Phase II Study of Combination Obinutuzumab, Ibrutinib, and Venetoclax in Treatment-Naïve and Relapsed or Refractory Chronic Lymphocytic Leukemia

Kerry A. Rogers, Ying Huang, Amy S. Ruppert, Lynne V. Abruzzo, Barbara L. Andersen, Farrukh T. Awan, Seema A. Bhat, Allison Dean, Margaret Lucas, Christin Banks, Cara Grantier, Nyla A. Heerema, Gerard Lozanski, Kami J. Maddocks, Thomas R. Valentine, David M. Weiss, Jeffrey A. Jones, Jennifer A. Woyach, John C. Byrd

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

PURPOSE The development of highly effective targeted agents for chronic lymphocytic leukemia offers the potential for fixed-duration combinations that achieve deep remissions without cytotoxic chemotherapy. PATIENTS AND METHODS This phase II study tested a combination regimen of obinutuzumab, ibrutinib, and venetoclax for a total of 14 cycles in both patients with treatment-naïve (n 5 25) and relapsed or refractory (n 5 25) chronic lymphocytic leukemia to determine the response to therapy and safety. RESULTS The primary end point was the rate of complete remission with undetectable minimal residual disease by flow cytometry in both the blood and bone marrow 2 months after completion of treatment, which was 28% in both groups. The overall response rate at that time was 84% in treatment-naïve patients and 88% in relapsed or refractory patients. At that time, 67% of treatment-naïve patients and 50% of relapsed or refractory patients had undetectable minimal residual disease in both the blood and marrow. At a median follow-up of 24.2 months in treatment-naïve patients and 21.5 months in relapsed or refractory patients, the median progression-free and overall survival times were not yet reached, with only 1 patient experiencing progression and 1 death. Neutropenia and thrombocytopenia were the most frequent adverse events, followed by hypertension. Grade 3 or 4 neutropenia was experienced by 66% of patients, with more events in the relapsed or refractory cohort. There was only 1 episode of neutropenic fever. A favorable impact on both perceived and objective cognitive performance during treatment was observed. CONCLUSION The combination regimen of obinutuzumab, ibrutinib, and venetoclax offers time-limited treatment that results in deep remissions and is now being studied in phase III cooperative group trials.

Original languageEnglish (US)
Pages (from-to)3626-3637
Number of pages12
JournalJournal of Clinical Oncology
Volume38
Issue number31
DOIs
StatePublished - Nov 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Phase II Study of Combination Obinutuzumab, Ibrutinib, and Venetoclax in Treatment-Naïve and Relapsed or Refractory Chronic Lymphocytic Leukemia'. Together they form a unique fingerprint.

Cite this