Difference between revisions of "Systemic mastocytosis"

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m (Text replacement - "====Supportive medications" to "====Supportive therapy")
m (Text replacement - "==[https://www.nccn.org/ NCCN]==" to "==NCCN==")
 
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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
</div>
 
</div>
{| class="wikitable" style="text-align:center; width:50%;"
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{{#lst:Editorial board transclusions|mpn}}
!colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26"|'''Section editor'''
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''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Systemic mastocytosis - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''
|-
 
|style="background-color:#F0F0F0"|[[File:Sanjay_mohan.png|frameless|upright=0.3|center]]
 
|<big>[[User:Sanjaymohan|Sanjay R. Mohan, MD, MSCI]]<br>Vanderbilt University<br>Nashville, TN</big>
 
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|}
 
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
|}
 
|}
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<big>Note: most published trials in this area are for "advanced systemic mastocytosis", which includes more than one WHO category. See individual regimens for details.</big>
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 
''Note: most published trials in this area are for "advanced systemic mastocytosis", which includes more than one WHO category. See individual regimens for details.''
 
 
=Guidelines=
 
=Guidelines=
==[https://www.nccn.org/ NCCN]==
+
'''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.'''
*[https://www.nccn.org/professionals/physician_gls/pdf/mastocytosis.pdf NCCN Guidelines - Systemic Mastocytosis]
+
==NCCN==
 +
*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1490 NCCN Guidelines - Systemic Mastocytosis]
  
 
=All lines of therapy=
 
=All lines of therapy=
 
 
==Avapritinib monotherapy {{#subobject:16ab1a|Regimen=1}}==
 
==Avapritinib monotherapy {{#subobject:16ab1a|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 25 mg/day {{#subobject:q89gib|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|}
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/evidoa2200339 Gotlib et al. 2023 (PIONEER)]
 +
|2020-09 to 2022-01
 +
|style="background-color:#1a9851"|Randomized Phase 2 (E-RT-esc)
 +
|[[Systemic_mastocytosis_-_null_regimens#Placebo|Placebo]]
 +
| style="background-color:#1a9850" |Superior mean change in total symptom score (primary endpoint)
 +
|-
 +
|}
 +
''Note: this is the dosing for indolent systemic mastocytosis (ISM).''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Avapritinib (Ayvakit)]] 25 mg PO once per day
 +
'''Continued indefinitely'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
  
===Regimen {{#subobject:q8bx4b|Variant=1}}===
+
===Regimen variant #2, 200 mg/day {{#subobject:q8bx4b|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
 
|<small>'''FDA-recommended dose'''</small>
 
|<small>'''FDA-recommended dose'''</small>
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{| 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%"|Years of enrollment
+
!style="width: 33%"|Dates of enrollment
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
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|2018-2020
 
|2018-2020
 
| style="background-color:#91cf61" |Phase 2 (RT)
 
| style="background-color:#91cf61" |Phase 2 (RT)
 +
|-
 
|}
 
|}
 +
''Note: this is the dosing for advanced systemic mastocytosis (ASM).''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
[[Avapritinib (Ayvakit)]] 200 mg PO once per day
+
*[[Avapritinib (Ayvakit)]] 200 mg PO once per day
 
 
 
'''Continued indefinitely'''
 
'''Continued indefinitely'''
 
+
</div></div>
 
===References===
 
===References===
#'''EXPLORER:''' DeAngelo DJ, Radia DH, George TI, Robinson WA, Quiery AT, Drummond MW, Bose P, Hexner EO, Winton EF, Horny HP, Tugnait M, Schmidt-Kittler O, Evans EK, Lin HM, Mar BG, Verstovsek S, Deininger MW, Gotlib J. Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. Nat Med. 2021 Dec;27(12):2183-2191. Epub 2021 Dec 6. [https://doi.org/10.1038/s41591-021-01538-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8674134/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34873347/ PubMed] NCT02561988
+
#'''EXPLORER:''' DeAngelo DJ, Radia DH, George TI, Robinson WA, Quiery AT, Drummond MW, Bose P, Hexner EO, Winton EF, Horny HP, Tugnait M, Schmidt-Kittler O, Evans EK, Lin HM, Mar BG, Verstovsek S, Deininger MW, Gotlib J. Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. Nat Med. 2021 Dec;27(12):2183-2191. Epub 2021 Dec 6. [https://doi.org/10.1038/s41591-021-01538-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8674134/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34873347/ PubMed] [https://clinicaltrials.gov/study/NCT02561988 NCT02561988]
#'''PATHFINDER:''' Gotlib J, Reiter A, Radia DH, Deininger MW, George TI, Panse J, Vannucchi AM, Platzbecker U, Alvarez-Twose I, Mital A, Hermine O, Dybedal I, Hexner EO, Hicks LK, Span L, Mesa R, Bose P, Pettit KM, Heaney ML, Oh ST, Sen J, Lin HM, Mar BG, DeAngelo DJ. Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial. Nat Med. 2021 Dec;27(12):2192-2199. Epub 2021 Dec 6. [https://doi.org/10.1038/s41591-021-01539-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8674139/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34873345/ PubMed] NCT03580655
+
#'''PATHFINDER:''' Gotlib J, Reiter A, Radia DH, Deininger MW, George TI, Panse J, Vannucchi AM, Platzbecker U, Alvarez-Twose I, Mital A, Hermine O, Dybedal I, Hexner EO, Hicks LK, Span L, Mesa R, Bose P, Pettit KM, Heaney ML, Oh ST, Sen J, Lin HM, Mar BG, DeAngelo DJ. Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial. Nat Med. 2021 Dec;27(12):2192-2199. Epub 2021 Dec 6. [https://doi.org/10.1038/s41591-021-01539-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8674139/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34873345/ PubMed] [https://clinicaltrials.gov/study/NCT03580655 NCT03580655]
 +
#'''PIONEER:''' Gotlib J, Castells M, Elberink HO, Siebenhaar F, Hartmann K, Broesby-Olsen S, George TI, Panse J, Alvarez-Twose I, Radia DH, Tashi T, Bulai Livideanu C, Sabato V, Heaney M, Van Daele P, Cerquozzi S, Dybedal I, Reiter A, Pongdee T, Barete S, Ustun C, Schwartz L, Ward BR, Schafhausen P, Vadas P, Bose P, DeAngelo DJ, Rein L, Vachhani P, Triggiani M, Bonadonna P, Rafferty M, Butt NM, Oh ST, Wortmann F, Ungerstedt J, Guilarte M, Taparia M, Kuykendall AT, Arana Yi C, Ogbogu P, Gaudy-Marqueste C, Mattsson M, Shomali W, Giannetti MP, Bidollari I, Lin HM, Sulllivan E, Mar B, Scherber R, Roche M, Akin C, Maurer M. Avapritinib versus Placebo in Indolent Systemic Mastocytosis. NEJM Evidence. 2023 Jun;2(6):EVIDoa2200339. Epub 2023 May 23. [https://doi.org/10.1056/evidoa2200339 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38320129/ PubMed] [https://clinicaltrials.gov/study/NCT03731260 NCT03731260]
  
 
==Cladribine monotherapy {{#subobject:993a3e|Regimen=1}}==
 
==Cladribine monotherapy {{#subobject:993a3e|Regimen=1}}==
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
 
 
===Regimen variant #1, 0.13 mg/kg {{#subobject:bcf2f3|Variant=1}}===
 
===Regimen variant #1, 0.13 mg/kg {{#subobject:bcf2f3|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
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|-
 
|-
 
|[http://www.bloodjournal.org/content/102/13/4270.long Kluin-Nelemans et al. 2003]
 
|[http://www.bloodjournal.org/content/102/13/4270.long Kluin-Nelemans et al. 2003]
|style="background-color:#ffffbe"|Pilot, <20 patients reported
+
|style="background-color:#ffffbe"|Pilot, fewer than 20 patients reported
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Cladribine (Leustatin)]] 0.13 mg/kg IV over 2 hours once per day on days 1 to 5
 
*[[Cladribine (Leustatin)]] 0.13 mg/kg IV over 2 hours once per day on days 1 to 5
 
 
====Supportive therapy====
 
====Supportive therapy====
*[[Clemastine (Tavist)]] 1 to 2 mg IV once per day on days 1 to 5, prior to [[Cladribine (Leustatin)]]
+
*[[Clemastine (Tavist)]] 1 to 2 mg IV once per day on days 1 to 5, prior to cladribine
*[[Dexamethasone (Decadron)]] 5 mg IV once per day on days 1 to 5, prior to [[Cladribine (Leustatin)]]
+
*[[Dexamethasone (Decadron)]] 5 mg IV once per day on days 1 to 5, prior to cladribine
 
*[[Fluconazole (Diflucan)]] (dose not specified)
 
*[[Fluconazole (Diflucan)]] (dose not specified)
 
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS) | Co-trimaxazole]] (dose not specified)
 
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS) | Co-trimaxazole]] (dose not specified)
 
*[[Valacyclovir (Valtrex)]] (dose not specified) "in some patients"
 
*[[Valacyclovir (Valtrex)]] (dose not specified) "in some patients"
 
 
'''4- to 6-week cycle for 6 cycles'''
 
'''4- to 6-week cycle for 6 cycles'''
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #2, 0.14 mg/kg {{#subobject:9afc99|Variant=1}}===
 
===Regimen variant #2, 0.14 mg/kg {{#subobject:9afc99|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
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|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Cladribine (Leustatin)]] 0.14 mg/kg SC or IV over 2 hours once per day on days 1 to 5
 
*[[Cladribine (Leustatin)]] 0.14 mg/kg SC or IV over 2 hours once per day on days 1 to 5
 
 
'''4- to 12-week cycle for 1 to 6 cycles'''
 
'''4- to 12-week cycle for 1 to 6 cycles'''
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #3, 5 mg/m<sup>2</sup> {{#subobject:39c8f|Variant=1}}===
 
===Regimen variant #3, 5 mg/m<sup>2</sup> {{#subobject:39c8f|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
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|-
 
|-
 
|}
 
|}
''This is a retrospective series; a range of weight-based dosing was also reported.''
+
''Note: This was a retrospective series; a range of weight-based dosing was also reported.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 
*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 
 
'''Median number of treatment cycles was 3 (range 1 to 9)'''
 
'''Median number of treatment cycles was 3 (range 1 to 9)'''
 
+
</div></div>
 
===References===
 
===References===
# Kluin-Nelemans HC, Oldhoff JM, Van Doormaal JJ, Van 't Wout JW, Verhoef G, Gerrits WB, van Dobbenburgh OA, Pasmans SG, Fijnheer R. Cladribine therapy for systemic mastocytosis. Blood. 2003 Dec 15;102(13):4270-6. Epub 2003 Aug 21. [http://www.bloodjournal.org/content/102/13/4270.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12933573 PubMed]  
+
# Kluin-Nelemans HC, Oldhoff JM, Van Doormaal JJ, Van 't Wout JW, Verhoef G, Gerrits WB, van Dobbenburgh OA, Pasmans SG, Fijnheer R. Cladribine therapy for systemic mastocytosis. Blood. 2003 Dec 15;102(13):4270-6. Epub 2003 Aug 21. [http://www.bloodjournal.org/content/102/13/4270.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12933573/ PubMed]  
# '''Retrospective:''' Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009 Dec;84(12):790-4. [https://doi.org/10.1002/ajh.21561 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19890907 PubMed]
+
# '''Retrospective:''' Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009 Dec;84(12):790-4. [https://doi.org/10.1002/ajh.21561 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19890907/ PubMed]
 
<!-- # '''Abstract: Retrospective:''' Hermine, Olivier, Hirsh, Isabelle, Damaj, Gandhi, Granpeix, Catherine, Barete, Stephane, Suarez, Felipe, Chansderis, Olivia, Ghez, David, Delarue, Richard, Lanternier, Fanny, Deau, Benedicte, Coignard, Helene, Fraitag, Sylvie, Canioni, Danielle, Casassus, Philippe, Dubreuil, Patrice, Lortholary, Olivier. Long Term Efficacy and Safety of Cladribine In Adult Systemic mastocytosis: a French Multicenter Study of 44 Patients. ASH Annual Meeting Abstracts 2010 116: 1982 [http://abstracts.hematologylibrary.org/cgi/content/abstract/116/21/1982 link to original abstract] -->
 
<!-- # '''Abstract: Retrospective:''' Hermine, Olivier, Hirsh, Isabelle, Damaj, Gandhi, Granpeix, Catherine, Barete, Stephane, Suarez, Felipe, Chansderis, Olivia, Ghez, David, Delarue, Richard, Lanternier, Fanny, Deau, Benedicte, Coignard, Helene, Fraitag, Sylvie, Canioni, Danielle, Casassus, Philippe, Dubreuil, Patrice, Lortholary, Olivier. Long Term Efficacy and Safety of Cladribine In Adult Systemic mastocytosis: a French Multicenter Study of 44 Patients. ASH Annual Meeting Abstracts 2010 116: 1982 [http://abstracts.hematologylibrary.org/cgi/content/abstract/116/21/1982 link to original abstract] -->
# '''Retrospective:''' Barete S, Lortholary O, Damaj G, Hirsch I, Chandesris MO, Elie C, Hamidou M, Durieu I, Suarez F, Grosbois B, Limal N, Gyan E, Larroche C, Guillet G, Kahn JE, Casassus P, Amazzough K, Coignard-Biehler H, Georgin-Lavialle S, Lhermitte L, Fraitag S, Canioni D, Dubreuil P, Hermine O. Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis. Blood. 2015 Aug 20;126(8):1009-16. Epub 2015 May 22. [https://doi.org/10.1182/blood-2014-12-614743 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26002962 PubMed]
+
# '''Retrospective:''' Barete S, Lortholary O, Damaj G, Hirsch I, Chandesris MO, Elie C, Hamidou M, Durieu I, Suarez F, Grosbois B, Limal N, Gyan E, Larroche C, Guillet G, Kahn JE, Casassus P, Amazzough K, Coignard-Biehler H, Georgin-Lavialle S, Lhermitte L, Fraitag S, Canioni D, Dubreuil P, Hermine O. Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis. Blood. 2015 Aug 20;126(8):1009-16. Epub 2015 May 22. [https://doi.org/10.1182/blood-2014-12-614743 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26002962/ PubMed]
 
 
 
==Dasatinib monotherapy {{#subobject:6e70d7|Regimen=1}}==
 
==Dasatinib monotherapy {{#subobject:6e70d7|Regimen=1}}==
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
 
 
===Regimen {{#subobject:996fa2|Variant=1}}===
 
===Regimen {{#subobject:996fa2|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
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|-
 
|-
 
|}
 
|}
 
+
''Note: Only 9 of 67 patients studied had ASM; 18 has ISM and 6 had SM-AHNMD.''
''Only 9 of 67 patients studied had ASM; 18 has ISM and 6 had SM-AHNMD.''
+
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
*[[Dasatinib (Sprycel)]] 70 mg PO twice per day
+
*[[Dasatinib (Sprycel)]] 70 mg PO twice per day on days 1 to 28
 
**Alternative dosing: 140 mg PO once per day
 
**Alternative dosing: 140 mg PO once per day
 
 
====Supportive therapy====
 
====Supportive therapy====
 
*[[:Category:Hematopoietic_growth_factors|Hematopoietic growth factors]] at investigator discretion
 
*[[:Category:Hematopoietic_growth_factors|Hematopoietic growth factors]] at investigator discretion
 
 
'''28-day cycles'''
 
'''28-day cycles'''
 
+
</div></div>
 
===References===
 
===References===
# Verstovsek S, Tefferi A, Cortes J, O'Brien S, Garcia-Manero G, Pardanani A, Akin C, Faderl S, Manshouri T, Thomas D, Kantarjian H. Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis. Clin Cancer Res. 2008 Jun 15;14(12):3906-15. [http://clincancerres.aacrjournals.org/content/14/12/3906.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018899/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18559612 PubMed]
+
# Verstovsek S, Tefferi A, Cortes J, O'Brien S, Garcia-Manero G, Pardanani A, Akin C, Faderl S, Manshouri T, Thomas D, Kantarjian H. Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis. Clin Cancer Res. 2008 Jun 15;14(12):3906-15. [https://doi.org/10.1158/1078-0432.CCR-08-0366 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018899/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18559612/ PubMed]
 
 
 
==Imatinib monotherapy {{#subobject:825018|Regimen=1}}==
 
==Imatinib monotherapy {{#subobject:825018|Regimen=1}}==
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #1, 100 mg/day {{#subobject:2aae47|Variant=1}}===
 
===Regimen variant #1, 100 mg/day {{#subobject:2aae47|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
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|-
 
|-
 
|[https://doi.org/10.1016/S0140-6736(03)14115-3 Pardanani et al. 2003]
 
|[https://doi.org/10.1016/S0140-6736(03)14115-3 Pardanani et al. 2003]
|style="background-color:#ffffbe"|Phase 2, <20 pts reported
+
|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts reported
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Imatinib (Gleevec)]] 100 mg PO once per day
 
*[[Imatinib (Gleevec)]] 100 mg PO once per day
 
 
'''Continued indefinitely'''
 
'''Continued indefinitely'''
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #2, 400 mg/day x 6 mo {{#subobject:abb8c6|Variant=1}}===
 
===Regimen variant #2, 400 mg/day x 6 mo {{#subobject:abb8c6|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
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|-
 
|-
 
|[https://doi.org/10.1002/cncr.21996 Droogendijk et al. 2006]
 
|[https://doi.org/10.1002/cncr.21996 Droogendijk et al. 2006]
|style="background-color:#ffffbe"|Phase 2, <20 pts reported
+
|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts reported
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Imatinib (Gleevec)]] 400 mg PO once per day
 
*[[Imatinib (Gleevec)]] 400 mg PO once per day
 
 
====Supportive therapy====
 
====Supportive therapy====
 
*[[Prednisone (Sterapred)]] 15 mg PO twice per day on days 1 to 14
 
*[[Prednisone (Sterapred)]] 15 mg PO twice per day on days 1 to 14
 
 
'''6-month course'''
 
'''6-month course'''
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #3, 400 mg/day indefinitely {{#subobject:avv8c6|Variant=1}}===
 
===Regimen variant #3, 400 mg/day indefinitely {{#subobject:avv8c6|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
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|-
 
|-
 
|[https://doi.org/10.1016/S0140-6736(03)14115-3 Pardanani et al. 2003]
 
|[https://doi.org/10.1016/S0140-6736(03)14115-3 Pardanani et al. 2003]
|style="background-color:#ffffbe"|Phase 2, <20 pts reported
+
|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts reported
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Imatinib (Gleevec)]] 400 mg PO once per day
 
*[[Imatinib (Gleevec)]] 400 mg PO once per day
 
 
'''Continued indefinitely'''
 
'''Continued indefinitely'''
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #4, 400 mg/day with dose escalation {{#subobject:1e79f9|Variant=1}}===
 
===Regimen variant #4, 400 mg/day with dose escalation {{#subobject:1e79f9|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
Line 193: Line 213:
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Imatinib (Gleevec)]] as follows:
 
*[[Imatinib (Gleevec)]] as follows:
Line 198: Line 219:
 
**Cycle 2: 600 mg PO once per day
 
**Cycle 2: 600 mg PO once per day
 
**Cycle 3 onwards: 800 mg PO once per day
 
**Cycle 3 onwards: 800 mg PO once per day
 
 
====Supportive therapy====
 
====Supportive therapy====
 
*[[:Category:Hematopoietic_growth_factors|Hematopoietic growth factors]] at investigator discretion
 
*[[:Category:Hematopoietic_growth_factors|Hematopoietic growth factors]] at investigator discretion
 
 
'''Monthly cycles'''
 
'''Monthly cycles'''
 
+
</div></div>
 
===References===
 
===References===
# Pardanani A, Elliott M, Reeder T, Li CY, Baxter EJ, Cross NC, Tefferi A. Imatinib for systemic mast-cell disease. Lancet. 2003 Aug 16;362(9383):535-6. [https://doi.org/10.1016/S0140-6736(03)14115-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12932387 PubMed]
+
# Pardanani A, Elliott M, Reeder T, Li CY, Baxter EJ, Cross NC, Tefferi A. Imatinib for systemic mast-cell disease. Lancet. 2003 Aug 16;362(9383):535-6. [https://doi.org/10.1016/S0140-6736(03)14115-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12932387/ PubMed]
# Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, Oranje AP, van de Loosdrecht AA, van Daele PL. Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. Cancer. 2006 Jul 15;107(2):345-51. [https://doi.org/10.1002/cncr.21996 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16779792 PubMed]
+
# Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, Oranje AP, van de Loosdrecht AA, van Daele PL. Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. Cancer. 2006 Jul 15;107(2):345-51. [https://doi.org/10.1002/cncr.21996 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16779792/ PubMed]
# '''Retrospective:''' Pagano L, Valentini CG, Caira M, Rondoni M, Van Lint MT, Candoni A, Allione B, Cattaneo C, Marbello L, Caramatti C, Pogliani EM, Iannitto E, Giona F, Ferrara F, Invernizzi R, Fanci R, Lunghi M, Fianchi L, Sanpaolo G, Stefani PM, Pulsoni A, Martinelli G, Leone G, Musto P. Advanced mast cell disease: an Italian Hematological Multicenter experience. Int J Hematol. 2008 Dec;88(5):483-8. Epub 2008 Nov 26. [http://link.springer.com/article/10.1007/s12185-008-0166-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19034614 PubMed]  
+
# '''Retrospective:''' Pagano L, Valentini CG, Caira M, Rondoni M, Van Lint MT, Candoni A, Allione B, Cattaneo C, Marbello L, Caramatti C, Pogliani EM, Iannitto E, Giona F, Ferrara F, Invernizzi R, Fanci R, Lunghi M, Fianchi L, Sanpaolo G, Stefani PM, Pulsoni A, Martinelli G, Leone G, Musto P. Advanced mast cell disease: an Italian Hematological Multicenter experience. Int J Hematol. 2008 Dec;88(5):483-8. Epub 2008 Nov 26. [http://link.springer.com/article/10.1007/s12185-008-0166-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19034614/ PubMed]  
# Vega-Ruiz A, Cortes JE, Sever M, Manshouri T, Quintás-Cardama A, Luthra R, Kantarjian HM, Verstovsek S. Phase II study of imatinib mesylate as therapy for patients with systemic mastocytosis. Leuk Res. 2009 Nov;33(11):1481-4. Epub 2009 Feb 3. [https://www.lrjournal.com/article/S0145-2126(08)00567-5 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184059/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19193436 PubMed]
+
# Vega-Ruiz A, Cortes JE, Sever M, Manshouri T, Quintás-Cardama A, Luthra R, Kantarjian HM, Verstovsek S. Phase II study of imatinib mesylate as therapy for patients with systemic mastocytosis. Leuk Res. 2009 Nov;33(11):1481-4. Epub 2009 Feb 3. [https://doi.org/10.1016/j.leukres.2008.12.020 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184059/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19193436/ PubMed]
# '''Retrospective:''' Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009 Dec;84(12):790-4. [https://doi.org/10.1002/ajh.21561 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19890907 PubMed]
+
# '''Retrospective:''' Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009 Dec;84(12):790-4. [https://doi.org/10.1002/ajh.21561 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19890907/ PubMed]
 
 
 
==Interferon alfa-2b monotherapy {{#subobject:c47eaf|Regimen=1}}==
 
==Interferon alfa-2b monotherapy {{#subobject:c47eaf|Regimen=1}}==
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
 
 
===Regimen {{#subobject:ed4b3f|Variant=1}}===
 
===Regimen {{#subobject:ed4b3f|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
Line 223: Line 240:
 
|-
 
|-
 
|}
 
|}
''Doses were escalated based on tolerance.''
+
''Note: Doses were escalated based on tolerance.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
 
*[[Interferon alfa-2b (Intron-A)]] as follows:
 
*[[Interferon alfa-2b (Intron-A)]] as follows:
Line 230: Line 248:
 
**Weeks 3 & 4: 3,000,000 units/m<sup>2</sup> SC once per day
 
**Weeks 3 & 4: 3,000,000 units/m<sup>2</sup> SC once per day
 
**Week 5 onwards: 5,000,000 units/m<sup>2</sup> SC once per day
 
**Week 5 onwards: 5,000,000 units/m<sup>2</sup> SC once per day
 
 
'''6-month course, continued at physician's and patient's discretion'''
 
'''6-month course, continued at physician's and patient's discretion'''
 
+
</div></div>
 
===References===
 
===References===
# Casassus P, Caillat-Vigneron N, Martin A, Simon J, Gallais V, Beaudry P, Eclache V, Laroche L, Lortholary P, Raphaël M, Guillevin L, Lortholary O. Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients. Br J Haematol. 2002 Dec;119(4):1090-7. [https://doi.org/10.1046/j.1365-2141.2002.03944.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12472593 PubMed]
+
# Casassus P, Caillat-Vigneron N, Martin A, Simon J, Gallais V, Beaudry P, Eclache V, Laroche L, Lortholary P, Raphaël M, Guillevin L, Lortholary O. Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients. Br J Haematol. 2002 Dec;119(4):1090-7. [https://doi.org/10.1046/j.1365-2141.2002.03944.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12472593/ PubMed]
# '''Retrospective:''' Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009 Dec;84(12):790-4. [https://doi.org/10.1002/ajh.21561 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19890907 PubMed]
+
# '''Retrospective:''' Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009 Dec;84(12):790-4. [https://doi.org/10.1002/ajh.21561 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19890907/ PubMed]
 
 
 
==Midostaurin monotherapy {{#subobject:99c398|Regimen=1}}==
 
==Midostaurin monotherapy {{#subobject:99c398|Regimen=1}}==
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:91hbb2|Variant=1}}===
 
===Regimen {{#subobject:91hbb2|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
Line 246: Line 262:
 
{| class="wikitable sortable" style="width: 80%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 80%; text-align:center;"  
 
!style="width: 25%"|Study
 
!style="width: 25%"|Study
!style="width: 25%"|Years of enrollment
+
!style="width: 25%"|Dates of enrollment
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
Line 261: Line 277:
 
|-
 
|-
 
|}
 
|}
''CPKC412D2201 included untreated and previously untreated patients.''
+
''Note: CPKC412D2201 included untreated and previously untreated patients.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
*[[Midostaurin (Rydapt)]] 100 mg PO twice per day  
+
*[[Midostaurin (Rydapt)]] 100 mg PO twice per day on days 1 to 28
 
 
 
'''28-day cycles'''
 
'''28-day cycles'''
 
+
</div></div>
 
===References===
 
===References===
# '''CPKC412D2201:''' Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, Awan FT, Hexner E, Mauro MJ, Sternberg DW, Villeneuve M, Huntsman Labed A, Stanek EJ, Hartmann K, Horny HP, Valent P, Reiter A. Efficacy and safety of midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2530-41. [https://doi.org/10.1056/NEJMoa1513098 link to original article] '''contains dosing details in manuscript''' [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1513098/suppl_file/nejmoa1513098_appendix.pdf link to supplementary appendix] [https://pubmed.ncbi.nlm.nih.gov/27355533 PubMed] NCT00233454
+
# '''CPKC412D2201:''' Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, Awan FT, Hexner E, Mauro MJ, Sternberg DW, Villeneuve M, Huntsman Labed A, Stanek EJ, Hartmann K, Horny HP, Valent P, Reiter A. Efficacy and safety of midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2530-41. [https://doi.org/10.1056/NEJMoa1513098 link to original article] '''contains dosing details in manuscript''' [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1513098/suppl_file/nejmoa1513098_appendix.pdf link to supplementary appendix] [https://pubmed.ncbi.nlm.nih.gov/27355533/ PubMed] [https://clinicaltrials.gov/study/NCT00233454 NCT00233454]
# '''CEREMAST:''' Chandesris MO, Damaj G, Canioni D, Brouzes C, Lhermitte L, Hanssens K, Frenzel L, Cherquaoui Z, Durieu I, Durupt S, Gyan E, Beyne-Rauzy O, Launay D, Faure C, Hamidou M, Besnard S, Diouf M, Schiffmann A, Niault M, Jeandel PY, Ranta D, Gressin R, Chantepie S, Barete S, Dubreuil P, Bourget P, Lortholary O, Hermine O; CEREMAST Study Group. Midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2605-7. [https://doi.org/10.1056/NEJMc1515403 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27355555 PubMed]
+
# '''CEREMAST:''' Chandesris MO, Damaj G, Canioni D, Brouzes C, Lhermitte L, Hanssens K, Frenzel L, Cherquaoui Z, Durieu I, Durupt S, Gyan E, Beyne-Rauzy O, Launay D, Faure C, Hamidou M, Besnard S, Diouf M, Schiffmann A, Niault M, Jeandel PY, Ranta D, Gressin R, Chantepie S, Barete S, Dubreuil P, Bourget P, Lortholary O, Hermine O; CEREMAST Study Group. Midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2605-7. [https://doi.org/10.1056/NEJMc1515403 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27355555/ PubMed]
 
 
 
==Nilotinib monotherapy {{#subobject:91cff9|Regimen=1}}==
 
==Nilotinib monotherapy {{#subobject:91cff9|Regimen=1}}==
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:56025f|Variant=1}}===
 
===Regimen {{#subobject:56025f|Variant=1}}===
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable" style="width: 60%; text-align:center;"  
!style="width: 25%"|Study
+
!style="width: 33%"|Study
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
 
|[https://doi.org/10.1056/NEJMoa055104 Kantarjian et al. 2006 (A2101)]
 
|[https://doi.org/10.1056/NEJMoa055104 Kantarjian et al. 2006 (A2101)]
 +
|2004-2005
 
|style="background-color:#91cf61"|Phase 1/2
 
|style="background-color:#91cf61"|Phase 1/2
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
*[[Nilotinib (Tasigna)]] 400 mg PO twice per day
+
*[[Nilotinib (Tasigna)]] 400 mg PO twice per day on days 1 to 28
 
 
 
'''28-day cycles'''
 
'''28-day cycles'''
 
+
</div></div>
 
===References===
 
===References===
# '''A2101:''' Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006 Jun 15;354(24):2542-51. [https://doi.org/10.1056/NEJMoa055104 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16775235 PubMed] NCT00109707
+
# '''A2101:''' Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006 Jun 15;354(24):2542-51. [https://doi.org/10.1056/NEJMoa055104 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16775235/ PubMed] [https://clinicaltrials.gov/study/NCT00109707 NCT00109707]
 
<!-- 2006: http://www.bloodjournal.org/content/108/11/2703.abstract -->
 
<!-- 2006: http://www.bloodjournal.org/content/108/11/2703.abstract -->
## '''Subgroup analysis:''' Hochhaus A, Baccarani M, Giles FJ, le Coutre PD, Müller MC, Reiter A, Santanastasio H, Leung M, Novick S, Kantarjian HM. Nilotinib in patients with systemic mastocytosis: analysis of the phase 2, open-label, single-arm nilotinib registration study. J Cancer Res Clin Oncol. 2015 Nov;141(11):2047-60. Epub 2015 May 23.  '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768228/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26002753 PubMed]
+
## '''Subgroup analysis:''' Hochhaus A, Baccarani M, Giles FJ, le Coutre PD, Müller MC, Reiter A, Santanastasio H, Leung M, Novick S, Kantarjian HM. Nilotinib in patients with systemic mastocytosis: analysis of the phase 2, open-label, single-arm nilotinib registration study. J Cancer Res Clin Oncol. 2015 Nov;141(11):2047-60. Epub 2015 May 23. [https://doi.org/10.1007/s00432-015-1988-0 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768228/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26002753/ PubMed]
 
 
==Placebo==
 
 
 
===Regimen===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985971/ Lortholary et al. 2017 (AB06006)]
 
|2009-2015
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|Masitinib
 
|style="background-color:#d73027"|Inferior cumulative response
 
|-
 
|}
 
''No active antineoplastic treatment.''
 
===References===
 
# '''AB06006:''' Lortholary O, Chandesris MO, Bulai Livideanu C, Paul C, Guillet G, Jassem E, Niedoszytko M, Barete S, Verstovsek S, Grattan C, Damaj G, Canioni D, Fraitag S, Lhermitte L, Georgin Lavialle S, Frenzel L, Afrin LB, Hanssens K, Agopian J, Gaillard R, Kinet JP, Auclair C, Mansfield C, Moussy A, Dubreuil P, Hermine O. Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study. Lancet. 2017 Feb 11;389(10069):612-620. Epub 2017 Jan 6. [https://doi.org/10.1016/S0140-6736(16)31403-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985971/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28069279 PubMed] NCT00814073
 
  
 
=Response criteria=
 
=Response criteria=
 
 
==IWG-MRT & ECNM consensus response criteria (2013)==
 
==IWG-MRT & ECNM consensus response criteria (2013)==
# Gotlib J, Pardanani A, Akin C, Reiter A, George T, Hermine O, Kluin-Nelemans H, Hartmann K, Sperr WR, Brockow K, Schwartz LB, Orfao A, Deangelo DJ, Arock M, Sotlar K, Horny HP, Metcalfe DD, Escribano L, Verstovsek S, Tefferi A, Valent P. International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis. Blood. 2013 Mar 28;121(13):2393-401. Epub 2013 Jan 16. [http://www.bloodjournal.org/content/121/13/2393.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612852/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23325841 PubMed]
+
# Gotlib J, Pardanani A, Akin C, Reiter A, George T, Hermine O, Kluin-Nelemans H, Hartmann K, Sperr WR, Brockow K, Schwartz LB, Orfao A, Deangelo DJ, Arock M, Sotlar K, Horny HP, Metcalfe DD, Escribano L, Verstovsek S, Tefferi A, Valent P. International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis. Blood. 2013 Mar 28;121(13):2393-401. Epub 2013 Jan 16. [http://www.bloodjournal.org/content/121/13/2393.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612852/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23325841/ PubMed]
 
 
 
[[Category:Systemic mastocytosis regimens]]
 
[[Category:Systemic mastocytosis regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
 
[[Category:Myeloproliferative neoplasms]]
 
[[Category:Myeloproliferative neoplasms]]

Latest revision as of 11:29, 13 May 2024

Section editor
Sanjay mohan.png
Sanjay R. Mohan, MD, MSCI
Vanderbilt University
Nashville, TN, USA

Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!

7 regimens on this page
13 variants on this page

Note: most published trials in this area are for "advanced systemic mastocytosis", which includes more than one WHO category. See individual regimens for details.


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.

NCCN

All lines of therapy

Avapritinib monotherapy

Regimen variant #1, 25 mg/day

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gotlib et al. 2023 (PIONEER) 2020-09 to 2022-01 Randomized Phase 2 (E-RT-esc) Placebo Superior mean change in total symptom score (primary endpoint)

Note: this is the dosing for indolent systemic mastocytosis (ISM).

Targeted therapy

Continued indefinitely


Regimen variant #2, 200 mg/day

FDA-recommended dose
Study Dates of enrollment Evidence
DeAngelo et al. 2021 (EXPLORER) 2016-2020 Phase 1 (RT)
Gotlib et al. 2021 (PATHFINDER) 2018-2020 Phase 2 (RT)

Note: this is the dosing for advanced systemic mastocytosis (ASM).

Targeted therapy

Continued indefinitely

References

  1. EXPLORER: DeAngelo DJ, Radia DH, George TI, Robinson WA, Quiery AT, Drummond MW, Bose P, Hexner EO, Winton EF, Horny HP, Tugnait M, Schmidt-Kittler O, Evans EK, Lin HM, Mar BG, Verstovsek S, Deininger MW, Gotlib J. Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. Nat Med. 2021 Dec;27(12):2183-2191. Epub 2021 Dec 6. link to original article link to PMC article contains dosing details in abstract PubMed NCT02561988
  2. PATHFINDER: Gotlib J, Reiter A, Radia DH, Deininger MW, George TI, Panse J, Vannucchi AM, Platzbecker U, Alvarez-Twose I, Mital A, Hermine O, Dybedal I, Hexner EO, Hicks LK, Span L, Mesa R, Bose P, Pettit KM, Heaney ML, Oh ST, Sen J, Lin HM, Mar BG, DeAngelo DJ. Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial. Nat Med. 2021 Dec;27(12):2192-2199. Epub 2021 Dec 6. link to original article link to PMC article contains dosing details in manuscript PubMed NCT03580655
  3. PIONEER: Gotlib J, Castells M, Elberink HO, Siebenhaar F, Hartmann K, Broesby-Olsen S, George TI, Panse J, Alvarez-Twose I, Radia DH, Tashi T, Bulai Livideanu C, Sabato V, Heaney M, Van Daele P, Cerquozzi S, Dybedal I, Reiter A, Pongdee T, Barete S, Ustun C, Schwartz L, Ward BR, Schafhausen P, Vadas P, Bose P, DeAngelo DJ, Rein L, Vachhani P, Triggiani M, Bonadonna P, Rafferty M, Butt NM, Oh ST, Wortmann F, Ungerstedt J, Guilarte M, Taparia M, Kuykendall AT, Arana Yi C, Ogbogu P, Gaudy-Marqueste C, Mattsson M, Shomali W, Giannetti MP, Bidollari I, Lin HM, Sulllivan E, Mar B, Scherber R, Roche M, Akin C, Maurer M. Avapritinib versus Placebo in Indolent Systemic Mastocytosis. NEJM Evidence. 2023 Jun;2(6):EVIDoa2200339. Epub 2023 May 23. link to original article PubMed NCT03731260

Cladribine monotherapy

Regimen variant #1, 0.13 mg/kg

Study Evidence
Kluin-Nelemans et al. 2003 Pilot, fewer than 20 patients reported

Chemotherapy

Supportive therapy

4- to 6-week cycle for 6 cycles


Regimen variant #2, 0.14 mg/kg

Study Evidence
Barete et al. 2015 Retrospective

Chemotherapy

4- to 12-week cycle for 1 to 6 cycles


Regimen variant #3, 5 mg/m2

Study Evidence
Lim et al. 2009 Retrospective

Note: This was a retrospective series; a range of weight-based dosing was also reported.

Chemotherapy

Median number of treatment cycles was 3 (range 1 to 9)

References

  1. Kluin-Nelemans HC, Oldhoff JM, Van Doormaal JJ, Van 't Wout JW, Verhoef G, Gerrits WB, van Dobbenburgh OA, Pasmans SG, Fijnheer R. Cladribine therapy for systemic mastocytosis. Blood. 2003 Dec 15;102(13):4270-6. Epub 2003 Aug 21. link to original article contains dosing details in manuscript PubMed
  2. Retrospective: Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009 Dec;84(12):790-4. link to original article PubMed
  3. Retrospective: Barete S, Lortholary O, Damaj G, Hirsch I, Chandesris MO, Elie C, Hamidou M, Durieu I, Suarez F, Grosbois B, Limal N, Gyan E, Larroche C, Guillet G, Kahn JE, Casassus P, Amazzough K, Coignard-Biehler H, Georgin-Lavialle S, Lhermitte L, Fraitag S, Canioni D, Dubreuil P, Hermine O. Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis. Blood. 2015 Aug 20;126(8):1009-16. Epub 2015 May 22. link to original article PubMed

Dasatinib monotherapy

Regimen

Study Evidence
Verstovsek et al. 2008 Phase 2

Note: Only 9 of 67 patients studied had ASM; 18 has ISM and 6 had SM-AHNMD.

Targeted therapy

  • Dasatinib (Sprycel) 70 mg PO twice per day on days 1 to 28
    • Alternative dosing: 140 mg PO once per day

Supportive therapy

28-day cycles

References

  1. Verstovsek S, Tefferi A, Cortes J, O'Brien S, Garcia-Manero G, Pardanani A, Akin C, Faderl S, Manshouri T, Thomas D, Kantarjian H. Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis. Clin Cancer Res. 2008 Jun 15;14(12):3906-15. link to original article contains dosing details in manuscript link to PMC article PubMed

Imatinib monotherapy

Regimen variant #1, 100 mg/day

Study Evidence
Pardanani et al. 2003 Phase 2, fewer than 20 pts reported

Targeted therapy

Continued indefinitely


Regimen variant #2, 400 mg/day x 6 mo

Study Evidence
Droogendijk et al. 2006 Phase 2, fewer than 20 pts reported

Targeted therapy

Supportive therapy

6-month course


Regimen variant #3, 400 mg/day indefinitely

Study Evidence
Pardanani et al. 2003 Phase 2, fewer than 20 pts reported

Targeted therapy

Continued indefinitely


Regimen variant #4, 400 mg/day with dose escalation

Study Evidence
Vega-Ruiz et al. 2009 Phase 2

Targeted therapy

  • Imatinib (Gleevec) as follows:
    • Cycle 1: 400 mg PO once per day
    • Cycle 2: 600 mg PO once per day
    • Cycle 3 onwards: 800 mg PO once per day

Supportive therapy

Monthly cycles

References

  1. Pardanani A, Elliott M, Reeder T, Li CY, Baxter EJ, Cross NC, Tefferi A. Imatinib for systemic mast-cell disease. Lancet. 2003 Aug 16;362(9383):535-6. link to original article contains dosing details in abstract PubMed
  2. Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, Oranje AP, van de Loosdrecht AA, van Daele PL. Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. Cancer. 2006 Jul 15;107(2):345-51. link to original article contains dosing details in manuscript PubMed
  3. Retrospective: Pagano L, Valentini CG, Caira M, Rondoni M, Van Lint MT, Candoni A, Allione B, Cattaneo C, Marbello L, Caramatti C, Pogliani EM, Iannitto E, Giona F, Ferrara F, Invernizzi R, Fanci R, Lunghi M, Fianchi L, Sanpaolo G, Stefani PM, Pulsoni A, Martinelli G, Leone G, Musto P. Advanced mast cell disease: an Italian Hematological Multicenter experience. Int J Hematol. 2008 Dec;88(5):483-8. Epub 2008 Nov 26. link to original article PubMed
  4. Vega-Ruiz A, Cortes JE, Sever M, Manshouri T, Quintás-Cardama A, Luthra R, Kantarjian HM, Verstovsek S. Phase II study of imatinib mesylate as therapy for patients with systemic mastocytosis. Leuk Res. 2009 Nov;33(11):1481-4. Epub 2009 Feb 3. link to original article contains dosing details in manuscript link to PMC article PubMed
  5. Retrospective: Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009 Dec;84(12):790-4. link to original article PubMed

Interferon alfa-2b monotherapy

Regimen

Study Evidence
Casassus et al. 2002 Phase 2

Note: Doses were escalated based on tolerance.

Immunotherapy

  • Interferon alfa-2b (Intron-A) as follows:
    • Week 1: 1,000,000 units SC once per day
    • Week 2: 3,000,000 units SC once per day
    • Weeks 3 & 4: 3,000,000 units/m2 SC once per day
    • Week 5 onwards: 5,000,000 units/m2 SC once per day

6-month course, continued at physician's and patient's discretion

References

  1. Casassus P, Caillat-Vigneron N, Martin A, Simon J, Gallais V, Beaudry P, Eclache V, Laroche L, Lortholary P, Raphaël M, Guillevin L, Lortholary O. Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients. Br J Haematol. 2002 Dec;119(4):1090-7. link to original article contains dosing details in manuscript PubMed
  2. Retrospective: Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009 Dec;84(12):790-4. link to original article PubMed

Midostaurin monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Efficacy
Gotlib et al. 2016 (CPKC412D2201) 2009-2012 Phase 2 (RT) ORR: 60% (95% CI 49 to 70)
Chandesris et al. 2016 (CEREMAST) 2012-2015 Phase 2 (RT)

Note: CPKC412D2201 included untreated and previously untreated patients.

Targeted therapy

28-day cycles

References

  1. CPKC412D2201: Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, Awan FT, Hexner E, Mauro MJ, Sternberg DW, Villeneuve M, Huntsman Labed A, Stanek EJ, Hartmann K, Horny HP, Valent P, Reiter A. Efficacy and safety of midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2530-41. link to original article contains dosing details in manuscript link to supplementary appendix PubMed NCT00233454
  2. CEREMAST: Chandesris MO, Damaj G, Canioni D, Brouzes C, Lhermitte L, Hanssens K, Frenzel L, Cherquaoui Z, Durieu I, Durupt S, Gyan E, Beyne-Rauzy O, Launay D, Faure C, Hamidou M, Besnard S, Diouf M, Schiffmann A, Niault M, Jeandel PY, Ranta D, Gressin R, Chantepie S, Barete S, Dubreuil P, Bourget P, Lortholary O, Hermine O; CEREMAST Study Group. Midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2605-7. link to original article PubMed

Nilotinib monotherapy

Regimen

Study Dates of enrollment Evidence
Kantarjian et al. 2006 (A2101) 2004-2005 Phase 1/2

Targeted therapy

28-day cycles

References

  1. A2101: Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006 Jun 15;354(24):2542-51. link to original article PubMed NCT00109707
    1. Subgroup analysis: Hochhaus A, Baccarani M, Giles FJ, le Coutre PD, Müller MC, Reiter A, Santanastasio H, Leung M, Novick S, Kantarjian HM. Nilotinib in patients with systemic mastocytosis: analysis of the phase 2, open-label, single-arm nilotinib registration study. J Cancer Res Clin Oncol. 2015 Nov;141(11):2047-60. Epub 2015 May 23. link to original article contains dosing details in manuscript link to PMC article PubMed

Response criteria

IWG-MRT & ECNM consensus response criteria (2013)

  1. Gotlib J, Pardanani A, Akin C, Reiter A, George T, Hermine O, Kluin-Nelemans H, Hartmann K, Sperr WR, Brockow K, Schwartz LB, Orfao A, Deangelo DJ, Arock M, Sotlar K, Horny HP, Metcalfe DD, Escribano L, Verstovsek S, Tefferi A, Valent P. International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis. Blood. 2013 Mar 28;121(13):2393-401. Epub 2013 Jan 16. link to original article link to PMC article PubMed