Experts weigh mutation testing, comorbidities, and patient preference to guide second-line CLL options after BTK inhibitor resistance.
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Optimizing Second-Line Therapy in CLL After Covalent BTK Inhibitor Exposure
Dr. Marin Xavier from Scripps Cancer Center and Dr. Raji Shameem from Orlando Health Cancer Institute discussed evolving second-line treatment strategies for chronic lymphocytic leukemia (CLL) following prior covalent BTK inhibitor therapy. The discussion emphasized how recent clinical trial data, particularly the BRUIN CLL-321 study, have reshaped sequencing decisions with pirtobrutinib (LOXO-305) now approved for second-line treatment after covalent BTK inhibitor exposure. Two patient scenarios illustrated common scenarios: disease progression with acquired resistance mutations (BTK C481S, TP53) and treatment intolerance due to cardiac toxicities. The CLL-321 trial demonstrated pirtobrutinib’s efficacy with 14-month median progression-free survival versus 8.7 months for investigator's choice, including sustained benefits in venetoclax-exposed and TP53-aberrant populations.
Optimizing Second-Line Therapy in CLL After Covalent BTK Inhibitor Exposure
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Experts discuss relapsed CLL workup, using PET-CT and lymph node biopsy to rule out Richter’s, plus resistance testing to guide next therapy.
Experts outline relapse workup in CLL, using PET-CT and biopsy for suspected Richter’s, plus resistance and TP53 testing to guide next therapy.
Phase 3 results: pirtobrutinib boosts PFS, delays next treatment after prior BTK therapy, and shows low cardiac toxicity.
Phase 3 data show pirtobrutinib extends PFS and delays next therapy after BTK inhibitors, with low atrial fibrillation and hypertension rates.
A 72-year-old CLL patient stops covalent BTK therapy due to AFib and hypertension; experts weigh switching BTK agents, pirtobrutinib, or venetoclax.
CLL therapy evolves fast: frontline trial updates, pirtobrutinib in second line, and BTK degraders promise simpler, better-tolerated options.
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