Data + Perspectives: Investigators Discuss the Optimal Management of Chronic Lymphocytic Leukemia — Webinar Proceedings

Faculty

Faculty

Catherine C Coombs

MD

UCI Health, Orange County, California

Associate Clinical Professor, Division of Hematology/Oncology, Department of Medicine

Faculty

Matthew S Davids

MD, MMSc

Dana-Farber Cancer Institute, Boston, Massachusetts

Chief, Division of Lymphoma, Harold and Virginia Lash Endowed Chair in Lymphoma Research

Harvard Cancer Consortium, Boston, Massachusetts

Leader, Lymphoma Program

Harvard Medical School, Boston, Massachusetts

Associate Professor of Medicine

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

• Recognize the prognostic and clinical significance of various biomarkers (eg, del[17p], TP53 mutations, IGHV gene rearrangements) in chronic lymphocytic leukemia (CLL), and refine molecular testing algorithms for patients newly diagnosed with this disease.
• Individualize the selection of systemic therapy for newly diagnosed CLL, considering risk profile, clinical presentation, coexisting medical conditions and patient preferences.
• 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 clinical research demonstrating the efficacy and safety of covalent and noncovalent BTK inhibitors for newly diagnosed and relapsed/refractory (R/R) CLL, and identify patients for whom treatment with these agents would be appropriate.
• Appreciate the scientific rationale for the investigation of combined BTK and Bcl-2 inhibition, and review recently presented data with this strategy for patients with newly diagnosed and R/R CLL.
• Appraise clinical investigator best practices for various CLL management situations, and leverage this information to facilitate improved clinical decision-making.
• Recall available and emerging data with novel agents and combination strategies currently under investigation for CLL, and as applicable, discuss clinical trial participation with eligible patients.

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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.

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

Dr Coombs — 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. Dr Davids — 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.

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.

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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: October 8, 2026
Expiration date: October 8, 2027

A prospective, open-label, randomized, multicenter phase-III trial to evaluate the efficacy of pirtobrutinib and epcoritamab compared with R-(mini)-CHOP for treatment of patients with Richter transformation. CLL-RT2

A randomized phase III study of pirtobrutinib plus R-CHOP vs. R-CHOP for participants with previously untreated Richter transformation (PIRAMID). NCT07220187

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. Fixed-duration pirtobrutinib plus venetoclax–rituximab versus venetoclax–rituximab for patients with previously treated CLL/SLL: A phase 3, randomized trial (BRUIN CLL-322). EHA 2026;Abstract LB5001.

Davids MS et al. MAJIC: A phase 3 prospective, multicenter, randomized, open-label trial of acalabrutinib plus venetoclax versus venetoclax plus obinutuzumab in previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. ASH 2021;Abstract 1553.

Jurczak W et al. BRUIN CLL-313: Randomized phase III trial of pirtobrutinib versus bendamustine plus rituximab in untreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol 2026;44(6):466-75. Abstract

Kater AP et al. The MURANO study: Final analysis and retreatment/crossover substudy results of VenR for patients with relapsed/refractory CLL. Blood 2025;145(23):2733-45. Abstract

Munir T et al. Updated efficacy and safety data from an ongoing phase 1a/b trial of the BTK degrader bexobrutideg (NX-5948) in patients with CLL across lines of therapy. EHA 2026;Abstract S150.

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

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 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.

Stilgenbauer S et al. BGB-16673, a Bruton tyrosine kinase (BTK) degrader, in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): A phase 1 CADANCE-101 study update. EHA 2026;Abstract S152.

Wierda WG et al. Characteristics associated with response to lisocabtagene maraleucel (liso-cel) in patients (pts) with R/R CLL/SLL: Exploratory analyses from TRANSCEND CLL 004. EHA 2024;Abstract S158.

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;11(9):e682-92. Abstract

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

Woyach JA 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 in post-cBTKi CLL/SLL: ~30 months follow-up and subgroup analysis with/without prior BCL2i from the phase 1/2 BRUIN study. ASH 2023;Abstract 325.