This protocol addresses fit patients with stage I–II extranodal NK/T-cell lymphoma who are able to tolerate chemotherapy and eligible for haematopoietic stem-cell transplantation (HSCT), and whose disease has not responded adequately to the initial treatment line.
The patient is fit, chemotherapy-tolerant, and HSCT-eligible, with limited-stage (stage I–II) disease. The question is how to proceed after first-line combined-modality therapy has not produced the required response.
First-line treatment — involved-site radiotherapy (ISRT) combined with an anthracycline-free, L-asparaginase-containing chemotherapy regimen (DDGP or modified SMILE) — did not achieve the required treatment goal. The critical biomarker endpoint that was not met: reduction or clearance of Epstein-Barr virus (EBV) DNA in peripheral blood. Failure to achieve this EBV DNA response is the trigger for escalation to this salvage protocol.
For fit patients with localised stage I-II disease, concomitant, interposed ('sandwich schedule') or rapidly sequential chemoradiotherapy (CRT), with an early RT dose of 50 Gy and a platinum- and/or L-asparaginase-containing regimen, have been applied.
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].
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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