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Early-Phase Study of Combination BTK and PI3K Inhibition as B-Cell Lymphoma Therapy

By: Vanessa A. Carter, BS
Posted: Tuesday, February 1, 2022

Results of a phase I/Ib trial performed by Connie Lee Batlevi, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues suggest that BTK and PI3K inhibition demonstrates promising efficacy in the treatment of B-cell lymphoma. This study, which evaluated the safety and efficacy of the BTK inhibitor ibrutinib combined with the pan-PI3K inhibitor buparlisib in patients with relapsed or refractory B-cell lymphoma, was published in Clinical Cancer Research.

This trial enrolled 37 adults with histologically confirmed mantle cell lymphoma (n = 18), diffuse large B-cell lymphoma (DLBCL; n = 14), or follicular lymphoma (n = 5) who received at least one prior therapy and received, declined, or were ineligible for stem cell transplantation. Participants were administered oral buparlisib and ibrutinib once daily in 28 cycles, until unacceptable toxicity or disease progression.

Participants with mantle cell lymphoma had a 94% overall response rate and a median progression-free survival of 33 months. Individuals with DLBCL and follicular lymphoma had overall response rates of 31% and 20%, respectively, with a median progression-free survival of 3.7 and 1.6 months, respectively. Additionally, event-free survival was much higher among patients with mantle cell lymphoma (8.9 months) than in those with follicular lymphoma (3.7 months) or DLBCL (1.6 months).

Of note, results from serial monitoring of cell-free DNA samples correlated with radiographic resolution of disease, effectively tracking the development of mutations associated with BTK inhibitor resistance.

The maximum tolerated dose was 100 mg of buparlisib plus 560 mg of ibrutinib. Adverse events were reported in all patients except one, who experienced early disease progression and completed fewer than 14 days of treatment. The most common grade 3 adverse events were dermatitis/rash/pruritus (19%), hypertension (11%), diarrhea (11%), and hyperglycemia (11%). Mood disturbances of all grades such as anxiety, depression, and agitation were reported in 22% of individuals.

Disclosure: For full disclosures of the study authors, visit clincancerres.aacrjournals.org.


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