Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules (“molecular targets”) involved in cancer growth. Targeted agents for treating chronic lymphocytic leukemia (CLL) have been available for several years now. Ibrutinib, a BTK inhibitor, was approved for the treatment of CLL in 2014, and venetoclax, a BCL2 inhibitor, was approved in 2016. Early data from lab studies suggested that ibrutinib and venetoclax might actually work synergistically together through different mechanisms of action to kill CLL cells.
At the annual meeting of the European Hematology Association (EHA) 2021, our own Dr. Brian Koffman interviewed Dr. Matthew Davids, Associate Director of the Center for Chronic Lymphocytic Leukemia (CLL) at Dana-Farber Cancer Institute in Boston, MA. They discussed new data from a phase 3 clinical trial testing fixed-duration ibrutinib + venetoclax vs. chlorambucil + obinutuzumab for treating CLL.
Takeaways:
- Early phase clinical trials have shown that the combination ibrutinib + venetoclax is safe and effective for treating CLL.
- Phase 3 trials are needed to allow researchers to compare the efficacy of new regimens to existing standards of care.
- The GLOW trial is a Phase 3 clinical trial comparing fixed-duration ibrutinib + venetoclax (15 months) with chlorambucil + obinutuzumab (6 months) in over 200 patients.
- An early look at the data (after about 2 years) showed that most patients receiving ibrutinib + venetoclax were doing well (no recurrence or progression), and about half had achieved undetectable measurable residual disease (uMRD).
- The results thus far indicate that patients treated with combination ibrutinib + venetoclax have longer progression-free survival than patients treated with chlorambucil + obinutuzumab.
- Researchers also observed some of the side effects typical of ibrutinib such as atrial fibrillation, high blood pressure, and infections.
- Because this is a combination therapy, patients do tend to experience more side effects, which may be difficult to tolerate for older patients with other medical conditions.
- Another clinical trial looking at combination ibrutinib + venetoclax is the Phase 2 CAPTIVATE study.
- One arm receives fixed-duration ibrutinib + venetoclax similar to the GLOW study.
- The other arm is MRD-guided treatment with ibrutinib + venetoclax, where treatment duration is guided by how long it takes to achieve MRD.
Conclusions:
Combination therapies such as ibrutinib + venetoclax are very promising, but they may also be more difficult to tolerate for some patients due to the increased number of side effects. Some unanswered questions remain, including how combination ibrutinib + venetoclax compares to treatment with just ibrutinib or venetoclax + obinituzumab. Researchers are working hard to figure out what therapies should be used and in what order to best help patients with CLL.
Please enjoy this interview with Dr. Davids from June 2021 at the EHA virtual conference.
You can read the actual abstract here: Fixed-duration ibrutinib and venetoclax versus chlorambucil plus obinutuzumab for first-line chronic lymphocytic leukemia: Primary analysis of the phase 3 GLOW study
Take care of yourself first.
Ann Liu, PhD
