Clinical Investigator Perspectives on the Most Relevant New Datasets and Advances in Chronic Lymphocytic Leukemia — Webinar Video Proceedings

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

• 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.
• 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 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.
• 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 for 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 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 management 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 to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Video Program: 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.

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 CME 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/YiR2024/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 conflicts of interest 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, BeiGene Ltd, Bristol-Myers Squibb, EcoR1 Capital LLC, Galapagos NV,Genentech, a member of the Roche Group, Grifols Worldwide Operations Ltd, InnoCare Pharma, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Magnet Biomedicine, Merck, Pharmacyclics LLC, an AbbVie Company; Contracted Research: BeiGene Ltd, Gilead Sciences Inc, iOnctura SA, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, MEI Pharma Inc, Nagoon Therapeutics, TG Therapeutics Inc; Data and Safety Monitoring Boards/Committees: Grifols; Nonrelevant Financial Relationships: UpToDate.

Paolo Ghia, MD, PhD
Professor of Medical Oncology
Università Vita-Salute San Raffaele
Director, CLL Strategic Program
IRCCS Ospedale San Raffaele
Milano, Italy

Advisory Committees: AstraZeneca Pharmaceuticals LP, BeiGene Ltd, Johnson & Johnson Pharmaceuticals, Lilly; Consulting Agreements: AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeiGene Ltd, Bristol Myers Squibb, Galapagos NV, Johnson & Johnson Pharmaceuticals, Lilly, MSD, Roche Laboratories Inc; Contracted Research: AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeiGene Ltd, Bristol Myers Squibb, Johnson & Johnson Pharmaceuticals, Lilly, MSD.

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: 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, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Jazz Pharmaceuticals Inc, Karyopharm Therapeutics, Kite, A Gilead Company, 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 conflicts of interest 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 and Lilly.

Release date: April 2025
Expiration date: April 2026

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. 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

Brown JR et al. Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: Final comparative analysis of ALPINE. Blood 2024;144(26):2706-17. Abstract

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.

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. Primary endpoint evaluation of a multicenter, phase 2 study of acalabrutinib, venetoclax, obinutuzumab (AVO) in a population of previously untreated patients with CLL enriched for high-risk disease. ASH 2024;Abstract 1865.

Fürstenau M et al. Acalabrutinib, venetoclax, and obinutuzumab in relapsed/refractory CLL: Final efficacy and ctDNA analysis of the CLL2-BAAG trial. Blood 2024;144(3):272-82. Abstract

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

Ghia P et al. Impact of acalabrutinib treatment by line of therapy in patients with chronic lymphocytic leukemia: Pooled analysis from ELEVATE-TN, ELEVATE-RR, and ASCEND. EHA 2024;Abstract P703.

Jain N et al. Combined pirtobrutinib, venetoclax, and obinutuzumab as first-line treatment of patients with chronic lymphocytic leukemia (CLL). ASH 2024;Abstract 1011.

Kater AP et al. Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: Analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial. Lancet Oncol 2024;25(4):463-73. Abstract

Kozarac S et al. BTKi-induced cardiovascular toxicity in CLL: Risk mitigation and management strategies. Blood Rev 2025:70:101268. Abstract

Langerbeins P et al. Ibrutinib in early-stage chronic lymphocytic leukemia: The randomized, placebo-controlled, double-blind, phase III CLL12 trial. J Clin Oncol 2025;43(4):392-402. Abstract

Ma S et al. Combination of zanubrutinib + venetoclax for treatment-naïve (TN) CLL/SLL with del(17p) and/or TP53: Preliminary results from SEQUOIA arm D. EHA 2024;Abstract S160.

Roeker L et al. Minimal residual disease (MRD)-adapted duration of front-line venetoclax and obinutuzumab treatment for fit patients with chronic lymphocytic leukemia (CLL). ASH 2024;Abstract 1010.

Roeker LE et al. Fixed-duration pirtobrutinib plus venetoclax with or without rituximab in relapsed/refractory CLL: The phase 1b BRUIN trial. Blood 2024;144(13):1374-86. Abstract

Shadman M et al. Sustained superiority of zanubrutinib vs bendamustine + rituximab in treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (TN CLL): 5-year follow-up of cohort 1 from the SEQUOIA study. ASH 2024;Abstract 3249.

Shah 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.

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.

Sharman JP et al. CRISTALLO: Results from a phase III trial of venetoclax-obinutuzumab versus fludarabine, cyclophosphamide and rituximab or bendamustine-rituximab in patients with untreated chronic lymphocytic leukemia without del(17p) or TP53 mutations. ASH 2024;Abstract 3237.

Siddiqi T et al. Lisocabtagene maraleucel (liso-cel) in patients (pts) with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Updated follow-up of TRANSCEND CLL 004. ASH 2024;Abstract 4633.

Simon F et al. Efficacy and safety of acalabrutinib treatment in very old (≥80y) and/or frail patients with chronic lymphocytic leukemia (CLL) – Primary endpoint analysis of the phase II CLL-Frail trial. ASH 2024;Abstract 4618.

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.

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.

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.

Wierda WG et al. Pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in patients with B-cell malignancies: Analysis of the Richter transformation subgroup from the multicentre, open-label, phase 1/2 BRUIN study. Lancet Haematol 2024 Sep;11(9):e682-e692. Abstract