The Risk of Opportunistic Infections and the Role of Antibiotic Prophylaxis in Patients on Checkpoint Inhibitors Requiring Steroids

Abstract

Background: Immune-related adverse events (irAEs) often require treatment with high-dose systemic steroids (SS) and other immunosuppressive agents (ISAs). NCCN Guidelines recommend prophylactic antibiotics for Pneumocystis jirovecii pneumonia (PJP) for patients receiving prolonged SS/ISAs. However, there is a paucity of evidence regarding the incidence of opportunistic infections (OIs) and non-OIs and the role of prophylactic antibiotics in patients on SS/ISAs for irAEs. Methods: A retrospective analysis was conducted of patients treated using immune checkpoint inhibitor (ICI) therapy at 5 MedStar Health hospitals from January 2011 to April 2018. OIs were defined per the Infectious Diseases Society of America guidelines for the prevention and treatment of OIs in patients with HIV. The study cohort included patients who received ≥20 mg daily of a prednisone equivalent for ≥4 weeks to manage irAEs. Results: The study cohort identified 112 (15%) of 758 total patients treated using ICIs. Baseline characteristics included the following: median age was 64 years, 74% (n=82) of patients were White, 89% (n=100) had an ECOG performance status ≤1, 61% (n=68) had melanoma, 19% (n=21) had non–small cell lung cancer, 45% (n=50) were treated using an anti–PD-(L)1 ICI, and 33% (n=37) were treated using an anti–PD-1/anti–CTLA-4 combination. The median starting SS dose was 100 mg of a prednisone equivalent, and 25% of patients required additional ISAs, with infliximab (n=15) and mycophenolate mofetil (n=9) being the most common. We found that 20% (n=22) of patients developed any infection, including 7% (n=8) with OIs (oral candidiasis [n=4], nondisseminated varicella zoster infection [n=2], PJP [n=1], and Listeria monocytogenes endophthalmitis [n=1]) and 13% (n=14) with non-OIs (most common: Clostridium difficile and pneumonia [n=5 each]). PJP prophylaxis with sulfamethoxazole/trimethoprim was given to 13% (n=14) patients, of whom 43% (n=6) developed OIs/non-OIs. Conclusions: Our study highlights the fundamental issues for patients on ICI therapy who require SS/ISAs for irAEs: the degree of immunosuppression and the relative risk of OI. We noted a low incidence of OIs overall and breakthrough infections despite PJP prophylaxis. We question whether PJP prophylaxis is efficacious or necessary. Prospective trials are required to answer these questions.

Optimizing Inpatient Care for Lung Cancer Patients with Immune Checkpoint Inhibitor- Related Pneumonitis Using a Clinical Care Pathway Algorithm

“…We observed no signi cant changes in ICU admissions or inpatient mortality from the pre-intervention phase to the post-intervention phases 1 and 2 (p = 0.5 and p = 0.6, respectively). The overall mortality rate for patients with ICI-P was 22%, which is higher than the typically reported mortality rate of approximately 10% in the literature 37 . However, our ndings are consistent with those of a real-world cohort investigation involving 315 patients with lung cancer who were treated with ICIs in 6 healthcare centers (1 academic center, 1 community referral center, and 4 community centers) within the University of North Carolina network.…”

The Safety of Immunosuppressants Used in the Treatment of Immune-Related Adverse Events due to Immune Checkpoint Inhibitors: a Systematic Review

“…However, 3 studies included patients experiencing all irAE 31 , 32 , 36 . Treatment with systemic corticosteroids was a prerequisite for inclusion in many studies 22 , 23 , 29 - 30 , 32 , 33 , 36 . Two studies examined steroid-refractory and/or steroid-resistant irAEs and required patients to be treated with corticosteroids and additional immunosuppressants.…”

“…Of the considered articles, 119 articles were identified for full-text review, of these 73 articles did not meet our inclusion criteria. Of the 46 remaining articles, 11 studies were included in the final analysis, as the others did not assess the safety of irAE treatments (Figure 1) [22,23,[28][29][30][31][32][33][34][35].…”