Exploring BTK Inhibitors in Classic HCL and HCL Variants
During our April HCL variant community roundtable, there was an engaging discussion about the role of BTK inhibitors in hairy cell leukemia (HCL) treatment.
What are BTK inhibitors?
BTK stands for Bruton's tyrosine kinase, a crucial B-cell receptor signaling pathway enzyme. B-cells, vital to our immune defense, depend on this pathway to function correctly. When the pathway malfunctions, it can lead to rapid B-cell reproduction and potentially cancer. BTK inhibitors bind to the BTK enzyme, disrupting signals that trigger cell reproduction, leading to cell death instead.
Ibrutinib, the pioneering BTK inhibitor, has shown promising results in treating diseases such as chronic lymphocytic leukemia (CLL). However, it's not yet FDA-approved for hairy cell leukemia (HCL). Nonetheless, ibrutinib trials involving HCL patients have reported positive outcomes. Several attendees shared their positive personal experiences with Ibrutinib during our recent roundtable.
What research in HCL has used BTK inhibitors?
In 2021, the Hairy Cell Leukemia Foundation held a webinar where Dr. Kerry Rogers of the Ohio State University extensively discussed her research on ibrutinib's effectiveness in classic HCL and HCL variants and presented data from a first-of-its-kind study.
In this study, Dr. Rogers found that ibrutinib has "substantial therapeutic benefit with durable disease control in patients with HCL that have [relapsed/refractory] disease." She noted that although the initial primary outcome objective of the study was not met (or the percentage of people in a study or treatment group who have a partial response or complete response to the treatment within a particular set of time), the long duration of disease control she saw with ibrutinib in her patients is important. Particularly notable are the positive results for patients with HCL variants, as these patients have fewer treatment options.
The presentation slides and a detailed webinar transcript are available for those interested. Click here. >>
Dr. Rogers' published study can be read here. >>
What about other BTK inhibitors?
Acalabrutinib, a second-generation BTK inhibitor, is FDA-approved for treating mantle cell lymphoma (MCL) and CLL. However, it still needs to be approved for HCL. Acalabrutinib stands out for its reduced side effects and quicker absorption than ibrutinib. Zanubrutinib, another newer BTK inhibitor, also exhibits fewer adverse effects than ibrutinib, particularly in reducing instances of atrial fibrillation and hypertension. This data has been corroborated anecdotally by patients who shared positive experiences with the drug during our April HCL variant roundtable.
Tirabrutinib and orelabrutinib are BTK inhibitors approved in some countries outside the U.S. for CLL. Still, they have yet to be extensively used or studied within the U.S. Furthermore, numerous BTK inhibitors are currently undergoing clinical trials targeting various diseases, highlighting the ongoing expansion of this drug class in therapeutic applications.
Looking forward to ongoing community roundtables
HCLF community roundtables have allowed our community to understand developments and topics in HCL and share valuable information on their experiences with HCL.
Our next community roundtable, set for May 16th, will focus on how family members can support their loved ones with HCL. In June, we will also have a women's group roundtable and another HCL variant roundtable.