Hyperprogression after pembrolizumab treatment in two patients with metastatic urothelial carcinoma

Hyperprogression has recently been recognized as a new pattern of progression in patients undergoing immune checkpoint inhibitor treatment. Here, we report two cases that showed hyperprogression during the initial phase of pembrolizumab treatment for metastatic urothelial carcinoma. The first patient, who received pembrolizumab as a second-line treatment, developed severe respiratory failure due to the rapid progression of lung metastases on the ninth day after the third pembrolizumab treatment. The second patient developed jaundice and hepatic dysfunction due to the progression of a metastatic lymph node of the liver hilum after the first administration of pembrolizumab. She developed multiple brain metastases with intraventricular bleeding on the 10th day after the second administration of pembrolizumab. It is important to be aware that hyperprogression sometimes occurs quite a while after starting treatment, and that both pseudoprogression and hyperprogression may occur in the early stage of treatment.