BTK Bruton Tyrosine Kinase Inhibitors

By Isabella Martire, MD, Board Certified In Oncology

Isabella C. Martire, MD, AC

. https://www.isabellamartire-md.com/

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BTK Bruton Tyrosine Kinase Inhibitors

Over the last five years there has been the development and FDA approval of a class of drugs called BTK, or Bruton's Tyrosine Kinase inhibitors, effective in B cell malignancies (chronic lymphocytic leukemia/mantle cell lymphoma/plasmacytoid lymphoma/marginal zone lymphoma/small lymphocytic lymphoma).

Imbruvica (ibrutinib) was the first BTK inhibitor FDA approved. It is an oral drug given once daily. Imbruvica inhibits BTK in the malignant B cells causing inhibition of proliferation and death, inhibits adhesion and chemotaxis.

BTK is present also in normal B cells therefore blocking this protein can cause side effects. The most common side effects are diarrhea, fatigue, fever, achiness and rash. The most dangerous side effect is bleeding which can occur in up to 6% of patients and can be intracranial, or gastrointestinal more commonly in patients on blood thinners.

Infections can occur in up to 30% of patients. Atrial fibrillation occurs in up to 6% of patients. Blood pressure needs to be monitored. Monthly blood counts are recommended as well since cytopenia may occur (leukopenia, anemia thrombocytopenia) in up to 30% of patients.

In general, Imbruvica is well tolerated even in elderly patients. The response rate of Imbruvica is approximately 80% with a 4% complete response, compared to 35% with chlorambucil.

Acalabrutinib is a second-generation BTK inhibitor. It is an irreversible inhibitor more potent and selective than Ibrutinib. It does not inhibit ITK, EGFR, ERBB2, ERBB4, JAK3, BLK, FGR, FYN, HCK, LCK, LYN, SRC, and YES1 therefore has fewer side effects compared to Ibrutinib.

Thrombus formation associated with Ibrutinib was not seen with Acalabrutinib. Also, atrial fibrillation was rarely seen with Acalabrutinib compared with Ibrutinib. The most common side effects are diarrhea, headache and weight gain. Bleeding risk is much less common than with Ibrutinib. Acalabrutinib is also an oral drug given every 12-24 hours with a response rate exceeding 90% and 100% response rate in patients with 17P13.1 deletion which is usually refractory to therapies. Acalabrutinib was FDA approved in February of 2016. Additional BTK inhibitors are currently under investigation.