Richter transformation in diffuse large B-cell lymphoma in patients with chronic lymphocytic leukemia receiving ibrutinib: risk factors and outcomes

作者：Sara Pepe, Candida Vitale, Diana Giannarelli, Andrea Visentin, Alessandro Sanna, Anna Maria Frustaci, Jacopo Olivieri, Francesca Maria Quaglia, Alessandro Gozzetti, Paolo Sportoletti, Roberta Murru, Idanna Innocenti, Gianluigi Reda, Livio Pupo, Luciano Levato, Marika Porrazzo, Fiorella Ilariucci, Riccardo Moia, Myriam Foglietta, Gian Matteo Rigolin, Federico Chiurazzi, Fabio Trastulli, Alessandro Cellini, Marina Deodato, Enrica Antonia Martino, Luca Laurenti, Marta Coscia, Antonio Cuneo, Gianluca Gaïdano, Davide Rossi, Massimo Gentile, Francesca Romana Mauro · 发表于：Leukemia · 年份：2025 · DOI：10.1038/s41375-025-02666-8 · 被引用次数：5 · 研究领域：Chronic Lymphocytic Leukemia Research、Lymphoma Diagnosis and Treatment、Chronic Myeloid Leukemia Treatments

This study aimed to define the incidence and risk factors for diffuse large B cell lymphoma variant of RT (DLBCL-RT) in 976 patients with CLL who received ibrutinib therapy. DLBCL-RT was recorded in 83 (8.5%) patients, with a 7-year 15.6% rate. Most patients exhibited clinical signs of aggressive lymphoma, enlarged lymph nodes in 83%, cytopenia in 60%, and Suv max values ≥ 5 at CT/PET in 98%. Among patients for whom the data was available, 83% had unmutated IGHV, 60% TP 53 disruption, 26% mutated NOTCH1 , 10% were categorized in subset #8 and 82% had a clonally-related lymphoma. Response to chemoimmunotherapy was achieved by 32% of patients. Median OS was 4.7 months, with cytopenia at DLBCL-RT diagnosis being the only significant factor for inferior survival (HR, 1.68). In multivariable analysis, factors predictive for increased risk of DLBCL-RT were age <70 years (HR: 1.98, p = 0.019), TP 53 disruption (HR: 1.72, p = 0.044), with a trend to significance for prior treatment (HR: 1.91, p = 0.065). According to the number of these risk factors, DLBCL-RT rate varied from 4% to 22.6% ( p < 0.0001). In conclusion, patients with CLL receiving ibrutinib with age <70 years, TP 53 disruption and previously treated are at increased risk for developing DLBCL-RT and deserve close monitoring.