Time-Out! Case-Based Application of Precision Therapeutic Sequencing in High-Risk Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) has undergone a remarkable therapeutic transformation with the availability of highly effective targeted therapies. However, molecular testing and the integration of prognostic and predictive biomarkers into treatment decisions remain inconsistent, particularly outside tertiary care centers. Because outcomes differ substantially among patients with higher-risk disease, timely biomarker assessment is essential to inform risk-adapted treatment selection, optimize sequencing, and avoid undertreatment. As treatment options continue to expand, clinicians must also interpret an increasingly complex database to individualize therapy across the disease continuum.

To address these challenges, this activity uses a series of interactive “Time-Outs” – brief, case-based discussions in which expert faculty pause at key clinical decision points to examine the rationale behind their approaches. Each Time-Out focuses on a common diagnostic or therapeutic dilemma in CLL care, highlighting how biomarker findings, patient characteristics, and evolving clinical evidence inform evidence-based decision-making.

At the conclusion of this activity, learners will be able to better:

• Apply evidence-based molecular testing strategies in newly diagnosed and progressive CLL to identify patients with high-risk mutational status and inform disease prognosis
• Evaluate clinical and genomic risk factors to guide the selection of evidence-based, risk-adapted treatment strategies for patients with newly diagnosed CLL
• Integrate emerging clinical data on resistance mechanisms and sequencing strategies, including the role of non-covalent BTKi following covalent BTKi failure, to individualize therapeutic approach and optimize long-term patient outcomes

Supported by a medical education grant from BeOne Medicines USA, Inc.

Medical and hematologic oncologists, hematology-oncology fellows, oncology physician associates (PAs) and nurse practitioners (NPs), and oncology pharmacists

It is the policy of CME Outfitters, LLC, to ensure independence, balance, objectivity, and scientific rigor and integrity in all of their CE activities. Faculty must disclose to the participants any relationships with commercial companies whose products or devices may be mentioned in faculty presentations, or with the commercial supporter of this CE activity. CME Outfitters, LLC, has evaluated, identified, and mitigated any potential conflicts of interest through a rigorous content validation procedure, use of evidence-based data/research, and a multidisciplinary peer review process. The following information is for participant information only. It is not assumed that these relationships will have a negative impact on the presentations.

Dr. Lamanna reports the following financial relationships:

Advisory Board: Abbvie Inc; AstraZeneca; BeOne Medicines; Eli Lilly; Genentech Inc; Genmab; and Octapharma AG

Consultant: Nurix

Research Support: Abbvie Inc; AstraZeneca; BeOne Medicines; Eli Lilly; Genentech Inc; Genmab; Octapharma AG and Oncternal Therapeutics

Dr. Rudolph reports the following financial relationships:

Advisory Board: DSI; and Pfizer Inc

Consultant: Gilead Inc

Speakers Bureau: AstraZeneca; DSI; Gilead Inc; Pfizer Inc; and Stemline Therapeutics, Inc.

Dr. Sandoval-Sus reports the following financial relationships:

Advisory Board: AstraZeneca; Acrotech Biopharma Inc; ADC Therapeutics; BeOne Medicines; Bristol-Myers Squibb; Genentech Inc; Genmab; Janssen Pharmaceuticals, Inc.; Kite Pharma/ Gilead Sciences; Novartis; and Roche

Speakers Bureau: Pfizer Inc

Dr. Shadman reports the following financial relationships:

Advisory Board: AbbVie Inc; ADC Therapeutics; Ascentage Pharma; AstraZeneca; BeOne Medicines; Bristol- Myers Squibb; Eli Lilly; Fate Therapeutics; Genentech Inc; Genmab; Janssen Pharmaceuticals, Inc; Kite Pharma/Gilead Sciences; Merck & Co., Inc.; Morphosys/Incyte; Nurix Therapeutics, Inc.; Pfizer Inc; and Pierre Fabre

Consultant: AbbVie Inc; ADC Therapeutics; Ascentage Pharma; AstraZeneca; BeOne Medicines; Bristol- Myers Squibb; Eli Lilly; Fate Therapeutic; Genentech Inc; Genmab; Janssen Pharmaceuticals, Inc.; Kite Pharma/Gilead Sciences; Merck & Co., Inc.; Morphosys/Incyte; Nurix Therapeutics, Inc.; Pfizer Inc; and Pierre Fabre

Research Support: AstraZeneca; BeOne Medicines; Genentech Inc; Genmab; Janssen Therapeutics, Inc.; Merck & Co., Inc.; Morphosys/Incyte; Nurix Therapeutics Inc; and Sana Biotechnology

Employment: Spouse’s employer: Bristol- Myers Squibb

Other financial or material support: Stock options – Koi Biotherapeutics

The following individuals have no financial relationships to disclose:

Alaa Bawaneh, MD, PhD (Peer Reviewer)
Andrea Edwards, PA-C (Peer Reviewer)
Thomas Mitchell, MSW, LSW (Planning Committee)
Sarah Hertich  (Planning Committee)
Brian Moss (Planning Committee)
Andrea Perseghin, EdD (Planning Committee)
Sandra Caballero, PharmD (Planning Committee)
Sharon Tordoff (Planning Committee)

*All identified conflicts of interest have been mitigated.

Unlabeled Use Disclosure
Faculty of this CME/CE activity may include discussions of products or devices that are not currently labeled for use by the FDA. The faculty have been informed of their responsibility to disclose to the audience if they will be discussing off-label or investigational uses (any uses not approved by the FDA) of products or devices. CME Outfitters, LLC, the faculty, planners, and reviewers do not endorse the use of any product outside of the FDA labeled indications. Medical professionals should not utilize the procedures, products, or diagnosis techniques discussed during this activity without evaluation of their patient for contraindications or dangers of use.

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