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2 result(s) for "Hunis, Brian"
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Pancreatic adverse events in patients treated with immune checkpoint inhibitors
Background and Aim The inhibition of cytotoxic T‐lymphocyte associated antigen‐4 (CTLA‐4) and programmed cell death‐1 (PD‐1) has been a target for multiple drugs to enhance the T‐cell antitumor activity. However, these immune checkpoint inhibitors (ICIs) come with a panel of immune‐related adverse events (irAEs) that include mainly endocrine, skin, and gastrointestinal effects. We report seven cases of pancreatic irAEs in patients treated with ICIs at our institute. Methods This is a case series; data was collected through chart review by 3 different data collectors and was analyzed separately by 2 physicians. Results Of these seven cases, two had diabetic ketoacidosis (DKA), while five had pancreatitis diagnosed by a substantial rise in serum lipase. Pancreatitis was asymptomatic in two cases. A pancreatic biopsy in one case revealed type 2 autoimmune pancreatitis. The ICIs used included pembrolizumab, nivolumab, durvalumab, and avelumab. Treatment included steroids and holding the ICI therapy: three cases had complete resolution of pancreatitis while two cases required either a prolonged taper or a second course of prednisone for recurrence of pancreatitis. On the other hand, the DKA cases were treated with withdrawal of the ICI and starting insulin with no steroid therapy. Conclusions Pancreatitis and DKA are rare adverse events of ICIs that can be controlled by holding the ICI with or without starting steroids. Rechallenging the patient with the same ICI is possible in selected cases. This case series identifies seven patients treated with immune checkpoint inhibitors at Memorial Cancer Institute, who developed the rare pancreatic endocrine and exocrine immune‐related adverse events (irAEs). It highlights their outcomes and discusses some possible predisposing factors for such irAEs.
Immunotherapeutic Agents in Non-small-cell Lung Cancer Finally Coming to the Front Lines
Non-small-cell lung cancer usually carries a dismal prognosis. Novel treatment approaches are clearly warranted. Immunotherapy has emerged as a promising area of research developing agents that manipulate the immune system to induce antitumor responses while avoiding major toxicity. New vaccines and checkpoint inhibitors are currently undergoing investigation in phase II and phase III clinical trials. In advanced non-small-cell lung cancer (NSCLC), belagenpumatucel-L, an allogeneic cell vaccine directed against transforming growth factor β in the tumor microenvironment, knocks down the immune suppression caused by the tumor and has demonstrated a dose- and time-dependent efficacy in some subgroups of patients. L-BLP25 and TG4010 are both antigenic vaccines that target mucin 1, whose encoding proto-oncogene is commonly mutated in solid tumors. The L-BLP25 vaccine achieved a significant improvement in overall survival in the subgroup of patients with stage IIIB NSCLC treated with chemoradiotherapy. TG4010 vaccination resulted in better progression-free survival when added to cisplatin–gemcitabine chemotherapy. These results are being addressed in the currently ongoing phase III TIME trial. In the adjuvant setting, MAGE-A3, an antigen-based vaccine, showed promising results in melanoma-associated antigen A3 positive lung cancer patients who underwent resection in the phase II study; however, no improvement in progression-free survival was observed in the phase III MAGRIT study. CIMAVax is a recombinant human epidermal growth factor (EGF) vaccine that induces anti-EGF antibody production and prevents EGF from binding to its receptor. It has improved overall survival in patients with advanced NSCLC who achieve seroconversion. Ipilimumab, an immune checkpoint inhibitor that targets cytotoxic T-lymphocyte antigen 4, demonstrated improved progression-free survival in advanced NSCLC patients who received the drug after chemotherapy in a phased regimen. Finally, anti-programmed death receptor 1 agents have achieved durable response rates in phase I studies. This review gives an overview of the current data and the most promissory immunotherapeutic agents for NSCLC.