Extranodal NK/T-cell lymphoma (NKTCL) is an aggressive EBV-associated lymphoma with poor prognosis, highly prevalent in China. Early-stage NKTCL achieves favorable long-term survival, while advanced disease shows dismal outcomes with no standard therapy. Notably, 10%-20% of patients develop secondary hemophagocytic lymphohistiocytosis (NKTCL-HLH), a life-threatening complication with median survival \<2 months and mortality over 90%. Current treatments fail to simultaneously control lymphoma and hyperinflammation, with poor tolerance and high resistance.
The JAK/STAT pathway drives EBV-induced inflammation and tumor progression. Golidocitinib, a selective JAK1 inhibitor, demonstrates potent anti-NKTCL activity and rapid inflammation control. Liposomal mitoxantrone offers targeted efficacy with lower toxicity, while etoposide, methylprednisolone, and pegaspargase provide synergistic anti-tumor and anti-HLH effects.
This study proposes the novel MEPL-G regimen (liposomal mitoxantrone, etoposide, methylprednisolone, pegaspargase, golidocitinib) for NKTCL-HLH. By targeting both HLH and NKTCL, this combination aims to achieve rapid disease control, improve tolerance, and prolong survival, addressing the unmet critical clinical need for this high-risk population.
Histologically confirmed extranodal NK/T-cell lymphoma.
Meeting the HLH-2004 diagnostic criteria (≥ 5 criteria).
Age ≥ 18 years, regardless of gender.
Negative HIV antigen or antibody.
New York Heart Association (NYHA) cardiac function class ≥ II;
Female patients who are pregnant or breastfeeding;
Known hypersensitivity to any of the study drugs;
Presence of other concurrent malignancies (except non-melanoma skin cancer);
Single group
Mitoxantrone liposome
DrugIn the Phase Ib part, 3 patients will be enrolled at the starting dose of liposomal mitoxantrone: 18 mg/m²/d on day 1, every 3 weeks (q3w). If no DLT occurs, the recommended phase 2 dose (RP2D) will be 18 mg/m²/d on day 1 q3w. If DLT occurs, the dose will be de-escalated sequentially (18→16→14→12 mg/m²/d on day 1 q3w).
Etoposide
Drug100mg/m²/d，d1、d8，q3w
Pegaspargase (PEG) Asparaginase
Drug2000IU/m²/d，d5，q3w
methylprednisolone
Drug15mg/kg/d，d1-3 7.5mg/kg/d，d4-7 1mg/kg/d d8-14 10mg/d，d15-21
golidocitinib
Drug150mg/d，d1-d21，q3w
6-month overall survival (OS) rate
OS was defined from the date of initiation of MEPL-G to the date fo death.
6-month progression free survival (PFS) rate
PFS was defined from the date of initiation of MEPL-G to the date of confirmed disease progression or death of any reason
overall response rate (ORR)
Overall response rate means sum of complete response rate and partial response rate
complete response (CR) rate
CR was defined as complete response evaluated using PET-CT scan
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
measured using CTCAE version 5.0
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