Patients with chronic lymphocytic leukemia with aberrations in the oncogene TP53 respond poorly to first-line chemoimmunotherapy, which leads to early relapse and shortened patient survival. Genetic damage caused by deletion of chromosome band 17p13.1 resulted in P53 pathway-induced cell death, and inactivation of this pathway was associated with chemoresistance. Selection for chemoresistant genes during treatment increased the occurrence of TP53 aberrations at relapse. Erutinib is an oral BTK covalent inhibitor that causes sustained inactivation, which in turn leads to inhibition of B-cell receptor signaling and tumor microenvironment interactions. Based on the high activity of ibrutinib in slow gonorrhea and the few treatment options for patients with TP53 aberrations, Mohammed Z HFarooqui and others at the National Institutes of Health, National Heart, Lung, and Blood Institute conducted a study to evaluate the safety and efficacy of ibrutinib in high-risk patients. The study was published online in The lancet oncology. Subjects were required to have a diagnosis of slow gonorrhea, identified by fluorescence in situ hybridization (FISH) with 17p13.1 deletion or without 17p13.1 deletion but with TP53 aberrations; active disease according to the International Working Group on Chronic Lymphocytic Leukemia (IWCLL) entry criteria; age 18 years and older; ECOG physical status score of 0, 1 or 2; neutrophil count of not less than 500/μL; platelet count of not less than 30 000/μL. Patients received 28-day cycles of oral ibrutinib 420 mg daily until disease progression or onset of restrictive toxicity. The primary endpoint was the overall effectiveness of treatment in all evaluable patients after 6 treatment cycles, with secondary endpoints of safety, overall survival, progression-free survival, optimal effectiveness, and nodal effectiveness. A total of 51 patients with slow gonorrhea were included in the study: 47 patients with 17p13.1 deletion and 4 without 17p13.1. deletion but with TP53 aberrations. All patients had active disease and required treatment. Thirty-five of these patients had primary treatment and 16 had relapsed/refractory disease. The median follow-up time was 24 months. Response was evaluable over 6 treatment cycles in 33 primary and 15 relapsed/refractory patients. 97% of primary patients achieved objective effectiveness, 1 patient had progressive disease at 0-4 months, and 80% of relapsed/refractory patients achieved objective effectiveness. 3rd degree or greater treatment-related adverse events were neutropenia in 24% of patients, anemia in 14%, thrombocytopenia in 10%, pneumonia in 6%, and rash in 3% . The encouraging safety and activity of ibrutinib alone in patients with TP53 aberrations in slow gonorrhea supports its use as a new first- and second-line treatment option for this high-risk patient. Tumor microenvironment interactions and B-cell receptor signaling are key pathogenic pathways and targets for new therapeutic approaches in slow-onset gonorrhea. The substantial reduction in disease load and the significant reduction in intracellular signaling, cell activation and value-added across different anatomical structures are consistent with BTK acting as a key node in many signaling pathways. Single-agent ibrutinib induces sustained remission in patients with TP53 aberrations in slow gonorrhea. Treatment failure was rare in primary patients. 17p13.1 deletion was equally sensitive to ibrutinib as subclones without this deletion, which is consistent with the P53-independent mechanism of action of the drug. Longer follow-up is needed to assess the impact of this targeted agent on long-term survival, which will shed light on whether ibrutinib can eventually replace allogeneic stem cell transplantation.