The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has been the standard of care for older patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) because it offers longer progression-free survival compared with chemoimmunotherapy. However, ibrutinib often has to be taken indefinitely because it does not produce complete responses (or disappearance of all signs of the cancer). In addition, this long-term exposure to ibrutinib can lead to undesirable side effects, especially in older patients, including abnormal heart rhythms and high blood pressure. Thus, researchers are looking for alternative treatment strategies to limit the amount of time patients need to be on ibrutinib.
At the annual meeting of the American Society of Hematology (ASH) 2021, Dr. Anthony Mato, Director of the CLL program at Memorial Sloan Kettering Cancer Center in New York, interviewed Dr. Jennifer Woyach, a hematologist-oncologist at the James Cancer Center of the Ohio State University in Columbus, OH. They discussed a phase 3 clinical trial in progress, investigating the efficacy of the triple combination of ibrutinib plus venetoclax and obinutuzumab with response-dependent discontinuation.
- This is a phase 3 clinical trial in progress, meaning that it is ongoing and has not yet reported any data.
- Because it is a phase 3 clinical trial, it is very large and is meant to be a definitive comparison of the efficacy of the two treatments.
- Eligible patients are 70+ years of age, diagnosed with CLL or SLL, and are receiving their first treatment.
- Patients will be randomly assigned to receive either:
- Ibrutinib + obinutuzumab (IO)
- Ibrutinib + venetoclax + obinutuzumab (IVO)
- After one year, both groups will undergo a response assessment.
- The IO group will continue to receive ibrutinib treatment indefinitely.
- If patients in the IVO group have reached undetectable measurable residual disease (uMRD), they will stop treatment. However, if they still have detectable disease, they will continue treatment with ibrutinib.
- The primary outcome is progression-free survival (or the length of time that a patient lives with the disease, but it does not get worse).
- It will likely be 3-5 years before they have data for the final comparison.
- This study is being led by the Alliance for Clinical Trials in Oncology, and it is enrolling patients at over 700 sites across the US. If you are interested in participating, more information can be found here.
Large phase 3 clinical trials like this one are vital for helping establish standards of care by directly comparing the efficacy of different treatment regimens. This one is exciting because researchers are looking at whether patients with good responses to treatment (i.e., reaching uMRD) can discontinue therapy and still have good progression-free survival. If successful, response-dependent discontinuation could significantly reduce the burden on patients who might otherwise be receiving continuous treatment. It will take a few years for the final results to come in, but we look forward to hearing much more in the future.
Please enjoy this interview with Dr. Woyach from the ASH meeting held in December 2021 in Atlanta, GA, and virtually.
A041702: A Randomized Phase III Study of Ibrutinib Plus Obinutuzumab Versus Ibrutinib Plus Venetoclax and Obinutuzumab in Untreated Older Patients (≥ 70 Years of Age) with Chronic Lymphocytic Leukemia (CLL)
Take care of yourself first.
Ann Liu, PhD