A 68-year-old man is diagnosed with chronic lymphocytic leukemia (CLL). His lymph node biopsy shows diffuse infiltration by prolymphocytes and the Ki-67 proliferation index is >30%. FISH shows del(17p) affecting TP53. Which treatment regimen is most appropriate for this high-risk CLL?
- A FCR (fludarabine, cyclophosphamide, rituximab)
- B Ibrutinib (BTK inhibitor) or venetoclax-based regimen ✓
- C Chlorambucil monotherapy
- D Allogenic stem cell transplantation as first-line
Correct answer: B. Ibrutinib (BTK inhibitor) or venetoclax-based regimen
Explanation
Del(17p)/TP53 mutation confers resistance to chemotherapy-based regimens including FCR, which relies on intact p53 for apoptosis induction. Current guidelines (iwCLL, NCCN) recommend BTK inhibitors (ibrutinib, acalabrutinib) or venetoclax-obinutuzumab combinations as preferred first-line therapy in del(17p)/TP53-mutated CLL. FCR remains effective only in younger fit patients with IGHV-mutated CLL without del(17p). Chlorambucil is for frail elderly patients with low-risk disease.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.