Long‐term efficacy of first‐line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a pooled analysis from four clinical trials

TP53 aberrations [del(17p) or TP53 mutation] predict poor survival with chemoimmunotherapy in patients with chronic lymphocytic leukaemia (CLL). We evaluated long‐term efficacy and safety of first‐line ibrutinib‐based therapy in patients with CLL bearing TP53 aberrations in a pooled analysis across four studies: PCYC‐1122e, RESONATE‐2 (PCYC‐1115/16), iLLUMINATE (PCYC‐1130) and ECOG‐ACRIN E1912. The pooled analysis included 89 patients with TP53 aberrations receiving first‐line treatment with single‐agent ibrutinib (n = 45) or ibrutinib in combination with an anti‐CD20 antibody (n = 44). All 89 patients had del(17p) (53% of 89 patients) and/or TP53 mutation (91% of 58 patients with TP53 sequencing results available). With a median follow‐up of 49·8 months (range, 0·1–95·9), median progression‐free survival was not reached. Progression‐free survival rate and overall survival rate estimates at four years were 79% and 88%, respectively. Overall response rate was 93%, including complete response in 39% of patients. No new safety signals were identified in this analysis. Forty‐six percent of patients remained on ibrutinib treatment at last follow‐up. With median follow‐up of four years (up to eight years), results from this large, pooled, multi‐study data set suggest promising long‐term outcomes of first‐line ibrutinib‐based therapy in patients with TP53 aberrations. Registered at ClinicalTrials.gov (NCT01500733, NCT01722487, NCT02264574 and NCT02048813).