Difference between revisions of "NK- and T-cell lymphoma"
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==[https://www.nccn.org/ NCCN]== | ==[https://www.nccn.org/ NCCN]== | ||
*[https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf NCCN Guidelines - T-cell Lymphomas] | *[https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf NCCN Guidelines - T-cell Lymphomas] | ||
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=Untreated= | =Untreated= | ||
==DDGP {{#subobject:abc3fd|Regimen=1}}== | ==DDGP {{#subobject:abc3fd|Regimen=1}}== | ||
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DDGP: '''<u>D</u>'''examethasone, '''<u>D</u>'''DP (Cisplatin), '''<u>G</u>'''emcitabine, '''<u>P</u>'''egaspargase | DDGP: '''<u>D</u>'''examethasone, '''<u>D</u>'''DP (Cisplatin), '''<u>G</u>'''emcitabine, '''<u>P</u>'''egaspargase | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:d2e0fd|Variant=1}}=== | ===Regimen {{#subobject:d2e0fd|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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''Note: dosing information is from the [https://clinicaltrials.gov/show/NCT01501149 NCT record].'' | ''Note: dosing information is from the [https://clinicaltrials.gov/show/NCT01501149 NCT record].'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Glucocorticoid therapy==== | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 15 mg/m<sup>2</sup> IV once per day on days 1 to 5 | *[[Dexamethasone (Decadron)]] 15 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
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*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8 | *[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8 | ||
*[[Pegaspargase (Oncaspar)]] 2500 IU/m<sup>2</sup> IM once on day 1 | *[[Pegaspargase (Oncaspar)]] 2500 IU/m<sup>2</sup> IM once on day 1 | ||
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'''21-day cycle for at least 3 cycles''' | '''21-day cycle for at least 3 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
# '''CTTNKTL-III/IV:''' Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in newly diagnosed advanced natural killer/T-cell lymphoma: a randomized controlled, multicenter, open-label study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. [http://clincancerres.aacrjournals.org/content/22/21/5223.long link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/27060152 PubMed] NCT01501149 | # '''CTTNKTL-III/IV:''' Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in newly diagnosed advanced natural killer/T-cell lymphoma: a randomized controlled, multicenter, open-label study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. [http://clincancerres.aacrjournals.org/content/22/21/5223.long link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/27060152 PubMed] NCT01501149 | ||
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==SMILE {{#subobject:db70b|Regimen=1}}== | ==SMILE {{#subobject:db70b|Regimen=1}}== | ||
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SMILE: '''<u>S</u>'''teroid (Dexamethasone), '''<u>M</u>'''ethotrexate, '''<u>I</u>'''fosfamide, '''<u>L</u>'''-asparaginase, '''<u>E</u>'''toposide | SMILE: '''<u>S</u>'''teroid (Dexamethasone), '''<u>M</u>'''ethotrexate, '''<u>I</u>'''fosfamide, '''<u>L</u>'''-asparaginase, '''<u>E</u>'''toposide | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:9874b6|Variant=1}}=== | ===Regimen {{#subobject:9874b6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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|} | |} | ||
''Note: [[Asparaginase (Elspar)]] was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include [[Pegaspargase (Oncaspar)]] or [[Asparaginase Erwinia chrysanthemi (Erwinaze)]]. Neither paper nor supplement specified the length of each cycle, but other SMILE regimens, e.g. Yamaguchi et al. 2011, describe 28-day cycles.'' | ''Note: [[Asparaginase (Elspar)]] was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include [[Pegaspargase (Oncaspar)]] or [[Asparaginase Erwinia chrysanthemi (Erwinaze)]]. Neither paper nor supplement specified the length of each cycle, but other SMILE regimens, e.g. Yamaguchi et al. 2011, describe 28-day cycles.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Glucocorticoid therapy==== | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 2 to 4 | *[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 2 to 4 | ||
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**Skin test done for asparaginase before each dose; Asparaginase Erwinia chrysanthemi used for patients who developed sensitivity to L-asparaginase from E. coli | **Skin test done for asparaginase before each dose; Asparaginase Erwinia chrysanthemi used for patients who developed sensitivity to L-asparaginase from E. coli | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 4 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 4 | ||
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====Supportive therapy==== | ====Supportive therapy==== | ||
*[[Folinic acid (Leucovorin)]] 45 mg PO every 6 hours on days 2 to 4 (or until serum methotrexate level is below the toxic range), starting 24 hours after completion of [[Methotrexate (MTX)]] | *[[Folinic acid (Leucovorin)]] 45 mg PO every 6 hours on days 2 to 4 (or until serum methotrexate level is below the toxic range), starting 24 hours after completion of [[Methotrexate (MTX)]] | ||
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*[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg PO once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]] | *[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg PO once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]] | ||
*[[Hydrocortisone (Cortef)]] 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]] | *[[Hydrocortisone (Cortef)]] 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]] | ||
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'''28-day cycle for up to 6 cycles (see note)''' | '''28-day cycle for up to 6 cycles (see note)''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
# Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS; Asia Lymphoma Study Group. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012 Oct 11;120(15):2973-80. Epub 2012 Aug 23. [http://www.bloodjournal.org/content/120/15/2973.long link to original article] [http://www.bloodjournal.org/content/120/15/2973/suppl/DC1 supplemental materials] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/22919026 PubMed] | # Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS; Asia Lymphoma Study Group. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012 Oct 11;120(15):2973-80. Epub 2012 Aug 23. [http://www.bloodjournal.org/content/120/15/2973.long link to original article] [http://www.bloodjournal.org/content/120/15/2973/suppl/DC1 supplemental materials] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/22919026 PubMed] | ||
# '''CTTNKTL-III/IV:''' Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in newly diagnosed advanced natural killer/T-cell lymphoma: a randomized controlled, multicenter, open-label study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. [http://clincancerres.aacrjournals.org/content/22/21/5223.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/27060152 PubMed] NCT01501149 | # '''CTTNKTL-III/IV:''' Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in newly diagnosed advanced natural killer/T-cell lymphoma: a randomized controlled, multicenter, open-label study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. [http://clincancerres.aacrjournals.org/content/22/21/5223.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/27060152 PubMed] NCT01501149 | ||
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=Relapsed or refractory= | =Relapsed or refractory= | ||
==FluBuCy, then allo HSCT {{#subobject:84acb0|Regimen=1}}== | ==FluBuCy, then allo HSCT {{#subobject:84acb0|Regimen=1}}== | ||
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FluBuCy: '''<u>Flu</u>'''darabine, '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide | FluBuCy: '''<u>Flu</u>'''darabine, '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:bfe434|Variant=1}}=== | ===Regimen {{#subobject:bfe434|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
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{{#lst:Allogeneic HSCT|bfe434}} | {{#lst:Allogeneic HSCT|bfe434}} | ||
− | + | </div></div> | |
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===References=== | ===References=== | ||
<!-- # Glass B, rabbits Kamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N. High-dose chemotherapy Followed by allogeneic stem cell transplantation in relapsed and refractory high-risk aggressive non-Hodgkin's lymphoma: Results of a prospective study of the German high-grade non-Hodgkin's lymphoma study group. J Clin Oncol 30, 2012 (suppl; abstr 8004) --> | <!-- # Glass B, rabbits Kamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N. High-dose chemotherapy Followed by allogeneic stem cell transplantation in relapsed and refractory high-risk aggressive non-Hodgkin's lymphoma: Results of a prospective study of the German high-grade non-Hodgkin's lymphoma study group. J Clin Oncol 30, 2012 (suppl; abstr 8004) --> | ||
# '''DSHNHL R3:''' Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. [https://doi.org/10.1016/S1470-2045(14)70161-5 link to original article] [http://www.dshnhl.org/app/download/9495510598/Studienprotokoll+DSHNHL+alloFBC+final+vollst.pdf link to original protocol (in German)] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24827808 PubMed] NCT00785330 | # '''DSHNHL R3:''' Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. [https://doi.org/10.1016/S1470-2045(14)70161-5 link to original article] [http://www.dshnhl.org/app/download/9495510598/Studienprotokoll+DSHNHL+alloFBC+final+vollst.pdf link to original protocol (in German)] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24827808 PubMed] NCT00785330 | ||
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==Pembrolizumab monotherapy {{#subobject:84ac5y|Regimen=1}}== | ==Pembrolizumab monotherapy {{#subobject:84ac5y|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:ga3na4|Variant=1}}=== | ===Regimen {{#subobject:ga3na4|Variant=1}}=== | ||
{| class="wikitable" style="width: 40%; text-align:center;" | {| class="wikitable" style="width: 40%; text-align:center;" | ||
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|} | |} | ||
''Note: prospective trials are underway.'' | ''Note: prospective trials are underway.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
*[[Pembrolizumab (Keytruda)]] 2 mg/kg IV once on day 1 | *[[Pembrolizumab (Keytruda)]] 2 mg/kg IV once on day 1 | ||
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'''21-day cycles''' | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
#Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B, Khong PL, Loong F, Au-Yeung R, Iqbal J, Phipps C, Tse E. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017 Apr 27;129(17):2437-2442. Epub 2017 Feb 10. [https://doi.org/10.1182/blood-2016-12-756841 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28188133/ PubMed] | #Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B, Khong PL, Loong F, Au-Yeung R, Iqbal J, Phipps C, Tse E. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017 Apr 27;129(17):2437-2442. Epub 2017 Feb 10. [https://doi.org/10.1182/blood-2016-12-756841 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28188133/ PubMed] | ||
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==SMILE {{#subobject:db70b|Regimen=1}}== | ==SMILE {{#subobject:db70b|Regimen=1}}== | ||
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SMILE: '''<u>S</u>'''teroid (Dexamethasone), '''<u>M</u>'''ethotrexate, '''<u>I</u>'''fosfamide, '''<u>L</u>'''-asparaginase, '''<u>E</u>'''toposide | SMILE: '''<u>S</u>'''teroid (Dexamethasone), '''<u>M</u>'''ethotrexate, '''<u>I</u>'''fosfamide, '''<u>L</u>'''-asparaginase, '''<u>E</u>'''toposide | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:9874b6|Variant=1}}=== | ===Regimen {{#subobject:9874b6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
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|} | |} | ||
''Note: [[Asparaginase (Elspar)]] was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include [[Pegaspargase (Oncaspar)]] or [[Asparaginase Erwinia chrysanthemi (Erwinaze)]]. Neither paper nor supplement specified the length of each cycle, but other SMILE regimens, e.g. Yamaguchi et al. 2008, describe 28-day cycles.'' | ''Note: [[Asparaginase (Elspar)]] was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include [[Pegaspargase (Oncaspar)]] or [[Asparaginase Erwinia chrysanthemi (Erwinaze)]]. Neither paper nor supplement specified the length of each cycle, but other SMILE regimens, e.g. Yamaguchi et al. 2008, describe 28-day cycles.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Glucocorticoid therapy==== | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 2 to 4 | *[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 2 to 4 | ||
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**Skin test done for asparaginase before each dose; Asparaginase Erwinia chrysanthemi used for patients who developed sensitivity to L-asparaginase from E. coli | **Skin test done for asparaginase before each dose; Asparaginase Erwinia chrysanthemi used for patients who developed sensitivity to L-asparaginase from E. coli | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 4 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 4 | ||
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====Supportive therapy==== | ====Supportive therapy==== | ||
*[[Folinic acid (Leucovorin)]] 45 mg PO every 6 hours on days 2 to 4 (or until serum methotrexate level is below the toxic range), starting 24 hours after completion of [[Methotrexate (MTX)]] | *[[Folinic acid (Leucovorin)]] 45 mg PO every 6 hours on days 2 to 4 (or until serum methotrexate level is below the toxic range), starting 24 hours after completion of [[Methotrexate (MTX)]] | ||
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*[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg PO once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]] | *[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg PO once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]] | ||
*[[Hydrocortisone (Cortef)]] 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]] | *[[Hydrocortisone (Cortef)]] 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]] | ||
− | |||
'''28-day cycle for up to 6 cycles (see note)''' | '''28-day cycle for up to 6 cycles (see note)''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
# '''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. [https://doi.org/10.1111/j.1349-7006.2008.00768.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18294294 PubMed] content property of [http://hemonc.org HemOnc.org] | # '''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. [https://doi.org/10.1111/j.1349-7006.2008.00768.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18294294 PubMed] content property of [http://hemonc.org HemOnc.org] | ||
# Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS; Asia Lymphoma Study Group. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012 Oct 11;120(15):2973-80. Epub 2012 Aug 23. [http://www.bloodjournal.org/content/120/15/2973.long link to original article] [http://www.bloodjournal.org/content/120/15/2973/suppl/DC1 supplemental materials] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/22919026 PubMed] | # Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS; Asia Lymphoma Study Group. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012 Oct 11;120(15):2973-80. Epub 2012 Aug 23. [http://www.bloodjournal.org/content/120/15/2973.long link to original article] [http://www.bloodjournal.org/content/120/15/2973/suppl/DC1 supplemental materials] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/22919026 PubMed] | ||
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[[Category:NK- and T-cell lymphoma regimens]] | [[Category:NK- and T-cell lymphoma regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:T-cell lymphomas]] | [[Category:T-cell lymphomas]] |
Revision as of 12:06, 29 October 2022
5 regimens on this page
5 variants on this page
|
Note: a variant of this disease, aggressive NK-cell leukemia, is usually considered a separate entity (somewhat analogous to plasma cell leukemia and multiple myeloma). There are no prospective trials reported for this variant.
Guidelines
ESMO
- 2015: d'Amore et al. Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
"How I Treat"
- 2013: Tse E, Kwong YL. How I treat NK/T-cell lymphomas. Blood. 2013 Jun 20;121(25):4997-5005. Epub 2013 May 7. link to original article PubMed
NCCN
Untreated
DDGP
DDGP: Dexamethasone, DDP (Cisplatin), Gemcitabine, Pegaspargase
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Li et al. 2016 (CTTNKTL-III/IV) | 2011-2014 | Phase 4 (E-switch-ic) | SMILE | Seems to have superior OS OS24: 74% vs 45% |
Note: dosing information is from the NCT record.
Glucocorticoid therapy
- Dexamethasone (Decadron) 15 mg/m2 IV once per day on days 1 to 5
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 4
- Gemcitabine (Gemzar) 800 mg/m2 IV over 30 minutes once per day on days 1 & 8
- Pegaspargase (Oncaspar) 2500 IU/m2 IM once on day 1
21-day cycle for at least 3 cycles
References
- CTTNKTL-III/IV: Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in newly diagnosed advanced natural killer/T-cell lymphoma: a randomized controlled, multicenter, open-label study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. link to original article does not contain dosing details PubMed NCT01501149
SMILE
SMILE: Steroid (Dexamethasone), Methotrexate, Ifosfamide, L-asparaginase, Etoposide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kwong et al. 2012 | 2005-2012 | Phase 2 | ||
Li et al. 2016 (CTTNKTL-III/IV) | 2011-2014 | Phase 4 (E-switch-ic) | DDGP | Seems to have inferior OS |
Note: Asparaginase (Elspar) was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include Pegaspargase (Oncaspar) or Asparaginase Erwinia chrysanthemi (Erwinaze). Neither paper nor supplement specified the length of each cycle, but other SMILE regimens, e.g. Yamaguchi et al. 2011, describe 28-day cycles.
Glucocorticoid therapy
- Dexamethasone (Decadron) 40 mg PO once per day on days 2 to 4
Chemotherapy
- Methotrexate (MTX) 2000 mg/m2 IV over 6 hours once on day 1
- Ifosfamide (Ifex) 1500 mg/m2 IV over 6 hours once per day on days 2 to 4, given with mesna
- Asparaginase (Elspar) 6000 units/m2 IV over 2 hours once per day on days 8, 10, 12, 14, 16, 18, 20
- Skin test done for asparaginase before each dose; Asparaginase Erwinia chrysanthemi used for patients who developed sensitivity to L-asparaginase from E. coli
- Etoposide (Vepesid) 100 mg/m2 IV over 2 hours once per day on days 2 to 4
Supportive therapy
- Folinic acid (Leucovorin) 45 mg PO every 6 hours on days 2 to 4 (or until serum methotrexate level is below the toxic range), starting 24 hours after completion of Methotrexate (MTX)
- Methotrexate levels checked at 24, 48, and 72 hours after methotrexate is given, or until methotrexate levels fall below toxic range. Folinic acid should be continued until methotrexate levels are below toxic range.
- Mesna (Mesnex) 900 mg/m2 IV over 6 hours once per day on days 2 to 4, given with Ifosfamide (Ifex)
- Hydration with normal saline (no volume specified) every 8 hours on the day prior to Methotrexate (MTX)
- Patients told to drink at least 2 liters of fluid per day on days 1 to 4; target urine output of greater than or equal to 3 liters per day on days 1 to 4
- Filgrastim (Neupogen) 300 mcg SC once per day, starting on day 6, given until ANC greater than 1000/uL
- Cotrimoxazole or Pentamidine (Nebupent) for PJP prophylaxis
- Famotidine (Pepcid) and potassium slow release tablets (no dose specified) "for Dexamethasone (Decadron)" on days 2 to 4
- Chlorpheniramine (Chlor-Trimeton) 10 mg PO once per day on days 8, 10, 12, 14, 16, 18, 20, prior to Asparaginase (Elspar)
- Hydrocortisone (Cortef) 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to Asparaginase (Elspar)
28-day cycle for up to 6 cycles (see note)
References
- Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS; Asia Lymphoma Study Group. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012 Oct 11;120(15):2973-80. Epub 2012 Aug 23. link to original article supplemental materials contains dosing details in supplement PubMed
- CTTNKTL-III/IV: Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in newly diagnosed advanced natural killer/T-cell lymphoma: a randomized controlled, multicenter, open-label study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. link to original article PubMed NCT01501149
Relapsed or refractory
FluBuCy, then allo HSCT
FluBuCy: Fludarabine, Busulfan, Cyclophosphamide
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Glass et al. 2014 (DSHNHL R3) | 2004-2009 | Phase 2 |
Chemotherapy
- Fludarabine (Fludara) 25 mg/m2/day IV on days -8 to -4
- Busulfan (Myleran) 4 mg/kg/day PO on days -6 to -4
- Cyclophosphamide (Cytoxan) 60 mg/kg/day IV on days -3 and -2
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Antithymocyte globulin, rabbit ATG (Thymoglobulin) 2 mg/kg IV from day -3 to -1 (unclear if this is a total dose or a daily dose)
- Option also to use ATG-Fresenius S at a higher dose of 10 mg/kg
- Tacrolimus (Prograf) 8 to 12 mcg/L (route/frequency not specified) starting on day -1, tapered from day +100 in absence of GVHD
- Mycophenolate mofetil (CellCept) 1000 mg (route not specified) twice per day from day +1 to +28
One course
References
- DSHNHL R3: Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. link to original article link to original protocol (in German) contains dosing details in manuscript PubMed NCT00785330
Pembrolizumab monotherapy
References
- Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B, Khong PL, Loong F, Au-Yeung R, Iqbal J, Phipps C, Tse E. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017 Apr 27;129(17):2437-2442. Epub 2017 Feb 10. link to original article PubMed
SMILE
SMILE: Steroid (Dexamethasone), Methotrexate, Ifosfamide, L-asparaginase, Etoposide
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Yamaguchi et al. 2008 | 2005-2006 | Phase 1 |
Kwong et al. 2012 | 2005-2012 | Phase 2 |
Note: Asparaginase (Elspar) was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include Pegaspargase (Oncaspar) or Asparaginase Erwinia chrysanthemi (Erwinaze). Neither paper nor supplement specified the length of each cycle, but other SMILE regimens, e.g. Yamaguchi et al. 2008, describe 28-day cycles.
Glucocorticoid therapy
- Dexamethasone (Decadron) 40 mg PO once per day on days 2 to 4
Chemotherapy
- Methotrexate (MTX) 2000 mg/m2 IV over 6 hours once on day 1
- Ifosfamide (Ifex) 1500 mg/m2 IV over 6 hours once per day on days 2 to 4, given with mesna
- Asparaginase (Elspar) 6000 units/m2 IV over 2 hours once per day on days 8, 10, 12, 14, 16, 18, 20
- Skin test done for asparaginase before each dose; Asparaginase Erwinia chrysanthemi used for patients who developed sensitivity to L-asparaginase from E. coli
- Etoposide (Vepesid) 100 mg/m2 IV over 2 hours once per day on days 2 to 4
Supportive therapy
- Folinic acid (Leucovorin) 45 mg PO every 6 hours on days 2 to 4 (or until serum methotrexate level is below the toxic range), starting 24 hours after completion of Methotrexate (MTX)
- Methotrexate levels checked at 24, 48, and 72 hours after methotrexate is given, or until methotrexate levels fall below toxic range. Folinic acid should be continued until methotrexate levels are below toxic range.
- Mesna (Mesnex) 900 mg/m2 IV over 6 hours once per day on days 2 to 4, given with Ifosfamide (Ifex)
- Hydration with normal saline (no volume specified) every 8 hours on the day prior to Methotrexate (MTX)
- Patients told to drink at least 2 liters of fluid per day on days 1 to 4; target urine output of greater than or equal to 3 liters per day on days 1 to 4
- Filgrastim (Neupogen) 300 mcg SC once per day, starting on day 6, given until ANC greater than 1000/uL
- Cotrimoxazole or Pentamidine (Nebupent) for PJP prophylaxis
- Famotidine (Pepcid) and potassium slow release tablets (no dose specified) "for Dexamethasone (Decadron)" on days 2 to 4
- Chlorpheniramine (Chlor-Trimeton) 10 mg PO once per day on days 8, 10, 12, 14, 16, 18, 20, prior to Asparaginase (Elspar)
- Hydrocortisone (Cortef) 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to Asparaginase (Elspar)
28-day cycle for up to 6 cycles (see note)
References
- 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
- Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS; Asia Lymphoma Study Group. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012 Oct 11;120(15):2973-80. Epub 2012 Aug 23. link to original article supplemental materials contains dosing details in supplement PubMed