Ibrutinib plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia: Primary Analysis Results from the Minimal Residual Disease Cohort of the Randomized Phase II CAPTIVATE Study

William G. Wierda, John N. Allan, Tanya Siddiqi, Thomas J. Kipps, Stephen Opat, Alessandra Tedeschi, Xavier C. Badoux, Bryone J. Kuss, Sharon Jackson, Carol Moreno, Ryan M.D. Jacobs, John M. Pagel, Ian Flinn, Yvonne Pak, Cathy Zhou, Edith Szafer-Glusman, Joi Ninomoto, James P. Dean, Danelle F. James, Paolo GhiaConstantine S. Tam

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

PURPOSE CAPTIVATE (NCT02910583), a randomized phase II study, evaluates minimal residual disease (MRD)-guided treatment discontinuation following completion of first-line ibrutinib plus venetoclax treatment in patients with chronic lymphocytic leukemia (CLL). 

METHODS Previously untreated CLL patients age, 70 years received three cycles of ibrutinib and then 12 cycles of combined ibrutinib plus venetoclax. Patients in the MRD cohort who met the stringent random assignment criteria for confirmed undetectable MRD (Confirmed uMRD) were randomly assigned 1:1 to double-blind placebo or ibrutinib; patients without Confirmed uMRD (uMRD Not Confirmed) were randomly assigned 1:1 to open-label ibrutinib or ibrutinib plus venetoclax. Primary end point was 1-year disease-free survival (DFS) rate with placebo versus ibrutinib in the Confirmed uMRD population. Secondary end points included response rates, uMRD, and safety. 

RESULTS One hundred sixty-four patients initiated three cycles of ibrutinib lead-in. After 12 cycles of ibrutinib plus venetoclax, best uMRD response rates were 75% (peripheral blood) and 68% (bone marrow). Patients with Confirmed uMRD were randomly assigned to receive placebo (n 5 43) or ibrutinib (n 5 43); patients with uMRD Not Confirmed were randomly assigned to ibrutinib (n 5 31) or ibrutinib plus venetoclax (n 5 32). Median followup was 31.3 months. One-year DFS rate was not significantly different between placebo (95%) and ibrutinib (100%; arm difference: 4.7% [95% CI, –1.6 to 10.9]; P 5 .15) in the Confirmed uMRD population. After ibrutinib lead-in tumor debulking, 36 of 40 patients (90%) with high tumor lysis syndrome risk at baseline shifted to medium or low tumor lysis syndrome risk categories. Adverse events were most frequent during the first 6 months of ibrutinib plus venetoclax and generally decreased over time. 

CONCLUSION The 1-year DFS rate of 95% in placebo-randomly assigned patients with Confirmed uMRD suggests the potential for fixed-duration treatment with this all-oral, once-daily, chemotherapy-free regimen in first-line CLL.

Original languageEnglish
Pages (from-to)3853-3865
Number of pages13
JournalJournal of Clinical Oncology
Volume39
Issue number34
DOIs
Publication statusPublished - 1 Dec 2021

Keywords

  • Lymphocytic Leukemia
  • Ibrutinib
  • Venetoclax
  • Patient outcomes

Fingerprint

Dive into the research topics of 'Ibrutinib plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia: Primary Analysis Results from the Minimal Residual Disease Cohort of the Randomized Phase II CAPTIVATE Study'. Together they form a unique fingerprint.

Cite this