Pepe Sara, Vitale Candida, Giannarelli Diana, Visentin Andrea, Sanna Alessandro, Frustaci Anna Maria, Olivieri Jacopo, Quaglia Francesca Maria, Gozzetti Alessandro, Sportoletti Paolo, Murru Roberta, Innocenti Idanna, Reda Gianluigi, Pupo Livio, Levato Luciano, Porrazzo Marika, Ilariucci Fiorella, Moia Riccardo, Foglietta Myriam, Rigolin Gian Matteo, Chiurazzi Federico, Trastulli Fabio, Cellini Alessandro, Deodato Marina, Martino Enrica, Laurenti Luca, Coscia Marta, Cuneo Antonio, Gaidano Gianluca, Rossi Davide, Gentile Massimo, Mauro Francesca R
Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy.
Department of Molecular Biotechnology and Health Sciences, University of Torino and Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy.
Leukemia. 2025 Jun 25. doi: 10.1038/s41375-025-02666-8.
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 values ≥ 5 at CT/PET in 98%. Among patients for whom the data was available, 83% had unmutated IGHV, 60% TP53 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), TP53 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, TP53 disruption and previously treated are at increased risk for developing DLBCL-RT and deserve close monitoring.
本研究旨在确定976例接受依鲁替尼治疗的慢性淋巴细胞白血病（CLL）患者中，RT弥漫性大B细胞淋巴瘤变体（DLBCL-RT）的发病率及危险因素。83例（8.5%）患者记录有DLBCL-RT，7年发病率为15.6%。大多数患者表现出侵袭性淋巴瘤的临床体征，83%有淋巴结肿大，60%有血细胞减少，98%在CT/PET检查时Suv值≥5。在有可用数据的患者中，83%的患者IGHV未突变，60%的患者TP53功能破坏，26%的患者NOTCH1突变，10%属于8号亚组，82%有克隆相关淋巴瘤。32%的患者对化疗免疫疗法有反应。中位总生存期为4.7个月，DLBCL-RT诊断时血细胞减少是生存较差的唯一显著因素（风险比[HR]，1.68）。在多变量分析中，预测DLBCL-RT风险增加的因素为年龄<70岁（HR：1.98，p = 0.019）、TP53功能破坏（HR：1.72，p = 0.044），既往治疗有显著趋势（HR：1.91，p = 0.065）。根据这些危险因素的数量，DLBCL-RT发生率从4%到22.6%不等（p < 0.0001）。总之，年龄<70岁、TP53功能破坏且既往接受过治疗的接受依鲁替尼治疗的CLL患者发生DLBCL-RT的风险增加，值得密切监测。
