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Counseling on BTKis
The Nurse’s Role in Counseling Patients Starting BTK Inhibitors

Released: July 15, 2021

Expiration: July 14, 2022

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As a nurse practitioner, I regularly counsel patients who are just starting Bruton tyrosine kinase (BTK) inhibitors for B-cell malignancies. Below, I highlight key safety and adherence considerations for nurses and other healthcare professionals to discuss with patients initiating BTK inhibitors.

Counseling and Monitoring for Adverse Events

Three BTK inhibitors are currently FDA approved in multiple settings for B-cell malignancies: ibrutinib, acalabrutinib, and zanubrutinib.

  • Ibrutinib: This oral, potent, irreversible BTK inhibitor has been well studied and approved for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and Waldenström macroglobulinemia (WM), along with chronic graft-vs-host disease. Ibrutinib is dosed at 420 mg PO daily for CLL and WM and 560 mg PO daily for MCL and MZL. Its well-established safety profile makes this agent an attractive option for patients with newly diagnosed and relapsed CLL/SLL, especially those with 17p deletion. Special considerations for those receiving ibrutinib include an increased risk of bleeding, infection, hypertension, and atrial fibrillation.
  • Acalabrutinib: This agent is highly selective for BTK, leading to a different safety profile than that of ibrutinib. Acalabrutinib is currently approved for CLL/SLL and MCL and has a dosing schedule of 100 mg PO every 12 hours rather than once daily like ibrutinib. Headaches are more common with this agent compared with ibrutinib and zanubrutinib, but they tend to be mild and are best managed with acetaminophen and caffeine. Remind your patients to avoid nonsteroidal anti-inflammatory drugs for these headaches because of a higher risk of bleeding with the BTK inhibitor class.
  • Zanubrutinib: The newest of the approved BTK inhibitors is indicated for once or twice daily dosing at 320 mg and 160 mg, respectively, for patients with MCL. Although the mechanism of action are similar to ibrutinib and acalabrutinib, zanubrutinib has greater selectivity for BTK and consequently a different safety profile. Rashes are more common with this agent and can range from mild to severe. Patients with new rashes should report immediately to their healthcare professional for evaluation. If the rash is mild and itchy, topical antihistamines and corticosteroids might help. More severe rashes may require oral antihistamines or corticosteroids along with dose interruption or reduction.

Other common adverse events across the BTK inhibitor class include gastrointestinal and musculoskeletal events, rash, fatigue, headache, and an increased risk of bleeding and infections (Table). Lymphocytosis and cytopenias of varying degrees can occur. Therefore, patients should be monitored regularly for these hematologic toxicities with blood counts and for other adverse events when starting BTK inhibitors.

Table. Key Adverse Events of Available BTK inhibitors

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Because there is an increased risk of bleeding and infections with BTK inhibitors, concurrent antiplatelet and anticoagulant therapy should be avoided, if possible. Nurses should inform patients to monitor for signs and symptoms of bleeding (eg, easy bruising) and advise them to report signs of bleeding immediately. Patients should also monitor for and report signs and symptoms of infection such as fever, cough, and increased fatigue.

Serious cardiovascular adverse events, such as atrial fibrillation and hypertension, can also occur with BTK inhibitors. Nurses should perform a risk assessment for atrial fibrillation and hypertension and encourage patients to monitor for shortness of breath or edema. Nurses should also counsel patients on how to optimize modifiable risk factors such as obesity, smoking, and excessive alcohol use.

A final but important safety consideration is the risk of drug–drug or drug–food interactions. BTK inhibitors are metabolized through cytochrome P450 3A, and certain foods that also interact with this pathway (of note, grapefruit juice and Seville oranges) should be avoided as they can increase the risk of toxicity. In addition, before starting any over-the-counter or prescription drugs, patients and/or caregivers should notify their oncology professional in case the new drugs may require modifying the BTK inhibitor dose.

Counseling on Adherence
Adherence to therapy is one of the most challenging topics to discuss with patients and their caregivers, especially as individuals are often prescribed additional drugs to treat other conditions. Strategies that lead to improved adherence include reinforcing the importance of taking the medication at the same time every day, along with educating on the risks of relapse or suboptimal response if BTK inhibitors are not taken as prescribed. I recommend that patients maintain a drug diary or journal so they can record when they take their medication, monitor for adverse events, and be reminded of serious concerns to notify their healthcare professionals.

Final Thoughts
BTK inhibitors are highly effective and generally safe agents for treating multiple B-cell malignancies. Patient and caregiver education is critical to patient success. By educating patients on the adverse events to expect, symptoms to report, and the importance of adherence, patients can be effectively monitored and treated for better outcomes.

To view individualized recommendations from 5 experts on managing BTK inhibitor–related adverse events, please visit CCO’s Interactive Tool for Managing BTK Inhibitor–Related AEs in Hematologic Malignancies.

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Which of the following is the most common concern among your patients starting BTK inhibitor therapy?
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