Belantamab mafodotin-blmf (Blenrep) combined with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (BVRd) produced robust efficacy across all dosing cohorts in patients with transplant-ineligible, newly diagnosed multiple myeloma, according to data from the final analysis of the phase 1 DREAMM-9 trial (NCT04091126) presented at the
Data from the trial showed that patients who received belantamab mafodotin at 1.9 mg/kg or 1.4 mg/kg every 6 weeks during induction and every 8 weeks during maintenance (n = 24) achieved an overall response rate (ORR) of 96%, a complete response (CR) or stringent CR (sCR) rate of 88%, and a minimal residual disease (MRD)–negativity rate of 54%.
Patients who received belantamab mafodotin at 1.9 kg/mg, 1.4 kg/mg, or 1 kg/mg every 3 weeks during induction and every 4 weeks during maintenance (n = 40) experienced an ORR, sCR/CR rate, and MRD-negativity rate of 90%, 68%, and 55%, respectively. Finally, patients who received belantamab mafodotin at ranges from 1.9 kg/mg to 1.4 kg/mg or 1.4 kg/mg to 1 kg/mg every 9 weeks during induction and every 12 weeks during maintenance or 1 kg/mg every 12 weeks for induction and maintenance achieved an ORR of 85%, sCR/CR rate of 59%, and MRD-negativity rate of 43%.
“BVRd had high ORRs across all cohorts, highlighting promising efficacy of all regimens,” said Saad Z. Usmani, MD, MBA, FACP, FASCO, during a presentation of the data. “Belantamab dosing in the induction phase with the higher dose intensity appears to be optimal in getting to the MRD-negativity rate. The longer dosing intervals during maintenance help improve the tolerability and sustainability of response.”
Usmani is chief of Myeloma Service at Memorial Sloan Kettering Cancer Center in New York, New York, and the recipient of the
The study enrolled patients who met International Myeloma Working Group (IMWG) diagnostic criteria, had an ECOG performance status of 2 or less, were not candidates for high-dose therapy with autologous stem cell transplant due to frailty or significant comorbid conditions, and had measurable disease per IMWG criteria.
Patients with prior systemic therapy for multiple myeloma, smoldering multiple myeloma, current corneal epithelial disease, or had major surgery within 4 weeks of their first dose of BRVd were excluded.1,2
Belantamab mafodotin was administered at doses of 1.0 kg/mg, 1.4 kg/mg, and 1.9 kg/mg, every 3, 4, 6, 8, 9, or 12 weeks. All dosing cohorts underwent a 21-day screening phase and received induction with BVRd for cycles 1 to 8.1 Then, patients received belantamab mafodotin maintenance with Rd every 4 weeks for the remaining cycles. Finally, patients had a 7-day follow-up visit after their last cycle of treatment.
Safety, specifically dose-limiting toxicities and adverse effects (AEs) was the primary end point of the trial. Secondary end points for the trial included ORR, sCR/CR rate, and very good partial response (VGPR) or better rate per IMWG criteria. MRD-negativity in patients who achieved sCR/CR was an exploratory end point.
Baseline characteristics among all patients (n = 118) revealed that patients had a median age of 74 years (range, 51-88) and were mostly White (87%) and male (55%). Additionally, 13% of patients had extramedullary disease, and 16% had high-risk cytogenetics.
Regarding safety, grade or higher ocular AEs occurred 74% of patients in the every 3 weeks group, 88% in the every 6 weeks group, and 35% in the every 9 or 12 weeks group. Resolution of first grade 3 or higher AEs was 97%, 86%, and 100%, respectively, and the median time to first onset was 72, 136, and 193 days across these subgroups, respectively. Overall, 92% of all grade or higher ocular AEs resolved with adequate follow-up, and belantamab mafodotin discontinuation due to grade 3 or higher ocular events was at 3%, occurring only in 3 patients who received belantamab mafodotin every 3 weeks during induction.
These data support of 1.9 mg/kg every 8 weeks for 24 weeks, followed by every 12 weeks dosing of belantamab mafodotin in the ongoing phase 3 DREAMM-10 trial (NCT06679101) evaluating belantamab mafodotin plus Rd vs daratumumab (Darzalex) plus Rd in patients with transplant-ineligible, newly diagnosed multiple myeloma, and the phase 3 PrE1005 trial (NCT07285239), which is evaluating belantamab mafodotin plus VRd vs daratumumab plus VRd in patients with transplant-ineligible, newly diagnosed multiple myeloma.
