Clinical Investigator Perspectives on the Most Relevant New Datasets and Advances in Bruton Tyrosine Kinase Inhibitors for Chronic Lymphocytic Leukemia — Faculty Presentation: Jennifer R Brown, MD, PhD

Faculty

TARGET AUDIENCE
This program is intended for medical oncologists, hematologists, hematology-oncology fellows and other allied healthcare professionals involved in the treatment of chronic lymphocytic leukemia.

LEARNING OBJECTIVES

• Appraise available Phase III data documenting the comparative efficacy and tolerability of first- and second-generation Bruton tyrosine kinase (BTK) inhibitors, and consider the implications of these findings for clinical decision-making for patients with newly diagnosed chronic lymphocytic leukemia (CLL).
• Appreciate the scientific rationale for the investigation of combined BTK and Bcl-2 inhibition, and review recently presented data documenting the safety and efficacy of this strategy for patients with CLL.
• Discuss available clinical research demonstrating the efficacy and safety of noncovalent BTK inhibitors for CLL, and consider the current and future role of these agents for patients with newly diagnosed and relapsed/refractory disease.
• Implement a plan of care to recognize and manage side effects and toxicities associated with covalent and noncovalent BTK inhibitors commonly employed in the treatment of CLL.
• Recall ongoing research studies attempting to further define the optimal role of BTK inhibitor-based strategies in therapy for CLL, and appropriately counsel patients regarding potential clinical trial participation.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Research To Practice designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of this CME activity, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 1 Medical Knowledge MOC point in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology and hematology. 

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HOW TO USE THIS CME ACTIVITY
This CME activity consists of a video component. To receive credit, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better and fill out the evaluation located at ResearchToPractice.com/YIR2025/BTKiCLL/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations. 

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Jennifer R Brown, MD, PhD
Director, CLL Center and Institute Physician
Dana-Farber Cancer Institute
Worthington and Margaret Collette Professor of Medicine in the Field of Hematologic Oncology
Harvard Medical School
Boston, Massachusetts

Consulting Agreements: AbbVie Inc, Acerta Pharma — A member of the AstraZeneca Group, Alloplex Biotherapeutics, BeOne, Bristol Myers Squibb, EcoR1 Capital LLC, Galapagos NV, Genentech, a member of the Roche Group, Grifols, InnoCare Pharma, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Magnet Biomedicine, Nurix Therapeutics Inc, Pharmacyclics LLC, an AbbVie Company; Contracted Research: BeOne, iOnctura SA, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Nagoon Therapeutics Inc; Data and Safety Monitoring Boards/Committees: Grifols; Nonrelevant Financial Relationships: UpToDate.

Wojciech Jurczak, MD, PhD
Department of Clinical Oncology
Head of Lymphoma Team
Maria Skłodowska-Curie National Research Institute of Oncology
Krakow, Poland

Advisory Committees and Contracted Research: AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeOne, Janssen Biotech Inc, Lilly, MSD, Nurix Therapeutics Inc, Regeneron Pharmaceuticals Inc, Roche Laboratories Inc, Takeda Pharmaceutical Company Limited.

MODERATOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Biotheranostics Inc, A Hologic Company, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Celcuity, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Helsinn Therapeutics (US) Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Nuvation Bio Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP, BeOne, and Lilly.

Release date: May 2026
Expiration date: May 2027

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Al-Sawaf O et al. Fixed-duration versus continuous targeted treatment for previously untreated chronic lymphocytic leukemia: Results from the randomized CLL17 trial. ASH 2025;Abstract 1.

Brown JR et al. Fixed-duration acalabrutinib combinations in untreated chronic lymphocytic leukemia.N Engl J Med 2025;392(8):748-62. Abstract

Davids MS et al. Phase II study of acalabrutinib, venetoclax, and obinutuzumab in a treatment-naïve chronic lymphocytic leukemia population enriched for high-risk disease. J Clin Oncol 2025;43(7):788-99. Abstract

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Munir T et al. Measurable residual disease-guided therapy for chronic lymphocytic leukemia. N Engl J Med 2025;393(12):1177-90. Abstract

Seymour J et al. A post hoc safety analysis of fixed-duration acalabrutinib-venetoclax combinations vs chemoimmunotherapy: Results from the phase 3 AMPLIFY trial. ASH 2025;Abstract 2118.

Shadman M et al. Zanubrutinib + venetoclax for treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including patients with del(17p) and/or TP53 mutation and unmutated immunoglobulin heavy-chain variable status: 3-year results from SEQUOIA arm D. ASH 2025;Abstract 5669.

Sharman JP et al. Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN. Blood 2025;146(11):1276-85. Abstract

Sharman JP et al. Phase III trial of pirtobrutinib versus idelalisib/rituximab or bendamustine/rituximab in covalent Bruton tyrosine kinase inhibitor-pretreated chronic lymphocytic leukemia/small lymphocytic lymphoma (BRUIN CLL-321). J Clin Oncol 2025;43(22):2538-49. Abstract

Simon F et al. Acalabrutinib treatment for older (aged ≥80 years) and/or frail patients with CLL: Primary end point analysis of the CLL-Frail trial. Blood 2025;146(26):3153-62. Abstract

Soumerai J et al. Zanubrutinib + obinutuzumab + sonrotoclax in patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (TN CLL/SLL): Initial results from an ongoing phase 1/1b study, BGB-11417-101. ASH 2025;Abstract 3890.

Swaminathan M et al. Addition of obinutuzumab after one year of combined acalabrutinib and venetoclax is safer and [more] effective than early obinutuzumab in a randomized phase II trial for treatment naïve CLL. ASH 2025;Abstract 681.

Tam C et al. Frontline treatment of sonrotoclax (BGB-11417) and zanubrutinib for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) demonstrates high undetectable minimal residual disease (uMRD) rates with favorable tolerability: Updated data from BGB-11417-101, an ongoing phase 1/1b study. ASH 2025;Abstract 3891.

Tam C et al. Long-term results of patients receiving zanubrutinib in the phase 3 ALPINE study confirm sustained benefit of zanubrutinib in patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (R/R CLL/SLL): Up to 6 years of follow-up with the long-term extension (LTE1). ASH 2025;Abstract 2123.

Tam C et al. Sustained efficacy of zanubrutinib (zanu) vs bendamustine + rituximab (BR) in treatment (tx)-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (TN SLL/CLL) and continued favorable survival in non-randomized patients (pts) with del(17p): 6-year follow-up in the phase 3 SEQUOIA study. ASH 2025;Abstract2129.

Tariq B et al. Relative bioavailability, food effect, and bioequivalence studies to assess a new zanubrutinib 160-mg tablet: Results from 2 phase 1 studies in healthy volunteers. Clin Pharmacol Drug Dev 2026;15(1):e1584. Abstract

Wierda W et al. Pirtobrutinib in post-cBTKi CLL/SLL: Final update from the phase 1/2 BRUIN study with more than 5 years follow-up. ASH 2025;Abstract 2115.

Woyach J et al. Updates of R/R CLL with prior exposure to Bruton’s tyrosine kinase (BTK) inhibitor and/or Bcl-2 inhibitor in the phase 1 trial of LP-168 (rocbrutinib), a novel covalent and non-covalent BTK inhibitor. ASH 2025;Abstract 87.

Woyach JA et al. Pirtobrutinib versus ibrutinib in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol 2026;44(6):476-85. Abstract.