Extranodal NK- and T-cell lymphoma, nasal type

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Bhagirathbhai Dholaria, MBBS
Vanderbilt University
Nashville, TN
12 regimens on this page
12 variants on this page


Guidelines

ESMO

"How I Treat"

NCCN

Untreated

Cisplatin & RT

Cisplatin & RT: Cisplatin & Radiation Therapy

Regimen

Study Evidence Efficacy
Kim et al. 2009 (CISL 2004-10-08) Phase 2 ORR: 83%

Chemotherapy

Radiotherapy

  • Concurrent radiation therapy to the primary tumor, 1.8 to 2 Gy fractions (median total dose: 40 Gy), given 5 times per week.

4-week course

Subsequent treatment

  • VIPD consolidation, 3 to 5 weeks after the last dose of cisplatin

References

  1. CISL 2004-10-08: Kim SJ, Kim K, Kim BS, Kim CY, Suh C, Huh J, Lee SW, Kim JS, Cho J, Lee GW, Kang KM, Eom HS, Pyo HR, Ahn YC, Ko YH, Kim WS; Consortium for Improving Survival of Lymphoma. 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 Dec 10;27(35):6027-32. link to original article contains dosing details in manuscript PubMed NCT00418535

DEP & RT

DEP & RT: Dexamethasone, Etoposide, Platinol (Cisplatin), Radiation Therapy

Regimen

Study Evidence Efficacy
Tsai et al. 2014 (T1405) Phase 2 ORR: 81%

Dosing details not available in the abstract.

Glucocorticoid therapy

Chemotherapy

28-day cycle for 2 cycles

Radiotherapy

5.5-week course

Subsequent treatment

References

  1. T1405: Tsai HJ, Lin SF, Chen CC, Chen TY, Su WC, Hwang WL, Lin JC, Chiou TJ, Kao WY, Chiu CF, Chang YF, Chang JS, Chang MC, Su IJ. Long-term results of a phase II trial with frontline concurrent chemoradiotherapy followed by consolidation chemotherapy for localized nasal natural killer/T-cell lymphoma. Eur J Haematol. 2015 Feb;94(2):130-7. Epub 2014 Oct 10. link to original article PubMed NCT00292695

DeVIC & RT

DeVIC & RT: Dexamethasone, VP-16 (Etoposide), Ifosfamide, Carboplatin, Radiation Therapy

Regimen

Study Evidence Efficacy
Yamaguchi et al. 2009 (JCOG0211) Phase 2 ORR: 81%

Glucocorticoid therapy, Dose Level I

Chemotherapy, Dose Level I

Glucocorticoid therapy, Dose Level II

Chemotherapy, Dose Level II

Supportive medications

  • Filgrastim (Neupogen) (dose/route/schedule not specified) started for WBC count less than 2 x 109/L or ANC less than 1000/uL; discontinued if WBC count greater than 5 x 109/L.

21-day cycle for 3 cycles

Radiotherapy

Started simultaneously with the beginning of cycle 1 of chemotherapy

  • Concurrent radiation therapy by the following stage-based criteria:
    • Stage IE disease: 2 Gy fractions x 25 fractions (total dose: 50 Gy)
    • Stage IIE disease: 1.8 Gy fractions x 28 fractions (total dose: 50.4 Gy)

5- to 6-week course

References

  1. JCOG0211: Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, Ishizawa K, Maseki N, Itoh K, Usui N, Wasada I, Kinoshita T, Ohshima K, Matsuno Y, Terauchi T, Nawano S, Ishikura S, Kagami Y, Hotta T, Oshimi K. Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan Clinical Oncology Group Study JCOG0211. J Clin Oncol. 2009 Nov 20;27(33):5594-600. link to original article contains dosing details in manuscript PubMed
    1. Update: Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, Ishizawa K, Maseki N, Itoh K, Usui N, Wasada I, Kinoshita T, Hotta T, Tsukasaki K, Oshimi K. 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 Nov 10;30(32):4044-6. Epub 2012 Oct 8. link to original article PubMed

GELOX/RT

GELOX/RT: Gemcitabine, L-asparaginase, Oxaliplatin, alternating with Radiation Therapy

Protocol

Study Evidence Efficacy
Wang et al. 2012 Phase 2 ORR: 96%

Note: total number of chemotherapy cycles was limited to 6.

Chemotherapy, part 1

21-day cycle for at least 2 cycles, followed by:

Radiotherapy

  • IFRT to 56 Gy in 28 fractions, 5 fractions per week

5.5-week course, followed within one week by:

Chemotherapy, part 2

21-day cycle for up to 4 cycles

References

  1. Wang L, Wang ZH, Chen XQ, Li YJ, Wang KF, Xia YF, Xia ZJ. First-line combination of gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE extranodal natural killer/T-cell lymphoma. Cancer. 2013 Jan 15;119(2):348-55. Epub 2012 Jul 18. link to original article contains dosing details in manuscript PubMed

LVP "Sandwich"

LVP: L-asparaginase, Vincristine, Prednisolone

Protocol

Study Evidence Efficacy
Jiang et al. 2011 Phase 2 ORR: 84%

Chemotherapy, part 1

Glucocorticoid therapy, part 1

21-day cycle for 2 cycles, followed by:

Radiotherapy

5.5-week course, followed in one week by:

Chemotherapy, part 2

Glucocorticoid therapy, part 2

21-day cycle for up to 4 cycles

References

  1. Jiang M, Zhang H, Jiang Y, Yang Q, Xie L, Liu W, Zhang W, Ji X, Li P, Chen N, Zhao S, Wang F, Zou L. Phase 2 trial of "sandwich" L-asparaginase, vincristine, and prednisone chemotherapy with radiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma. Cancer. 2012 Jul 1;118(13):3294-301. Epub 2011 Dec 2. link to original article contains dosing details in manuscript PubMed

MESA/RT

MESA/RT: Methotrexate, Etoposide, Steroid (dexamethasone), PEG-A-sparaginase alternating with Radiation Ttherapy

Protocol

Study Evidence Efficacy
Liang et al. 2016 Phase 2 ORR: 87%

Note: this regimen also incorporates radiation, see text for details.

Chemotherapy, part 1

Glucocorticoid therapy, part 1

21-day cycle for at least 3 cycles, followed by:

Radiotherapy

One course, followed by:

Chemotherapy, part 2

Glucocorticoid therapy, part 1

21-day cycle for a maximum of 7 cycles

References

  1. Liang R, Gao GX, Chen JP, Wang JS, Wang XM, Zeng Y, Bai QX, Zhang T, Yang L, Dong BX, Gu HT, Shu MM, Hao CX, Wang JH, Zhang N, Chen XQ. A phase 2 study of methotrexate, etoposide, dexamethasone, and pegaspargase chemotherapy for newly diagnosed, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type: a multicenter trial in Northwest China. Hematol Oncol. 2017 Dec;35(4):619-629. Epub 2016 Oct 10. link to original article link to PMC article contains dosing details in manuscript PubMed

SMILE

SMILE: Steroid (Dexamethasone), Methotrexate, Ifosfamide, L-asparaginase, Etoposide

Regimen

Study Evidence Efficacy
Yamaguchi et al. 2011 Phase 2 ORR: 79%

Glucocorticoid therapy

Chemotherapy

Supportive medications

28-day cycle for 2 cycles

After 2 cycles, patients could receive additional treatment with SMILE and/or other chemotherapy, with or without autologous/allogeneic stem cell transplant.

References

  1. Phase 1: Yamaguchi M, Suzuki R, Kwong YL, Kim WS, Hasegawa Y, Izutsu K, Suzumiya J, Okamura T, Nakamura S, Kawa K, Oshimi K. Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia. Cancer Sci. 2008 May;99(5):1016-20. Epub 2008 Feb 19. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
  2. Yamaguchi M, Kwong YL, Kim WS, Maeda Y, Hashimoto C, Suh C, Izutsu K, Ishida F, Isobe Y, Sueoka E, Suzumiya J, Kodama T, Kimura H, Hyo R, Nakamura S, Oshimi K, Suzuki R; NK-Cell Tumor Study Group. 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 Nov 20;29(33):4410-6. Epub 2011 Oct 11. link to original article contains dosing details in manuscript PubMed

Consolidation after upfront therapy

VIPD

VIPD: VP-16 (Etoposide), Ifosfamide, Platinol (Cisplatin), Dexamethasone

Regimen

Study Evidence
Kim et al. 2009 (CISL 2004-10-08) Phase 2
Tsai et al. 2014 (T1405) Phase 2

Details here are from CISL 2004-10-08.

Preceding treatment

Chemotherapy

Glucocorticoid therapy

Supportive medications

  • Mesna (Mesnex) 240 mg/m2 IV over 15 minutes once per day on days 1 to 3
  • G-CSF given for grade 3 or 4 neutropenia

21-day cycle for up to 3 cycles

References

  1. CISL 2004-10-08: Kim SJ, Kim K, Kim BS, Kim CY, Suh C, Huh J, Lee SW, Kim JS, Cho J, Lee GW, Kang KM, Eom HS, Pyo HR, Ahn YC, Ko YH, Kim WS; Consortium for Improving Survival of Lymphoma. 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 Dec 10;27(35):6027-32. link to original article contains dosing details in manuscript PubMed NCT00418535
  2. T1405: Tsai HJ, Lin SF, Chen CC, Chen TY, Su WC, Hwang WL, Lin JC, Chiou TJ, Kao WY, Chiu CF, Chang YF, Chang JS, Chang MC, Su IJ. Long-term results of a phase II trial with frontline concurrent chemoradiotherapy followed by consolidation chemotherapy for localized nasal natural killer/T-cell lymphoma. Eur J Haematol. 2015 Feb;94(2):130-7. Epub 2014 Oct 10. link to original article PubMed NCT00292695

Relapsed or refractory

AspaMetDex

AspaMetDex: Asparaginase, Methotrexate, Dexamethasone

Regimen

Study Evidence Efficacy
Jaccard et al. 2011 (I05009) Phase 2 ORR: 78%

Chemotherapy

  • Asparaginase (Elspar) 6000 units/m2 IM once per day on days 2, 4, 6, 8
  • Methotrexate (MTX) by the following age-based criteria:
    • Age up to 70: 3000 mg/m2 (route not specified) once on day 1
    • Older than 70: 2000 mg/m2 (route not specified) once on day 1

Glucocorticoid therapy

  • Dexamethasone (Decadron) by the following age-based criteria:
    • Age up to 70: 40 mg PO once per day on days 1 to 4
    • Older than 70: 20 mg PO once per day on days 1 to 4

Supportive medications

21-day cycle for 3 cycles

Subsequent treatment

  • See paper for details about further treatment

References

  1. I05009: Jaccard A, Gachard N, Marin B, Rogez S, Audrain M, Suarez F, Tilly H, Morschhauser F, Thieblemont C, Ysebaert L, Devidas A, Petit B, de Leval L, Gaulard P, Feuillard J, Bordessoule D, Hermine O; GELA; GOELAMS. 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 Feb 10;117(6):1834-9. link to original article contains dosing details in manuscript PubMed NCT00283985

AspaMetDex (Erwinaze)

AspaMetDex: Asparaginase, Methotrexate, Dexamethasone

Regimen

Study Evidence Efficacy
Jaccard et al. 2011 (I05009) Phase 2 ORR: 78%

Note: this regimen is for patients with allergies to asparaginase.

Chemotherapy

Glucocorticoid therapy

  • Dexamethasone (Decadron) by the following age-based criteria:
    • Age up to 70: 40 mg PO once per day on days 1 to 4
    • Older than 70: 20 mg PO once per day on days 1 to 4

Supportive medications

21-day cycle for 3 cycles

Subsequent treatment

  • See paper for details about further treatment

References

  1. I05009: Jaccard A, Gachard N, Marin B, Rogez S, Audrain M, Suarez F, Tilly H, Morschhauser F, Thieblemont C, Ysebaert L, Devidas A, Petit B, de Leval L, Gaulard P, Feuillard J, Bordessoule D, Hermine O; GELA; GOELAMS. 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 Feb 10;117(6):1834-9. link to original article contains dosing details in manuscript PubMed NCT00283985

L-Asparaginase, Vincristine, Prednisolone

LVP: L-asparaginase, Vincristine, Prednisolone

Regimen

Study Evidence Efficacy
Yong et al. 2003 Phase 2, <20 patients ORR: 83%

Regimen details are from a review article; original article is not available through PubMed

Chemotherapy

Glucocorticoid therapy

References

  1. Yong W, Zheng W, Zhang Y, Zhu J, Wei Y, Zhu D, Li J. L-asparaginase-based regimen in the treatment of refractory midline nasal/nasal-type T/NK-cell lymphoma. Int J Hematol. 2003 Aug;78(2):163-7. link to original article PubMed

SMILE

SMILE: Steroid (Dexamethasone), Methotrexate, Ifosfamide, L-asparaginase, Etoposide

Regimen

Study Evidence Efficacy
Yamaguchi et al. 2011 Phase 2 ORR: 79%

Glucocorticoid therapy

Chemotherapy

Supportive medications

28-day cycle for 2 cycles

After 2 cycles, patients could receive additional treatment with SMILE and/or other chemotherapy, with or without autologous/allogeneic stem cell transplant.

References

  1. Phase 1: Yamaguchi M, Suzuki R, Kwong YL, Kim WS, Hasegawa Y, Izutsu K, Suzumiya J, Okamura T, Nakamura S, Kawa K, Oshimi K. Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia. Cancer Sci. 2008 May;99(5):1016-20. Epub 2008 Feb 19. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
  2. Yamaguchi M, Kwong YL, Kim WS, Maeda Y, Hashimoto C, Suh C, Izutsu K, Ishida F, Isobe Y, Sueoka E, Suzumiya J, Kodama T, Kimura H, Hyo R, Nakamura S, Oshimi K, Suzuki R; NK-Cell Tumor Study Group. 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 Nov 20;29(33):4410-6. Epub 2011 Oct 11. link to original article contains dosing details in manuscript PubMed