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ASCO 2023: Dr. Jennifer Woyach on Combination Ibrutinib, Venetoclax, and Obinutuzumab for Previously Untreated CLL

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

Reviewed by Dr. Brian Koffman

The Bottom Line:

In the setting of the COVID-19 pandemic, progression-free survival with ibrutinib combined with venetoclax and obinutuzumab given as a first-line treatment was not superior to ibrutinib combined with obinutuzumab in older patients with previously untreated CLL. Follow-up remains ongoing, and many patients in the ibrutinib + venetoclax + obinutuzumab arm achieved undetectable measurable residual disease (uMRD).

Who Performed the Research and Where Was it Presented:

Dr. Jennifer Woyach from the Ohio State University and colleagues presented the results at the 2023 American Society for Clinical Oncology (ASCO) Annual Meeting.


Treatment regimens that combine multiple targeted therapies are becoming more and more common in CLL / SLL treatment. Researchers hypothesize that combining drugs with different mechanisms of action will produce deeper remissions and better outcomes for patients. However, given that it is a relatively new area, it is vital to understand whether two drugs are better than one, or whether three drugs are better than two. This usually requires large phase 3 clinical trials where two active treatments are compared head-to-head against each other.

Dr. Brian Koffman interviewed Dr. Jennifer Woyach, Co-Director of the Leukemia Research Program at the James Cancer Center of the Ohio State University in Columbus, OH. They discussed interim results from a phase 3 clinical trial comparing ibrutinib + venetoclax + obinutuzumab (IVO) against ibrutinib + obinutuzumab (IO).

Methods and Participants:

This phase 3 clinical trial is comparing IO with IVO in previously untreated with CLL / SLL who are 70 years of age or older. The IO group receives ibrutinib indefinitely. Patients in the IVO group can stop treatment with ibrutinib if they reach uMRD. Venetoclax is given for one year. For both groups, response assessments are performed after one year.


  • Between January 2019 and July 2022, 465 patients were enrolled in the trial.
  • Large clinical trials usually perform scheduled interim data analyses to ensure that the treatments are not hurting patients (safety) and that the treatments are helping them (efficacy). This is important so that you don’t get to the end of a 5-year study and find out there was no benefit for the patients.
  • After a certain number of patients progressed, an interim analysis was performed.
  • The interim analysis (with approximately 14 months of follow-up data) showed that in no way could IVO provide better progression-free survival than IO.
  • So while IVO was not better than IO for progression-free survival, it still might have other benefits, such as a shorter duration of therapy.
  • Over 80% of patients in the IVO group had uMRD in the bone marrow, allowing them to discontinue therapy.
  • One of the complicating factors with this study was that it was conducted during the height of the COVID-19 pandemic, and a high proportion of patients (5%) died from COVID-19.
  • There were more deaths from COVID-19 in the IVO arm (n=19) than in the IO arm (n=11). We don’t know if this was because more immunosuppression resulted from three drugs versus two.
  • Rates of moderate/severe side effects and treatment discontinuation were similar in the two arms.
  • The study is ongoing, and long-term follow-up will continue.


In the setting of the COVID-19 pandemic, progression-free survival with first-line IVO treatment was not superior to IO for older patients with previously untreated CLL / SLL. Follow-up remains ongoing, and many patients in the IVO arm achieved uMRD. Valuable information is still to be mined from this trial. Still, at least this analysis during the COVID-19 pandemic reminds us why we need more clinical trials and must not automatically assume that three drugs are better than two.

Links and Resources:

Watch the interview on the abstract here:

ASCO 2023: Dr. Jennifer Woyach on the Combo Ibrutinib, Venetoclax, & Obinutuzumab for Untreated CLL

You can read the actual ASCO abstract here: Results of a phase 3 study of IVO vs. IO for previously untreated older patients (pts) with chronic lymphocytic leukemia (CLL) and impact of COVID-19 (Alliance)

Take care of yourself first.

Ann Liu, PhD