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Venetoclax and Obinutuzumab Induces Deep Responses in CLL

Key clinical point: Venetoclax-obinutuzumab provided high response rates and deep remissions in patients with chronic lymphocytic leukemia.

Major finding: Undetectable minimal residual disease was seen in 64% of relapsed/refractory patients and 91% of previously untreated patients.

Study details: A phase 1b, dose-escalation study that enrolled 32 patients with chronic lymphocytic leukemia who were previously untreated and 46 patients with relapsed/refractory disease.

Disclosures: Genentech and AbbVie provided financial support for the study. Dr. Flinn reported receiving research funding for his institution from Genentech, AbbVie, and several other companies.

Citation:

Flinn IW et al. Blood. 2019 Mar 12. doi: 10.1182/blood-2019-01-896290.

Commentary:

Dr. David Henry, Editor in Chief of MDedge Hematology/Oncology, comments:

In a phase IB study of venetoclax-obinutuzumab, Ian W. Flinn, MD, PhD, and his colleagues report results in a previously untreated and/or relapsed refractory patient group of chronic lymphocytic leukemia (CLL) patients. The current study enrolled 32 patients previously untreated and 46 patients relapsed refractory, with a mean age of 61 to 63 years old. In standard fashion, venetoclax was escalated from 100 mg to 400 mg to determine maximum tolerated dose and combined with obinutuzumab.

Interestingly, some patients received venetoclax first while others received obinutuzumab first for a total of 1 year of treatment. Best results were for those patients receiving venetoclax at a dose of 400 mg with the standard dose of obinutuzumab.

Incredibly, there was a 95% response rate in relapsed/refractory CLL patients, with 37% reporting complete response. In untreated patients, the overall best response rate was 100%, with 78% reporting complete remission.

Undetectable minimal residual disease (MRD) was observed in 64% of relapsed/refractory patients and 91% of previously untreated patients.

Grade 3-4 neutropenia was the most significant adverse event while grade 3-4 infections were seen in 29% and 13% of the relapsed/refractory and previously untreated patients, respectively.

While this is a phase IB study and phase 3 comparative trials are underway, this article might better be entitled “move over FCR” as the response rates - partial and complete - were quite impressive and the toxicity rates were quite low with this regimen, which is rather easy to handle in the outpatient setting.