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Caution: chemoimmunotherapy in del(17p)/TP53 CLL
Chemotherapy-based regimens barely work when the p53 gene is lost; these patients need BTK inhibitors or venetoclax from the start.
FCR and BR give short remissions (median PFS ~1 year) in del(17p)/TP53-mutated CLL and may select resistant clones. Guidelines (NCCN, ESMO, iwCLL) restrict chemoimmunotherapy to TP53-intact, IGHV-mutated, fit patients, and even there targeted therapy is preferred.
Rationale
Alkylators and purine analogues kill via p53-dependent apoptosis; TP53 loss removes the mechanism.
Evidence
Consistent across CLL8, CLL10, and registry data.