A combination of 3 pathway inhibitors is well tolerated with activity observed in heavily pre-treated and high-risk B-cell malignancies, according to research that will be presented at the ASCO Annual Meeting (June 2-6, 2017; Chicago, IL).
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Targeting agents are overwhelmingly involved in B-cell malignancy treatment advancements. However, limited data exists regarding the combination of targeting agents in such malignancies.
Loretta J Nastoupil, MD, MD Anderson Cancer Center, University of Texas, and colleagues conducted a trial to evaluate the efficacy of a triple combination in treating B-cell malignancies. Researchers used ublituximab, a CD20 inhibitor; TGR-1202, a PI3Kδ inhibitor; and ibrutinib, a BTK inhibitor. A total of 38 patients were enrolled in the study, 20 of whom had chronic lymphocytic leukemia and 18 of whom has non-Hodgkin lymphoma, including follicular lymphoma (n = 6), diffuse large B-cell lymphoma (n = 6), mantle cell lymphoma (n = 4), and marginal zone lymphoma (n = 2).
Eligible patients had no limit to prior therapies, including those treated with prior TGR-1202 or ibrutinib.
Ublituximab was dosed continuously through 12 cycles, while TGR-1202 (dose escalated from 400mg to 800 mg) and ibrutinib (420 mg-560 mg) were dosed on the first day of the first cycle.
Median follow-up time was 10 months (range, 1-27 months).
Results of the triple combination therapy showed favorable overall response rates in chronic lymphocytic leukemia (100%), follicular lymphoma (86%), mantle cell lymphoma (100%), and marginal zone lymphoma (86%). Only those patients with diffuse large B-cell lymphoma did not respond well to the treatment (overall response rate, 17%).
Authors concluded that their study is the first known triple combination of ublituximab, TGR-1202, and ibrutinib to be well tolerated with observable activity in heavily pre-treated and high-risk B-cell malignancies. Further trials are needed to confirm the effectiveness of the triple combination, including a study that examines larger cohorts at the highest dosage (800 mg TGR-1202 plus full dose ibrutinib) which is already underway.—Zachary Bessette
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