Difference between revisions of "NK- and T-cell lymphoma"
Warner-admin (talk | contribs) m (Text replacement - "====Supportive medications" to "====Supportive therapy") |
Warner-admin (talk | contribs) m (Text replacement - "*<big>We have moved How I Treat articles to a dedicated page.</big>" to "*''We have moved How I Treat articles to a dedicated page.''") |
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[[#top|Back to Top]] | [[#top|Back to Top]] | ||
</div> | </div> | ||
− | {| | + | {{#lst:Editorial board transclusions|tcl}} |
− | + | ''Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the [[NK-_and_T-cell_lymphoma_-_historical|historical regimens page]].''<br> | |
− | + | '''<big>Note: The most common subtype of this condition (ENKTCL, nasal type) has a [[Extranodal NK- and T-cell lymphoma, nasal type|dedicated page]].</big>''' | |
− | + | *''We have moved [[How I Treat]] articles to a dedicated page.'' | |
− | |||
− | |||
− | |||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
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''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.'' | ''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= | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
==[http://www.esmo.org/ ESMO]== | ==[http://www.esmo.org/ ESMO]== | ||
− | *'''2015:''' d'Amore et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Peripheral-T-Cell-Lymphomas Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] | + | *'''2015:''' d'Amore et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Peripheral-T-Cell-Lymphomas Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/26314772 PubMed] |
− | + | ||
− | + | ==NCCN== | |
− | == | + | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1483 NCCN Guidelines - T-cell Lymphomas].'' |
− | *[https://www.nccn.org/ | ||
=Untreated= | =Untreated= | ||
==DDGP {{#subobject:abc3fd|Regimen=1}}== | ==DDGP {{#subobject:abc3fd|Regimen=1}}== | ||
− | |||
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;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 38: | Line 35: | ||
|- | |- | ||
|[http://clincancerres.aacrjournals.org/content/22/21/5223.long Li et al. 2016 (CTTNKTL-III/IV)] | |[http://clincancerres.aacrjournals.org/content/22/21/5223.long Li et al. 2016 (CTTNKTL-III/IV)] | ||
− | |2011- | + | |2011-01 to 2019-02 |
|style="background-color:#1a9851"|Phase 4 (E-switch-ic) | |style="background-color:#1a9851"|Phase 4 (E-switch-ic) | ||
|[[#SMILE|SMILE]] | |[[#SMILE|SMILE]] | ||
− | |style="background-color:#91cf60"|Seems to have superior OS<br> | + | |style="background-color:#91cf60"|Seems to have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: NYR vs 75.2 mo<br>(HR 0.41, 95% CI 0.19-0.89)<br><br>Superior PFS<sup>1</sup> (primary endpoint)<br>Median PFS: NYR vs 6.8 mo<br>(HR 0.42, 95% CI 0.23-0.77) |
|- | |- | ||
|} | |} | ||
− | ''Note: dosing information is from the | + | ''<sup>1</sup>Reported efficacy is based on the 2023 update.''<br> |
+ | ''Note: dosing information is from the update.'' | ||
+ | <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 | ||
− | + | '''21-day cycle for 6 cycles''' | |
− | '''21-day cycle for | + | </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] [https://clinicaltrials.gov/study/NCT01501149 NCT01501149] |
+ | ##'''Update:''' Wang X, Zhang L, Liu X, Li X, Li L, Fu X, Sun Z, Wu J, Zhang X, Yan J, Chang Y, Nan F, Zhou Z, Wu X, Tian L, Ma M, Li Z, Yu H, Zhu L, Wang Y, Shi C, Feng X, Li J, Ding M, Zhang J, Dong M, Xue H, Wang J, Zou L, Su L, Wu J, Liu L, Bao H, Zhang L, Guo Y, Guo S, Lu Y, Young KH, Li W, Zhang M. Efficacy and Safety of a Pegasparaginase-Based Chemotherapy Regimen vs an L-asparaginase-Based Chemotherapy Regimen for Newly Diagnosed Advanced Extranodal Natural Killer/T-Cell Lymphoma: A Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1035-1041. [https://doi.org/10.1001/jamaoncol.2022.1968 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9204617/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35708709/ PubMed] | ||
==SMILE {{#subobject:db70b|Regimen=1}}== | ==SMILE {{#subobject:db70b|Regimen=1}}== | ||
− | |||
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;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 76: | Line 74: | ||
|- | |- | ||
|[http://clincancerres.aacrjournals.org/content/22/21/5223.long Li et al. 2016 (CTTNKTL-III/IV)] | |[http://clincancerres.aacrjournals.org/content/22/21/5223.long Li et al. 2016 (CTTNKTL-III/IV)] | ||
− | |2011- | + | |2011-01 to 2019-02 |
|style="background-color:#1a9851"|Phase 4 (E-switch-ic) | |style="background-color:#1a9851"|Phase 4 (E-switch-ic) | ||
|[[#DDGP|DDGP]] | |[[#DDGP|DDGP]] | ||
− | |style="background-color:#fc8d59"|Seems to have inferior OS | + | |style="background-color:#fc8d59"|Seems to have inferior OS (secondary endpoint)<br><br>Inferior PFS (primary endpoint) |
|- | |- | ||
|} | |} | ||
− | ''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)]] | + | ''<sup>1</sup>Reported efficacy for CTTNKTL-III/IV is based on the 2023 update.''<br> |
+ | ''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)]].'' | ||
+ | <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 | ||
Line 88: | Line 88: | ||
*[[Methotrexate (MTX)]] 2000 mg/m<sup>2</sup> IV over 6 hours once on day 1 | *[[Methotrexate (MTX)]] 2000 mg/m<sup>2</sup> IV over 6 hours once on day 1 | ||
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with mesna''' | *[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with mesna''' | ||
− | *[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IV over 2 hours once per day on days | + | *[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IV over 2 hours once per day on days 3 to 9 |
**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 | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 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 |
**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. | **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/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with | + | *[[Mesna (Mesnex)]] 900 mg/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with ifosfamide''' |
− | *Hydration with normal saline (no volume specified) every 8 hours on the day prior to | + | *Hydration with normal saline (no volume specified) every 8 hours on the day prior to methotrexate |
*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 | *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/ | + | *[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6, given until ANC greater than 1000/μL |
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] or [[Pentamidine (Nebupent)]] for PJP prophylaxis | *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|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 | *[[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 | + | *[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg PO once per day on days 8, 10, 12, 14, 16, 18, 20, prior to asparaginase |
− | *[[Hydrocortisone (Cortef)]] 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to | + | *[[Hydrocortisone (Cortef)]] 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to asparaginase |
− | + | '''21-day cycle for 6 cycles''' | |
− | ''' | + | </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] [https://clinicaltrials.gov/study/NCT01501149 NCT01501149] |
+ | ##'''Update:''' Wang X, Zhang L, Liu X, Li X, Li L, Fu X, Sun Z, Wu J, Zhang X, Yan J, Chang Y, Nan F, Zhou Z, Wu X, Tian L, Ma M, Li Z, Yu H, Zhu L, Wang Y, Shi C, Feng X, Li J, Ding M, Zhang J, Dong M, Xue H, Wang J, Zou L, Su L, Wu J, Liu L, Bao H, Zhang L, Guo Y, Guo S, Lu Y, Young KH, Li W, Zhang M. Efficacy and Safety of a Pegasparaginase-Based Chemotherapy Regimen vs an L-asparaginase-Based Chemotherapy Regimen for Newly Diagnosed Advanced Extranodal Natural Killer/T-Cell Lymphoma: A Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1035-1041. [https://doi.org/10.1001/jamaoncol.2022.1968 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9204617/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35708709/ PubMed] | ||
=Relapsed or refractory= | =Relapsed or refractory= | ||
− | == | + | ==AspaMetDex {{#subobject:407753|Regimen=1}}== |
− | + | AspaMetDex: '''<u>Aspa</u>'''raginase, '''<u>Met</u>'''hotrexate, '''<u>Dex</u>'''amethasone | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:305a48|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
+ | |- | ||
+ | |[http://www.bloodjournal.org/content/117/6/1834.long Jaccard et al. 2010 (I05009)] | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | | style="background-color:#e0ecf4" |ORR: 78% | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IM once per day on days 2, 4, 6, 8 | ||
+ | *[[Methotrexate (MTX)]] by the following age-based criteria: | ||
+ | **Younger than 70 years old: 3000 mg/m<sup>2</sup> (route not specified) once on day 1 | ||
+ | **Older than 70 years old: 2000 mg/m<sup>2</sup> (route not specified) once on day 1 | ||
+ | ====Glucocorticoid therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] by the following age-based criteria: | ||
+ | **Younger than 70 years old: 40 mg PO once per day on days 1 to 4 | ||
+ | **Older than 70 years old: 20 mg PO once per day on days 1 to 4 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] (dose/route/schedule not specified) prophylaxis, discontinued during methotrexate administration | ||
+ | *[[Valacyclovir (Valtrex)]] (dose/route/schedule not specified) prophylaxis | ||
+ | *[[:Category:Hydration|Alkaline hydration]] (type/dose/schedule not specified) | ||
+ | *[[Leucovorin (Folinic acid)]] rescue (dose/route/schedule not specified) | ||
+ | '''21-day cycle for 3 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *See paper for details about further treatment | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''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. Epub 2010 Dec 1. [http://www.bloodjournal.org/content/117/6/1834.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21123825/ PubMed] [https://clinicaltrials.gov/study/NCT00283985 NCT00283985] | ||
+ | ==AspaMetDex (Erwinaze) {{#subobject:402253|Regimen=1}}== | ||
+ | AspaMetDex: '''<u>Aspa</u>'''raginase, '''<u>Met</u>'''hotrexate, '''<u>Dex</u>'''amethasone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:308gy8|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
+ | |- | ||
+ | |[http://www.bloodjournal.org/content/117/6/1834.long Jaccard et al. 2010 (I05009)] | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | | style="background-color:#e0ecf4" |ORR: 78% | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this regimen is for patients with allergies to asparaginase.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Asparaginase Erwinia chrysanthemi (Erwinaze)]] 20,000 units/m<sup>2</sup> IM once per day on days 2, 4, 6, 8 | ||
+ | *[[Methotrexate (MTX)]] by the following age-based criteria: | ||
+ | **Younger than 70 years old: 3000 mg/m<sup>2</sup> (route not specified) once on day 1 | ||
+ | **Older than 70 years old: 2000 mg/m<sup>2</sup> (route not specified) once on day 1 | ||
+ | ====Glucocorticoid therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] by the following age-based criteria: | ||
+ | **Younger than 70 years old: 40 mg PO once per day on days 1 to 4 | ||
+ | **Older than 70 years old: 20 mg PO once per day on days 1 to 4 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] (dose/route/schedule not specified) prophylaxis, discontinued during methotrexate administration | ||
+ | *[[Valacyclovir (Valtrex)]] (dose/route/schedule not specified) prophylaxis | ||
+ | *[[:Category:Hydration|Alkaline hydration]] (type/dose/schedule not specified) | ||
+ | *[[Leucovorin (Folinic acid)]] rescue (dose/route/schedule not specified) | ||
+ | '''21-day cycle for 3 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *See paper for details about further treatment | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''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. Epub 2010 Dec 1. [http://www.bloodjournal.org/content/117/6/1834.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21123825/ PubMed] [https://clinicaltrials.gov/study/NCT00283985 NCT00283985] | ||
+ | ==Fludarabine, Busulfan, Cyclophosphamide, then allo HSCT {{#subobject:84acb0|Regimen=1}}== | ||
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 | ||
− | ===Regimen {{#subobject:bfe434|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, oral {{#subobject:bfe434|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1016/S1470-2045(14)70161-5 Glass et al. 2014 (DSHNHL R3)] | |[https://doi.org/10.1016/S1470-2045(14)70161-5 Glass et al. 2014 (DSHNHL R3)] | ||
− | |2004-2009 | + | |2004-06-16 to 2009-03-24 |
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
{{#lst:Allogeneic HSCT|bfe434}} | {{#lst:Allogeneic HSCT|bfe434}} | ||
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #2, intravenous {{#subobject:bfe434|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | < | + | !style="width: 33%"|Study |
− | + | !style="width: 33%"|Dates of enrollment | |
− | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | == | ||
− | |||
− | ===Regimen {{#subobject: | ||
− | {| class="wikitable" style="width: | ||
− | !style="width: | ||
− | !style="width: | ||
|- | |- | ||
− | |[https://doi.org/10. | + | |[https://doi.org/10.1016/S1470-2045(14)70161-5 Glass et al. 2014 (DSHNHL R3)] |
− | | style="background-color:# | + | |2004-06-16 to 2009-03-24 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | + | {{#lst:Allogeneic HSCT|bfe435}} | |
− | + | </div></div> | |
− | |||
− | |||
− | |||
===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) --> |
− | + | # '''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] [https://clinicaltrials.gov/study/NCT00785330 NCT00785330] | |
==SMILE {{#subobject:db70b|Regimen=1}}== | ==SMILE {{#subobject:db70b|Regimen=1}}== | ||
− | |||
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;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
Line 172: | Line 237: | ||
|} | |} | ||
''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 | ||
Line 180: | Line 246: | ||
**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 | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 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 |
**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. | **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/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with | + | *[[Mesna (Mesnex)]] 900 mg/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with ifosfamide''' |
− | *Hydration with normal saline (no volume specified) every 8 hours on the day prior to | + | *Hydration with normal saline (no volume specified) every 8 hours on the day prior to methotrexate |
*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 | *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/ | + | *[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6, given until ANC greater than 1000/μL |
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] or [[Pentamidine (Nebupent)]] for PJP prophylaxis | *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|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 | *[[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 | + | *[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg PO once per day on days 8, 10, 12, 14, 16, 18, 20, prior to asparaginase |
− | *[[Hydrocortisone (Cortef)]] 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to | + | *[[Hydrocortisone (Cortef)]] 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to asparaginase |
− | |||
'''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] |
− | |||
[[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 11:35, 15 May 2024
Section editor | |
---|---|
Bhagirathbhai Dholaria, MBBS Vanderbilt University Nashville, TN, USA |
Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the historical regimens page.
Note: The most common subtype of this condition (ENKTCL, nasal type) has a dedicated page.
- We have moved How I Treat articles to a dedicated page.
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
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ESMO
- 2015: d'Amore et al. Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - T-cell Lymphomas.
Untreated
DDGP
DDGP: Dexamethasone, DDP (Cisplatin), Gemcitabine, Pegaspargase
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Li et al. 2016 (CTTNKTL-III/IV) | 2011-01 to 2019-02 | Phase 4 (E-switch-ic) | SMILE | Seems to have superior OS1 (secondary endpoint) Median OS: NYR vs 75.2 mo (HR 0.41, 95% CI 0.19-0.89) Superior PFS1 (primary endpoint) Median PFS: NYR vs 6.8 mo (HR 0.42, 95% CI 0.23-0.77) |
1Reported efficacy is based on the 2023 update.
Note: dosing information is from the update.
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 6 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
- Update: Wang X, Zhang L, Liu X, Li X, Li L, Fu X, Sun Z, Wu J, Zhang X, Yan J, Chang Y, Nan F, Zhou Z, Wu X, Tian L, Ma M, Li Z, Yu H, Zhu L, Wang Y, Shi C, Feng X, Li J, Ding M, Zhang J, Dong M, Xue H, Wang J, Zou L, Su L, Wu J, Liu L, Bao H, Zhang L, Guo Y, Guo S, Lu Y, Young KH, Li W, Zhang M. Efficacy and Safety of a Pegasparaginase-Based Chemotherapy Regimen vs an L-asparaginase-Based Chemotherapy Regimen for Newly Diagnosed Advanced Extranodal Natural Killer/T-Cell Lymphoma: A Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1035-1041. 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 | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kwong et al. 2012 | 2005-2012 | Phase 2 | ||
Li et al. 2016 (CTTNKTL-III/IV) | 2011-01 to 2019-02 | Phase 4 (E-switch-ic) | DDGP | Seems to have inferior OS (secondary endpoint) Inferior PFS (primary endpoint) |
1Reported efficacy for CTTNKTL-III/IV is based on the 2023 update.
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).
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 3 to 9
- 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
- Leucovorin (Folinic acid) 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
- 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
- Hydration with normal saline (no volume specified) every 8 hours on the day prior to methotrexate
- 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/μL
- 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
- Hydrocortisone (Cortef) 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to asparaginase
21-day cycle for 6 cycles
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
- Update: Wang X, Zhang L, Liu X, Li X, Li L, Fu X, Sun Z, Wu J, Zhang X, Yan J, Chang Y, Nan F, Zhou Z, Wu X, Tian L, Ma M, Li Z, Yu H, Zhu L, Wang Y, Shi C, Feng X, Li J, Ding M, Zhang J, Dong M, Xue H, Wang J, Zou L, Su L, Wu J, Liu L, Bao H, Zhang L, Guo Y, Guo S, Lu Y, Young KH, Li W, Zhang M. Efficacy and Safety of a Pegasparaginase-Based Chemotherapy Regimen vs an L-asparaginase-Based Chemotherapy Regimen for Newly Diagnosed Advanced Extranodal Natural Killer/T-Cell Lymphoma: A Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1035-1041. link to original article link to PMC article contains dosing details in manuscript PubMed
Relapsed or refractory
AspaMetDex
AspaMetDex: Asparaginase, Methotrexate, Dexamethasone
Regimen
Study | Evidence | Efficacy |
---|---|---|
Jaccard et al. 2010 (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:
- Younger than 70 years old: 3000 mg/m2 (route not specified) once on day 1
- Older than 70 years old: 2000 mg/m2 (route not specified) once on day 1
Glucocorticoid therapy
- Dexamethasone (Decadron) by the following age-based criteria:
- Younger than 70 years old: 40 mg PO once per day on days 1 to 4
- Older than 70 years old: 20 mg PO once per day on days 1 to 4
Supportive therapy
- Trimethoprim-Sulfamethoxazole (Bactrim DS) (dose/route/schedule not specified) prophylaxis, discontinued during methotrexate administration
- Valacyclovir (Valtrex) (dose/route/schedule not specified) prophylaxis
- Alkaline hydration (type/dose/schedule not specified)
- Leucovorin (Folinic acid) rescue (dose/route/schedule not specified)
21-day cycle for 3 cycles
Subsequent treatment
- See paper for details about further treatment
References
- 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. Epub 2010 Dec 1. link to original article contains dosing details in manuscript PubMed NCT00283985
AspaMetDex (Erwinaze)
AspaMetDex: Asparaginase, Methotrexate, Dexamethasone
Regimen
Study | Evidence | Efficacy |
---|---|---|
Jaccard et al. 2010 (I05009) | Phase 2 | ORR: 78% |
Note: this regimen is for patients with allergies to asparaginase.
Chemotherapy
- Asparaginase Erwinia chrysanthemi (Erwinaze) 20,000 units/m2 IM once per day on days 2, 4, 6, 8
- Methotrexate (MTX) by the following age-based criteria:
- Younger than 70 years old: 3000 mg/m2 (route not specified) once on day 1
- Older than 70 years old: 2000 mg/m2 (route not specified) once on day 1
Glucocorticoid therapy
- Dexamethasone (Decadron) by the following age-based criteria:
- Younger than 70 years old: 40 mg PO once per day on days 1 to 4
- Older than 70 years old: 20 mg PO once per day on days 1 to 4
Supportive therapy
- Trimethoprim-Sulfamethoxazole (Bactrim DS) (dose/route/schedule not specified) prophylaxis, discontinued during methotrexate administration
- Valacyclovir (Valtrex) (dose/route/schedule not specified) prophylaxis
- Alkaline hydration (type/dose/schedule not specified)
- Leucovorin (Folinic acid) rescue (dose/route/schedule not specified)
21-day cycle for 3 cycles
Subsequent treatment
- See paper for details about further treatment
References
- 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. Epub 2010 Dec 1. link to original article contains dosing details in manuscript PubMed NCT00283985
Fludarabine, Busulfan, Cyclophosphamide, then allo HSCT
FluBuCy: Fludarabine, Busulfan, Cyclophosphamide
Regimen variant #1, oral
Study | Dates of enrollment | Evidence |
---|---|---|
Glass et al. 2014 (DSHNHL R3) | 2004-06-16 to 2009-03-24 | 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
Regimen variant #2, intravenous
Study | Dates of enrollment | Evidence |
---|---|---|
Glass et al. 2014 (DSHNHL R3) | 2004-06-16 to 2009-03-24 | Phase 2 |
Chemotherapy
- Fludarabine (Fludara) 25 mg/m2/day IV on days -8 to -4
- Busulfan (Myleran) 3.2 mg/kg/day IV 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
SMILE
SMILE: Steroid (Dexamethasone), Methotrexate, Ifosfamide, L-asparaginase, Etoposide
Regimen
Study | Dates 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
- Leucovorin (Folinic acid) 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
- 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
- Hydration with normal saline (no volume specified) every 8 hours on the day prior to methotrexate
- 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/μL
- 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
- Hydrocortisone (Cortef) 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to asparaginase
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