As we have learned more about the biology of chronic lymphocytic leukemia (CLL), scientists have been able to design highly effective targeted therapies. Targeted includes ibrutinib, a BTK inhibitor, and venetoclax, a BCL2 inhibitor. Because these drugs work through different mechanisms of action, scientists wanted to know if they might work synergistically to treat CLL.
At the annual meeting of the American Society of Hematology (ASH) 2019, our own Dr. Brian Koffman interviewed Dr. Nitin Jain, an Associate Professor in the Department of Leukemia at MD Anderson Cancer Center, about recent results from a clinical trial testing the combination of ibrutinib and venetoclax.
These are new results from a phase II clinical trial of the combination ibrutinib and venetoclax in 80 patients who were newly diagnosed with CLL and had not received any previous treatments.
Takeaways:
- To prevent tumor lysis syndrome, a potentially life-threatening condition caused by the rapid breakdown of cancer cells, patients were first treated with ibrutinib for three months to reduce the number of cancer cells before adding venetoclax.
- Patients continued on combination therapy for two years (24 cycles), and researchers looked at how many patients had undetectable minimal residual disease (less than 1 CLL cell per 10,000 lymphocytes in the bone marrow).
- After one year of treatment, 65% of patients had remission with undetectable minimal residual disease in the bone marrow.
- After two years of treatment, 79% of patients had remission with undetectable minimal residual disease in the bone marrow.
- The results are very similar to those seen in another multi-center clinical trial of ibrutinib and venetoclax (CAPTIVATE study), where 73% of patients had undetectable minimal residual disease after one year of treatment.
- Common toxicity was low neutrophil counts, neutropenia, which occurred in approximately 50% of patients and increased the risk of infection. The risk of disease was expected since low neutrophil counts are a known side effect of both ibrutinib and venetoclax.
- Doctors thinking about using this combination should be aware that low neutrophil counts are a side effect and that it can be easily managed by reducing the dose of the drugs or using growth factors that stimulate the bone marrow to make more neutrophils.
Conclusions:
These are exciting results for the use of combination ibrutinib and venetoclax as a first-line treatment for CLL. Both drugs are taken orally, and no chemotherapy is required. However, the combination still needs to be tested in more extensive phase III clinical trials and reviewed by the FDA, so it hasn’t been approved for use just yet.
Please enjoy this interview with Dr. Jain from December 2019 at ASH in Orlando, FL.
You can read the actual ASH abstract here: Combined Ibrutinib and Venetoclax for First-Line Treatment of Patients with Chronic Lymphocytic Leukemia (CLL)
You can also read the full results of the phase II clinical trial here: Ibrutinib and Venetoclax for First-Line Treatment of CLL.
Take care of yourself first.
Ann Liu, PhD
