LAUSR

Long‐term follow up of prospective studies has shown that continuous Bruton's tyrosine kinase inhibitor (BTKi) therapy leads to durable remissions in previously untreated patients with TP53‐altered chronic lymphocytic leukemia (CLL); however, it is unknown how variant allele frequency (VAF) of TP53 mutation (TP53‐m) or percentage of cells with deletion of chromosome 17p [del(17p)] influences efficacy of firstline BTKi. We performed a retrospective analysis of 130 patients with CLL with baseline del(17p) and/or TP53‐m treated with BTKi with or without the BCL2 inhibitor venetoclax (VEN) and with or without CD20 antibody in the firstline setting. A total of 104/130 (80%) patients had del(17p). TP53‐m was noted in 89/110 (81%) patients tested; there were 101 unique TP53‐m with an available VAF. The 4‐year progression‐free survival (PFS) and overall survival (OS) rates were 72.9% and 83.6%. No baseline characteristics including IGHV mutation status and number of TP53 alterations were associated with significant differences in PFS or OS, though a trend toward shorter PFS with increasing karyotypic complexity (hazard ratio 1.08, p = .066) was observed. Del(17p) was identified in <25% of cells in 26/104 (25%) of patients, and 28/101 (28%) of TP53‐m were low‐burden with a VAF of <10%; outcomes of these patients were similar to those with high‐burden lesions. This study suggests that low‐burden TP53 alterations should not be ignored when assessing genomic risk in CLL in the era of targeted therapy.