Dissociated response and treatment outcome with immune checkpoint blockade in advanced cancer

Immune-related dissociated response (DR) has been recently recognized and have become a subject of ongoing interest. The purpose of the present study was to evaluate the frequency, treatment outcome, and predictors of DR in cancer patients with immune checkpoint inhibitors. We retrospectively collected clinicopathological data from a cohort of patients with cancer who received PD-1/PD-L1 inhibitor-based monotherapy or combination therapy at a single institution (developing cohort). An independent cohort of advanced non-small cell lung cancer (NSCLC) patients treated with immunotherapy at two institutions was used as the validating cohort. Progression‐free survival (PFS) and overall survival (OS) were used as outcome measures. The pantumor cohort included 177 patients. DR were observed in 12 (6.8%) patients. The median PFS and OS were significantly longer in patients with atypical response versus nonresponse but shorter versus true response. Patients with DR had a longer median PFS and OS than those with true PD. Local treatment seemed to have a positive influence on DR patient outcomes, with a median OS of 32.3 months versus 21.9 months for no local treatment. No clinical characteristics remained significant predictors for DR. In the NSCLC cohort, DR was observed in 10 (12.5%) patients. Inferior PFS and OS were validated in patients with real PD when compared with patients with DR. Patients who experience DR exhibit a relatively favorable prognosis. Some patients with DR may benefit from thecontinuation of ICI administration and local treatment to the growing lesions and achieve a longer survival.