NHL: Extranodal NK/T-cell Lymphoma
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NON-HODGKIN LYMPHOMA TREATMENT REGIMENS: Extranodal NK/T-Cell Lymphoma, Nasal Type |
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Clinical Trials: The National Comprehensive Cancer Network recommends cancer patient participation in clinical trials as the gold standard for treatment. |
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Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. |
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Systemic Therapy for Extranodal NK/T-cell Lymphomas, Nasal Type1 |
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Note: All recommendations are Category 2A unless otherwise indicated. |
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Combination Chemotherapy Regimens (asparaginase-based)c |
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REGIMEN |
DOSING |
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AspaMetDex4,a,b |
Day 1: Methotrexate 3g/m2 IV Days 1–4: Dexamethasone 40mg orally Days 2, 4, 6, and 8: L-asparaginase 6000U/m2 IM. Repeat every 21 days for 3 cycles. |
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Modified-SMILE2,3,6 |
Day 1: Methotrexate 2g/m2 IV Days 2-4: Dexamethasone 40mg IV + ifosfamide 1500mg/m2 IV + etoposide 100mg/m2 Day 8: Pegasparaginase 1500-2500 IU/m2 IV or IM. Repeat every 21 days for 4 to 6 cycles for advanced stage disease. |
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P-GEMOX5,6 |
Day 1: Oxaliplatin 130mg/m2 IV + pegaspargase 2500U/m2 IM Days 1 and 8: Gemcitabine 1000mg/m2 IV. Repeat every 21 days for a maximum of 6 cycles (including 3 cycles induction chemotherapy for stage stage IE/IIE patients followed by involved-field radiotherapy). |
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Concurrent Chemoradiation Therapy |
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DeVIC + RT7,9 |
Radiation 50Gy and 3 courses of DeVIC (dexamethasone, etoposide, ifosfamide, carboplatin) Level 1 (2/3 DeVIC) Day 1: Carboplatin 200mg/m2 IV over 30 minutes Days 1–3: Dexamethasone 40mg IV + etoposide 67mg/m2 IV over 2 hours + ifosfamide 1g/m2 IV over 3 hours. Level 2 (100% DeVIC) Day 1: Carboplatin 300mg/m2 Days 1–3: Dexamethasone 40mg IV + etoposide 100mg/m2 IV + ifosfamide 1.5mg/m2. Repeat chemotherapy every 3 weeks for 3 cycles. |
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VIPD + RT8 |
Radiation 40–52.8Gy and cisplatin 30mg/m2 IV for 3–5 weeks followed by 3 cycles of VIPD: Days 1–3: Etoposide 100mg/m2 IV over 90 minutes + ifosfamide 1200mg/m2 IV over 1 hour + cisplatin 33mg/m2 IV over 1 hour + dexamethasone 40mg orally or IV. Repeat chemotherapy every 3 weeks for 3 cycles. |
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Sequential Chemoradiation |
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Modified-SMILE + RT (for stage I, II disease)3 |
Day 1: Methotrexate 2g/m2 IV Days 2-4: Dexamethasone 40mg IV + ifosfamide 1500mg/m2 IV + etoposide 100 mg/m2 Day 8: Pegasparaginase 1500-2500 IU/m2 IV or IM. Repeat every 21 days for 3 cycles, following by radiation treatment at a dose of 45–50.4Gy for 2 to 4 cycles. |
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(Revised 3/2018; NCCN Non-Hodgkin’s Lymphomas Guidelines v3.2018) © 2018 by Haymarket Media, Inc. |
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Sandwich Chemoradiation |
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P-GEMOX + RT10–12,c |
Day 1: Oxaliplatin 100mg/m2 IV + pegaspargase 2500U/m2 IM Days 1 and 8: Gemcitabine 800mg/m2 IV. Repeat every 21 days for 2 cycles, followed by radiation treatment at a dose of 56Gy, followed by 2 to 4 additional cycles of GELOX. |
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Radiotherapy Alone (Unfit for Chemotherapy) |
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Radiotherapy13 |
• Recommended tumor dose is ≥ 50Gy • Early or up-front RT had an essential role in improved overall survival and disease-free survival in patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract • Up-front RT may yield more benefits on survival in patients with stage I disease. |
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a Reported as a second-line regimen. b In patients older than 70 years old: methotrexate and dexamethasone doses were decreased to 2g/m2 and 20mg for 4 days, respectively. c Pegaspargase-based regimens are preferred. However, there are no data to recommend 1 particular regimen over another. Treatment should be individualized based on patient’s tolerance and comorbidities. P-GEMOX is an option for selected patients who cannot tolerate intensive chemotherapy. |
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References |
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1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Hodgkin’s Lymphomas V.3.2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf. Accessed March 13, 2018. 2. Yamaguchi M, Kwong YL, Kim WS, et al. Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: The NK-Cell Tumor Study Group Study. J Clin Oncol. 2011;29:4410-4416. 3. Lunning M, Pamer E, Maraguila J, et al. Modified SMILE (mSMILE) is active in the treatment of extranodal natural killer/T-cell lymphoma: a single center US experience. Clinical Lymphoma, Myeloma, and Leukemia. 2014;14: S143-S144. 4. Jaccard A, Gachard N, Marin B, et al. Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study. Blood. 2011;117:1834-1839. 5. Wang JH, Wang H, Wang YJ, et al. Analysis of the efficacy and safety of a combined gemcitabine, oxaliplatin, and pegaspargase regimen for NJ/T-cell lymphoma. Oncotarget. 2018;7: 35412-35422. 6. Qi S, Yahalom J, Hsu M, et al. Encouraging experience in the treatment of nasal type extra-nodal NK/T-cell lymphoma in a non-Asian population. Leuk Lymphoma. 2018;57:2575-2583. 7. Yamaguchi M, Tobinai K, Oguchi M, et al. Concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: an updated analysis of the Japan clinical oncology group study JCOG0211. J Clin Oncol. 2012;30:4044-4046. 8. Kim SJ, Kim K, Kim BS, et al. Phase II trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-cell lymphoma: Consortium for Improving Survival of Lymphoma study. J Clin Oncol. 2009;27:6027-6032. 9. Yamaguchi M, Suzuki R, Oguchi M, et al. Treatments and outcomes of patients with extranodal natural killer/T-cell lymphoma diagnosed between 2000 and 2013: a cooperative study in Japan. J Clin Oncol. 2018;35:32-39. 10. Tse E, Kwong YL. The diagnosis and management of NK/T-cell lymphomas. J Hematol Oncol. 2018;10:85. 11. Wang L, Wang ZH, Chen XQ, et al. First-line combination of GELOX followed by radiation therapy for patients with stage IE/IIE ENKTL: an updated analysis with long-term follow-up. Oncol Lett. 2015;10:1036-1040. 12. Bi X-w, Zhang W-w, Sun P, et al. Radiotherapy and PGEMOX/GELOX regimen improved prognosis in elderly patients with early-stage extranodal NK/T-cell lymphoma. Ann Hematol. 2015;94(9):1525-1533. 13. Huang MJ, Jiang Y, Liu WP, et al. Early or up-front radiotherapy improved survival of localized extranodal NK/T-cell lymphoma, nasal-type in the upper aerodigestive tract. Int J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):166-174. |
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