Efficacy of local therapy for oligoprogressive disease after programmed cell death 1 blockade in advanced non‐small cell lung cancer

Immune checkpoint inhibitors (ICIs) have dramatically changed the strategy used to treat patients with non‐small‐cell lung cancer (NSCLC); however, the vast majority of patients eventually develop progressive disease (PD) and acquire resistance to ICIs. Some patients experience oligoprogressive disease. Few retrospective studies have evaluated clinical efficacy in patients with oligometastatic progression who received local therapy after ICI treatment. We conducted a retrospective analysis of advanced NSCLC patients who received PD‐1 inhibitor monotherapy with nivolumab or pembrolizumab to evaluate the effects of ICIs on the patterns of progression and the efficacy of local therapy for oligoprogressive disease. Of the 307 patients treated with ICIs, 148 were evaluated in our study; 42 were treated with pembrolizumab, and 106 were treated with nivolumab. Thirty‐eight patients showed oligoprogression. Male sex, a lack of driver mutations, and smoking history were significantly correlated with the risk of oligoprogression. Primary lesions were most frequently detected at oligoprogression sites (15 patients), and 6 patients experienced abdominal lymph node (LN) oligoprogression. Four patients showed evidence of new abdominal LN oligometastases. There was no significant difference in overall survival (OS) between the local therapy group and the switch therapy group (reached vs. not reached, P = .456). We summarized clinical data on the response of oligoprogressive NSCLC to ICI therapy. The results may help to elucidate the causes of ICI resistance and indicate that the use of local therapy as the initial treatment in this setting is feasible treatment option.     

Non–clinical efficacy,safety and stable clinical cell processing of induced pluripotent stem cell‐derived anti–glypican‐3 chimeric antigen receptor‐expressing natural killer/innate lymphoid cells

The use of allogeneic, pluripotent stem‐cell‐derived immune cells for cancer immunotherapy has been the subject of recent clinical trials. In Japan, investigator‐initiated clinical trials will soon begin for ovarian cancer treatment using human leukocyte antigen (HLA)‐homozygous‐induced pluripotent stem cell (iPSC)‐derived anti–glypican‐3 (GPC3) chimeric antigen receptor (CAR)‐expressing natural killer/innate lymphoid cells (NK/ILC). Using pluripotent stem cells as the source for allogeneic immune cells facilitates stringent quality control of the final product, in terms of efficacy, safety and producibility. In this paper, we describe our methods for the stable, feeder‐free production of CAR‐expressing NK/ILC cells from CAR‐transduced iPSC with clinically relevant scale and materials. The average number of cells that could be differentiated from 1.8‐3.6 × 10⁶ iPSC within 7 weeks was 1.8‐4.0 × 10⁹. These cells showed stable CD45/CD7/CAR expression, effector functions of cytotoxicity and interferon gamma (IFN‐γ) production against GPC3‐expressing tumor cells. When the CAR‐NK/ILC cells were injected into a GPC3‐positive, ovarian‐tumor‐bearing, immunodeficient mouse model, we observed a significant therapeutic effect that prolonged the survival of the animals. When the cells were injected into immunodeficient mice during non–clinical safety tests, no acute systemic toxicity or tumorigenicity of the final product or residual iPSC was observed. In addition, our test results for the CAR‐NK/ILC cells generated with clinical manufacturing standards are encouraging, and these methods should accelerate the development of allogeneic pluripotent stem cell‐based immune cell cancer therapies.     

Postpancreatoduodenectomy Hemorrhage Treated by Combined Transcatheter Arterial Embolization and Superior Mesenteric Artery to Iliac Artery Bypass: Report of a Case

Postpancreatectomy hemorrhage is a potentially life-threatening complication. We report herein our experience with a 65-year-old man with locally advanced pancreatic adenocarcinoma who underwent pancreatoduodenectomy with lymphadenectomy following neoadjuvant chemoradiotherapy. On postoperative day 45, he developed massive hematemesis. Angiography revealed active bleeding from the common hepatic artery, and transcatheter coil embolization of that vessel was successfully performed. On postoperative day 64, he again developed massive hematemesis. Angiography revealed active bleeding from the proximal superior mesenteric artery. Immediately after coil embolization of that vessel, bypass grafting between the superior mesenteric artery and the right common iliac artery was performed, using a greater saphenous vein graft. The combination of embolization and bypass grafting is an option for treatment of bleeding from the superior mesenteric artery in an emergent situation.Key words: Superior mesenteric artery, Bleeding, Bypass, Pancreatoduodenectomy, Postpancreatectomy hemorrhagePostpancreatectomy hemorrhage (PPH) is a rare but life-threatening complication, often associated with the presence of a pancreatic fistula or intraabdominal abscess.¹ The mortality associated with arterial bleeding after pancreatoduodenectomy is reportedly between 14.3% and 30.7%.^2–6 With recent advances in interventional radiology techniques, transcatheter arterial embolization (TAE) has become an alternative to surgical treatment.^3,5,7,8 However, it may be difficult to treat these patients with interventional radiology techniques alone, given their often unstable condition. In addition, the inappropriate use of TAE for arterial bleeding, especially after pancreatoduodenectomy, can lead to end-organ infarction and subsequent infection. We report herein our experience with a patient who had bleeding from the superior mesenteric artery (SMA) after pancreatoduodenectomy. This patient was successfully treated using SMA coil embolization followed by creation of an SMA-iliac artery bypass using a greater saphenous vein graft.