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Multi-hit TP53-Aberrant CLL: Focus on Prognostication and Management

By: Jenna Carter, PhD
Posted: Friday, July 16, 2021

A recent article published in Clinical Cancer Research reported on the clinical effects of ibrutinib in patients with multi-hit TP53-mutated chronic lymphocytic leukemia (CLL). Carsten U. Niemann, MD, PhD, of Copenhagen University Hospital, and colleagues focused on TP53 mutations, as they confer resistance to chemoimmunotherapy and are often considered a predictor of poor disease outcomes. Their findings revealed that overall survival, progression-free survival, and time to disease progression were shorter in patients with multi-hit TP53 aberrations.

“Although currently considered equal prognostic markers, patients treated with single-agent ibrutinib carrying only a single TP53 hit [del(17p) or a TP53 mutation] demonstrate excellent progression-free and overall survival on ibrutinib…,” stated the study authors. “An assessment of TP53 aberrations by using both FISH [fluorescence in situ hybridization] and deep NGS [next-generation sequencing] should be performed in all CLL patients considered for treatment with ibrutinib.”

A total of 51 patients with TP53-aberrant CLL in a phase II study of single-agent ibrutinib (420 mg/day) were included in this study. Patients were separated by the number of TP53 aberrations: single hit TP53 (n = 9) and multi-hit TP53 (n= 42). Single-hit and multi-hit TP53 were defined as having one TP53 aberration [del(17p) or a single TP53 mutation] and more than one TP53 aberration [del(17p) and TP53 mutation(s); or multiple TP53 mutations].

Results revealed that patients with multi-hit TP53 demonstrated poorer overall survival and progression-free survival than those with single-hit TP53 or no known aberration (P = .002). Additionally, mutations were enriched among patients with advanced Rai stage relapsed or refractory disease compared with treatment-naive patients (P = .006). Furthermore, multi-hit TP53 CLL was found to be independently associated with poorer progression-free survival and time to disease progression. Based on these findings, the authors concluded that although ibrutinib was successful in prolonging progression-free survival in the single-hit group, further testing is needed for the multi-hit population.

Disclosure: For full disclosure of the study authors, visit clincancerres.org.



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