{"entity":{"id":"cit-in-del17p-caution","kind":"pairing","name":"Caution: chemoimmunotherapy in del(17p)/TP53 CLL","aka":[],"tldr":"Chemotherapy-based regimens barely work when the p53 gene is lost; these patients need BTK inhibitors or venetoclax from the start.","summary":"This caution concerns rituximab-based chemoimmunotherapy in chronic lymphocytic leukaemia with del(17p) or TP53 mutation. Alkylators and purine analogues kill through p53-dependent apoptosis, so loss of TP53 removes the mechanism: FCR and BR give only short remissions in these patients and may select resistant clones. The pattern is consistent across the CLL8 and CLL10 trials and registry data, and guidelines from NCCN, ESMO and iwCLL restrict chemoimmunotherapy to fit patients with intact TP53 and mutated IGHV, with targeted therapy preferred even there. Patients with del(17p) or TP53 aberration should start on a BTK inhibitor such as zanubrutinib, tested in SEQUOIA, or on venetoclax.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03336333: SEQUOIA","url":"https://clinicaltrials.gov/study/NCT03336333"}],"tags":[],"related":[],"cancers":["cll"],"sections":[],"technologies":[],"targets":[],"drugs":["rituximab","zanubrutinib","venetoclax"],"companies":[],"institutions":[],"pathways":[],"terms":["del17p-tp53"],"trials":["sequoia"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"rituximab","b":"del17p-tp53","rationale":"Alkylators and purine analogues kill via p53-dependent apoptosis; TP53 loss removes the mechanism.","evidence":"Consistent across CLL8, CLL10, and registry data.","pairingType":"caution"},"route":"/pairings/cit-in-del17p-caution/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"cll-treatment-naive","kind":"cancer","name":"Chronic lymphocytic leukaemia, first treatment","route":"/cancers/cll-treatment-naive/"}],"drug":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"},{"id":"zanubrutinib","kind":"drug","name":"Zanubrutinib","route":"/drugs/zanubrutinib/"}],"term":[{"id":"del17p-tp53","kind":"term","name":"del(17p) / TP53 aberration in CLL","route":"/terms/del17p-tp53/"}],"trial":[{"id":"sequoia","kind":"trial","name":"SEQUOIA","route":"/trials/sequoia/"}]}}