Currently, only a few reports exist on the cytokine release syndrome (CRS) as one of the severe immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs). Notably, it is very rare that grade 4 CRS related to ICI therapy overlaps with the drug-induced hypersensitivity syndrome (DiHS). A 46-year old woman with metastatic kidney cancer had grade 3 interstitial pneumonitis induced by four cycles of combination therapy of anti-programmed death-1 and anti-cytotoxic T lymphocyte-4 antibodies after right cytoreductive nephrectomy. Prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) was started concomitantly with prednisolone therapy to treat the interstitial pneumonitis. She developed hypotensive shock when reducing the dosage of prednisolone, and required intubation and ventilation using vasopressors at the intensive care unit. She subsequently exhibited prominent leukocytosis and an increased level of C-reactive protein, suggesting markedly increased cytokine levels. Interestingly, facial edema and erythema increased in association with pyrexia, leukocytosis, liver dysfunction, and renal failure, suggesting that she developed DiHS. She received hemodialysis three times, a plasma exchange, and anti-interleukin-6 therapy to treat severe renal dysfunction, a thrombotic thrombocytopenic purpura-suspected condition, and possible grade 4 CRS, respectively. Although these therapies did not elicit sufficient effects, high-dose administration of intravenous immunoglobulin was successful. With steroid mini-pulse therapy and the subsequent administration of prednisolone, she recovered successfully. To the best of our knowledge, this is the first report that ICIs and TMP/SMX can induce hypotensive shock accompanied with CRS and DiHS during immunosuppressive therapy for an irAE. Importantly, the prophylactic administration of TMP/SMX should be performed cautiously to avoid severe drug reactions such as CRS or DiHS.

Background: The paradigm of medical treatment for metastatic urothelial carcinoma is dramatically changing through the introduction of pembrolizumab.Aim: We investigated the treatment effectiveness, the safety profile, and the prognostic factors of pembrolizumab in Japanese real‐world clinical practice.Methods and results: The medical records of 74 consecutive Japanese patients with metastatic urothelial cancer (UC), who started pembrolizumab as a second‐ or later‐line treatment at our institution between January 2018 and March 2020, were reviewed and statistically analyzed. The median follow‐up period after initiation of pembrolizumab was 8.5 (interquartile range: 3.5–15.7) months. The objective response rate was 30.2%, the median progression‐free survival period was 4.9 months, and the median overall survival (OS) period was 13.3 months. Evaluation revealed that 39 (52.9%) patients experienced adverse events (AEs), among whom eight patients (10.9%) had severe AEs (grade 3 or more), including grade 5 hemophagocytic syndrome. Multivariate analysis indicated that the presence of liver metastasis, worse performance status (≥2), elevated serum lactate dehydrogenase, and increased C‐reactive protein were predictive of shorter OS.Conclusion: We studied the effectiveness and safety profile of pembrolizumab therapy in Japanese UC patients. We believe that the data presented here will be useful for clinical physicians.

Introduction: We report the case of a patient with metastatic castration‐resistant prostate cancer with microsatellite instability‐high who was treated with pembrolizumab after cabazitaxel administration.Case presentation: A 58‐year‐old patient with heavily pretreated metastatic castration‐resistant prostate cancer, whose prostate surgical specimen was disclosed as microsatellite instability‐high, underwent pembrolizumab therapy. After initiation of pembrolizumab, his prostate‐specific antigen level decreased, imaging findings showed good response with lymph node shrinkage, and his walking difficulty decreased dramatically.Conclusion: The rarity of microsatellite instability‐high tumor in castration‐resistant prostate cancer may hamper pembrolizumab administration. This potentially active agent should be considered as part of a treatment regimen for patients with microsatellite instability‐high castration‐resistant prostate cancer. To the best of our knowledge, this is the first report of a Japanese castration‐resistant prostate cancer patient who demonstrated clinical benefit from pembrolizumab treatment.