median time to resolution was 102 days (range, 28-476).
Onset of vision impairment occurred during the first and second years of maintenance therapy in 75.0% and 25.0% of patients with this AE, respectively. The median time to improvement of vision impairment to grade 2 or lower was 98 days (range, 28-244). Blurred vision events resolved in all evaluable patients, and the median time to resolution was 196 days (range, 28-244).
In total, eye-related AEs led to dose reductions or delays in 41 patients. The rates of patients requiring at least 1 belantamab mafodotin dose modification, dose delay, or discontinuation due to toxicity were 92.7%, 92.7%, and 26.8%, respectively. Patients received a median of 6 cycles of belantamab mafodotin (range, 0-12). The median relative dose intensity of belantamab mafodotin was 36.8% (range, 0%-83.3%).
“Maintenance with 2 years of belantamab mafodotin and continuous lenalidomide in [patients with] transplant-eligible, newly diagnosed multiple myeloma [demonstrated] a safety profile consistent with previous studies with lenalidomide maintenance and belantamab mafodotin combinations,” Veronica González-Calle, MD, PhD, said in the presentation.
González-Calleis a hematologist in the myeloma unit in the Department of Hematology, at the University Hospital of Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONC in Spain.
The open-label, multicenter, nonrandomized, single-arm trial enrolled patients at least 18 years of age with symptomatic and measurable newly diagnosed multiple myeloma, and an ECOG performance status of 0 to 2.2 In the induction phase, patients received 6 cycles of belantamab mafodotin at 2.5 mg/kg every 8 weeks plus VRd (bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 of each cycle; lenalidomide at 25 mg per day on days 1 to 21; and dexamethasone on days 1 to 4 and 9 to 12).1 In the consolidation phase, patients received belantamab mafodotin at the same dose level during cycle 1 plus VRd at the same dose levels for 2 cycles. During the maintenance phase, patients received belantamab mafodotin at 1.9 mg/kg every 8 weeks until progressive disease (PD), patient withdrawal, or death for up to 2 years as maintenance therapy; plus lenalidomide at 10 mg/kg on days 1 to 28, with the option to increase up to 15 mg/kg, continuously until PD or patient withdrawal.
Safety, including eye-related AEs, served as the primary end point. Key secondary end points included overall response rate (ORR); complete response (CR) rate; minimal residual disease (MRD)–negativity rates after induction, consolidation, and maintenance; efficiency of CD34-positive cell collection; progression-free survival (PFS); and overall survival (OS).
GEM-Bela-VRd enrolled 50 patients, all of whom received induction therapy. In total, 46 patients underwent autologous stem cell transplant (ASCT), and 45 patients received consolidation therapy. Eighty-two percent, 74%, and 66% of patients received 1, 13, and 25 cycles of maintenance therapy, respectively.
Initial findings from GEM-Bela-VRd showed that the addition of belantamab mafodotin to VRd generated deep responses. The CR rates were 36% following induction therapy, 56% following ASCT, and 70% following consolidation therapy. Additionally, among MRD-evaluable patients, MRD negativity was reached in 61%, 69%, and 84% following induction therapy, ASCT, and consolidation therapy, respectively.
At a clinical cutoff date of July 1, 2025, 4 patients had discontinued induction therapy due to death (COVID-19, n = 2; GI toxicity, n = 1; disease progression, n = 1), 1 patient had discontinued ASCT due to toxicity (toxic pneumonitis), and 4 patients had discontinued consolidation therapy due to death (COVID-19, n = 3; sepsis, n = 1) and patient withdrawal (n = 1). In the maintenance phase, during cycles 1 through 12, 4 patients discontinued therapy due to toxicity (n = 2; infection and neutropenia), patient withdrawal (n = 1), and unknown death (n = 1). During maintenance cycles 13 through 24, 4 patients discontinued therapy due to toxicity (n = 2; COVID-19 and cytopenias) and disease progression (n = 2). During maintenance cycle 25 and beyond, 1 patient had discontinued therapy due to recurrent respiratory infections.
AEs that occurred in the ITT population during the first year of belantamab mafodotin/lenalidomide maintenance therapy included thrombocytopenia (any-grade, 34%; grade ≥3, 14%); neutropenia (54%; 36%); anemia (8%; 4%); infections (76%; 26%) including respiratory infections (52%; 18%) like pneumonia (8%; 6%) and COVID-19 (18%; 8%), urinary infections (4%; 0%), catheter infections (2%; 2%), acute gastroenteritis (12%; 4%), and other infections (6%; 2%); peripheral neuropathy (6%; 0%); rash (8%; 0%), and gastrointestinal (GI) toxicities (32%; 6%) including diarrhea (20%; 4%), constipation (4%; 0%), and nausea (8%; 2%). AEs that occurred in the ITT population during the second year of belantamab mafodotin/lenalidomide maintenance therapy included thrombocytopenia (any-grade, 26%; grade ≥ 3, 12%); neutropenia (48%; 22%); anemia (2%; 0%); infections (66%; 12%) including respiratory infections (44%; 8%) like COVID-19 (14%; 0%), urinary infections (4%; 0%), acute gastroenteritis (10%; 2%), and other infections (8%; 2%); peripheral neuropathy (2%; 0%); rash (4%; 0%), and GI toxicities (22%; 4%), including diarrhea (22%; 4%).
Maintenance therapy with belantamab mafodotin plus lenalidomide led to improved depth of response. At a median follow-up of 40.0 months (range, 36.2-49.0), the ORR was 96%, including best responses of CR (80%), very good partial response (VGPR; 12%), PR (4%), and SD (2%). After 1 year of maintenance therapy, the ORR was 94%, including best responses of CR (80%), VGPR (11%), PR (4%), and stable disease (SD; 2%). After 2 years of maintenance therapy, the ORR was 90%, including best responses of CR (78%), VGPR (10%), PR (2%), and SD (2%).
In comparison, the response rates at earlier study time points were as follows:
Among MRD-evaluable patients, the rates of MRD negativity improved during maintenance therapy. The overall rate of MRD negativity was 88.0% (n = 44/50). After the first and second years of maintenance, this rate was 91.9% (n = 34.37) and 93.9% (n = 31/33), respectively.
In comparison, the MRD negativity rates at earlier study time points were as follows:
Only 3 patients relapsed or progressed, translating to a 36-month PFS rate of 78%. Additionally, 10 patients died due to PD (n = 2), infection (COVID-19, n = 4; sepsis, n = 1), inflammatory colitis (n = 1), unknown reason (n = 1), and unrelated reason (n = 1), translating to a 36-month OS rate of 82%.
The addition of belantamab mafodotin to lenalidomide maintenance therapy also benefitted patients with high-risk cytogenetics. In total, 30.4% of patients had high-risk cytogenetics. Best responses in these patients included CR or better (86%), VGPR (14%), disease progression (7%), and death (n = 7). After the first year of maintenance, 3 of these patients were lost to follow-up; the remaining 11 patients all achieved MRD negativity. After the second year of maintenance, 4 total patients had been lost to follow-up; 9 of the remaining 10 patients achieved MRD negativity, and the remaining 1 patient had a conversion from MRD negativity to MRD positivity.
Among high-risk and standard-risk patients, the 36-month PFS rates were 93% and 78%, respectively. The respective 36-month OS rates were also 93% and 78%.
“These findings support further evaluation of benaltamab mafodotin in the frontline setting in [patients] transplant-eligible, newly diagnosed multiple myeloma,” González-Calle concluded.
Disclosures: González-Calle reported receiving honoraria from GSK and Johnson & Johnson; participating in advisory board meetings for GSK and Johnson & Johnson; receiving research support from GSK and Pfizer; and receiving travel support from Sanofi, GSK, and Johnson & Johnson.
