Study Finds Comparable Outcomes of Multihit Versus Single-Hit TP53 Alterations in CLL

Treatment outcomes did not differ significantly between patients with chronic lymphocytic leukemia (CLL) who had single-hit versus multihit TP53 alterations, according to a study presented at the Eleventh Annual Meeting of the Society of Hematologic Oncology in Houston, Texas.

Multihit TP53 was characterized as the occurrence of multiple TP53 mutations or the combination of TP53 mutation(s) and del(17p). Investigators from the Mayo Clinic identified 145 patients with CLL who were treated between 2014-2021, of which 82 had received treatment prior to the identification of their TP53 mutation.

Of these patients, 90 had multihit TP53 disruptions and 55 patients had single-hit TP53 disruptions. The primary outcome measurements included event-free survival (EFS) and overall survival (OS).

The median EFS for patients with single-hit TP53 disruption was 26.4 months (95% CI, 8.4 to not evaluable [NE]; P=.76), while it was 26.3 months (95% CI, 16.6-NE) in those with multihit TP53 disruptions. Patients in the single-hit TP53 disruption group did not reach the median OS (95% CI, 40.3-NE;P=.87), while patients in the multihit cohort had a median OS of 61.8 months (95% CI, 47.1-NE).

Of the patients who received previous treatment, 44 had undergone Bruton’s tyrosine kinase inhibitor treatment and 38 received chemoimmunotherapy (CIT) only.

In the subgroup analysis, patients with single-hit TP53 alterations (n=9) and those with multihit TP53 alterations (n=19) experienced a median EFS of 8.4 months (95% CI, 4.2-NE) and 4.6 months (95% CI, 2.7-NE; P=.76) respectively. For the single-hit and multihit cohorts, the median OS was NE (95% CI, 8.4-NE) and 46 months (95% CI, 13.1-NE; P=.81) respectively.

For patients in the CIT subgroup, patients with single-hit TP53 alterations (n=11) and those with multihit TP53 alterations (n=17) exhibited a median EFS of 29.8 months (95% CI, 5.4-NE) and 26.3 months (95% CI, 16.1-NE; P=.69), respectively. The median OS was 40.3 months (95% CI, 29.8-NE) and 53.7 months (95% CI, 25.6-NE; P=.52) for single-hit and multihit, respectively.

Reference

Hwang S, Wang Y, Rabe K, et al. Impact of multi-hit vs single-hit TP53 mutations in chronic lymphocytic leukemia. Abstract CLL-081. Presented at the Eleventh Annual Meeting of the Society of Hematologic Oncology; September 6-9, 2023; Houston, Texas.