Belantamab Mafodotin Combination Shows Durable Efficacy in Relapsed or Refractory Multiple Myeloma

Belantamab mafodotin plus lenalidomide and dexamethasone was found tolerable with no new safety signals and enhanced response rates in patients with multiple myeloma.

The combination of belantamab mafodotin-blmf (Blenrep) plus lenalidomide (Revlimid) and dexamethasone showed a promising clinical response in a small population of patients with relapsed or refractory multiple myeloma (RRMM). These findings were from an interim analysis of arm A of the DREAMM-6 clinical trial (NCT03544281) presented during the Annual Meeting of the Society of Hematologic Oncology (SOHO).

Presenter Sagar Lonial, MD, FACP, said that belantamab mafodotin plus lenalidomide and dexamethasone was tolerable with no new safety signals and enhanced response rates over what would be expected with either agent administered individually.

Belantamab mafodotin, a B-cell maturation antigen (BCMA)-targeted antibody-drug conjugate (ADC), kills multiple myeloma cells via direct cytotoxicity and systemic anti-myeloma tumor immune responses. To date, it is the only ADC monotherapy approved by the FDA for patients with triple-class RRMM.

DREAMM-6 is a 2-part, 2-arm, open-label, dosing, and scheduling evaluation study that enrolled 221 patients with RRMM across 59 study sites. Forty-five patients enrolled in arm A were required to have an ECOG performance status of 0 to 2, have undergone stem cell transplant if eligible, and progressed during treatment with 1 or more prior therapies for multiple myeloma. The coprimary end points in part 1 of the study included the number of patients with dose-limiting toxicities, the proportion of patients experiencing adverse events (AEs) or serious AEs (SAEs), and the number of patients with abnormal vital signs or laboratory results. Part 2 of the study will analyze overall response rate (ORR), AEs, and SAEs.

Secondary end points include pharmacokinetics (PK), ophthalmic exam findings, changes in ocular symptoms, and health-related quality of life.

During part 1, the dose-escalation phase, patients receive belantamab mafodotin 2.5 mg/kg with lenalidomide/dexamethasone. If the combination is found intolerable at this dose, it will be reduced to 1.9 mg/kg and 2.5 mg/kg to evaluate the efficacy and safety of belantamab mafodotin with lenalidomide and dexamethasone. The patient population included in the interim analysis was comprised of males from 35 to 80 years of age with a median age of 68.0 years.

Responses were assessed by study investigators and evaluated by dose cohort. Among patients administered belantamab mafodotin 1.9 mg/kg every 8 weeks, the ORR was 42% (95% CI, 15.2%-72.3%) with 17% showing a very good partial response (VGPR) rate (95% CI, 2.1%-48.4%), and no complete responses (CRs) observed.

Patients administered 1.9 mg/kg every 4 weeks (Q4W) showed an ORR of 75% (95% CI, 19.4%-99.4%). The VGPR rate in this patient group was 50% (95% CI, 6.8%-93.2%), and the CR rate was 25% (95% CI, 0.6%-80.6%).

Among those administered 2.5 mg/kg every 4 weeks, the ORR was 63% (95% CI, 35.4%-84.8%) with a VGPR of 50% (95% CI, 24.7%-75.3%), and a CR of 38% (95% CI, 15.2%-64.6%). Patients administered a split dose of belantamab mafodotin 2.5 mg/kg showed an ORR of 69% (95% CI, 38.6%-90.9%), with a VGPR of 38% (95% CI, 13.9%-68.4%) and a CR rate of 19% (95% CI, 1.9%-45.4%).

Time-to-treatment showed that the median duration of response (DOR) was not reached in all but 1 patient group. Among 4 patients administered 1.9 mg/kg Q4W with lenalidomide and dexamethasone, the media DOR was 11.1 months (3.7-NR). Median time to response ranged from 1 month to 1.9 months across the patient group. Median progression-free survival was 8.6 months (95% CI, 1.0-NR) in patients administered the 1.9 mg/kg Q4W dose and 9.0 months (95% CI, 3.2-NR) in the 2.5mg/kg Q4W split cohort.

Any-grade AEs occurred in 100% of patients across all cohorts. The most common AEs were keratopathy, decreased visual acuity, reduced platelet count, reduced neutrophil count, insomnia, neutropenia, and thrombocytopenia.

SAEs were observed in 42% of patients administered 1.9 mg/kg Q8W, 50% of patients administered a 1.9 mg/kg Q4W dose, 56% of those administered the 2.5 mg/kg Q4W dose, and 40% of those administered the 2.5 mg/kg Q4W split dose. Treatment-related SAEs were found in 17%, 0%, 19%, and 23%, respectively. Fatal SAEs occurred in 13% of patients in the 2.5 mg/kg Q4W group, and 8% of patients in the 2.5 mg/kg Q4W split cohort.

References

Quach H, Gironella M, Lee C, et al. Safety and clinical activity of belantamab mafodotin with lenalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma: DREAMM-6 arm-A interim analysis. Presented at: 10th Annual Meeting of the Society of Hematologic Oncology.