Tubulointerstitial nephritis as adverse effect of programmed cell death 1 inhibitor, nivolumab, showed distinct histological findings.

Immune-checkpoint inhibitor nivolumab (anti-PD-1 antibody) blocks T cell inhibition and stimulate immunologic response toward cancer cells. It was also revealed that PD-1/PD-L1 interaction crucially controls the effector differentiation of auto-reactive T cells to maintain self-tolerance. Therefore, potential autoimmunological side-effect can occur in any organ. Here, we report a case of 67-year-old Japanese male with lung adenocarcinoma treated with nivolumab who developed acute tubulointerstitial nephritis after the third infusion of nivolumab. Kidney biopsy showed distinct histological findings: Proliferation of CD38 positive and IgG positive plasma cells, and affluent infiltration of FoxP3+ regulatory T cells. Herein, we do pathological discussion concerning acute tubulointerstitial nephritis occurred in this case based on these histological findings.

Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4 monoclonal antibody, mogamulizumab.

A 57-year-old male with acute-type adult T cell leukemia-lymphoma (ATL) developed persistent watery, non-bloody diarrhea at a volume of 2-3 L/day following the administration of the anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, mogamulizumab. An extensive examination revealed the absence of any pathogenic bacteria or parasites in his stool. Biopsied specimens from the colonic mucosa contained many small nests of apoptotic bodies in the colonic glands, which mimicked acute-colonic graft-versus-host disease. Activation of the auto-reactive immune system due to the depletion of regulatory T-cells by mogamulizumab was suspected as causative. Special attention should be paid to the risk of unique immune-related adverse events induced by mogamulizumab.

Safety and pharmacokinetic evaluation of repeated intravenous administration of palonosetron 0.75 mg in patients receiving highly or moderately emetogenic chemotherapy.

PURPOSE: The aims of this study were to evaluate the safety, efficacy, and pharmacokinetics of repeated doses of palonosetron 0.75 mg on days 1 and 3 in Japanese patients who received highly or moderately emetogenic chemotherapy. METHODS: Twenty- six patients received palonosetron 0.75 mg intravenously before chemotherapy on days 1 and 3 plus dexamethasone (12-16 mg before chemotherapy on day 1 and 4-8 mg on days 2 and 3). The primary endpoints were safety and pharmacokinetics. Pharmacokinetics were evaluated in a subset of patients (n=6). Complete response and complete protection were evaluated as secondary endpoints. RESULTS: The accumulation ratios for C max and AUClast after the second dose on day 3 were 1.42 and 1.37, respectively. These values were consistent with the theoretical values expected from the half-life of palonosetron on day 1. Almost all of the patients had no nausea or vomiting in the acute phase (complete response (CR) rate, 96.2% [25/26]; CP rate, 92.3% [24/26]). In the delayed phase (24-192 h post-chemotherapy), the complete response and complete protection rates were 76.9% (20/26) and 61.5% (16/26), respectively. Treatment was well tolerated. CONCLUSIONS: This is the first study to report the pharmacokinetics of multiple doses of palonosetron 0.75 mg, given on days 1 and 3, in Japanese patients. Repeated treatment with palonosetron was safe and well tolerated by patients who received highly or moderately emetogenic anticancer chemotherapy.