Reviewed by Dr. Brian Koffman
The Bottom Line:
In the setting of the COVID-19 pandemic, progression-free survival with first-line ibrutinib + venetoclax + obinutuzumab treatment was not superior to ibrutinib + obinutuzumab for older patients with previously untreated CLL. Follow-up remains ongoing, and many patients in the ibrutinib + venetoclax + obinutuzumab arm achieved undetectable measurable residual disease.
Who Performed the Research and Where Was it Presented:
Dr. Jennifer Woyach from the Ohio State University and colleagues presented the results at the American Society for Clinical Oncology (ASCO) Annual Meeting 2023.
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, similarly, 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 with ibrutinib + obinutuzumab.
Methods and Participants:
This phase 3 clinical trial compares ibrutinib + obinutuzumab (IO) with ibrutinib + venetoclax + obinutuzumab (IVO) in previously untreated older patients with CLL. Patients were to be 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 undetectable measurable residual disease (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) showed no way IVO could 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 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 resulted from more immunosuppression from three drugs versus two.
- Rates of moderate/severe side effects and treatment discontinuations were similar in the two arms.
- Study treatment 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. 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 pandemic reminds us why we need trials and must not automatically assume that three drugs are better than two.
Links and Resources:
Watch the interview on the abstract here:
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