Can checkpoint inhibitor therapy improve response to chemotherapy?

Abstract

e21024 Background: Even though immune checkpoint inhibitors (ICPI) are very effective with the wider use of single or combination treatment an increasing number of patients show resistance to treatment. If patients with metastatic melanoma progress and targeted therapy has also failed or is not feasible due to the lack of targetable mutations chemotherapy remains a treatment option. There is strong evidence that high mutational load leading to formation of so-called neoantigens is a major determinant of ICPI benefit. Additionally, chemotherapy has been described to modulate the microenvironment and the immune system. Here, we assess the efficacy of chemotherapy after checkpoint inhibitor failure in a series of advanced melanoma patients. Methods: We evaluated overall survival and response to chemotherapy of patients with progressive disease under previous treatment with the immune checkpoint inhibitors anti-CTLA4 and anti-PD1. Three skin cancer centers included a total of 17 patients. All BRAF-mutated patients had also progressed under previous BRAF/MEK-inhibitor therapy. Of all patients, 71% showed an elevated LDH, 41% had brain metastases and 35% an ECOG of 2 at initiation of chemotherapy. Results: Tumor control, defined as complete response, partial response, mixed response or stable disease was achieved in 53% (n = 9) of the patients who had previously been clearly progressive. The mean overall survival was 13.1 months with 65% (n = 11) of the patients still being alive. The choice of chemotherapy did not seem to influence the overall survival or tumor control rate. Conclusions: Immune checkpoint inhibitors could increase response to chemotherapy. The combination of chemotherapy and immunotherapy might be beneficial and increase tumor control.