Identifying the Optimal Doses of Ibrutinib and Venetoclax in Resistant Mantle Cell Lymphoma

By: Kayci Reyer
Posted: Tuesday, June 21, 2022

Optimal doses of the combination therapy of the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib and the BCL2 inhibitor venetoclax may have been identified for patients with relapsed or refractory mantle cell lymphoma, according to research presented in Blood Advances. In previous studies, the addition of venetoclax to ibrutinib treatment has resulted in improved efficacy in this patient population. “Our approach was novel in finding the optimal dose instead of the maximum tolerated dose, utilizing a [cross-reacting material] to allocate participants based on prior participants’ efficacy and toxicity,” noted Craig A. Portell, MD, of the University of Virginia, and colleagues.

Between August 2015 and May 2019, the study enrolled and treated 35 patients who had not previously undergone BTK inhibitor therapy. A total of six dose combinations were tested: daily oral ibrutinib at 280 mg, 420 mg, or 560 mg, plus daily oral venetoclax at a maximum dose of either 200 mg or 400 mg. A dose combination of 200 mg of venetoclax and 420 mg of ibrutinib was found to be optimal, with an overall response rate of 93.8% and a dose-limiting toxicity incidence rate of 6.2%. Higher doses did not appear to correlate with improved overall response rate but were associated with increased toxicity.

Initially, patients received 100 mg of daily venetoclax for 1 week prior to beginning ibrutinib therapy. However, a clinically significant episode of tumor-lysis syndrome occurred early in the study, prompting a change in venetoclax administration to 20 mg for 2 days, 50 mg for 5 days, and 100 mg for 7 days prior to initiating ibrutinib therapy. Overall, 25 patients (71.4%) completed all six cycles of treatment, 7 (17.1%) experienced disease progression or relapse during therapy, and 3 (8.6%) experienced an adverse event that led to treatment discontinuation.

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

Blood Advances

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