Efficacy and safety of mitoxantrone hydrochloride liposome combined with pegaspargase in the treatment of extranodal NK/T-cell lymphoma Free

Background:

Extranodal Natural Killer/T-cell Lymphoma (ENKTL) is a highly aggressive non-Hodgkin lymphoma originating from natural killer (NK) or T cells. It predominantly occurs in the upper respiratory tract (e.g., nasal cavity, nasopharynx) but may also involve extranodal sites such as the skin, gastrointestinal tract, and bone marrow. This disease exhibits higher incidence in Asian and Latin American populations and is closely associated with Epstein-Barr virus (EBV) infection, with over 90% of patients testing positive for EBV DNA. Currently, radiotherapy and asparaginase-based chemotherapy regimens serve as first-line treatments for ENKTL. However, conventional therapies face multiple limitations, and approximately 30%–40% of patients experience relapse or progression after initial treatment, resulting in poor prognosis and a 5-year overall survival rate below 50%. Therefore, exploring regimens with enhanced efficacy and improved safety is a critical focus in current ENKTL clinical research.

Mitoxantrone hydrochloride liposome (PLM60), an anthraquinone-based antitumor agent, was approved in China in early 2022 for treating relapsed/refractory peripheral T-cell lymphoma (PTCL) in adults who have received ≥1 prior lines of therapy. Previous studies have demonstrated promising efficacy of PLM60 monotherapy in ENKTL. Pegaspargase, a long-acting asparaginase formulation, reduces dosing frequency and allergy risks while showing significant efficacy against ENKTL. Thus, evaluating the efficacy and safety of PLM60 combined with pegaspargase holds substantial clinical significance for addressing current therapeutic limitations and providing optimized treatment options for ENKTL patients.

Objective:

This study aims to systematically evaluate the clinical efficacy of PLM60 combined with pegaspargase in treating ENKTL, determine its complete response rate, and analyze the safety profile of this regimen, thereby establishing new evidence-based support for the clinical management of ENKTL.

Methods:

This single-center study enrolled 8 patients with pathologically confirmed ENKTL at our institution.Inclusion criteria:Treatment-naïve patients diagnosed with ENKTL through histopathology and immunohistochemistry；ECOG performance status score 0-2；Normal baseline hepatic/renal function and cardiac enzyme profiles without severe comorbidities.Exclusion criteria:Concurrent malignancies;Central nervous system involvement.

All patients received the PLM60 (24 mg/m²) plus pegaspargase (2000 IU/m²) regimen administered intravenously on Day 1 of each 21-day treatment cycle. Regular monitoring included:Complete blood counts;Hepatic/renal function tests;Coagulation profiles;Cardiac enzyme panels;EBV DNA load quantification;Tumor response was assessed by CT or PET-CT imaging.

Efficacy evaluation followed the Lugano classification criteria CR, PR, SD, PD.Safety assessment adhered to CTCAE v5.0 standards, documenting adverse event incidence and severity.

Results:

Among the 8 patients, 4 were male and 4 were female. Five patients were EBV DNA positive before treatment. The primary site was the nasal cavity in 7 cases and the skin in 1 case. Five patients had Ann Arbor stage I-II disease, and 3 had stage III-IV disease.

Efficacy evaluation showed an ORR of 100% for the entire group, with a CR rate of 87.5%. The 6-month PFS rate was 100%, and the median DOR was 14 months. The EBV DNA clearance rate was 100%.

Regarding safety, all patients experienced adverse events of varying severity, with hematologic toxicities being the most common: leukopenia occurred in 100%, anemia in 100%, thrombocytopenia in 12.5%, and hypofibrinogenemia in 66.7% of patients. Grade III-IV adverse events occurred in 37.5% of patients. Among non-hematologic toxicities, liver function abnormalities occurred in 50%.No severe hemorrhage or anaphylactic shock occurred, and there were no treatment-related deaths. All adverse events resolved with supportive care and did not affect the completion of the overall treatment course.

Conclusion:

The regimen combining PLM60 with pegaspargase demonstrates high ORR and DCR in treating extranodal NK/T-cell lymphoma. Adverse events were primarily hematologic toxicities, which were manageable overall. The regimen exhibits a favorable safety profile, thereby providing a new effective treatment option for ENKTL patients.