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The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon’s design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years; 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2–37.9). Four patients were on treatment >6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment >6 months.

BackgroundThe search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator.MethodsBlood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations.ResultsIn this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival.ConclusionsIn conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL.