Zanubrutinib, Alone and in Combination With Tislelizumab, for the Treatment of Richter Transformation of Chronic Lymphocytic Leukemia

N ew therapies for Richter transformation (RT) of chronic lymphocytic leukemia (CLL) are necessary, as current treatments are ineffective for relapsed/ refractory disease and prognosis remains poor, particularly for those previously treated for CLL. 1–3 We report outcomes with the next-generation Bruton tyrosine kinase inhibitor zanubrutinib, alone or in combination with the programmed death-1 inhibitor tislelizumab, from 2 studies. BGB-3111-AU-003 (NCT02343120) was a 2-part, phase 1/2, open-label study of single-agent zanubrutinib conducted at 24 sites in 6 countries. Part 1 (dose escalation) determined the recommended phase 2 dose (RP2D); part 2 (expansion) evaluated zanubrutinib at the RP2D (160 mg twice daily) in histologic subtypes of B-cell malignancies, including patients with RT (transformation from CLL to diffuse large B-cell lymphoma per World Health Organization classification 4 ). All relevant ethics approvals were obtained. The trial was performed in accordance with the Declaration of Helsinki and guidelines for good clinical practice, and all patients provided written informed consent. The methods and results of the part 1 dose escalation have been described previously. 5 Thirteen patients with locally histologically confirmed RT were enrolled in part 2, with treatment continuing until unacceptable toxicity or disease progression. Median study follow-up was 27.4 months (range, 0.6– 33.8 mo) and median duration of zanubrutinib exposure was 18.7 months (range, 0.5–33.8