Rapid T-cell lymphoma progression associated with immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) are widely used for multiple types of malignancies and are considered the fourth pillar in cancer treatment. Anti-programmed death-1 (PD-1) antibodies pembrolizumab and nivolumab are approved for relapsed/refractory classical Hodgkin lymphoma. Nonetheless, two phase 2 trials for T-cell lymphoma were terminated because of hyperprogression after a single dose in some patients.In this review, we summarize available information on the rapid progression of peripheral T-cell lymphoma including adult T-cell leukemia/lymphoma (ATLL).In the abovementioned two trials, disease subtypes in patients who experienced hyperprogression were mostly ATLL or angioimmunoblastic T-cell lymphoma. Possible hyperprogression mechanisms induced by PD-1 blockade are the compensatory upregulation of the expression of other checkpoints, altered expression of lymphoma-promoting growth factors, functional blockade of stromal PD-ligand 1 acting as a tumor suppressor, and unique immune environment in indolent ATLL. The differentiation between hyperprogression and pseudoprogression is practically essential. There are no established methods to predict hyperprogression before administration of an ICI. In the future, the progress of novel diagnostic modalities such as positron emission tomography with computed tomography and circulating tumor DNA is expected to facilitate early cancer detection.