Checkpoint Inhibition Prior to Stem Cell Transplantation Increases the Risk of Inflammatory Adverse Events.

Abstract

Background: Stem cell transplantation (SCT) and immune checkpoint inhibitors (ICIs) are both used in the treatment of hematological malignancies. There may be an overlap in patient exposure to both treatments. Theoretically, ICIs potentiate the graft-versus-tumor effect following SCT but may increase the risk of inflammatory adverse events (AEs). Conversely, immunosuppression following SCT may decrease the risk of immune-mediated AEs.

Objectives: We aimed to explore the effect of immunotherapy on the risk and severity of inflammatory AEs following SCT.

Patients and methods: We performed a single-center, retrospective chart review that included all patients with a hematological malignancy treated with immunotherapy and who received SCT. Patients who did not receive immunosuppressive regimens after their transplant (e.g., autologous transplants) were excluded. Patients were divided into two groups based on ICI timing: pre-SCT ICI (group 1) and post-SCT ICI (group 2).

Results: A total of 63 patients were included. Around 82% of patients in group 1 experienced a post-transplant AE compared with 50% in group 2 (p = 0.014). These AEs occurred earlier in group 1 patients (median 57 days in group 1 versus 195 in group 2; p = 0.007). Roughly 80% of the inflammatory conditions involved the gastrointestinal system. Severity and complication rates did not differ between groups, but gastrointestinal inflammation in group 1 was more likely to require immunosuppressive medication (75.7% and 37.8% requiring corticosteroids and selective immunosuppressive therapy, respectively, in group 1 patients versus 33.3% and 0% in group 2 patients; p < 0.05).

Conclusion: To our knowledge, our study is one of few exploring the impact of ICI timing in relation to SCT on the risk of post-SCT inflammatory AEs. Administration of immunotherapy prior to SCT may predispose patients to inflammatory AEs after SCT, which may occur earlier and last longer than if ICIs are started after SCT. Future studies are needed to further explore this phenomenon.