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<p>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<sub>max</sub> values ≥ 5 at CT/PET in 98%. Among patients for whom the data was available, 83% had unmutated IGHV, 60% <i>TP</i>53 disruption, 26% mutated <i>NOTCH1</i>, 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 &lt;70 years (HR: 1.98, <i>p</i> = 0.019), <i>TP</i>53 disruption (HR: 1.72, <i>p</i> = 0.044), with a trend to significance for prior treatment (HR: 1.91, <i>p</i> = 0.065). According to the number of these risk factors, DLBCL-RT rate varied from 4% to 22.6% (<i>p</i> &lt; 0.0001). In conclusion, patients with CLL receiving ibrutinib with age &lt;70 years, <i>TP</i>53 disruption and previously treated are at increased risk for developing DLBCL-RT and deserve close monitoring.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月25日

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  • 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 Martino,
  • Luca Laurenti,
  • Marta Coscia,
  • Antonio Cuneo,
  • Gianluca Gaidano,
  • Davide Rossi,
  • Massimo Gentile,
  • Francesca R. Mauro

摘要

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 Suvmax 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.