Autoimmune cytopenias (AICs) affect 5% to 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 AICs is largely unknown. In this study, we evaluated the characteristics and outcome of preexisting AICs and described the incidence, quality, and management of treatment-emergent AICs 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 preexisting AICs was reported in 104 (13%) of 815 patients. Interestingly, 80% of patients whose AICs had not resolved when treatment with a targeted drug was started experienced an improvement or a resolution during therapy. Treatment-emergent AICs occurred in 1% of patients during ibrutinib therapy, in 0.9% during idelalisib therapy, and in 7% during venetoclax therapy, with an estimated incidence rate of 5, 6, and 69 episodes per 1000 patients per year of exposure in the 3 treatment groups, respectively. The vast majority of patients who developed treatment-emergent AICs had unfavorable biological features such as an unmutated IGHV and a del(17p) and/or TP53 mutation. Notably, despite AICs, 83% of patients were able to continue the targeted drug, in some cases in combination with additional immunosuppressive agents. Overall, treatment with ibrutinib, idelalisib, or venetoclax seems to have a beneficial impact on CLL-associated AICs, inducing an improvement or even a resolution of preexisting AICs in most cases and eliciting treatment-emergent AICs in a negligible portion of patients.

Vitale, C., Salvetti, C., Griggio, V., Porrazzo, M., Schiattone, L., Zamprogna, G., Visentin, A., Vassallo, F., Cassin, R., Rigolin, G. M., Murru, R., Laurenti, L., Rivela, P., Marchetti, M., Pennese, E., Gentile, M., Boccellato, E., Perutelli, F., Montalbano, M. C., De Paoli, L., Reda, G., Orsucci, L., Trentin, L., Cuneo, A., Tedeschi, A., Scarfo, L., Gaidano, G., Mauro, F. R., Foa, R., Boccadoro, M., Coscia, M., Preexisting and treatment-emergent autoimmune cytopenias in patients with CLL treated with targeted drugs, <<BLOOD>>, 2021; 137 (25): 3507-3517. [doi:10.1182/blood.2020008201] [http://hdl.handle.net/10807/184587]

Preexisting and treatment-emergent autoimmune cytopenias in patients with CLL treated with targeted drugs

Salvetti C.;Laurenti L.;Gentile M.;Tedeschi A.;Foa R.;
2021

Abstract

Autoimmune cytopenias (AICs) affect 5% to 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 AICs is largely unknown. In this study, we evaluated the characteristics and outcome of preexisting AICs and described the incidence, quality, and management of treatment-emergent AICs 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 preexisting AICs was reported in 104 (13%) of 815 patients. Interestingly, 80% of patients whose AICs had not resolved when treatment with a targeted drug was started experienced an improvement or a resolution during therapy. Treatment-emergent AICs occurred in 1% of patients during ibrutinib therapy, in 0.9% during idelalisib therapy, and in 7% during venetoclax therapy, with an estimated incidence rate of 5, 6, and 69 episodes per 1000 patients per year of exposure in the 3 treatment groups, respectively. The vast majority of patients who developed treatment-emergent AICs had unfavorable biological features such as an unmutated IGHV and a del(17p) and/or TP53 mutation. Notably, despite AICs, 83% of patients were able to continue the targeted drug, in some cases in combination with additional immunosuppressive agents. Overall, treatment with ibrutinib, idelalisib, or venetoclax seems to have a beneficial impact on CLL-associated AICs, inducing an improvement or even a resolution of preexisting AICs in most cases and eliciting treatment-emergent AICs in a negligible portion of patients.
eng
Vitale, C., Salvetti, C., Griggio, V., Porrazzo, M., Schiattone, L., Zamprogna, G., Visentin, A., Vassallo, F., Cassin, R., Rigolin, G. M., Murru, R., Laurenti, L., Rivela, P., Marchetti, M., Pennese, E., Gentile, M., Boccellato, E., Perutelli, F., Montalbano, M. C., De Paoli, L., Reda, G., Orsucci, L., Trentin, L., Cuneo, A., Tedeschi, A., Scarfo, L., Gaidano, G., Mauro, F. R., Foa, R., Boccadoro, M., Coscia, M., Preexisting and treatment-emergent autoimmune cytopenias in patients with CLL treated with targeted drugs, <>, 2021; 137 (25): 3507-3517. [doi:10.1182/blood.2020008201] [http://hdl.handle.net/10807/184587]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/184587
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