Optimizing Treatment for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia — Webinar Proceedings

Faculty

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

LEARNING OBJECTIVES

• Analyze how age, performance status, prior therapeutic exposure and other biological and disease-related factors affect the selection of therapy for patients who experience relapse after first-line treatment for chronic lymphocytic leukemia (CLL).
• Appraise the similarities and differences between covalent and noncovalent Bruton tyrosine kinase (BTK) inhibitors, and recognize the implications for clinical activity and tolerability.
• Discuss available and emerging clinical research demonstrating the efficacy and safety of noncovalent BTK inhibitors, alone and in combination with other therapies, for relapsed/refractory CLL, and use this information to effectively incorporate these agents into the treatment of disease that has previously been treated with a covalent BTK inhibitor.
• Appreciate recent clinical research with noncovalent BTK inhibitors for patients with treatment-naïve or BTK inhibitor-naïve CLL, and discern the implications of these findings for therapeutic selection and sequencing.
• 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.
• Appraise clinical investigator best practices for various relapsed/refractory CLL management situations, and leverage this information to improve shared decision-making with patients.
• Recall available and emerging data with novel agents and combination strategies currently under investigation in CLL, and appropriately refer 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 this CME activity, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 1.25 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 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, this program has been specifically designed for the following ABIM specialties: medical oncology and hematology.

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HOW TO USE THIS CME ACTIVITY
To receive credit for this activity, 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.

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:

Dr Wierda — Consulting/Advisory Boards, No Compensation: AbbVie Inc, Acerta Pharma — A member of the AstraZeneca Group, AstraZeneca Pharmaceuticals LP, BeOne, Bristol Myers Squibb, Intellisphere, Johnson & Johnson, Lilly, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company; Contracted Research: AbbVie Inc, Acerta Pharma — A member of the AstraZeneca Group, BeOne, Bristol Myers Squibb, Genentech, a member of the Roche Group, Gilead Sciences Inc, Janssen Biotech Inc, Juno Therapeutics, a Bristol Myers Squibb Company, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Nurix Therapeutics Inc, Pharmacyclics LLC, an AbbVie Company; Nonrelevant Financial and Nonfinancial Relationships: National Comprehensive Cancer Network (Chair, CLL), Supported by the NIH/NCI under award number P30 CA016672 and used MD Anderson Cancer Center Support Grant (CCSG) shared resources, Wiley China (consulting/advisory board, no compensation).

CONTRIBUTING CLINICAL INVESTIGATORS
Inhye Ahn, MD — Consulting Agreements: AstraZeneca Pharmaceuticals LP, BeOne, Lilly; Contracted Research: BeOne, Genentech, a member of the Roche Group, Lilly.  Catherine C Coombs, MD — Advisory Committees: AbbVie Inc, Allogene Therapeutics, AstraZeneca Pharmaceuticals LP, BeOne, Bristol Myers Squibb, Genentech, a member of the Roche Group, Invivyd, Janssen Biotech Inc, Johnson & Johnson, Lilly, Octapharma, Pharmacyclics LLC, an AbbVie Company; Contracted Research: AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeOne, Carna Biosciences, Lilly; Speakers Bureaus: AstraZeneca Pharmaceuticals LP, BeOne, Lilly; Stock Options/Stock — Public Companies: Geron Corporation.  Matthew S Davids, MD, MMSc — Consulting Agreements: AbbVie Inc, Ascentage Pharma, AstraZeneca Pharmaceuticals LP, BeOne, Bristol Myers Squibb, Galapagos NV, Genentech, a member of the Roche Group, Genmab US Inc, Janssen Scientific Affairs LLC, Lilly, MEI Pharma Inc, Merck, Nuvalent, Schrödinger; Contracted Research: Ascentage Pharma, AstraZeneca Pharmaceuticals LP,Flindr Therapeutics, MEI Pharma Inc; Nonrelevant Financial Relationships: UpToDate.  Bita Fakhri, MD, MPH — 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.  Nicole Lamanna, MD — Advisory Committees and Consulting Agreements: AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeOne, Genmab US Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company; Contracted Research: AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeOne, Genmab US Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Octapharma, Oncternal Therapeutics.  Jennifer Woyach, MD — 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, Catalyst Pharmaceuticals Inc, 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, Summit Therapeutics, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, Tesaro, A GSK Company, and Verastem Inc.

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.

This educational activity contains 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.

This activity is supported by an educational grant from Lilly.

Release date: August 2026
Expiration date: August 2027

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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.

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.

Ghia P et al. Nemtabrutinib plus venetoclax in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL): Results from the dose escalation and confirmation segment of the phase 3 bellwave-010 study. ASH 2025;Abstract 2119.

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 BTK inhibitor in untreated patients. ASH 2025;Abstract LBA3.

Omer Z et al. Bexobrutideg (NX-5948), 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.

Shah NN et al. Pirtobrutinib monotherapy in Bruton tyrosine kinase inhibitor-intolerant patients with B-cell malignancies: Results of the phase I/II BRUIN trial. Haematologica 2025;110(1):92-102. 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

Siddiqi T et al. Lisocabtagene maraleucel (liso-cel) in R/R CLL/SLL: 24-month median follow-up of TRANSCEND CLL 004. ASH 2023;Abstract 330.

Thompson PA, Tam CS. Pirtobrutinib: A new hope for patients with BTK inhibitor-refractory lymphoproliferative disorders. Blood 2023;141(26):3137-42. Abstract

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.

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 J 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