Spotlight on BTK Inhibitors in the Management of B-Cell Malignancies

PTCE would like to acknowledge Pharmacyclics LLC., an AbbVie Company and Janssen Biotech, Inc. for their generous support of pharmacist education.

Kirollos S. Hanna, PharmD, BCPS, BCOP, described the role of Bruton tyrosine kinase (BTK) inhibitors in the treatment of mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), Waldenstrӧm macroglobulinemia (WM), and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in a live 2020 Directions in Oncology Pharmacy^® conference session titled B-Cell Malignancies: Exploring the Influence of BTK Inhibitors and Pharmacist-Led Interventions on Patient Outcomes. These subtypes of lymphoma represent over 90,000 combined cases diagnosed annually in the United States.

Dr Hanna began the presentation with pharmacology basics to illustrate how BTK inhibitors work in B-cell malignancies, as well as differences between available agents, which include acalabrutinib, ibrutinib, and zanubrutinib. He explained the recommended place in therapy for BTK inhibitors in B-cell malignancies based on the National Comprehensive Cancer Network (NCCN) guidelines, noting that ibrutinib is first line for patients with CLL harboring a 17p deletion, in older patients without an immunoglobulin heavy chain (IGHV) mutation, or is an alternative to traditional chemotherapy with fludarabine, cyclophosphamide, and rituximab for patients with IGHV-mutated CLL. Both ibrutinib and acalabrutinib are category 1 recommendations in the NCCN guidelines for management of relapsed or refractory CLL. Acalabrutinib, ibrutinib with or without rituximab, and zanubrutinib are preferred options for patients with a short duration of response to initial therapy for MCL. Ibrutinib is used in second-line and subsequent therapy of MZL and is preferred for elderly or infirm patients. Lastly, clinical trial data with acalabrutinib, ibrutinib, and zanubrutinib in WM were reviewed, including a phase 3 comparison of ibrutinib with zanubrutinib.

The presentation also emphasized pharmacist involvement in optimizing therapy with BTK inhibitors. Similarities and differences among BTK inhibitors were highlighted, including key concepts in:

• Drug interactions
• Medication administration considerations
• Antimicrobial prophylaxis and infectious complications
• Adverse effect incidence and management

Essential information for pharmacists includes drug interactions with BTK inhibitors; all BTK inhibitors are substrates of CYP3A and are subject to drug interactions with both CYP3A inhibitors and inducers. There is no standard infection prophylaxis for patients receiving BTK inhibitors; however, “high-risk” patients may need antimicrobial prophylaxis for fungal and Pneumocystis jirovecii infections, and monitoring for Epstein-Barr virus, hepatitis B, and cytomegalovirus infections. Patients with atrial fibrillation and a CHA2DS2-VASc score greater than or equal to 2 should receive anticoagulation, as atrial fibrillation has been reported with the BTK inhibitors, although the preferred anticoagulant should be decided on a patient-specific basis based on risk factors and the BTK inhibitor prescribed. Dr Hanna wrapped up the session by highlighting pharmacist involvement with clinical services, such as ensuring medication adherence, patient counseling, comprehensive medication review, and monitoring for drug safety and efficacy. He also stressed the importance of operational best practices, including potential benefits investigation, patient assistance programs, and medication distribution, including refills, to optimize oral chemotherapy dispensing and management. A sample patient education checklist for patients receiving BTK inhibitors was included.