A 72-year-old man with CLL has Rai stage III disease (with anemia, Hb 9.2 g/dL). FISH cytogenetics show 17p deletion (TP53 mutation). According to current CLL management guidelines, the preferred first-line therapy for this patient is:
- A FCR (Fludarabine + Cyclophosphamide + Rituximab)
- B Ibrutinib (BTK inhibitor) based therapy ✓
- C Chlorambucil + Obinutuzumab
- D BR (Bendamustine + Rituximab)
Explanation
17p deletion (del17p) or TP53 mutation in CLL confers resistance to chemo-immunotherapy (FCR, BR) because fludarabine-based regimens require functional p53 for apoptosis induction. BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) are the preferred first-line treatment for del17p/TP53-mutated CLL, as they work through a p53-independent pathway. FCR is excellent for young fit patients with IGHV-mutated CLL without del17p. Chlorambucil + obinutuzumab is for elderly frail patients without high-risk cytogenetics. The CLL guidelines (IWCLL 2018, updated 2024) strongly recommend targeted therapy (BTKi or venetoclax+obinutuzumab) for del17p regardless of age.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.