<![CDATA[Disease Assessment and Mutational Testing in Progressive CLL]]>

Advertisement Opinion|Videos|May 6, 2026 Disease Assessment and Mutational Testing in Progressive CLL Author(s)Marin F. Xavier, MD, Raji Shameem, MD Experts discuss relapsed CLL workup, using PET-CT and lymph node biopsy to rule out Richter’s, plus resistance testing to guide next therapy. Advertisement Episodes in this seriesEP. 1 Clinical Scenario Presentation and Treatment Approach for Progressive DiseaseNow PlayingEP. 2 Disease Assessment and Mutational Testing in Progressive CLL Dr. Xavier addresses Richter transformation concerns and biopsy considerations for progressive patients. Dr. Shameem explains that certain features warrant transformation evaluation, including severe symptomatic progression, lymphadenopathy, and discordant lactate dehydrogenase elevation. This particular patient does not demonstrate concerning transformation features, but PET-CT imaging would be pursued if transformation were suspected, with SUVmax values much higher than expected for CLL prompting excisional lymph node biopsy consideration.Regarding resistance mutational testing upon covalent BTKi progression, Dr. Shameem routinely checks for biological rationale understanding of progression mechanisms. Most patients demonstrate C481S mutations at the covalent BTKi binding site, providing biological rationale for non-covalent BTKi utilization. Additional rare mutation analysis is performed alongside repeat molecular testing, with this patient's acquired TP53 mutation helping stratify second-line risk assessment.Dr. Xavier discusses variable practices for resistance testing, noting that many resistance mutations are now included in next-generation sequencing panels and CLL panels at reference laboratories. His personal approach involves PET-CT imaging for clearly progressing patients to obtain functional imaging information about SUV uptake while simultaneously risk-stratifying patients for tumor lysis syndrome when considering BCL-2i pathways. This approach addresses both Richter transformation assessment and treatment planning considerations efficiently. NewsletterStay up to date on the most recent and practice-changing oncology dataSubscribe Now! Advertisement Latest CMEVideoProactive Adverse Event Management for HER2+ BTC TreatmentsRahul Gosain, MD, MBA; Rohit Gosain, MD; Rachna T. Shroff, MD, MS, FASCOView moreMultimediaCommunity Practice Connections™: Empowering Interventional Radiologists in the Emerging Era of Oncolytic Immunotherapies for MelanomaYana G. Najjar, MD; Douglas B. Johnson, MD, MSCI; Rahul A. 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