Development of Acute Adult T-cell Leukemia Following PD-1 Blockade Therapy for Lung Cancer

Abstract

Immune checkpoint inhibitors (ICIs) are widely used for the treatment of various cancers. However, paradoxical exacerbation of neoplasms, referred to as "hyperprogressive disease," has been reported in a proportion of patients treated with anti-programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1) blockade. We herein report a case of acute adult T-cell leukemia (ATL) that developed shortly after the administration of nivolumab, a PD-1 inhibitor, to treat non-small-cell lung cancer. There were no signs of ATL before the administration of nivolumab, and seropositivity for human T-cell leukemia virus type-1 (HTLV-1) was confirmed after the development of acute ATL. We speculate that nivolumab likely contributed to the development of acute ATL.

Whole-genome CRISPR screening identifies molecular mechanisms of PD-L1 expression in adult T-cell leukemia/lymphoma

“…Therapeutic approaches using anti–PD-1 antibodies as checkpoint inhibitors have led to rapid hyperprogression in some ATLL cases. 38 , 39 These observations suggested that T-cell receptor signaling might be active but kept in check by the PD-1/PD-L1 axis in such ATLL cases, and anti–PD-1 antibodies would disrupt the equilibrium state. In this context, avelumab may hold an advantage for safety in terms of ATLL treatment due to its dual role of PD-1/PD-L1 blockage and ADCC function.…”