Immune checkpoint inhibitors-associated thrombosis in patients with lung cancer and melanoma: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group.

PURPOSE: Immune Checkpoint Inhibitors (ICI) can be associated with thrombotic events, both venous and arterial (VTE/AT). However, there is a paucity of information regarding patients in routine clinical practice. METHODS/PATIENTS: Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Patients with melanoma and lung cancer who initiated ICI between 01/01/2015 and 31/12/2019 were recruited. Minimum follow-up was 6 months (unless it was not possible because of death). The primary objective was to calculate the incidence of ICI-associated VTE/AT and the secondary objectives included to analyze its impact on survival and to identify predictor variables for VTE/AT. RESULTS: 665 patients with lung cancer were enrolled. The incidence of VTE/AT during follow-up was 8.4%. Median overall survival (OS) was lower in the VTE/AT group (12 months 95% CI 4.84-19.16 vs. 19 months 95% CI 16.11-21.9; p = 0.0049). Neutrophil/lymphocyte ratio (NLR) and anemia upon initiation of IT, as well as a history of thrombosis between cancer diagnosis and the start of ICI, were predictive variables for developing of VTE/AT (p < 0.05). 291 patients with melanoma were enrolled. There was a 5.8% incidence rate of VTE/AT during follow-up. Median OS was lower in the VTE/AT group (10 months 95% CI 0.0-20.27 vs. 29 months 95% CI 19.58-36.42; p = 0.034). NLR and lactate dehydrogenase (LDH) at the beginning of ICI were predictor variables for VTE/AT (p < 0.05). CONCLUSIONS: ICI increases the risk of VTE/AT in patients with lung cancer and melanoma, which impact OS.

Trial Watch: Immunostimulation with recombinant cytokines for cancer therapy.

Cytokines regulate virtually aspects of innate and adaptive immunity, including the initiation, execution and extinction of tumor-targeting immune responses. Over the past three decades, the possibility of using recombinant cytokines as a means to elicit or boost clinically relevant anticancer immune responses has attracted considerable attention. However, only three cytokines have been approved so far by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, namely, recombinant interleukin (IL)-2 and two variants of recombinant interferon alpha 2 (IFN-α2a and IFN-α2b). Moreover, the use of these cytokines in the clinics is steadily decreasing, mostly as a consequence of: (1) the elevated pleiotropism of IL-2, IFN-α2a and IFN-α2b, resulting in multiple unwarranted effects; and (2) the development of highly effective immunostimulatory therapeutics, such as immune checkpoint blockers. Despite this and other obstacles, research in the field continues as alternative cytokines with restricted effects on specific cell populations are being evaluated. Here, we summarize research preclinical and clinical developments on the use of recombinant cytokines for immunostimulation in cancer patients.