Pegasparaginase silent inactivation during therapy for NK/T cell lymphoma

Natural Killer/T cell (NK/T cell) lymphoma is a rare, yet aggressive T cell lymphoma, which often displays resistance to traditional chemotherapies. Asparagainse (ASNase), through its unique mechanism of action, has become a vital component in the treatment of NK/T cell lymphoma. However, because ASNase is of bacterial origin, antibody formation can render the therapy ineffective, even in the absence of clinical hypersensitivity, which has been coined 'silent inactivation.' While the phenomenon of silent inactivation of PEG-ASNase is well documented in the treatment of ALL, it has not been described in NK/T cell lymphoma patients. Herein, we report a case series of six patients treated for NK/T cell lymphoma with PEG-ASNase who subsequently developed silent inactivation identified using therapeutic drug monitoring (TDM). The goal of this manuscript is to alert clinicians of this phenomenon, and review the importance of TDM in NK/T cell lymphoma patients receiving ASNase.