Treatment of Erdheim–Chester disease (ECD), a rare non-Langerhans histiocytosis, relies on interferon-a, chemotherapeutic agents such as purine analogs, cytokine-blocking agents and BRAF inhibitors. Since interleukin (IL)-6 levels are elevated in serum and lesions of ECD patients, we evaluated the therapeutic efficacy and safety of IL-6 blockade with tocilizumab. We conducted an open-label, single-arm, phase II, prospective study of tocilizumab in three patients with multisystem ECD and poor tolerance/contraindications to IFN-a. Modifications of symptoms attributed to ECD represented the criteria for evaluation of clinical response. Changes at positron emission tomography scan, computed tomography scan, and magnetic resonance imaging at month 6 represented the main criteria for the evaluation of radiological response. Sustained complete clinical response and partial radiological improvement were observed in two patients, paralleled by modulation of systemic pro-inflammatory mediators. In spite of disease stabilization or improvement at extra-neurological sites, a third patient experienced a radiologic and clinical progression of central nervous system involvement, mirrored by a dramatic increase of circulating IL-6 and related cytokines. These findings indicate that IL-6 inhibition can be effective in ECD, but caution is advisable in patients with neurologic involvement. IL-6 emerges as a central mediator in ECD pathogenesis.

Tocilizumab in patients with multisystem Erdheim-Chester disease / Berti, A; Cavalli, G; Guglielmi, B; Biavasco, R; Campochiaro, C; Tomelleri, A; Nicoletti, R; Panzacchi, A; Ferrarini, M; Dagna, L. - In: ONCOIMMUNOLOGY. - ISSN 2162-4011. - 2017, 6:6(2017), pp. e13182371-e13182376. [10.1080/2162402X.2017.1318237]

Tocilizumab in patients with multisystem Erdheim-Chester disease

Berti A
Primo
;
2017-01-01

Abstract

Treatment of Erdheim–Chester disease (ECD), a rare non-Langerhans histiocytosis, relies on interferon-a, chemotherapeutic agents such as purine analogs, cytokine-blocking agents and BRAF inhibitors. Since interleukin (IL)-6 levels are elevated in serum and lesions of ECD patients, we evaluated the therapeutic efficacy and safety of IL-6 blockade with tocilizumab. We conducted an open-label, single-arm, phase II, prospective study of tocilizumab in three patients with multisystem ECD and poor tolerance/contraindications to IFN-a. Modifications of symptoms attributed to ECD represented the criteria for evaluation of clinical response. Changes at positron emission tomography scan, computed tomography scan, and magnetic resonance imaging at month 6 represented the main criteria for the evaluation of radiological response. Sustained complete clinical response and partial radiological improvement were observed in two patients, paralleled by modulation of systemic pro-inflammatory mediators. In spite of disease stabilization or improvement at extra-neurological sites, a third patient experienced a radiologic and clinical progression of central nervous system involvement, mirrored by a dramatic increase of circulating IL-6 and related cytokines. These findings indicate that IL-6 inhibition can be effective in ECD, but caution is advisable in patients with neurologic involvement. IL-6 emerges as a central mediator in ECD pathogenesis.
2017
6
Berti, A; Cavalli, G; Guglielmi, B; Biavasco, R; Campochiaro, C; Tomelleri, A; Nicoletti, R; Panzacchi, A; Ferrarini, M; Dagna, L
Tocilizumab in patients with multisystem Erdheim-Chester disease / Berti, A; Cavalli, G; Guglielmi, B; Biavasco, R; Campochiaro, C; Tomelleri, A; Nicoletti, R; Panzacchi, A; Ferrarini, M; Dagna, L. - In: ONCOIMMUNOLOGY. - ISSN 2162-4011. - 2017, 6:6(2017), pp. e13182371-e13182376. [10.1080/2162402X.2017.1318237]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/376470
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