ABSTRACT
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.
Subject(s)
Antineoplastic Agents/therapeutic use , Asparaginase/therapeutic use , Inactivation, Metabolic , Lymphoma, Extranodal NK-T-Cell/drug therapy , Adult , Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Asparaginase/pharmacology , Biopsy , Combined Modality Therapy , Fatal Outcome , Female , Humans , Lymphoma, Extranodal NK-T-Cell/diagnosis , Male , Middle Aged , Positron Emission Tomography Computed Tomography/methods , Treatment OutcomeABSTRACT
Optimal salvage therapy for primary refractory peripheral T-cell lymphomas (PTCL) and the role of hematopoietic stem cell transplant (SCT) remain poorly defined. We conducted a retrospective review of clinical outcomes and prognostic factors in a single-center cohort of 93 patients with primary refractory PTCL, defined as progression during first-line therapy or relapse within 6 months of its completion. Clinical outcomes were poor in this population, with median event-free survival (EFS) of 3.5 months, median overall survival (OS) of 9.1 months, and 34% 3-year survival. Outcomes were comparable in patients who progressed through first-line therapy and patients who achieved CR/PR and subsequently relapsed within 6 months. A majority exhibited high-risk features and had intermediate to high risk IPI, which correlated with inferior outcomes. There was no difference in outcomes between patients who received single-agent salvage regimens and patients who underwent traditional, multi-agent salvage regimens. Thus, participation in well-designed clinical trials should be encouraged in this population. Additionally, there may be a trend toward improved EFS and OS in patients who underwent autologous or allogeneic SCT compared to patients who achieved CR or PR but were not transplanted.