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

Media type: E-Article

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

Contributor: Vitale, Candida; Salvetti, Chiara; Griggio, Valentina; Porrazzo, Marika; Schiattone, Luana; Zamprogna, Giulia; Visentin, Andrea; Vassallo, Francesco; Cassin, Ramona; Rigolin, Gian Matteo; Murru, Roberta; Laurenti, Luca; Rivela, Paolo; Marchetti, Monia; Pennese, Elsa; Gentile, Massimo; Boccellato, Elia; Perutelli, Francesca; Montalbano, Maria Chiara; De Paoli, Lorenzo; Reda, Gianluigi; Orsucci, Lorella; Trentin, Livio; Cuneo, Antonio; [...]

imprint: American Society of Hematology, 2021

Language: English

DOI: 10.1182/blood.2020008201

ISSN: 0006-4971; 1528-0020

Keywords: Cell Biology ; Hematology ; Immunology ; Biochemistry

Origination:

Footnote:

Description: AbstractAutoimmune 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.

Access State: Open Access

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