Leukocytes with bound platelets as a predictive biomarker for immune-related adverse events (irAEs) in advanced non-small cell lung cancer (NSCLC) patients (pts) receiving anti-PD-(L)1 agents.

Abstract

e15047 Background: Anti-PD-(L)1 blocking agents can induce irAEs, compromising treatment continuation and patient safety. Since complexes of leukocyte-platelet have been shown to play a role in inflammation by reducing cytokine production, we hypothesize that the percentage of these complexes could be used as a predictor of irAEs in pts receiving anti-PD-(L)1 agents. Methods: From May 2015 to January 2019, 87 advanced NSCLC pts treated with anti-PD-(L)1 agents at our institution were prospectively included. Percentages of circulating CD4+T lymphocytes and monocytes with bound platelets (CD4+PLT+ and CD14+PLT+, respectively) were obtained by flow cytometry and compared between NSCLC pts and healthy donors (HD, n = 26). The association of leukocyte-platelet complexes with the presence of irAEs was analyzed. According to CD4+PLT+ and CD14+PLT+ levels, NSCLC pts were grouped as CD4+PLT+ high (n = 29), CD4+PLT+ low (n = 58) and as CD14+PLT+ high (n = 36) and CD14+PLT+ low (n = 51). Frequencies and grade of irAEs were compared between groups using Chi-square test. Results: NSCLC pts showed significant higher percentages of circulating CD4+PLT+ and CD14+PLT+ than HD (9.41±0.54% vs. 6.01±0.45% and 57.44±2.42 vs. 35.43±2.22, respectively; p< 0.001). No significant differences in CD4+PLT+ and CD14+PLT+ were found according to the presence of irAEs. CD4+PLT+ high group presented a higher rate of dermatological irAEs while CD4+PLT+ low group showed higher rate of non-dermatological irAEs (dermatological: 44.85% vs. 8.6%; non-dermatological: 10.3% vs. 39.7%, respectively; p< 0.001). Lower percentage of grade ≥2 irAEs was observed in the CD4+PLT+ high group than in the CD4+PLT+ low group (17.3% vs. 41.4%; p< 0.05). No significant differences in the type of irAEs were observed between CD14+ PLT+ high and low groups. Pts with CD4+PLT+ high and CD14+PLT+ low levels showed the lowest rate of irAEs, presenting only grade ≤1 irAEs (53.8% dermatological, 7.7% dermatological + non-dermatological, 38.5% no-irAEs). In contrast, pts with CD4+PLT+ low and CD14+PLT+ high levels presented higher rate of grade ≥3 irAEs (50% grade 0-1, 20% grade 2, 30% grade ≥3; p< 0.05) and predominantly developed non-dermatological irAEs (45% non-dermatological, 30% dermatological + non-dermatological, 25% no-irAEs; p< 0.01). Conclusions: Combining CD4+ PLT+ and CD14+ PLT+ levels may be used as predictive of development and severity of irAEs in advanced NSCLC pts receiving anti-PD-(L)1 agents.