Inhibition of Bruton tyrosine kinase in patients with severe COVID-19
At the 2017 ASH Annual Meeting held in Atlanta, GA, I spoke with Dr. Richard Furman from Weill Cornell Medical College regarding a novel drug currently in clinical trials for the treatment of CLL in patients who have relapsed following first-line treatment.
Acalabrutinib is approved by the FDA to treat mantle cell lymphoma, but is not yet approved in chronic lymphocytic leukemia.
Take Away Points:
- Similar to ibrutinib, acalabrutinib is a novel Bruton Tyrosine Kinase (BTK) inhibitor that functions to reduce B-cell activity and survival by blocking the B cell receptor (BCR) that drives the chronic lymphocytic leukemia cells to stay alive and grow.
- Compared to ibrutinib, acalabrutinib is more highly specific for BTK. It interacts less with other kinases (enzymes), therefore potentially reducing adverse events.
- It is generally well tolerated with common adverse events including headache, diarrhea, weight gain, fever, and upper respiratory tract infections.
- More frequent headaches were one new side effect reported. These adverse events were typically mild and diminished over time.
- Hemorrhage and atrial fibrillation which can lead to treatment discontinuation with ibrutinib were rarely associated with acalabrutinib treatment.
A prior study published in NEJM reported that acalabrutinib was effective in patients with both low- and high-risk CLL. 95% of patients responded to treatment with acalabrutinib though there were no complete remission. Importantly, 100% of patients with del17p achieved a response.
Summary
Acalabrutinib is a novel BTK inhibitor currently being investigated for the treatment of patients with relapsed CLL. Early trial results indicated that nearly all patients respond to treatment and adverse events are mild and easily managed.
The potential advantages of a more specific BTK inhibitor are possibly fewer side effects and less drug to drug interactions. This could be increasingly important as combinations of novel agents are being researched.
The potential disadvantage of the more focused blocking of BTK is the possible loss of clinically relevant immune-modulating effects of ibrutinib.
For more on this topic, please see this interview with Dr. Mark Wildgust of Janssen from ASH 2016.
Dr. Byrd discusses the choice of BTK inhibitor in combination therapy for CLL in this one minute ONCLIVE video.
Here is my interview with Dr. Furman from last year at ASH 2016 to give some perspective on the progress of the research on acalabrutinib in CLL.
Additional clinical trials are needed and are currently underway to further elucidate the efficacy and safety of acalabrutinib for the treatment of CLL, but it is an exciting and positive development to have another treatment option in the pipeline.
You can watch my interview with Dr. Furman below: Here is the link to the ASH abstract.
Brian Koffman, MD 3-20-18
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