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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Oncology · Extranodal Nasal NK/T-cell Lymphoma

Current Standard of Care and Treatment Options

At a Glance

Extranodal nasal NK/T-cell lymphoma (ENKTL) requires specialized treatment because it is naturally resistant to standard chemotherapy. L-asparaginase regimens, like DDGP or P-GEMOX, and concurrent chemoradiotherapy are the standard of care to effectively target these lymphoma cells.

Treating Extranodal nasal NK/T-cell lymphoma (ENKTL) requires a very specific approach. Because this lymphoma is biologically different from other types, “standard” lymphoma treatments often do not work [1]. Modern medicine has developed tailored protocols that have significantly improved outcomes for patients with both localized and advanced disease [2][3].

Why Standard Chemo (CHOP) Often Fails

In many common lymphomas, a regimen called CHOP (a combination of four drugs) is the go-to treatment. However, ENKTL cells produce a protein called P-glycoprotein (encoded by the MDR1 gene) [1][4]. This protein acts like a “pump” that sits on the surface of the cancer cell and literally pumps out the chemotherapy drugs before they can work [5]. This makes ENKTL naturally resistant to anthracyclines, a key drug class in the CHOP regimen [6].

The Essential “Backbone”: L-asparaginase

To bypass the “pumps” and kill the cancer, doctors use a drug called L-asparaginase (or its longer-acting version, pegaspargase) [3][7]. Unlike other drugs, L-asparaginase is not affected by the P-glycoprotein pump [8]. It works by starving the cancer cells of an amino acid (asparagine) they need to survive, making it the cornerstone of effective ENKTL treatment [9][10].

Treatment for Early-Stage Disease (I/II)

For lymphoma that is localized (usually in the nasal area), the goal is typically to cure the disease using a combination of chemotherapy and radiation [2].

  • Concurrent Chemoradiotherapy (CCRT): This is currently the standard approach, where radiation and chemotherapy are given at the same time [7]. Giving them together has been shown to be more effective than giving one after the other [11].
  • Consolidation: After the radiation and initial chemo are finished, patients often receive a few more rounds of “consolidation” chemotherapy to ensure all remaining cancer cells are gone [2].

Treatment for Advanced-Stage Disease (III/IV)

When the lymphoma has spread to other parts of the body, treatment focuses on intensive systemic chemotherapy [3]. Several regimens are used:

  • DDGP (Dexamethasone, Cisplatin, Gemcitabine, Pegaspargase): This is currently a preferred frontline option. Research has shown it provides better survival rates and is easier for patients to tolerate than older, more intensive regimens [3].
  • P-GEMOX (Pegaspargase, Gemcitabine, Oxaliplatin): Another effective and safe option often used for both newly diagnosed and relapsed cases [12].
  • SMILE: A more intensive regimen that was once the gold standard. While effective, it often has higher toxicity and more side effects than DDGP [3].

New Frontiers: Immunotherapy

If the lymphoma does not respond to initial treatment (refractory) or comes back (relapsed), doctors may turn to PD-1 inhibitors [13]. These are immunotherapy drugs (like pembrolizumab or sugemalimab) that help your own immune system recognize and attack the cancer cells [14][15]. These treatments have shown great promise and are currently being studied to see if they should be used even earlier in the treatment process [16][17].

Common questions in this guide

Why is the standard CHOP chemotherapy not used for ENKTL?
ENKTL cells produce a protein called P-glycoprotein that acts like a pump to remove common chemotherapy drugs before they can work. This makes the tumor naturally resistant to the CHOP regimen, which is why specialized treatments are required.
What is the main chemotherapy drug used to treat ENKTL?
L-asparaginase, or its longer-acting version pegaspargase, is the cornerstone of ENKTL treatment. It works by starving cancer cells of an essential amino acid and, importantly, is not affected by the cell's drug-pumping defense mechanism.
How is early-stage ENKTL usually treated?
Early-stage, localized ENKTL is typically treated with concurrent chemoradiotherapy, where radiation and chemotherapy are given at the exact same time. This is often followed by consolidation chemotherapy to destroy any remaining cancer cells.
What treatment options are available for advanced ENKTL?
Advanced ENKTL is treated with intensive systemic chemotherapy combinations like DDGP, P-GEMOX, or SMILE. DDGP is currently a preferred option because research shows it offers good survival rates while being easier for patients to tolerate than the older SMILE regimen.
Are there immunotherapy options for ENKTL?
Yes, if the lymphoma does not respond to initial treatment or comes back, doctors may use PD-1 inhibitors like pembrolizumab or sugemalimab. These drugs help your own immune system recognize and attack the cancer cells.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Why is CHOP therapy not recommended for my specific type of lymphoma?
  2. 2.Will I be receiving "concurrent" chemoradiotherapy (radiation and chemo at the same time), or will they be given separately?
  3. 3.Are we using an L-asparaginase or pegaspargase-based regimen, such as DDGP or P-GEMOX?
  4. 4.What are the specific side effects of the DDGP or P-GEMOX regimens compared to the SMILE regimen?
  5. 5.If the initial treatment doesn't work, will we consider PD-1 inhibitors like pembrolizumab or sugemalimab?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (17)
  1. 1

    New Approaches for Treatment of Advanced Extranodal NK/T-Cell Lymphoma.

    Yi W, Yang T, Lin S, et al.

    Cancer management and research 2022; (14()):401-407 doi:10.2147/CMAR.S328846.

    PMID: 35115837
  2. 2

    Efficacy of a short sandwich protocol, methotrexate, gemcitabine, L-asparaginase and dexamethasone chemotherapy combined with radiotherapy, in localised newly diagnosed NK/T-cell lymphoma: A French retrospective study.

    Chaubard S, Marouf A, Lavergne D, et al.

    British journal of haematology 2023; (201(4)):673-681 doi:10.1111/bjh.18689.

    PMID: 36799516
  3. 3

    DDGP versus SMILE in Newly Diagnosed Advanced Natural Killer/T-Cell Lymphoma: A Randomized Controlled, Multicenter, Open-label Study in China.

    Li X, Cui Y, Sun Z, et al.

    Clinical cancer research : an official journal of the American Association for Cancer Research 2016; (22(21)):5223-5228 doi:10.1158/1078-0432.CCR-16-0153.

    PMID: 27060152
  4. 4

    NK/T Cell Lymphoma: Updates in Therapy.

    Suzuki R

    Current hematologic malignancy reports 2018; (13(1)):7-12 doi:10.1007/s11899-018-0430-5.

    PMID: 29368155
  5. 5

    Conserved cell populations in doxorubicin-resistant human nasal natural killer/T cell lymphoma cell line: super multidrug resistant cells?

    Zhang X, Fu X, Dong M, et al.

    Cancer cell international 2018; (18()):150 doi:10.1186/s12935-018-0644-6.

    PMID: 30302057
  6. 6

    ATP-binding cassette sub-family C member 4 (ABCC4) is overexpressed in human NK/T-cell lymphoma and regulates chemotherapy sensitivity: Potential as a functional therapeutic target.

    Zhang X, Zhao L, Li X, et al.

    Leukemia research 2015; (39(12)):1448-54.

    PMID: 26499190
  7. 7

    Pegaspargase Combined with Concurrent Radiotherapy for Early-Stage Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Two-Center Phase II Study.

    Wang H, Wang L, Li C, et al.

    The oncologist 2020; (25(11)):e1725-e1731 doi:10.1634/theoncologist.2020-0144.

    PMID: 32627928
  8. 8

    Recent advances in the diagnosis and treatment of natural killer/T-cell lymphomas.

    Tse E, Au-Yeung R, Kwong YL

    Expert review of hematology 2019; (12(11)):927-935 doi:10.1080/17474086.2019.1660640.

    PMID: 31487202
  9. 9

    Phase II trial of concurrent chemoradiotherapy with L-asparaginase and MIDLE chemotherapy for newly diagnosed stage I/II extranodal NK/T-cell lymphoma, nasal type (CISL-1008).

    Yoon DH, Kim SJ, Jeong SH, et al.

    Oncotarget 2016; (7(51)):85584-85591 doi:10.18632/oncotarget.11319.

    PMID: 27542213
  10. 10

    The diagnosis and management of NK/T-cell lymphomas.

    Tse E, Kwong YL

    Journal of hematology & oncology 2017; (10(1)):85 doi:10.1186/s13045-017-0452-9.

    PMID: 28410601
  11. 11

    Concurrent Chemoradiation Therapy Followed by Consolidation Chemotherapy for Localized Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type.

    Oh D, Ahn YC, Kim SJ, et al.

    International journal of radiation oncology, biology, physics 2015; (93(3)):677-83.

    PMID: 26461010
  12. 12

    Efficacy of combined gemcitabine, oxaliplatin and pegaspargase (P-gemox regimen) in patients with newly diagnosed advanced-stage or relapsed/refractory extranodal NK/T-cell lymphoma.

    Wang JH, Wang L, Liu CC, et al.

    Oncotarget 2016; (7(20)):29092-101 doi:10.18632/oncotarget.8647.

    PMID: 27093153
  13. 13

    Use of PD-1 blockade in refractory/relapsed natural killer T-cell lymphomas: a systematic review and synthesis of case reports.

    Rivera-Francia VM, Failoc-Rojas VE, Villacorta-Carranza R, et al.

    Leukemia & lymphoma 2024; (65(1)):37-47 doi:10.1080/10428194.2023.2264431.

    PMID: 37794819
  14. 14

    Efficacy and safety of PD-1 inhibitor alone or combined with chemotherapy in patients with relapsed or refractory extranodal natural Killer/T cell lymphoma: A retrospective study.

    Tian J, Hao M, Liu Q, et al.

    Hematological oncology 2023; (41(3)):396-406 doi:10.1002/hon.3116.

    PMID: 36516297
  15. 15

    PD-1/PD-L1 Pathway: A Therapeutic Target in CD30+ Large Cell Lymphomas.

    Xie W, Medeiros LJ, Li S, et al.

    Biomedicines 2022; (10(7)) doi:10.3390/biomedicines10071587.

    PMID: 35884893
  16. 16

    Genomic features reveal potential benefit of adding anti-PD-1 immunotherapy to treat non-upper aerodigestive tract natural killer/T-cell lymphoma.

    Chen Z, Huang H, Huang H, et al.

    Leukemia 2024; (38(4)):829-839 doi:10.1038/s41375-024-02171-4.

    PMID: 38378844
  17. 17

    An evaluation of sugemalimab for the treatment of relapsed or refractory extranodal natural killer T-cell lymphoma.

    Feng Y, Liu X, Yu J, et al.

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    PMID: 39702924

This page provides educational information on ENKTL treatment options. Always consult your oncologist to determine the best treatment plan for your specific stage and medical history.

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