Belantamab Mafodotin Plus Pomalidomide/Dexamethasone Prolongs PFS, Compared With Historical Control in Relapsed/Refractory Multiple Myeloma

The combination of belantamab mafodotin (Belamaf; Blenrep), pomalidomide, (Pomalyst) and dexamethasone (B-Pd) elicited encouraging responses and a progression-free survival (PFS) benefit in patients with triple class–exposed or refractory multiple myeloma, according to findings from the phase 1/2 Algonquin study (NCT03715478), which were compared with a historical control cohort from the LocoMMotion study (NCT04035226).¹

“In the recent LocoMMotion study, triple class–exposed multiple myeloma patients who prospectively received widely available standard-of-care [SOC] therapies demonstrated an overall response rate [ORR] of only 29.8%, a median duration of response [DOR] of 4.6 months, and an overall survival [OS] of 12.4 months,” explained Suzanne Trudel, MSc, MD, during a poster presentation at the 2022 ASH Annual Meeting.

The median PFS was 16.8 months (95% CI, 15.7-not yet reached [NYR]) with B-Pd vs 4.6 months with the historical control. The Algonquin study showed that patients with triple class–exposed 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 SOC therapies. Moreover, the safety of the regimen was consistent with that of each agent individually.

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 who received the median of 3 prior lines of therapy ranging from 2 to 5 lines of therapy was 67 years. Consistent with the inclusion criteria, 100% of patients were lenalidomide refractory and exposed to a proteosome inhibitor. One-hundred percent of patients were triple class 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 ORR. The secondary end points of the study were PFS, OS, 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), the ORR in triple class–exposed 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 because of toxicity, the recommended phase 2 dose was determined to be 2.5 mg/kg Q8W.

The median OS 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 adverse effects (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 because of AEs. The occurrence of AEs and serious AEs led to dose modifications 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.