Pre-existing and treatment-emergent autoimmune cytopenias in patients with CLL treated with targeted drugs.

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Autoimmune cytopenias (AIC) affect 5-9% of patients with chronic lymphocytic leukemia (CLL). Targeted drugs - ibrutinib, idelalisib and venetoclax - have a prominent role in the treatment of CLL, but their impact on CLL-associated AIC is largely unknown. In this study, we evaluated the characteristics and outcome of pre-existing AIC, and described the incidence, quality and management of treatment-emergent AIC during therapy with targeted drugs in patients with CLL. We collected data from 572 patients treated with ibrutinib (9% in combination with an anti-CD20 monoclonal antibody), 143 treated with idelalisib-rituximab and 100 treated with venetoclax (12% in combination with an anti-CD20 monoclonal antibody). A history of pre-existing AIC was reported in 104/815 patients (13%). Interestingly, 80% of patients whose AIC was not resolved at the time of targeted drug start experienced an improvement or a resolution during therapy. Treatment-emergent AIC occurred in 1% of patients during ibrutinib therapy, in 0.9% during idelalisib and in 7% during venetoclax, with an estimated incidence rate of 5, 6 and 69 episodes per 1000 patients per year of exposure in the three treatment groups, respectively. The vast majority of patients who developed treatment-emergent AIC carried unfavorable biological features such as an unmutated IGHV, and a del(17p) and/or TP53 mutation. Notably, despite AIC, 83% of patients were able to continue the targeted drug, in some cases in combination with additional immunosuppressive agents. Overall, treatment with ibrutinib, idelalisib and venetoclax appears to have a beneficial impact on CLL-associated AIC, inducing an improvement or even a resolution of pre-existing AIC in most cases and eliciting treatment-emergent AIC in a negligible portion of patients.


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Authors: Candida Vitale, Chiara Salvetti, Valentina Griggio, Marika Porrazzo, Luana Schiattone, Giulia Zamprogna, Andrea Visentin, Francesco Vassallo, Ramona Cassin, Gian Matteo Rigolin, Roberta Murru, Luca Laurenti, Paolo Rivela, Monia Marchetti, Elsa Pennese, Massimo Gentile, Elia Boccellato, Francesca Perutelli, Maria Chiara Montalbano, Lorenzo De Paoli, Gianluigi Reda, Lorella Orsucci, Livio Trentin, Antonio Cuneo, Alessandra Tedeschi, Lydia Scarfò, Gianluca Gaidano, Francesca Romana Mauro, Robin Foà, Mario Boccadoro, Marta Coscia

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