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.
Submitted February 22, 2022; final revision received April 20, 2022; accepted for publication April 20, 2022.
Author contributions:Study concept and design: Shah, Cook, Lev-Ari, Blackburn, Serzan, Atkins. Data Collection: Shah, Cook, Lev-Ari, Blackburn, Serzan. Data analysis and interpretation: Shah, Cook, Lev-Ari, Blackburn, Serzan, Atkins. Statistical analysis: Wu, Ahn. Bioinformatics support: Alaoui. Database development: Alaoui. Manuscript preparation: All authors.
Disclosures: Dr. Shah has disclosed receiving institutional grant/research support and clinical trial support from Aravive, Inc.; and serving as a consultant for and receiving travel compensation from Merck & Co., Inc. Dr. Atkins has disclosed serving as a scientific advisor for Aveo Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Eisai Co., Ltd., Elpis Pharmaceuticals, Fathom Pharmaceutics, GlaxoSmithKline LLC, Leads Pharma, Merck & Co., Inc., Novartis International AG, PACT Pharma, Inc., Pfizer Inc., Pneuma Respiratory, Inc., Pyxis Oncology, Roche Holding AG, SAB Biotherapeutics, Inc., Scholar Rock, Inc., Simcha Therapeutics, Surface Ophthalmics, Inc., Takeda Pharmaceutical Company, Valo Health, Werewolf Therapeutics Inc., and X4 Pharmaceuticals, Inc.; serving as a consultant for Agenus Inc., Apexigen, Asher Biotherapeutics, Inc., AstraZeneca plc, Bristol-Myers Squibb Company, Calithera Biosciences, Inc., COTA, Inc., Exelixis, Inc., Idera, Inc., Iovance Biotherapeutics, Inc., Merck & Co., Inc., Neoleukin Therapeutics, Novartis International AG, Pfizer Inc., Roche Holding AG, Sanofi S.A., and SeaGen Inc.; receiving institutional grant/research support from Bristol-Myers Squibb Company, Merck & Co., Inc., and Pfizer Inc.; and having stock/stock options in Eplis Pharmaceuticals, Pyxis Oncology, and Werewolf Therapeutics Inc. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.
Correspondence: Michael B. Atkins, MD, Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3800 Lombardi Cancer Center, Washington DC 20007. Email: email@example.com
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