Clinical Investigators Provide Perspectives on the Current and Future Care of Patients with Chronic Lymphocytic Leukemia — Webinar Video Proceedings

Faculty

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

LEARNING OBJECTIVES

• Individualize the selection of systemic therapy for newly diagnosed chronic lymphocytic leukemia (CLL), considering new research findings, clinical presentation, biomarker profile, coexisting medical conditions and patient preferences for time-limited or continuous treatment.
• Appreciate the scientific rationale for the investigation of combined Bruton tyrosine kinase (BTK) and Bcl-2 inhibition, and review recently presented data documenting the safety and efficacy of this strategy for patients with CLL.
• Analyze how age, performance status, prior therapeutic exposure and other biological and disease-related factors affect the selection and sequencing of therapy for patients with relapsed/refractory (R/R) CLL.
• Discuss available clinical research findings demonstrating the efficacy and safety of noncovalent BTK inhibitors in CLL, and use this information to effectively incorporate these agents into the care of patients with R/R disease.
• Evaluate the biological rationale for the investigation of CD19-directed chimeric antigen receptor T-cell therapy for CLL, and identify patients for whom 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 for 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
Research To Practice designates this enduring material for a maximum of 1.25 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 component and a post-test, enables the participant to earn up to 1.25 (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 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/ASCO2025/CLL/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:

Catherine C Coombs, MD
Associate Clinical Professor
Division of Hematology/Oncology
Department of Medicine
UCI Health
Orange County, California

Advisory Committees: AbbVie Inc, Allogene Therapeutics, AstraZeneca Pharmaceuticals LP, BeiGene Ltd, Bristol Myers Squibb, Genentech, a member of the Roche Group, Janssen Biotech Inc, Lilly, MingSight Pharmaceuticals, Pharmacyclics LLC, an AbbVie Company; Consulting Agreements: AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeiGene Ltd, Lilly, Octapharma; Contracted Research: AbbVie Inc, BeiGene Ltd, Carna Biosciences, Lilly; Speakers Bureaus: AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeiGene Ltd, Genentech, a member of the Roche Group, Lilly; Stock Options/Stock — Public Companies: Geron Corporation, Pfizer Inc.

William G Wierda, MD, PhD
Jane and John Justin Distinguished Chair in Leukemia Research in Honor of Dr Elihu Estey
Section Chief, Chronic Lymphocytic Leukemia
Center Medical Director
Department of Leukemia, Division of Cancer Medicine
Executive Medical Director, Inpatient Medical Services
The University of Texas MD Anderson Cancer Center
Houston, Texas

Consulting Agreements: BeiGene Ltd, Numab Therapeutics AG; Contracted Research: AbbVie Inc, Acerta Pharma — A member of the AstraZeneca Group, Bristol Myers Squibb, Cyclacel Pharmaceuticals Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, GSK, Janssen Biotech Inc, Juno Therapeutics, a Celgene Company, Kite, A Gilead Company, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Novartis, Nurix Therapeutics Inc, Oncternal Therapeutics, Pharmacyclics LLC, an AbbVie Company; Nonrelevant Financial Relationships: National Comprehensive Cancer Network (Chair, CLL), Support by the NIH/NCI under award number P30 CA016672 and use of MD Anderson Cancer Center Support Grant (CCSG) shared resources.

SURVEY PARTICIPANTS
John N Allan, MD — Advisory Committees: NeoGenomics; Consulting Agreements: AbbVie Inc, Adaptive Biotechnologies Corporation, ADC Therapeutics, AstraZeneca Pharmaceuticals LP, BeiGene Ltd, Genentech, a member of the Roche Group, Janssen Biotech Inc, Lilly, Pharmacyclics LLC, an AbbVie Company; Contracted Research: BeiGene Ltd, Bristol Myers Squibb, Genentech, a member of the Roche Group; Data and Safety Monitoring Boards/Committees: Merck; Speakers Bureaus: AbbVie Inc, BeiGene Ltd. Matthew S Davids, MD, MMSc — Consulting Agreements: AbbVie Inc, Adaptive Biotechnologies Corporation, Ascentage Pharma, AstraZeneca Pharmaceuticals LP, BeiGene Ltd, 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, Secura Bio, Takeda Pharmaceuticals USA Inc, TG Therapeutics Inc; Contracted Research: Ascentage Pharma, MEI Pharma Inc, Novartis; Nonrelevant Financial Relationships: UpToDate. Jeff Sharman, MD — Consulting Agreements and Contracted Research: AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeiGene Ltd, Bristol Myers Squibb, Genentech, a member of the Roche Group, Lilly, Merck. Tanya Siddiqi, MD — Advisory Committees: AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeiGene Ltd, Bristol Myers Squibb, Celgene Corporation, Gilead Sciences Inc; Contracted Research: Bristol Myers Squibb; Data and Safety Monitoring Boards/Committees: BeiGene Ltd; Speakers Bureaus: AstraZeneca Pharmaceuticals LP.

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, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeiGene Ltd, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Clovis Oncology, Coherus BioSciences, 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, Hologic 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, 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, 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 grantor.

These activities are supported by an educational grant from Lilly.

Release date: July 2025
Expiration date: July 2026

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

Dr Wierda

Module 1: Selection and Sequencing of Therapy for Relapsed/Refractory (RR) Chronic Lymphocytic Leukemia (CLL)

Escalón MP et al. BRUIN CLL-314: A phase 3, open-label, randomized study of pirtobrutinib versus ibrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (trial in progress). iwCLL 2023;Abstract 1548596.

Eyre TA et al. BRUIN CLL-322: A phase 3 open-label, randomized study of fixed duration pirtobrutinib plus venetoclax and rituximab versus venetoclax and rituximab in previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma. ASCO 2023;Abstract TPS7583.

Jurczak W et al. BRUIN CLL-313: A phase 3 open-label, randomized study of pirtobrutinib versus bendamustine plus rituximab in untreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (trial in progress). ASH 2021;Abstract 3732.

Mato AR et al. Efficacy of pirtobrutinib in covalent BTK-inhibitor pre-treated relapsed / refractory CLL/SLL: Additional patients and extended follow-up from the phase 1/2 BRUIN study. ASH 2022;Abstract 961.

Ng J et al. Cardiovascular adverse effects of novel Bruton tyrosine kinase inhibitors: What all cardiologists should know. American College of Cardiology, August 16, 2023. https://www.acc.org/Latest-in-Cardiology/Articles/2023/08/15/16/45/CV-Adverse-Effects-of-Novel-Bruton-Tyrosine-Kinase-Inhibitors

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.

Wierda WG et al. Lisocabtagene maraleucel (liso-cel) combined with ibrutinib (ibr) for patients (pts) with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Primary results from the open-label, phase 1/2 Transcend CLL 004 study. ASH 2024;Abstract 887.

Module 3: Novel Agents and Strategies for RR CLL

Danilov A et al. Epcoritamab monotherapy in patients (Pts) with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL): Results from CLL expansion and optimization cohorts of Epcore CLL-1. ASH 2024;Abstract 883.

Shah NN et al. Efficacy and safety of the Bruton’s tyrosine kinase (BTK) degrader NX-5948 in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Updated results from an ongoing phase 1a/b study. ASH 2024;Abstract 884.

Thompson MC et al. Preliminary efficacy and safety of the Bruton tyrosine kinase degrader BGB-16673 in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: Results from the phase 1 cadance-101 study. ASH 2024​;Abstract 885.

 

Dr Coombs

Module 2: First-Line Therapy for CLL

Al-Sawaf O et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized CLL14 study. EHA 2023;Abstract S145.

Barr PM et al. Up to 8-year follow-up from RESONATE-2: First-line ibrutinib treatment for patients with chronic lymphocytic leukemia. Blood Adv 2022;6(11):3440-50. Abstract

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

Brown JR et al. Fixed-duration acalabrutinib plus venetoclax with or without obinutuzumab versus chemoimmunotherapy for first-line treatment of chronic lymphocytic leukemia: Interim analysis of the multicenter, open-label, randomized, phase 3 AMPLIFY trial. ASH 2024;Abstract 1009.

Brown JR et al. Extended follow-up of ALPINE randomized phase 3 study confirms sustained superior progression-free survival of zanubrutinib versus ibrutinib for treatment of relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL). ASH 2023;Abstract 202.

Burger J et al. Final analysis of the RESONATE-2 study: Up to 10 years of follow-up of first-line ibrutinib treatment in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. EHA 2024;Abstract P670.

Byrd JC et al. Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: Results of the first randomized phase III trial. J Clin Oncol 2021;39(31):3441-52. 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

Eichhorst B et al. Time-limited venetoclax-obinutuzumab +/- ibrutinib is superior to chemoimmunotherapy in frontline chronic lymphocytic leukemia (CLL): PFS co-primary endpoint of the randomized phase 3 GAIA/CLL13 trial. EHA 2022;Abstract LB2365.

Fürstenau M et al. First-line venetoclax combinations versus chemoimmunotherapy in fit patients with chronic lymphocytic leukaemia (GAIA/CLL13): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2024;25(6):744-59. Abstract

O’Brien SM et al. Monitoring and managing BTK inhibitor treatment-related adverse events in clinical practice. Front Oncol 2021;11. Abstract

Ryan CE et al. MAJIC: A phase III trial of acalabrutinib + venetoclax versus venetoclax + obinutuzumab in previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. Future Oncol 2022;18(33):3689-99. 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

Sharman JP et al. Acalabrutinib ± obinutuzumab vs obinutuzumab + chlorambucil in treatment-naive chronic lymphocytic leukemia: 6-year follow-up of Elevate-TN. ASH 2023;Abstract 636.

Sharman JP et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): A randomised, controlled, phase 3 trial. Lancet 2020;395(10232):1278-91. 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. ASH 2024;Abstract 1012.