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Immunotherapy in Multiple Myeloma

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Front. Immunol. | doi: 10.3389/fimmu.2018.02749

Promises and Pitfalls in the Use of PD-1/PD-L1 Inhibitors in Multiple Myeloma

Stefania Oliva1, Rossella Troia1, Mattia D'Agostino1,  Mario Boccadoro1 and  Francesca Gay1*
  • 1A.O.U. Citta della Salute e della Scienza di Torino, Italy

In the biology of multiple myeloma (MM), immune dysregulation has emerged as a critical component for novel therapeutic strategies. This dysfunction is due to a reduced antigen presentation, a reduced effector cell ability and a loss of reactive T cells against myeloma, together with a bone marrow microenvironment that favors immune escape. The Programmed Death-1 (PD-1) pathway is associated with the regulation of T cell activation and with the apoptotic pathways of effector memory T cells. Specifically, the binding with PD-1 ligand (PD-L1) on the surface of tumor plasma cells down-regulates T cell-proliferation, thus contributing to the immune escape of tumor cells. In relapsed and/or refractory MM (RRMM) patients, PD-1/PD-L1 blockade was analyzed by using nivolumab, pembrolizumab and durvalumab. Outcomes with single agents were unsatisfactory, whereas combination strategies with backbone immunomodulatory drugs (IMiDs) suggested a synergistic action in such a complex immunological landscape, even in patients previously refractory to these drugs. Nevertheless, these combinations were also associated with an increased incidence of adverse events. This review aims to analyze the available preclinical and clinical data on the role of PD-1/PD-L1 inhibitors in MM therapy, focusing on available preliminary efficacy and safety data and offering insights for future investigation.

Keywords: Multiple Myeloma, PD-1, PDL-1, Immune dysregulation, T cells

Received: 16 Jul 2018; Accepted: 08 Nov 2018.

Edited by:

Nicola Giuliani, Università degli Studi di Parma, Italy

Reviewed by:

William K. Decker, Baylor College of Medicine, United States
Fabienne McClanahan, The Ohio State University, United States  

Copyright: © 2018 Oliva, Troia, D'Agostino, Boccadoro and Gay. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Francesca Gay, A.O.U. Citta della Salute e della Scienza di Torino, Turin, Italy,