Faculty

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

LEARNING OBJECTIVES

• Individualize the selection of systemic therapy for patients with newly diagnosed CLL, considering new research findings, clinical presentation, biomarker profile, coexisting medical conditions and preferences for time-limited or continuous treatment.
• Review the similarities and differences between covalent and noncovalent Bruton tyrosine kinase (BTK) inhibitors, and assess the implications for the efficacy and tolerability of these agents.
• Evaluate available and emerging Phase III data demonstrating the efficacy of covalent and noncovalent BTK inhibitors as first-line therapy for CLL, and use this information to counsel patients regarding front-line treatment options.
• Understand published research findings with Bcl-2 inhibitors in combination with anti-CD20 antibodies as first-line treatment for CLL, and counsel patients regarding the risks and benefits of this novel treatment strategy.
• 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 relapsed/refractory CLL, and use this information to identify patients appropriate for treatment with these agents.
• Evaluate the biological rationale for the investigation of CD19-directed chimeric antigen receptor T-cell therapy for CLL, and identify patients for whom treatment with this novel therapeutic strategy would be appropriate.
• Implement a plan of care to recognize and manage side effects and toxicities associated with available systemic therapies commonly employed in the treatment of CLL.
• Recall available and emerging data with novel agents and combination strategies currently under investigation in CLL, and as applicable, refer eligible patients for 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
Video Program: Research To Practice designates this enduring material for a maximum of 2.25 AMA PRA Category 1 Credits™. 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 these CME activities, which includes participation in the evaluation components and post-tests, enables the participant to earn up to and 2.25 (video) Medical Knowledge MOC points 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 each 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 specialties: medical oncology and hematology.

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CE ACTIVITY
Video Program: 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/ASHCLL25/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:

Matthew S Davids, MD, MMSc
Associate Professor of Medicine
Harvard Medical School
Leader, Lymphoma Program
Dana-Farber/Harvard Cancer Center
Director of Clinical Research
Division of Lymphoma
Dana-Farber Cancer Institute
Boston, Massachusetts

Consulting Agreements: AbbVie Inc, Adaptive Biotechnologies Corporation, Ascentage Pharma, AstraZeneca Pharmaceuticals LP, BeOne, Bristol Myers Squibb, Galapagos NV, Genentech, a member of the Roche Group, Genmab US Inc, Janssen Biotech Inc, Lilly, MEI Pharma Inc, Merck, Nuvalent, Schrödinger, Takeda Pharmaceuticals USA Inc; Contracted Research: Ascentage Pharma, AstraZeneca Pharmaceuticals LP, MEI Pharma Inc, Novartis; Nonrelevant Financial Relationships: UpToDate.

Bita Fakhri, MD, MPH
Assistant Professor of Medicine (Hematology)
Stanford University School of Medicine
Stanford, California

Advisory Committees: AbbVie Inc, AstraZeneca Pharmaceuticals LP, Genentech, a member of the Roche Group, Pharmacyclics LLC, an AbbVie Company; Contracted Research: AbbVie Inc, BeOne, Genmab US Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company.

Professor Constantine Tam, MBBS, MD
Head of Lymphoma Service
Alfred Health
Professor of Haematology
Monash University
Melbourne, Australia

No relevant financial relationships to disclose.

Jennifer Woyach, MD
Professor
Division of Hematology
Department of Internal Medicine
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio

Advisory Committees and Consulting Agreements: AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeOne, Genentech, a member of the Roche Group, Janssen Biotech Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Merck, Newave, Pharmacyclics LLC, an AbbVie Company; Contracted Research: AbbVie Inc, Karyopharm Therapeutics, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, MingSight Pharmaceuticals, MorphoSys, Schrödinger, Verastem Inc.

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, 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 AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeOne, Bristol Myers Squibb, and Lilly.

Release date: January 2026
Expiration date: January 2027

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

Dr Davids

Al-Sawaf O et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study. Blood 2024;144(18):1924-35. Abstract

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

Burger JA et al. Final analysis of the RESONATE-2 study: Up to 10 years of follow-up of first-line ibrutinib treatment for CLL/SLL. Blood 2025;146(18):2168-76. 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

Davids MS et al. Acalabrutinib-based regimens in frontline or relapsed/refractory higher-risk CLL: Pooled analysis of 5 clinical trials. Blood Adv 2024;8(13):3345-59. Abstract

Davids MS et al. Real-world characteristics, treatment patterns, and outcomes of patients with 2 or more LOTs for CLL/SLL in the United States. Blood Neoplasia 2024;2(1):100047. Abstract

Fürstenau M et al. The triple combination of venetoclax-ibrutinib-obinutuzumab prolongs progression-free survival compared to venetoclax-CD20-antibody combinations and chemoimmunotherapy in treatment-naive chronic lymphocytic leukemia: Final analysis from the phase 3 GAIA/CLL13 trial. EHA 2025;Abstract S191.

Jurczak W et al. Pirtobrutinib vs bendamustine plus rituximab (BR) in patients with CLL/SLL: First results from a randomized phase III study examining a non-covalent BTG inhibitor in untreated patients. ASH 2025;Abstract LBA-3.

Liu J et al. Sonrotoclax overcomes BCL2 G101V mutation-induced venetoclax resistance in preclinical models of hematologic malignancy. Blood 2024;143(18):1825-36. Abstract

Shadman M et al. Zanubrutinib versus bendamustine and rituximab in patients with treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma: Median 5-year follow-up of SEQUOIA. J Clin Oncol 2025;43(7):780-7. Abstract

Shadman M et al. CELESTIAL-TNCLL: An ongoing, open-label, multiregional, phase 3 study of sonrotoclax (BGB-11417) + zanubrutinib vs venetoclax + obinutuzumab for treatment-naïve (TN) CLL. ASCO 2024;Abstract TPS7087.

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

Soumerai JD et al. Sonrotoclax and zanubrutinib as frontline treatment for CLL demonstrates high MRD clearance rates with good tolerability: Data from an ongoing phase 1/1b study BGB-11417-101. Blood 2024;144(1_Suppl):1012. Abstract

Tam CS et al. Zanubrutinib in the treatment of patients with del(17p) and/or TP53 CLL/SLL: Analysis across clinical studies. Blood Adv 2025;[Online ahead of print]. Abstract

Woyach J et al. Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized study III study comparing a non-covalent and covalent BTK inhibitor. ASH 2025;Abstract 87.

Prof Tam

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

Munir T et al. Practical management of cardiovascular adverse events with BTKi treatment in patients with chronic lymphocytic leukemia: A consensus report by hematologists and cardiologists. Acta Haematol 2025;[Online ahead of print]. Abstract

Shadman M et al. Zanubrutinib and venetoclax for patients with treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma with and without del(17p)/ TP53 mutation: SEQUOIA arm D results. J Clin Oncol 2025;43(21):2409-17. Abstract

Timofeeva N et al. Ibrutinib and venetoclax in combination for chronic lymphocytic leukemia: Synergy in practice. Blood Neoplasia 2024;1(3):100034. Abstract

Dr Woyach

Davids M et al. Preliminary results of the ongoing multicenter, phase 2 study of retreatment with venetoclax plus obinutuzumab (REVENG) in patients with recurrent chronic lymphocytic leukemia (CLL). EHA 2025;Abstract PF575.

Jain N et al. Absence of BTK, BCL2, and PLCG2 mutations in chronic lymphocytic leukemia relapsing after first-line treatment with fixed-duration ibrutinib plus venetoclax. Clin Cancer Res 2024;30(3):498-505. 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

Sharman JP et al. BRUIN CLL-321: Randomized phase III trial of pirtobrutinib versus idelalisib plus rituximab (idelar) or bendamustine plus rituximab (br) in BTK inhibitor pretreated chronic lymphocytic leukemia/small lymphocytic lymphoma. ASH 2024;Abstract 886.

Woyach J et al. Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor. ASH 2025;Abstract 683.

Woyach JA et al. First-in-human study of the reversible BTK inhibitor nemtabrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and B-cell non-hodgkin lymphoma. Cancer Discov 2024;14(1):66-75. Abstract

Dr Fakhri

Ahn I et al. Updated efficacy and safety results of the Bruton tyrosine kinase (BTK) degrader BGB- 16673 in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) from the ongoing phase 1 CaDAnCe-101 study. ASH 2025;Abstract 85.

Omer Z et al. Bexobrutideg (NX-958), a novel Bruton’s tyrosine kinase (BTK) degrader, demonstrates rapid and durable clinical responses in relapsed/refractory chronic lymphocytic leukemia (CLL): New and updated findings from an ongoing Phase 1a/b trial. ASH 2025;Abstract 86.

Winter AM et al. Real-world outcomes of lisocabtagene maraleucel (liso-cel) in patients (pt) with Richter transformation (RT) from the Center for International Blood and Marrow Transplant Research (CIBMTR). ASCO 2024;Abstract 7010.

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.

Zhou K et al. Results of a registrational phase 2 study of lisaftoclax monotherapy for treatment of patients (pts) with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who had failed Bruton’s tyrosine kinase inhibitors (BTKis). ASH 2025;Abstract 88.