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Anti-BCMA immunoconjugate appears effective for multiple myeloma
Belantamab mafodotin, an investigational anti-B-cell maturation antigen monoclonal antibody-drug conjugate, demonstrated clinically meaningful response rates among patients with heavily pretreated multiple myeloma, according to results of the randomized phase 2 DREAMM-2 trial published in Lancet Oncology.
The treatment also had a manageable safety profile.
“This is an important step forward for patients who currently have very limited treatment options when the commonly used agents are no longer effective against their myeloma,” Sagar Lonial, MD, FACP, chair and professor in the department of hematology and medical oncology at Winship Cancer Institute of Emory University, and a HemOnc Today Editorial Board Member, told Healio. “This represent the first off-the-shelf, BCMA-targeted treatment to be tested in phase 2 studies and hopefully will be available for patients with multiple myeloma next year.”
For the open-label, two-arm study, Lonial and colleagues enrolled 196 patients with relapsed or refractory multiple myeloma, of whom 97 (median age, 65 years; interquartile range [IQR], 60-70) were randomly assigned to 2.5 mg/kg belantamab mafodotin (GSK2857916, GlaxoSmithKline) and 99 (median age, 67 years; IQR, 61-72) to a 3.4 mg/kg dose. Patients received the regimens via IV infusion every 3 weeks on day 1 of each cycle until disease progression or unacceptable toxicity.
The trial participants had a median seven prior lines of treatment, were refractory to an immunomodulatory drug and a proteasome inhibitor and were refractory and/or intolerant to an anti-CD38 antibody.
The proportion of patients who achieved overall response per independent committee review served as the study’s primary endpoint. Researchers also evaluated safety among patients who received at least one dose of belantamab mafodotin.
Results showed an overall response rate of 31% (95% CI, 20.8-42.6) in the 2.5 mg/kg group compared with 34% (95% CI, 23.9-46) in the 3.4 mg/kg group. These included very good partial responses or better among 19% (n = 18) of patients in the lower-dose group vs. 20% (n = 20) of patients in the higher-dose group. Clinical benefit, defined as minimal response or better as assessed by independent committee review, had been achieved by 34% (95% CI, 24.7-44.3) of patients in the 2.5 mg/kg group and 39% (95% CI, 29.7-49.7) of those in the 3.4 mg/kg group.
Median duration of response had not been reached at median follow-up of 6.3 months (IQR, 3.7-7.7) in the 2.5 mg/kg group and 6.9 months (IQR, 4.8-7.9) in the 3.4 mg/kg group. At data cutoff on June 21, 2019, researchers observed responses of 4 months or longer among 18 patients in the 2.5 mg/kg group and 25 patients in the 3.4 mg/kg group.
OS and PFS data remained immature. However, 32 deaths occurred in the 2.5 mg/kg group vs. 31 deaths in the 3.4 mg/kg group, with median PFS of 2.9 months (95% CI, 2.1-3.7) vs. 4.9 months (95% CI, 2.3-6.2).
Common grade 3 or grade 4 adverse events among the 95 safety-evaluable patients in the 2.5 mg/kg group and the 99 patients in the 3.4 mg/kg group included keratopathy (27% vs. 21%), thrombocytopenia (20% vs. 33%) and anemia (20% vs. 25%). Forty percent of patients in the 2.5 mg/kg safety population experienced serious adverse events vs. 47% of patients in the 3.4 mg/kg group. Two deaths appeared treatment-related, including one case of sepsis in the 2.5 mg/kg group and one case of hemophagocytic lymphohistiocytosis in the 3.4 mg/kg group.
“There may now be an option that can control disease among a group of [patients with] refractory multiple myeloma,” Lonial told Healio. “There are many treatments currently in development targeting BCMA, but this is one that will hopefully be available very soon. There is ongoing research combining this agent with other commonly used myeloma drugs, as well as other immune-based treatments. Future work will evaluate how best to combine this as part of an earlier treatment strategy, and how to reduce side effects that were noted in this phase 2 trial.” – by Jennifer Southall
For more information:
Sagar Lonial, MD, can be reached at Winship Cancer Institute of Emory University, 1365 Clifton Road, Building C, Room 3000, Atlanta, GA 30322; email: sloni01@emory.edu.
Disclosures: GlaxoSmithKline funded the study. Lonial reports consultant/advisory roles with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis and Takeda, and research funding from Bristol-Myers Squibb, Celgene and Takeda. Please see the study for all other authors’ relevant financial disclosures.