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 pre-clinical mesothelioma model; however, the addition of dexamethasone to gemcitabine and immune checkpoint inhibitors nullified the synergistic clinical response. Further, treatment with gemcitabine plus anti-PD-1 resulted in an objective clinical response in two mesothelioma patients, who were resistant to gemcitabine or anti-PD-1 as monotherapy. Conclusion: Thus, treatment of mesothelioma with a combination of gemcitabine with immune checkpoint inhibitors is feasible and results in synergistic clinical response compared to single treatment in the absence of steroids.

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