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Safety and Efficacy of Venetoclax in Combination with Atezolizumab and Obinutuzumab in Richter Transformation of CLL

Richter syndrome, the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), occurs in about 2% to 10% of patients with CLL.1 These patients typically have a poor prognosis. Venetoclax, a Bcl-2 inhibitor, has shown clinical activity in DLBCL and in DLBCL-type Richter syndrome. Atezolizumab is a humanized immunoglobulin monoclonal antibody that prevents interaction with the PD-1 receptor. Preliminary data of atezolizumab alone or in combination with the CD-20 monoclonal antibody obinutuzumab demonstrated safety and efficacy in heavily pretreated patients with DLBCL.

In this phase 2 trial, the combination of venetoclax, atezolizumab, and obinutuzumab was evaluated in Richter syndrome. Adult patients with Eastern Cooperative Oncology Group performance status 0 to 2 with a diagnosis of DLBCL Richter syndrome from CLL/small lymphocytic lymphoma were eligible to participate. Patients with pretreated Richter syndrome, prior therapy with venetoclax or atezolizumab, central nervous system involvement, and/or a history of autoimmune disease were excluded from the study.

Of the 28 patients enrolled in the study, 9 will be included in the safety run-in phase. In the expansion phase, treatment will include obinutuzumab dosed at 1000 mg for cycles 1 through 8, atezolizumab dosed at 1200 mg for cycles 1 through 18, and venetoclax dosed at 20 mg in Cycle 1, escalating to 50 mg on days 1 through 8, 100 mg on days 8 through 15, and 200 mg on days 15 through 21 of Cycle 2, then 400 mg for cycles 3 through 18.

The primary end point of the study is safety and tolerability for the run-in phase and efficacy for the expansion phase. Efficacy end points will include overall response, complete remission, response duration, progression-free survival, and overall survival. Researchers will also evaluate rates of minimal residual disease negativity. Researchers hypothesize that this combination regimen may provide improved outcomes in a difficult-to-treat patient population.

Abstract TPS7575; Montillo M, et al.


Reference

  1. Parikh SA, Kay NE, Shanafelt TD. How we treat Richter syndrome. Blood. 2014;123:1647-1657.
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Last modified: June 6, 2019
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