Gemcitabine synergizes with immune checkpoint inhibitors and overcomes resistance in a preclinical model and mesothelioma patients.

Purpose: Combination of immune checkpoint inhibitors with chemotherapy is under investigation for cancer treatment. Experimental Design: We studied the rationale of such a combination for treating mesothelioma, a disease with limited treatment options. Results: The combination of gemcitabine and immune checkpoint inhibitors outperformed immunotherapy alone with regard to tumor control and survival in a preclinical mesothelioma model; however, the addition of dexametha-sone to gemcitabine and immune checkpoint inhibitors nullified the synergistic clinical response. Furthermore, treatment with gemcitabine plus anti-PD-1 resulted in an objective clinical response in two patients with mesothelioma, who were resistant to gemcitabine or anti-PD-1 as monotherapy. Conclusions: Thus, treatment of mesothelioma with a combination of gemcitabine with immune checkpoint inhibitors is feasible and results in synergistic clinical response compared with single treatment in the absence of steroids. (C) 2018 AACR.