"In this trial, we show deep and durable responses with single-agent [belantamab mafodotin] were sustained with longer follow-up in this relapsed/refractory multiple myeloma population."
Monotherapy with belantamab mafodotin (GSK2857916) in patients with relapsed or refractory multiple myeloma (RRMM), showed clinically meaningful deep responses and tolerability in a heavily pretreated population, updated findings from the phase 2 DREAMM-2 trial presented as part of the 2020 ASCO Virtual Scientific Program indicate.
When presenting the poster, lead author Sagar Lonial, MD, FACP, said that the analysis demonstrates the utility of the anti-body drug conjugate in patients whose depth and durability of responses to treatment are known to diminish with each line of therapy.
In a 13-month follow-up analysis, the overall response rate (ORR) was 32% (31/97; 97.5% CI, 21.7%-43.6%) for patients treated in the 2.5-mg/kg cohort and 35% (35/99; 97.5% CI, 23.9%-46.0%) in the 3.4-mg/kg cohort.
The duration of response (DoR) was not reached (NR) in either cohort. The median DoR estimate was 11.0 months (95% CI, 4.2-NR) and 6.2 months (95% CI, 4.8-NR), respectively. Further, more than half of patients who achieved a response in both cohorts, had a very good partial response (VGPR) or better (58% and 66%, respectively).1
The VGPR analyses included 11 patients with VGPR, 5 patients with complete response (CR), and 2 patients with stringent CR (sCR) in the 2.5-mg/kg cohort. In the 3.4-mg/kg cohort, 18 patients had VGPR, 3 had CR, and 2 had sCR.1
"In this trial, we show deep and durable responses with single-agent [belantamab mafodotin] were sustained with longer follow-up in this relapsed/refractory multiple myeloma population," said Lonial, professor and chair, Department of Hematology and Medical Oncology and the Anne and Bernard Gray Family Chair in Cancer at Emory University School of Medicine, as well as chief medical officer at Winship Cancer Institute of Emory University.
The 2-arm, DREAMM-2 trial (NCT03525678) accrued patients aged 18 years or older with RRMM with disease progression after 3 or more lines of therapy and who were refractory to immunomodulary drugs and proteasome inhibitors, as well as refractory and/or intolerant to an anti-CD38 monoclonal antibody. Patients were randomly assigned (1:1) to receive 2.5 mg/kg (n = 97) or 3.4 mg/kg (n = 99) belantamab mafodotin intravenously over at least 30 minutes every 3 weeks on day 1 of each cycle. Treatment continued until disease progression or unacceptable toxicity. The primary end point was ORR by independent review committee.2
The median PFS was 2.8 months (95% CI, 1.6-3.6) in the 2.5-mg/kg cohort and 3.9 months (95% CI, 2.0-5.8) in the 3.4-mg/kg cohort. The median overall survival estimates were 14.9 months (95% CI, 9.9-NR) and 14.0 months (95% CI, 10.0-NR), respectively. The estimated 1-year survival was approximately 58% in both groups.1
Safety end points included adverse events (AEs), serious AEs, treatment-related AEs (TRAEs), and AEs leading to dose delays and interruptions. AEs of any grade occurred in 98% and 100% of patients in the lower and higher-dose cohorts, respectively, with TRAEs reported in 88% and 95% of patients. Grade 3 or higher AEs were reported in 84% of patients in both cohorts and included keratopathy (46% and 42%), anemia (21% and 27%), thrombocytopenia (22% and 32%), lymphocyte count decreased (13% and 7%), and neutropenia (11% and 7%).
"The most common [adverse] events were thrombocytopenia, anemia, and keratopathy," Lonial said. Thrombocytopenia was reported in 38% and 57% of patients in the 2.5-mg/kg and 3.4-mg/kg groups. Infusion-related reactions were observed in 21% and 16%, respectively.
Keratopathy was observed in 75% of patients in the 2.5-mg/kg group and 77% of patients in the 3.4-mg/kg group. The median time to onset of the first event was 37.0 days and 22.5 days, respectively. Patients may experience symptoms of dry eye, blurred vision, and changes in visual acuity.
"Keratopathy are changes in the corneal epithelium that are observed on ocular exam either with or without symptoms…as of this analysis 77% and 63% of the patients with keratopathy had recovered from their first event. The median time to resolution of keratopathy from the first event was 86.5 days and 85.0 days, respectively." No permanent loss of vision has been reported to date.1
Dose modifications and reductions due to AEs were common and reported in 54% of patients in the 2.5-mg/kg cohort and 62% in the 3.4-mg/kg cohort. Forty-seven percent and 53% of patients, respectively delayed treatment due to keratopathy. Further, keratopathy led to dose reductions in 25% and 30% of patients. In spite of keratopathy observed on eye exams being a common AE, only 3 patients in each cohort discontinued treatment to control corneal events, suggesting that dose modification adequately managed the AE.
In post-hoc analysis approximately half of responders in the 2.5-mg/kg cohort (16/31) who experienced a treatment delay for 3 cycles or more were able to restart. Most patients (88%) maintained or improved their response category during dose delay. Thirteen percent (2/16) developed disease progression during or immediately following the dose delay.
"Although dose modifications and prolonged treatment interruptions were common in order to manage adverse events, patients maintained or even deepened their clinical responses with prolonged treatment interruptions," Lonial concluded. "Results support the recommended 2.5 mg/kg [every 3 weeks] dosing of single-agent [belantamab mafodotin] in this heavily pretreated relapsed and refractory multiple myeloma population."
In January, the FDA granted priority review to the biologics license application from GlaxoSmithKline, the manufacturer of the agent. The submission was based on previously reported data, published in Lancet Oncology, which showed an ORR greater than 30% in each cohort.2,3
A planned phase 3 trial (NCT04162210) is currently recruiting and will evaluate the efficacy of belantamab mafodotin versus pomalidomide (Pomalyst) plus low-dose dexamethasone in patients with RRMM.3
1. Lonial S, Lee HC, Badros A, et al. Pivotal DREAMM-2 study: single-agent belantamab mafodotin (GSK2857916) in patients with relapsed/refractory multiple myeloma (RRMM) refractory to proteasome inhibitors (PIs), immunomodulatory agents, and refractory and/or intolerant to anti-CD38 monoclonal antibodies (mAbs). Data presented as part of 2020 American Society of Clinical Oncology Virtual Scientific Program; May 29-31, 2020. Abstract 8536.
2. Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020;21(2):207‐221. doi:10.1016/S1470-2045(19)30788-0
3. US Food and Drug Administration (FDA) grants priority review of belantamab mafodotin for patients with relapsed or refractory multiple myeloma. News Release. London, England: GlaxoSmithKline plc; January 21, 2020. Accessed May 29, 2020. prn.to/3avqSkZ