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

Limited-Stage Extranodal NK/T-cell Lymphoma: When First-Line Chemoradiotherapy Fails to Clear EBV DNA

Clinical scenario

This protocol applies to a fit patient with stage I or II extranodal NK/T-cell lymphoma who is able to tolerate chemotherapy but is not eligible for haematopoietic stem-cell transplantation (HSCT).

First-line failure — escalation trigger

Initial management in this population consists of involved-site radiotherapy (ISRT) given concurrently, interposed, or sequentially with an anthracycline-free, L-asparaginase-containing chemotherapy regimen — AspMetDex or P-GEMOX. Escalation to salvage therapy is triggered when this approach fails to achieve reduction or clearance of Epstein-Barr virus (EBV) DNA in peripheral blood, the key biomarker of response.

Salvage approach — partial overview

Salvage therapy in this context centres on an anti-PD-1 antibody, considered as monotherapy or in combination with chemotherapy, with platinum-based regimens as an alternative option.

The complete evidence-based regimen — specific agents, combinations, sequencing, and evidence grades — is available in the full protocol.
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References

Fit patients with limited-stage disease should receive ISRT (50 Gy) with concurrent, interposed or sequential anthracycline-free, L-asparaginase-containing ChT [e.g. DDGP or modified SMILE (mSMILE) for HSCT-eligible and AspMetDex or P-GEMOX for HSCT-ineligible patients] [II, A].

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].

DOI: 10.1016/j.annonc.2025.01.023

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