Transforming the Treatment Paradigm in B-Cell Malignancies: Pharmacist Insights into BTK Inhibitors

Transforming the Treatment Paradigm in B-Cell Malignancies: Pharmacist Insights into BTK Inhibitors

This CPE activity is based on the slides and lectures presented by the faculty at an independent satellite symposium during the Hematology/Oncology Pharmacy Association’s 15th Annual Conference on Friday, April 5, 2019, at the Fort Worth Convention Center in Fort Worth, Texas.

Release Date

June 17, 2019

Expiration Date

June 17, 2020

FACULTY

John N. Allan, MD
Assistant Professor of Medicine
Division of Hematology and Medical Oncology
Weill Cornell Medical College
New York, New York

Megan Dillaman, PharmD, BCOP
Pharmacy Clinical Specialist–Stem Cell Transplant and Hematologic Malignancy
West Virginia University Medicine
Morgantown, West Virginia

Shilpa Paul, PharmD, BCOP
Clinical Pharmacy Specialist–Leukemia
The University of Texas MD Anderson Cancer Center
Houston, Texas

Needs Statement

B-cell non-Hodgkin lymphoma (NHL), the most common type of hematologic malignancy, is comprised of a heterogenous disease spectrum that includes mantle cell lymphoma (MCL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone lymphoma (MZL), Waldenstrom’s macroglobulinemia (WM), and hairy cell leukemia (HCL), among others.1,2 The emergence of pharmacologic agents that target enzymes in the B-cell receptor (BCR) pathway is transforming the established treatment calculus across the NHL spectrum.

One such class of agents binds and inhibits Bruton tyrosine kinase (BTK), an enzyme crucial for cell survival and proliferation.3 Ibrutinib, the first-in-class agent, has garnered approvals in MCL, CLL/SLL, WM, and MZL, as well as chronic graft vs host disease (cGVHD).3 However, despite boasting robust efficacy outcomes and prompting dramatic advances in the treatment of B-cell malignancies, ibrutinib’s safety profile is tarnished by its off-target activity, leading to such adverse events as atrial fibrillation, bleeding, skin toxicities, and infections. These safety concerns have provided impetus for the development of second-generation BTK inhibitors, such as acalabrutinib, which exhibit greater BTK selectivity, fewer off-target effects, and resultantly, enhanced safety profiles.4,5 Acalabrutinib has thus far been approved for relapsed/refractory MCL, and studies are ongoing in diffuse large B-cell lymphoma (DLBCL), CLL/SLL, WM, and follicular lymphoma (FL).3 Though BTK inhibitors have substantially broadened treatment horizons and enhanced patient flexibility with oral dosing, their novelty poses a number of important challenges for clinicians. Oncology pharmacists have extensive knowledge regarding the pharmacodynamic, pharmacokinetic, and financial aspects of oral chemotherapy, and are thus optimally positioned to facilitate implementation of oral cancer therapy protocols at their institutions.

Participants in this activity will examine how BTK inhibitors are renewing the treatment paradigm in B-cell cancers, with particular emphasis on the dynamic role of the BCR pathway, the safety and efficacy profiles of first- and second-generation BTK inhibitors, and the emerging problem of resistance mechanisms. Using a case-based approach, expert faculty will address challenging clinical questions and explore strategies oncology pharmacists can employ to improve patient adherence, minimize adverse events, and optimize outcomes for patients taking BTK inhibitors.

1Siegel RL, et al. CA Cancer J Clin. 2016; 2Swerdlow SH, et al. Blood. 2016; 3FDA Prescribing Information: Acalabrutinib, October 2017, and Ibrutinib, January 2019; 4Wu H, et al. Oncotarget. 2015; 5Barf T, et al. J Pharmacol Exp Ther. 2017.

Target Audience

This activity is designed to meet the educational needs of pharmacists with an interest in hematology/oncology, oncology pharmacists, pharmacy directors, and pharmacy residents.

Objectives

At the conclusion of this enduring activity, participants will be able to:

  1. Describe the role of the B-cell receptor (BCR) pathway in the development of B-cell malignancies and identify enzymes downstream of the BCR that can serve as therapeutic targets.
  2. Examine the safety and efficacy profiles of first- and second-generation BTK inhibitors as single agents and in combination with other anti-neoplastic therapies for patients with B-cell malignancies (e.g., CLL/SLL, MCL, WM, MZL, etc.).
  3. Explore resistance mechanisms that occur with BTK inhibitor therapy and discuss strategies to prevent or mitigate its occurrence.
  4. Using a case-based approach, assess challenging questions regarding BTK inhibitors and discuss the ways that pharmacists can optimize therapy, anticipate adverse effects, and improve adherence alongside other members of the oncology healthcare team.

Accreditation

CPE
In support of improving patient care, Creative Educational Concepts is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

This application-based activity is approved for 1.0 contact hours (0.10 CEUs) of continuing pharmacy education credit (UAN JA0007101-0000-19-010-H01-P).

Other

Creative Educational Concepts, Inc. certifies this activity for 1.0 hours of participation.

Faculty Disclosure

Planner and Faculty Disclosures

In accordance with the Food and Drug Administration, the speakers have disclosed that there is the potential for discussions concerning off-label uses of a commercial product/device during this educational activity.

Any person who may contribute to the content of this continuing education activity must disclose relevant relationships (and any known relationships of their spouse/partner) with commercial interests whose products or services are discussed in educational presentations. A commercial interest is defined as any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. Relevant relationships include receiving from a commercial interest research grants, consultant fees, travel, other benefits, or having a self-managed equity interest in a company.

Disclosure of a relationship is not intended to suggest or condone any bias in any presentation but is made to provide participants with information that might be of potential importance to their evaluation of a presentation.

Planner

Bryan Taylor, PharmD—has no relevant financial relationships to disclose in relation to the content of this activity.

Authors/Presenters

John N. Allan, MD—has disclosed that he is a consultant for AbbVie, Acerta, AstraZeneca, Genentech, Janssen, Pharmacyclics, Sunesis, and Verastem.

Megan Dillaman, PharmD, BCOP—has no relevant financial relationships to disclose in relation to the content of this activity.

Shilpa Paul, PharmD, BCOP—has no relevant financial relationships to disclose in relation to the content of this activity.

Content Reviewer

Jeannie Patrick, PharmD, BCOP—has no relevant financial relationships to disclose in relation to the content of this activity.

Activity Instructions

Media: Internet Web Activity (PowerPoint slides and audio)

Instructions:

To receive a statement of credit, you must:

  1. Read the target audience, learning objectives, and author disclosures.
  2. Review the full content of the activity and reflect upon its teaching.
  3. Complete the questions and evaluation at the end of the activity.
  4. You must have a passing score of 75% on the post-test. You will have two (2) opportunities to complete the post-test.

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