Ibrutinib induces durable remissions in treatment-naïve patients with CLL and 17p deletion and/or TP53 mutations

Bruton's tyrosine kinase (BTK) inhibitors and the BCL-2 antagonist venetoclax have significantly improved the outcome of patients with chronic lymphocytic leukemia (CLL). 1 Nonetheless, high-risk patients with 17p deletion (del17p) and/or TP53 mutations have an increased risk for treatment failure with BTK inhibitors in relapsed or refractory (R/R) CLL 2 and with venetoclax in first-line 3 and relapsed CLL therapy 4 when compared with patients with lower-risk features.For example, the median progression-free survival (PFS) of heavily pretreated R/R patients with CLL receiving ibrutinib in the PCYC-1102 study was 52 months, but it was only 26 months for those with del17p and/or TP53 mutations. 2The duration of remission is longer when BTK inhibitors are used in earlier lines of therapy, especially in patients with CLL who are treatment-naïve.Importantly, other CLL high-risk features (unmutated IGHV, del11q) no longer predict for inferior outcome when ibrutinib is used as first-line therapy for CLL, and consequently these high-risk patients have survival outcomes that are equivalent to those of patients with low-risk CLL. 5 Whether this also applies to patients with CLL who have TP53 aberrations is not well established, because these patients were excluded from pivotal CLL first-line trials. 5,6ecently, long-term outcome from a cohort of 34 treatmentnaïve patients with CLL and TP53 alterations reported a 6-year PFS of 61% and overall survival (OS) of 79%. 7Here, we report the long-term outcome of 27 treatment-naïve patients with CLL and del17p and/or TP53 mutations who are receiving ibrutinib alone or in combination with rituximab on an investigatorinitiated phase 2 trial.This trial was registered at www. clinicaltrials.