In patients with chronic lymphocytic leukemia (CLL), TP53 aberrations [del(17p) or TP53 mutation] indicated poor survival with chemoimmunotherapy. For a pooled analysis of 4 trials, researchers assessed the long-term effectiveness and safety of first-line ibrutinib-based treatment in patients with CLL who had TP53 mutations: PCYC-1122e, RESONATE-2 (PCYC-1115/16), iLLUMINATE (PCYC-1130), and ECOG-ACRIN E1912. The pooled study comprised 89 patients with TP53 mutations who received first-line therapy with either single-agent ibrutinib (n =45) or ibrutinib with an anti-CD20 antibody (n=44). All 89 patients (53%) had del(17p) and/or TP53 mutations (91% of 58 patients with TP53 sequencing results available). The median progression-free survival was not obtained after 498 months of follow-up (range, 0.1–95.9). At four years, the progression-free survival rate and overall survival rate were estimated to be 79 and 88%, respectively. The overall response rate was 93%, with 39% of patients receiving a full response. In the investigation, no new safety signals were discovered. At the time of the latest follow-up, 46% of patients were still taking ibrutinib.
The results of the large, pooled, multi-study data set reveal favorable long-term outcomes of first-line ibrutinib-based treatment in patients with TP53 abnormalities, with a median follow-up of four years (up to 8 years).