Combination of Mitoxantrone Liposome and Etoposide, Dexamethasone, Pegaspargase and Golidocitinib (MEPL-G) in the Treatment of NK/T-cell Lymphoma Associated Hemophagocytic Lymphohistiocytosis (NKTCL-HLH): a Prospective, Multi-center, Single Arm, Phase Ib/II Clinical Trial
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.
• Left ventricular ejection fraction (LVEF) ≥ 50% on cardiac echocardiography.
• No active visceral bleeding (e.g., gastrointestinal, pulmonary, cerebral).
• No uncontrolled infection (e.g., pulmonary infection, intestinal infection).
• Negative HCV antibody; or positive HCV antibody with negative HCV RNA.
• Negative HBsAg and negative HBcAb. If either is positive, peripheral blood HBV DNA load must be \< 1×10³ copies/mL to be eligible.
• Signed written informed consent and ability to understand and comply with all study requirements.