When L-Asparaginase-Based Chemotherapy Fails in Advanced ENKTCL (HSCT-Ineligible)
Clinical Scenario
This protocol addresses stage III–IV nasal extranodal NK/T-cell lymphoma or stage I–IV extranasal extranodal NK/T-cell lymphoma in patients who are not eligible for haematopoietic stem-cell transplantation and whose disease has progressed or failed to respond to first-line therapy.
Why Escalation to This Protocol Is Needed
First-line treatment for this population used a multiagent, anthracycline-free, L-asparaginase-containing regimen — such as AspMetDex or P-GEMOX — with or without additional components. The pivotal goal of that line was reduction or clearance of Epstein-Barr virus (EBV) DNA in peripheral blood as a biomarker of response. When that target is not achieved — or when disease progresses — a salvage approach becomes necessary.
Salvage Approach (Partial Overview)
Salvage options centre on immunotherapy with an anti-PD-1 antibody, used as monotherapy or in combination with selected chemotherapy agents. A platinum-based regimen is an established alternative. The full selection criteria, combination details, and treatment algorithm are available in the complete protocol.
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].
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