A 68-year-old man has CLL with del(17p) detected by FISH, TP53 mutation on sequencing, and Rai stage III disease. He requires treatment. Which frontline regimen is recommended?

• A FCR (fludarabine, cyclophosphamide, rituximab)
• B Ibrutinib (BTK inhibitor) or venetoclax plus obinutuzumab ✓
• C Chlorambucil plus obinutuzumab
• D Bendamustine plus rituximab

Explanation

CLL with del(17p)/TP53 mutation has impaired DNA damage response, rendering chemoimmunotherapy (FCR, BR, chlorambucil combinations) largely ineffective. BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) and the BCL-2 inhibitor venetoclax with obinutuzumab achieve durable responses regardless of TP53 status and are recommended as frontline in this high-risk group per IWCLL and NCCN 2024 guidelines. FCR is preferred only in young, fit patients with IGHV-mutated, del(17p)-negative CLL.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.