The present study investigated outcomes of infliximab (IFX) treatment among 8 Japanese patients with various types of cancer (4 with malignant melanoma, 3 with lung cancer and 1 with renal cancer) who developed severe steroid‑resistant immune‑related adverse events (irAEs) in association with immune checkpoint inhibitors (ICIs) to determine its efficacy and safety. Information, including patient background, treatment progress, examination data and imaging data, was collected retrospectively from electronic medical records. Adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Specific ICIs used were anti‑PD‑1, anti‑PD‑L1 and anti‑CTLA‑4 antibody preparations in 7, 2 and 5 patients, respectively. Specific irAEs included grade 3 diarrhea/colitis in 7 patients and disseminated intravascular coagulation and myocarditis attributed to autoimmune activation in 1 patient. The median duration between systemic steroid and IFX treatments was 9 (range, 2‑39) days. A total of 3 patients responded to IFX, 1 of whom responded after one dose and 2 responded after two doses. Respective diseases improved to grade 0 after a median of 18 (range, 9‑32) days. No AEs were attributable to IFX. Additionally, anti‑cytomegalovirus (CMV) and antibacterial agents were administered in parallel given the presence of CMV and Clostridium difficile (CD) infections in all patients, except in 1 exhibiting a marked IFX response after one dose. The combination of highly immunosuppressive IFX and high‑dose systemic steroid administration over a long period presumably predisposed the patients to opportunistic enteric infections. Accordingly, early initiation of IFX treatment in conjunction with systemic steroid therapy should be considered for severe diarrhea/colitis and other irAEs. However, the possibility for CMV and CD infections should be recognized, and for these the treatment strategy may need to be modified at an early stage.

Background and Aim: To investigate the outcomes in eight Japanese patients with cancer treated with mycophenolate mofetil (MMF) and corticosteroids for immune checkpoint inhibitor treatment‐induced severe immune‐related hepatitis (ir‐hepatitis) and the efficacy and safety of MMF.Methods: We retrospectively examined patient background, treatment course, as well as examination and imaging data using electronic medical records.Results: The ratio of male to female patients was 7:1, and the median age was 60 years (27–72 years). There were five and two cases of kidney cancer and malignant melanoma, respectively, and one case of lung cancer. The median number of days until MMF administration in addition to systemic corticosteroid therapy after the onset of ir‐hepatitis was 14.5 (2–42). The patients were categorized as four “good responders” who showed an improvement in the liver function tests following MMF treatment and four “poor responders” who did not. Furthermore, the time from the onset of ir‐hepatitis to initial MMF administration was significantly shorter in good responders (median 3 days, range 2–15 days) than in poor responders (median 25.5 days, range 14–42 days) (P = 0.042). No significant intergroup difference was observed in other clinical factors. No serious adverse events caused by MMF were observed in any case.Conclusions: According to these findings, early recognition of corticosteroid refractoriness and the use of MMF may be beneficial in patients with ir‐hepatitis.

The Effectiveness of a Liver Disease Education Class for Providing Information to Patients and Their Families

Ramucirumab (RAM) is a monoclonal antibody of human vascular endothelial growth factor receptor 2 (VEGFR-2). In Japan, it is indicated for combination therapy with paclitaxel (PTX) for advanced/recurrent gastric cancer that cannot be curatively resected. However, the development of severe neutropenia due to RAM administration is considered to be one of the major side effects. Therefore, the principal aims of the present study were to examine whether the risk of neutropenia increases due to RAM + PTX combination therapy compared with PTX monotherapy in Japanese patients with gastric cancer and to elucidate the risk factors of neutropenia due to RAM + PTX combination therapy. At the Osaka International Cancer Institute, we retrospectively investigated myelosuppression in 26 patients who received RAM + PTX combination therapy and in 25 patients who received PTX monotherapy for advanced/recurrent gastric cancer that cannot be curatively resected. The expression of neutropenia of all grades and of grade 3 or higher were significantly higher in the RAM + PTX group (P < 0.001 and P = 0.045, respectively). Investigation of the risk factors in patients with expression of neutropenia of grade 3 or higher revealed that a low initial lymphocyte count was a risk factor (P = 0.021); that is, the results suggest that neutropenia may be enhanced by administering RAM in combination with PTX. When RAM + PTX combination therapy is administered in patients with a low initial lymphocyte count, it may be necessary to consider measures against infectious diseases and administration of granulocyte-colony stimulating factor (G-CSF) agents, for example.