Extranodal NK/T-cell lymphoma
ICD-10 C86.0ICD-11 2A90.6&XH5LU6

Treatment of Advanced Extranodal NK/T-cell Lymphoma When First-Line L-Asparaginase-Based Chemotherapy Fails to Achieve EBV DNA Clearance

Clinical Scenario

This protocol addresses patients with stage III–IV nasal extranodal NK/T-cell lymphoma, or stage I–IV extranasal extranodal NK/T-cell lymphoma, who remain eligible for haematopoietic stem-cell transplantation (HSCT) and require a next treatment step.

First-Line Treatment Did Not Achieve Its Goal

Prior therapy: Multiagent, anthracycline-free, L-asparaginase-containing chemotherapy — DDGP or mSMILE — with or without involved-site radiotherapy; or alternatively sintilimab combined with an L-asparaginase-containing regimen.

Goal not reached: Reduction and clearance of Epstein-Barr virus (EBV) DNA in peripheral blood — the key biomarker of treatment response — was not achieved, triggering escalation to this salvage protocol.

Salvage Treatment Approach

Salvage therapy in this setting may involve an anti-PD-1 antibody, used alone or in combination, with further consolidation options for patients who respond.

The complete regimen options, sequencing, and transplant eligibility criteria are detailed in the full structured protocol.

Instant Access to Structured Evidence-Based Regimens
References

DOI: 10.1016/j.annonc.2025.01.023

A multiagent, anthracycline-free, L-asparaginase-containing regimen can be recommended for patients with stage III and IV nasal disease or stage I-IV extranasal disease (e.g. DDGP or mSMILE for HSCT-eligible and AspMetDex or P-GEMOX for HSCT-ineligible patients) [III, B].

If available, an anti-PD-1 antibody such as pembrolizumab (not EMA or FDA approved) or nivolumab (not EMA or FDA approved) can be considered as monotherapy or in combination with gemcitabine and/or L-asparaginase or crisantaspase [III, B].

As an alternative, platinum-based regimens (e.g. GDP) can be considered [III, B].

For HSCT-eligible patients responding to salvage therapy, HSCT (preferably allo-HSCT if not used in first line) may be considered [III, C].

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