Long-term follow-up of mTOR inhibition for Erdheim-Chester ...

LETTER TO BLOOD| MAY 28, 2020

Long-term follow-up of mTOR inhibition for Erdheim-Chester disease

Francesco Pegoraro, Valerio Maniscalco, Francesco Peyronel, Pieter J. Westenend, Tadek R. Hendriksz, Rosa M. Roperto, Alessandro A. Palumbo, Elena Sieni, Paola Romagnani, Eric F. H. van Bommel, Augusto Vaglio

Blood (2020) 135 (22): 1994–1997.

https://doi.org/10.1182/blood.2019004478

Subjects:

Clinical Trials and Observations, Immunobiology and Immunotherapy

Topics:

erdheim-chester disease, follow-up, mtor serine-threonine kinases, rapamycin, molecular targeted therapy, histiocytosis, myeloproliferative disease, braf gene

TO THE EDITOR:

Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytosis characterized by tissue infiltration by foamy CD68+ CD1a− histiocytes.1,2  ECD has a putative neoplastic and inflammatory nature. The neoplastic hypothesis is supported by the clonality of the infiltrating histiocytes, which harbor mitogen-activated protein kinase pathway mutations, of which BRAFV600E is the most common.3-5  Immune-mediated mechanisms contribute to histiocytic infiltration through a proinflammatory cytokine–chemokine network.6,7  Different treatments targeting these pathogenic mechanisms are considered first-line approaches for ECD, namely interferon-α (IFN-α), BRAFV600E, and MEK inhibitors. Their efficacy, however, is variable, depending on underlying mutations and organ involvement, and frequently limited by remarkable toxicity.8-16 

The mammalian target of rapamycin (mTOR) regulates cell growth, proliferation and apoptosis, and modulates immune responses. mTOR inhibitors (mTORi’s) (eg, sirolimus, everolimus) are used to treat several neoplastic and inflammatory...

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