Survival Benefit Observed Following Treatment With Belantamab Mafodotin for Relapsed/Refractory Myeloma

Belantamab mafodotin (Belamaf; Blenrep) combined with pomalidomide (Pomalyst) and dexamethasone (B-Pd) resulted in a significantly longer progression-free survival (PFS) in the phase 1/2 ALGONQUIN study (NCT03715478) vs the historical control cohort from the LocoMMotion trial (NCT04035226) in patients with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM), according to data presented at the 2022 American Society of Hematology (ASH) Annual Meeting.

The median PFS was 16.8 months (95% CI, 15.7) to not yet reached [NYR]) with B-Pd vs 4.6 months moths with the historical control. The Algonquin study showed that patients with TCE disease or triple class refractory (TCR) disease continue to be a difficult-to-treat population, therefore B-Pd is an improvement compared with widely available standard of care therapies. Moreover, the safety of the regimen was consistent with that of each agent individually.

“In the recent locomotion study, triple class-exposed multiple myeloma patients who prospectively received widely available standard of care therapies demonstrated an overall response rate of only 29.8%, a medium duration of response of 4.6 months and an overall survival of 12.4 months,” explained Suzanne Trudel, MSc, MD, during a poster presentation at the 2022 American Society of Hematology Annual Meeting.

Sixty-one patients were included in the 2-part Algonquin study. Part 1 was the 3 + 3 dose-escalation phase, which included up to 12 patients per cohort. In each cohort, patients were treated at a different dose level. The purpose of part 1 was to determine safety and tolerability as well as the recommended phase 2 dose (RP2D) of Belamaf and of the agent.1 Belamaf was administered as follows:

Cohort 1 received a single dose at 1.93 mg/kg every 4 weeks (Q4W).

Cohort 1a received a single 2.5 mg.kg dose of Belamaf with a 2.5 mg/kg loading dose and another dose at 1.92 mg/kg every 4 weeks.

Cohort 1b was treated with a 2.5 mg/kg SPLIT dose, every 4 weeks.

Cohort 2 was given a 3.4 mg/kg SPILT dose of Belamaf, every 4 weeks.

Cohort 3a received a bimonthly dose of the agent at 2.5 mg/kg.

Cohort 3b was administered at trimonthly 2.5 mg/kg dose of Belamaf.

According to Trudel, the median age of patients in the study is 67 who received the median of 3 prior lines of therapy ranging from 2 to 5 lines of therapy. Consistent with the inclusion criteria, 100% of patients were lenalidomide refractory, and exposed to a proteosome inhibitor. One-hundred percent of patients were triple classic exposed, and 98% of patients were triple class refractory, but 41% of patients were high risk.

In part 2, the study will investigate the primary end point of objective response rate (ORR). The secondary end points of the study were PFS, overall survival (OS), duration of response (DOR), and safety.

Fifty five of the 61 patients from part 1 of the study were evaluable for response. At a median follow-up of 10.2 months (range, 0 -35.0 months), the ORR in TCE patients was 85% with a very good partial response rate (VGPR) of 56%. In all patients, the ORR was 82% and the VGPR was 55%.

Trudel shared efficacy results for each dose level explored in part 1. Responses and survival were best at the 2.5 mg/kg QW4 dose level with a median PFS of 24.4 months, but due to toxicity, the recommended phase 2 dose was determined to be 2.5 mg/kg Q8W.

In terms of OS, the median was 22.5 months (95% CI, 21.4-NYR) with the RP2D of Belamaf.

Safety findings showed that the most frequent grade 3 non-ocular treatment-emergent adverse events (TEAEs) were, neutropenia (32.8%), thrombocytopenia (27.9%), and fatigue (8.2%). Serious AEs were observed in 45.9% of patients of which 4 events were fatal. Of the fatal AEs, 2 patents had upper respiratory tract infections, 1 had myelodysplastic syndrome, and the serious AE in the final patient was not specified.

Treatment was discontinued by 2 patients due to AEs. The occurrence of AEs and serious AEs led to dos modification in 45.9% of patients.

Grade 3/4 AEs of special interest included keratopathy decreased visual acuity, neutropenia, and thrombocytopenia. These events occurred in 63.6%, 27.3%, 45.5%, and 27.3% of patients, respectively. All AEs were reversible.

Enrollment in part 2 of the study is ongoing to investigate the B-Pd regimen with the RP2D of Belamaf.

Reference

Trudel S, McCurdy A, Sutherland H, et al. Belantamab mafodotin in combination with pomalidomide and dexamethasone demonstrates durable responses in triple class exposed/refractory multiple myeloma. Presented at: 2022 ASH Annual Meeting; December 10-13, 2022; New Orleans, LA. Abstract 3248.