Increased frequency of acute reactions to iodinated contrast media after anti-CTLA-4 immunomodulating antibodies in cancer patients

Abstract

Background: The aim of this study was to investigate whether cancer immunotherapy, in particular with immune checkpoint inhibitors, increased the incidence of allergy-like immediate adverse reactions to iodinated contrast media (ICM) with respect to “standard” cancer chemotherapy or targeted therapy. Methods: We retrospectively evaluated the incidence of contrast-enhanced computed tomography (CECT)-related immediate adverse reactions (ARs) in cancer patients undergoing treatment. Using an institutional radiological database (Elefante, Agfa), we identified all consecutive cancer patients who performed at least one CECT after starting any medical cancer treatment at our institute between January 1, 2006 and December 31, 2014. All patients were outpatients and with a performance status of 0-1 by ECOG scale. Each ICM-related AR was classified according to the American College of Radiology Manual on Contrast Media, version 10.1 as “allergy-like” or “physiologic” and graded as mild, moderate, or severe. Results: The final database included 3,521 patients who underwent first- or second-line systemic treatment for metastatic disease and were re-evaluated at the end of treatment with CECT. Fifty-nine of the 3521 patients received ipilimumab (Ipi), 75 received cytokines (Cy), and the remaining 3,387 received non-immunologic agents (CHT). The mean number of CT scans performed before the index CT scan did not significantly differ between groups (p = 0.190). Overall, 71 (2%) patients developed ICM-ARs. The distribution of events among the groups was: 11.9% of reactions in Ipi patients (7/59), 5.3% in ts (4/75), and 1.8% in the CHT ones (60/3,387) with a p < 0.001 that indicates a significant statistically difference between treatment groups and reactions number. All the ARs registered in the Ipi and Cy groups were allergy-like reactions, while 10% of the ARs observed in the CHT group were of the physiologic type (6/60). Conclusions: Our data show that immunological cancer treatments, Ipi in particular, considerably increase the risk of developing CECT-related immediate adverse reactions with respect to non-immunologic agents. Although these findings now need to be validated in larger prospective studies, they serve as a “wake-up call” to radiologists to closely monitor patients who have previously received cancer immunotherapy with anti- CTLA 4-antibodies when using ICM in order to reduce the risk of potentially severe immediate adverse reactions.