Non-Covalent BTK Inhibitors for B-Cell Malignancies (MCL/CLL): Setting the Stage for Future Use

Non-Covalent BTK Inhibitors for B-Cell Malignancies (MCL/CLL): Setting the Stage for Future Use

Non-Covalent BTK Inhibitors for B-Cell Malignancies (MCL/CLL): Setting the Stage for Future Use


Available credits: 0.50

Time to complete: 30 minutes


Valid until:

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  • Overview

    During the past 10 years, BTK inhibitors are increasingly replacing chemotherapy-based regimens, especially in patients with chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Current clinical practice is continuous long-term administration of covalent, irreversible BTK inhibitors, which can be complicated by side effects or the development of drug resistance. Resistance mutations and intolerance contribute to therapy interruption or discontinuation and abrogate clinical benefits associated with continued covalent BTK inhibitor therapy, leading to subsequent care that is suboptimal due to a dearth of effective treatment options (as reflected in lower progression-free survival, overall survival, or response duration). Non-covalent, reversible BTK inhibitors do not bind to C481, therefore providing a potentially effective option to patients with B cell malignancies that have developed resistance to covalent BTK inhibitors. Preliminary clinical studies have suggested that non-covalent BTK inhibitors are effective and well-tolerated.

    This educational activity will assist hematology-oncology professionals develop management plans designed to overcome these challenges and offer patients the full benefit of BTK inhibitor therapy. We will discuss the clinical implications of BTK inhibitor selectivity profiles and safety differences; the integration of BTK inhibitors into the management of different B-cell cancer patient populations; and the proactive adaptation of treatment plans to account for drug resistance and therapeutic intolerance associated with covalent BTK agents.

  • Disclosure of Conflicts of Interest

    Disclosure of Conflicts of Interest
    AXIS Medical Education requires faculty, instructors, authors, planners, directors, managers, reviewers, and other individuals who are in a position to control the content of this activity to disclose all real or apparent conflicts of interest they may have with ineligible companies. An ineligible entity is any organization whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients. All relevant conflicts of interest are identified and mitigated prior to initiation of the planning phase for an activity.

    AXIS has mitigated and disclosed to learners all relevant conflicts of interest disclosed by staff, planners, faculty/authors, peer reviewers, or others in control of content for this activity. Disclosure of a relationship is not intended to suggest or condone bias in any presentation but is made to provide participants with information that might be of potential importance to their evaluation of a presentation or activity. Disclosure information for faculty, authors, course directors, planners, peer reviewers, and/or relevant staff is provided with this activity.

    The faculty, Anthony Mato, MD, MSCE, reported the following relevant financial relationships or relationships he has with ineligible companies of any amount during the past 24 months: Research grant: TG Therapeutics, Inc; Pharmacyclics, Inc; AbbVie; Adaptive Biotechnologies; Johnson & Johnson; Acerta/AstraZeneca; DTRM BioPharma; Sunesis; BeiGene LTD; Genentech, Inc; Genmab; Janssen Pharmaceuticals, Inc; Loxo Oncology, Inc; and Nurix. Consulting: TG Therapeutics, Inc; Pharmacyclics, Inc; Adaptive Biotechnologies; AbbVie; Johnson & Johnson; Acerta/AstraZeneca; DTRM BioPharma; Sunesis; AstraZeneca Pharmaceuticals LP; BeiGene; Genentech, Inc; Janssen Oncology; and Loxo Oncology.

    The directors, planners, managers, and reviewers reported the following financial relationships they have with any ineligible company of any amount during the past 24 months: Linda Gracie-King, MS; Jocelyn Timko, BS; Laura Healy, BS; Marilyn L. Haas-Haseman, PhD, RN, CNS, ANP-BC; Melissa Duffy, PA-C; and Adrienne N. Nedved, MPA, PharmD, BCOP; hereby state that they do not have any financial relationships or relationships any ineligible company of any amount during the past 24 months. Robert Mocharnuk, MD, reported a financial interest/relationship or affiliation in the form of Common stock: Merck of any amount during the past 24 months.

  • Target Audience

    This educational activity is designed for hematologists, oncologists, pathologists/lab professionals, oncology nurses, nurse practitioners, pharmacists, physician assistants, and other healthcare professionals who are part of the interprofessional team responsible for the therapeutic management of patients with B-cell malignancies.

  • Learning Objectives

    At the conclusion of this activity, participants should be better able to:

    1. Summarize the mechanism of action and efficacy and safety data differences associated with covalent and non-covalent BTK inhibitors for B-cell malignancies, including implications related to therapeutic intolerance and resistance.
    2. Explain the mechanisms of BTK inhibitor resistance, including acquired resistance to covalent agents and how non-covalent BTK inhibitors can offset resistance mutations.
    3. Develop a theoretical treatment plan that includes non-covalent BTK inhibitors for patients with MCL or CLL/SLL previously treated with a BTK inhibitor, including in the context of a clinical trial.
  • Accreditation and Credit Designation Statements

    Accreditation Statement

    In support of improving patient care, AXIS Medical Education 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 activity was planned by and for the healthcare team, and learners will receive 0.5 Interprofessional Continuing Education (IPCE) credit for learning and change.

    Credit Designation for Physicians
    AXIS Medical Education designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Credit Designation for Physician Assistants

    AXIS Medical Education has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.5 AAPA Category 1 CME credits.  Approval is valid until April 17, 2023 PAs should only claim credit commensurate with the extent of their participation.

    Credit Designation for Pharmacists
    This knowledge-based activity is approved for 0.5 contact hour of continuing pharmacy education JA4008106-0000-22-002-H01-P.

    Credit Designation for Nursing
    AXIS Medical Education designates this continuing nursing education activity for 0.5 contact hour.
    Learners are advised that accredited status does not imply endorsement by the provider or ANCC of any commercial products displayed in conjunction with an activity.

  • Disclaimer

    Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

  • Commercial Support

    This activity is supported by an educational grant from Lilly. For further information concerning Lilly grant funding, visit

  • Method of Participation and Request for Credit

    To receive credit for this activity, participants must review the activity information including learning objectives and faculty/planner disclosures and actively participate in the educational activity. Upon successfully completing the post-test with a score of 75% or better and the post-activity evaluation, your certificate will be made available immediately. For pharmacists, your record will be uploaded to CPE Monitor.

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