Comprehensive adjusted outcome data are needed to assess the impact of immune checkpoint inhibitors in cancer patients with COVID-19: Results of a systematic review and meta-analysis

Background Determining how prior immune checkpoint inhibitor (ICI) therapy influences outcomes in cancer patients presenting with COVID-19 is essential for patient management but must account for confounding variables. Methods We performed a systematic review and meta-analysis of studies reporting adjusted effects of ICIs on survival, severe events, or hospitalisation in cancer patients with COVID-19 based on variables including age, gender, diabetes mellitus, hypertension (HTN), chronic obstructive pulmonary disease, and other comorbidities. When adjusted effects were unavailable, unadjusted data were analysed. Results Of 42 observational studies (38 retrospective), 7 reported adjusted outcomes for ICIs and 2 provided sufficient individual patient data to calculate adjusted outcomes. In eight studies, adjusted outcomes were based on <= 7 variables. Over all studies, only one included >100 ICI patients while 26 included <10. ICIs did not alter the odds ratio (95%CI) (OR) of death significantly (random effects model), across adjusted (n = 8) [1.31 (0.58-2.95) p = 0.46; I-2 = 42%, p = 0.10], unadjusted (n = 30) [1.06 (0.85-1.32) p = 0.58; I-2 = 0%, p = 0.76] or combined [1.09 (0.88;1.36) p = 0.41; I-2 = 0%, p = 0.5)] studies. Similarly, ICIs did not alter severe events significantly across adjusted (n = 5) [1.20 (0.30-4.74) p = 0.73; I-2 = 52%, p = 0.08], unadjusted (n = 19) [(1.23 (0.87-1.75) p = 0.23; I-2 = 16%, p = 0.26] or combined [1.26 (0.90-1.77) p = 0.16; I-2 = 25%, p = 0.14] studies. Two studies provided adjusted hospitalisation data and when combined with 13 unadjusted studies, ICIs did not alter hospitalisation significantly [1.19 (0.85-1.68) p = 029; I-2 = 5%, p = 0.40]. Results of sensitivity analyses examining ICI effects based on 5 variables were inconclusive. Certainty of evidence was very low. Conclusions Across studies with adjusted and unadjusted results, ICIs did not alter outcomes significantly. But studies with comprehensive adjusted outcome data controlling for confounding variables are necessary to determine whether ICIs impact COVID-19 outcomes in cancer patients.