Difference between revisions of "Chronic myelomonocytic leukemia"
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− | + | <span id="BackToTop"></span> | |
− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
− | + | [[#top|Back to Top]] | |
− | + | </div> | |
− | + | {{#lst:Editorial board transclusions|mpn}} | |
− | | | ||
− | |||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
− | |<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] | + | |<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] 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}}]] | + | <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> |
|} | |} | ||
+ | <big>'''Note: many trials consider CMML to be a subtype of MDS; please check the [[Myelodysplastic syndrome|MDS page]] for additional relevant studies.'''</big> | ||
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
=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.''' | ||
==International expert panel== | ==International expert panel== | ||
− | *[ | + | *'''2017:''' [https://doi.org/10.1182/blood-2016-06-724500 Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel] [https://pubmed.ncbi.nlm.nih.gov/28096091/ PubMed] |
− | + | ==NCCN== | |
− | == | + | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1446 NCCN Guidelines - Myelodysplastic Syndromes].'' |
− | *[https://www.nccn.org/ | ||
=First-line therapy= | =First-line therapy= | ||
− | |||
==Azacitidine monotherapy {{#subobject:3235e3|Regimen=1}}== | ==Azacitidine monotherapy {{#subobject:3235e3|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, 7 days {{#subobject:bad5a2|Variant=1}}=== | ===Regimen variant #1, 7 days {{#subobject:bad5a2|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 | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ Sekeres et al. 2017 (SWOG S1117)] |
|rowspan=2|2012-2014 | |rowspan=2|2012-2014 | ||
− | |rowspan=2 style="background-color:#91cf61"|Randomized Phase | + | |rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, fewer than 20 pts in subgroup (C) |
|1. [[#Azacitidine_.26_Lenalidomide|Azacitidine & Lenalidomide]] | |1. [[#Azacitidine_.26_Lenalidomide|Azacitidine & Lenalidomide]] | ||
− | |style="background-color:# | + | | style="background-color:#fc8d59" |Seems to have inferior ORR |
|- | |- | ||
|2. [[#Azacitidine_.26_Vorinostat|Azacitidine & Vorinostat]] | |2. [[#Azacitidine_.26_Vorinostat|Azacitidine & Vorinostat]] | ||
− | |style="background-color:#ffffbf"| | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of ORR |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7 | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 5-2-2 {{#subobject:38dc01|Variant=1}}=== | ===Regimen variant #2, 5-2-2 {{#subobject:38dc01|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 59: | Line 55: | ||
|[https://doi.org/10.1038/leu.2014.85 Drummond et al. 2014 (CTRU-CMML-201)] | |[https://doi.org/10.1038/leu.2014.85 Drummond et al. 2014 (CTRU-CMML-201)] | ||
|2010 | |2010 | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ Sekeres et al. 2017 (SWOG S1117)] |
|rowspan=2|2012-2014 | |rowspan=2|2012-2014 | ||
− | |rowspan=2 style="background-color:#91cf61"|Randomized Phase | + | |rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, fewer than 20 pts in subgroup (C) |
|1. [[#Azacitidine_.26_Lenalidomide|Azacitidine & Lenalidomide]] | |1. [[#Azacitidine_.26_Lenalidomide|Azacitidine & Lenalidomide]] | ||
− | |style="background-color:# | + | | style="background-color:#fc8d59" |Seems to have inferior ORR |
|- | |- | ||
|2. [[#Azacitidine_.26_Vorinostat|Azacitidine & Vorinostat]] | |2. [[#Azacitidine_.26_Vorinostat|Azacitidine & Vorinostat]] | ||
− | |style="background-color:#ffffbf"| | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of ORR |
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631625/ Adès et al. 2022 (PANTHER<sub>MDS</sub>)] | ||
+ | |2017-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Azacitidine_.26_Pevonedistat_999|Azacitidine & Pevonedistat]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of EFS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 5, 8 & 9 | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 5, 8 & 9 | ||
− | |||
'''28-day cycle for at least 6 cycles''' | '''28-day cycle for at least 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''CTRU-CMML-201:''' Drummond MW, Pocock C, Boissinot M, Mills J, Brown J, Cauchy P, Cross NC, Hartley S, Kell J, Szubert A, Cockerill PN, Bowen DT. A multi-centre phase 2 study of azacitidine in chronic myelomonocytic leukaemia. Leukemia. 2014 Jul;28(7):1570-2. Epub 2014 Feb 26. [https://doi.org/10.1038/leu.2014.85 link to original article] '''contains | + | # '''CTRU-CMML-201:''' Drummond MW, Pocock C, Boissinot M, Mills J, Brown J, Cauchy P, Cross NC, Hartley S, Kell J, Szubert A, Cockerill PN, Bowen DT. A multi-centre phase 2 study of azacitidine in chronic myelomonocytic leukaemia. Leukemia. 2014 Jul;28(7):1570-2. Epub 2014 Feb 26. [https://doi.org/10.1038/leu.2014.85 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24569776/ PubMed] [https://clinicaltrials.gov/study/NCT01235117 NCT01235117] |
− | # '''SWOG S1117:''' Sekeres MA, Othus M, List AF, Odenike O, Stone RM, Gore SD, Litzow MR, Buckstein R, Fang M, Roulston D, Bloomfield CD, Moseley A, Nazha A, Zhang Y, Velasco MR, Gaur R, Atallah E, Attar EC, Cook EK, Cull AH, Rauh MJ, Appelbaum FR, Erba HP. Randomized phase II study of azacitidine alone or in combination with lenalidomide or with vorinostat in higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia: North American Intergroup Study SWOG S1117. J Clin Oncol. 2017 Aug 20;35(24):2745-2753. Epub 2017 May 9. [https://doi.org/10.1200/JCO.2015.66.2510 link to original article] '''contains | + | # '''SWOG S1117:''' Sekeres MA, Othus M, List AF, Odenike O, Stone RM, Gore SD, Litzow MR, Buckstein R, Fang M, Roulston D, Bloomfield CD, Moseley A, Nazha A, Zhang Y, Velasco MR, Gaur R, Atallah E, Attar EC, Cook EK, Cull AH, Rauh MJ, Appelbaum FR, Erba HP. Randomized phase II study of azacitidine alone or in combination with lenalidomide or with vorinostat in higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia: North American Intergroup Study SWOG S1117. J Clin Oncol. 2017 Aug 20;35(24):2745-2753. Epub 2017 May 9. [https://doi.org/10.1200/JCO.2015.66.2510 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28486043/ PubMed] [https://clinicaltrials.gov/study/NCT01522976 NCT01522976] |
− | # '''PANTHER:''' NCT03268954 | + | # '''PANTHER<sub>MDS</sub>:''' Adès L, Girshova L, Doronin VA, Díez-Campelo M, Valcárcel D, Kambhampati S, Viniou NA, Woszczyk D, De Paz Arias R, Symeonidis A, Anagnostopoulos A, Munhoz EC, Platzbecker U, Santini V, Fram RJ, Yuan Y, Friedlander S, Faller DV, Sekeres MA. Pevonedistat plus azacitidine vs azacitidine alone in higher-risk MDS/chronic myelomonocytic leukemia or low-blast-percentage AML. Blood Adv. 2022 Sep 13;6(17):5132-5145. [https://doi.org/10.1182/bloodadvances.2022007334 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631625/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35728048/ PubMed] [https://clinicaltrials.gov/study/NCT03268954 NCT03268954] |
− | |||
==Azacitidine & Lenalidomide {{#subobject:92571f|Regimen=1}}== | ==Azacitidine & Lenalidomide {{#subobject:92571f|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, 7 days of azacitidine {{#subobject:dbee1c|Variant=1}}=== | ===Regimen variant #1, 7 days of azacitidine {{#subobject:dbee1c|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 | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ Sekeres et al. 2017 (SWOG S1117)] |
|rowspan=2|2012-2014 | |rowspan=2|2012-2014 | ||
− | |rowspan=2 style="background-color:#91cf61"|Randomized Phase | + | |rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, fewer than 20 pts in subgroup (E-esc) |
|1. [[#Azacitidine_monotherapy|Azacitidine]] | |1. [[#Azacitidine_monotherapy|Azacitidine]] | ||
− | |style="background-color:# | + | | style="background-color:#91cf60" |Seems to have superior ORR (primary endpoint) |
|- | |- | ||
|2. [[#Azacitidine_.26_Vorinostat|Azacitidine & Vorinostat]] | |2. [[#Azacitidine_.26_Vorinostat|Azacitidine & Vorinostat]] | ||
Line 106: | Line 104: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7 | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7 | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 5-2-2 azacitidine {{#subobject:8be395|Variant=1}}=== | ===Regimen variant #2, 5-2-2 azacitidine {{#subobject:8be395|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 | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ Sekeres et al. 2017 (SWOG S1117)] |
|rowspan=2|2012-2014 | |rowspan=2|2012-2014 | ||
− | |rowspan=2 style="background-color:#91cf61"|Randomized Phase | + | |rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, fewer than 20 pts in subgroup (E-esc) |
|1. [[#Azacitidine_monotherapy|Azacitidine]] | |1. [[#Azacitidine_monotherapy|Azacitidine]] | ||
− | |style="background-color:# | + | | style="background-color:#91cf60" |Seems to have superior ORR (primary endpoint) |
|- | |- | ||
|2. [[#Azacitidine_.26_Vorinostat|Azacitidine & Vorinostat]] | |2. [[#Azacitidine_.26_Vorinostat|Azacitidine & Vorinostat]] | ||
Line 131: | Line 130: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 5, 8 & 9 | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 5, 8 & 9 | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''SWOG S1117:''' Sekeres MA, Othus M, List AF, Odenike O, Stone RM, Gore SD, Litzow MR, Buckstein R, Fang M, Roulston D, Bloomfield CD, Moseley A, Nazha A, Zhang Y, Velasco MR, Gaur R, Atallah E, Attar EC, Cook EK, Cull AH, Rauh MJ, Appelbaum FR, Erba HP. Randomized phase II study of azacitidine alone or in combination with lenalidomide or with vorinostat in higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia: North American Intergroup Study SWOG S1117. J Clin Oncol. 2017 Aug 20;35(24):2745-2753. Epub 2017 May 9. [https://doi.org/10.1200/JCO.2015.66.2510 link to original article] '''contains | + | # '''SWOG S1117:''' Sekeres MA, Othus M, List AF, Odenike O, Stone RM, Gore SD, Litzow MR, Buckstein R, Fang M, Roulston D, Bloomfield CD, Moseley A, Nazha A, Zhang Y, Velasco MR, Gaur R, Atallah E, Attar EC, Cook EK, Cull AH, Rauh MJ, Appelbaum FR, Erba HP. Randomized phase II study of azacitidine alone or in combination with lenalidomide or with vorinostat in higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia: North American Intergroup Study SWOG S1117. J Clin Oncol. 2017 Aug 20;35(24):2745-2753. Epub 2017 May 9. [https://doi.org/10.1200/JCO.2015.66.2510 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28486043/ PubMed] [https://clinicaltrials.gov/study/NCT01522976 NCT01522976] |
− | |||
==Azacitidine & Vorinostat {{#subobject:a816bd|Regimen=1}}== | ==Azacitidine & Vorinostat {{#subobject:a816bd|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, 7 days of azacitidine {{#subobject:68c3a6|Variant=1}}=== | ===Regimen variant #1, 7 days of azacitidine {{#subobject:68c3a6|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 | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ Sekeres et al. 2017 (SWOG S1117)] |
|rowspan=2|2012-2014 | |rowspan=2|2012-2014 | ||
− | |rowspan=2 style="background-color:#91cf61"|Randomized Phase | + | |rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, fewer than 20 pts in subgroup (E-esc) |
|1. [[#Azacitidine_monotherapy|Azacitidine]] | |1. [[#Azacitidine_monotherapy|Azacitidine]] | ||
− | |style="background-color:#ffffbf"| | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of ORR |
|- | |- | ||
|2. [[#Azacitidine_.26_Lenalidomide|Azacitidine & Lenalidomide]] | |2. [[#Azacitidine_.26_Lenalidomide|Azacitidine & Lenalidomide]] | ||
Line 164: | Line 159: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7 | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7 | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Vorinostat (Zolinza)]] 300 mg PO twice per day on days 3 to 9 | *[[Vorinostat (Zolinza)]] 300 mg PO twice per day on days 3 to 9 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 5-2-2 azacitidine {{#subobject:fbb1d5|Variant=1}}=== | ===Regimen variant #2, 5-2-2 azacitidine {{#subobject:fbb1d5|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 | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ Sekeres et al. 2017 (SWOG S1117)] |
|rowspan=2|2012-2014 | |rowspan=2|2012-2014 | ||
− | |rowspan=2 style="background-color:#91cf61"|Randomized Phase | + | |rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, fewer than 20 pts in subgroup (E-esc) |
|1. [[#Azacitidine_monotherapy|Azacitidine]] | |1. [[#Azacitidine_monotherapy|Azacitidine]] | ||
− | |style="background-color:#ffffbf"| | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of ORR |
|- | |- | ||
|2. [[#Azacitidine_.26_Lenalidomide|Azacitidine & Lenalidomide]] | |2. [[#Azacitidine_.26_Lenalidomide|Azacitidine & Lenalidomide]] | ||
Line 189: | Line 185: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 5, 8 & 9 | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 5, 8 & 9 | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Vorinostat (Zolinza)]] 300 mg PO twice per day on days 3 to 9 | *[[Vorinostat (Zolinza)]] 300 mg PO twice per day on days 3 to 9 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''SWOG S1117:''' Sekeres MA, Othus M, List AF, Odenike O, Stone RM, Gore SD, Litzow MR, Buckstein R, Fang M, Roulston D, Bloomfield CD, Moseley A, Nazha A, Zhang Y, Velasco MR, Gaur R, Atallah E, Attar EC, Cook EK, Cull AH, Rauh MJ, Appelbaum FR, Erba HP. Randomized phase II study of azacitidine alone or in combination with lenalidomide or with vorinostat in higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia: North American Intergroup Study SWOG S1117. J Clin Oncol. 2017 Aug 20;35(24):2745-2753. Epub 2017 May 9. [https://doi.org/10.1200/JCO.2015.66.2510 link to original article] '''contains | + | # '''SWOG S1117:''' Sekeres MA, Othus M, List AF, Odenike O, Stone RM, Gore SD, Litzow MR, Buckstein R, Fang M, Roulston D, Bloomfield CD, Moseley A, Nazha A, Zhang Y, Velasco MR, Gaur R, Atallah E, Attar EC, Cook EK, Cull AH, Rauh MJ, Appelbaum FR, Erba HP. Randomized phase II study of azacitidine alone or in combination with lenalidomide or with vorinostat in higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia: North American Intergroup Study SWOG S1117. J Clin Oncol. 2017 Aug 20;35(24):2745-2753. Epub 2017 May 9. [https://doi.org/10.1200/JCO.2015.66.2510 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28486043/ PubMed] [https://clinicaltrials.gov/study/NCT01522976 NCT01522976] |
− | |||
==Decitabine monotherapy {{#subobject:c9cd47|Regimen=1}}== | ==Decitabine monotherapy {{#subobject:c9cd47|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:fbeb38|Variant=1}}=== | ===Regimen {{#subobject:fbeb38|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !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/PMC5808077/ Santini et al. 2017] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808077/ Santini et al. 2017 (DECI2009)] |
− | |style="background-color:#91cf61"|Phase | + | |2010-04 to 2011-10 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | |style="background-color:#d3d3d3"| | ||
|style="background-color:#8c96c6"|ORR: 48% | |style="background-color:#8c96c6"|ORR: 48% | ||
|- | |- | ||
− | | | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7414597/ Garcia-Manero et al. 2020 (ASTX727-01-B)] |
− | + | |2014-NR | |
− | + | | style="background-color:#91cf61" |Randomized Phase 2, fewer than 20 pts in this subgroup (C) | |
− | + | |[[#Decitabine_and_cedazuridine_monotherapy|Oral decitabine]] | |
− | + | | style="background-color:#d3d3d3" |Not reported | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | | | ||
− | |[[# | ||
− | | | ||
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/JCO.22.00437 Itzykson et al. 2023 (DACOTA)] |
− | |style="background-color:# | + | |2014-10 to 2019-09 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
+ | |[[#Hydroxyurea_monotherapy|Hydroxyurea]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of EFS | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: ASTX727-01-B was a randomized crossover trial examining PK/PD, and was not designed to compare efficacy.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 |
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # | + | #'''DECI2009:''' Santini V, Allione B, Zini G, Gioia D, Lunghi M, Poloni A, Cilloni D, Sanna A, Masiera E, Ceccarelli M, Abdel-Wahab O, Terenzi A, Angelucci E, Finelli C, Onida F, Pelizzari A, Ferrero D, Saglio G, Figueroa M, Levis A. A phase II, multicentre trial of decitabine in higher-risk chronic myelomonocytic leukemia. Leukemia. 2018 Feb;32(2):413-418. Epub 2017 Jun 13. [https://doi.org/10.1038/leu.2017.186 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808077/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28607470/ PubMed] [https://clinicaltrials.gov/study/NCT01251627 NCT01251627] |
+ | #'''ASTX727-01-B:''' Garcia-Manero G, Griffiths EA, Steensma DP, Roboz GJ, Wells R, McCloskey J, Odenike O, DeZern AE, Yee K, Busque L, O'Connell C, Michaelis LC, Brandwein J, Kantarjian H, Oganesian A, Azab M, Savona MR. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood. 2020 Aug 6;136(6):674-683. [https://doi.org/10.1182/blood.2019004143 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7414597/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32285126/ PubMed] [https://clinicaltrials.gov/study/NCT02103478 NCT02103478] | ||
+ | #'''DACOTA:''' Itzykson R, Santini V, Thepot S, Ades L, Chaffaut C, Giagounidis A, Morabito M, Droin N, Luebbert M, Sapena R, Nimubona S, Goasguen J, Wattel E, Zini G, Torregrosa Diaz JM, Germing U, Pelizzari AM, Park S, Jaekel N, Metzgeroth G, Onida F, Navarro R, Patriarca A, Stamatoullas A, Goetze K, Puttrich M, Mossuto S, Solary E, Gloaguen S, Chevret S, Chermat F, Platzbecker U, Fenaux P. Decitabine Versus Hydroxyurea for Advanced Proliferative Chronic Myelomonocytic Leukemia: Results of a Randomized Phase III Trial Within the EMSCO Network. J Clin Oncol. 2023 Apr 1;41(10):1888-1897. Epub 2022 Dec 1. [https://doi.org/10.1200/JCO.22.00437 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36455187/ PubMed] [https://clinicaltrials.gov/study/NCT02214407 NCT02214407] | ||
==Decitabine and cedazuridine monotherapy {{#subobject:c98ugac|Regimen=1}}== | ==Decitabine and cedazuridine monotherapy {{#subobject:c98ugac|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:5ocu131c|Variant=1}}=== | ===Regimen {{#subobject:5ocu131c|Variant=1}}=== | ||
{| class="wikitable sortable" style="color:white; background-color:#404040" | {| class="wikitable sortable" style="color:white; background-color:#404040" | ||
Line 260: | Line 243: | ||
{| 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 | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7414597/ Garcia-Manero et al. 2020 (ASTX727-01-B)] |
|2014-NR | |2014-NR | ||
− | | style="background-color:#91cf61" |Randomized Phase | + | | style="background-color:#91cf61" |Randomized Phase 2, fewer than 20 pts in this subgroup (E-RT-switch-ic) |
|[[#Decitabine_monotherapy|Decitabine]] | |[[#Decitabine_monotherapy|Decitabine]] | ||
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
Line 273: | Line 256: | ||
|} | |} | ||
''Note: this was a randomized crossover trial examining PK/PD, and was not designed to compare efficacy.'' | ''Note: this was a randomized crossover trial examining PK/PD, and was not designed to compare efficacy.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Decitabine and cedazuridine (Inqovi)]] 35/100 mg PO once per day on days 1 to 5 | *[[Decitabine and cedazuridine (Inqovi)]] 35/100 mg PO once per day on days 1 to 5 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''ASTX727-01-B:''' Garcia-Manero G, Griffiths EA, Steensma DP, Roboz GJ, Wells R, McCloskey J, Odenike O, DeZern AE, Yee K, Busque L, O'Connell C, Michaelis LC, Brandwein J, Kantarjian H, Oganesian A, Azab M, Savona MR. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood. 2020 Aug 6;136(6):674-683. [https://doi.org/10.1182/blood.2019004143 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7414597/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32285126/ PubMed] [https://clinicaltrials.gov/study/NCT02103478 NCT02103478] | ||
+ | ==Hydroxyurea monotherapy {{#subobject:c9cug8|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:fbhc38|Variant=1}}=== | ||
+ | {| 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/10.1200/JCO.22.00437 Itzykson et al. 2023 (DACOTA)] | ||
+ | |2014-10 to 2019-09 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Decitabine_monotherapy|Decitabine]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of EFS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Hydroxyurea (Hydrea)]] 1000 to 4000 mg/day PO | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''DACOTA:''' Itzykson R, Santini V, Thepot S, Ades L, Chaffaut C, Giagounidis A, Morabito M, Droin N, Luebbert M, Sapena R, Nimubona S, Goasguen J, Wattel E, Zini G, Torregrosa Diaz JM, Germing U, Pelizzari AM, Park S, Jaekel N, Metzgeroth G, Onida F, Navarro R, Patriarca A, Stamatoullas A, Goetze K, Puttrich M, Mossuto S, Solary E, Gloaguen S, Chevret S, Chermat F, Platzbecker U, Fenaux P. Decitabine Versus Hydroxyurea for Advanced Proliferative Chronic Myelomonocytic Leukemia: Results of a Randomized Phase III Trial Within the EMSCO Network. J Clin Oncol. 2023 Apr 1;41(10):1888-1897. Epub 2022 Dec 1. [https://doi.org/10.1200/JCO.22.00437 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36455187/ PubMed] [https://clinicaltrials.gov/study/NCT02214407 NCT02214407] | ||
+ | =Maintenance after first-line therapy= | ||
+ | ==Azacitidine monotherapy {{#subobject:2471cc|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:8044|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 40%; text-align:center;" | ||
+ | !style="width: 25%"|Study | ||
+ | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1111/j.1365-2141.2010.08235.x Grövdal et al. 2010] | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Azacitidine (Vidaza)]] 60 mg/m<sup>2</sup> SC once per day on days 1 to 5 | ||
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # Grövdal M, Karimi M, Khan R, Aggerholm A, Antunovic P, Astermark J, Bernell P, Engström LM, Kjeldsen L, Linder O, Nilsson L, Olsson A, Holm MS, Tangen JM, Wallvik J, Oberg G, Hokland P, Jacobsen SE, Porwit A, Hellström-Lindberg E. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. Br J Haematol. 2010 Aug;150(3):293-302. Epub 2010 May 20. [https://doi.org/10.1111/j.1365-2141.2010.08235.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20497178/ PubMed] content property of [https://hemonc.org HemOnc.org] |
[[Category:Chronic myelomonocytic leukemia regimens]] | [[Category:Chronic myelomonocytic leukemia regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Myeloproliferative neoplasms]] | [[Category:Myeloproliferative neoplasms]] |
Latest revision as of 00:40, 27 June 2024
Section editor | |
---|---|
Sanjay R. Mohan, MD, MSCI Vanderbilt University Nashville, TN, USA |
7 regimens on this page
10 variants on this page
|
Note: many trials consider CMML to be a subtype of MDS; please check the MDS page for additional relevant studies.
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.
International expert panel
- 2017: Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel PubMed
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Myelodysplastic Syndromes.
First-line therapy
Azacitidine monotherapy
Regimen variant #1, 7 days
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sekeres et al. 2017 (SWOG S1117) | 2012-2014 | Randomized Phase 2, fewer than 20 pts in subgroup (C) | 1. Azacitidine & Lenalidomide | Seems to have inferior ORR |
2. Azacitidine & Vorinostat | Did not meet primary endpoint of ORR |
Regimen variant #2, 5-2-2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Drummond et al. 2014 (CTRU-CMML-201) | 2010 | Phase 2 | ||
Sekeres et al. 2017 (SWOG S1117) | 2012-2014 | Randomized Phase 2, fewer than 20 pts in subgroup (C) | 1. Azacitidine & Lenalidomide | Seems to have inferior ORR |
2. Azacitidine & Vorinostat | Did not meet primary endpoint of ORR | |||
Adès et al. 2022 (PANTHERMDS) | 2017-2019 | Phase 3 (C) | Azacitidine & Pevonedistat | Did not meet primary endpoint of EFS |
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 IV once per day on days 1 to 5, 8 & 9
28-day cycle for at least 6 cycles
References
- CTRU-CMML-201: Drummond MW, Pocock C, Boissinot M, Mills J, Brown J, Cauchy P, Cross NC, Hartley S, Kell J, Szubert A, Cockerill PN, Bowen DT. A multi-centre phase 2 study of azacitidine in chronic myelomonocytic leukaemia. Leukemia. 2014 Jul;28(7):1570-2. Epub 2014 Feb 26. link to original article contains dosing details in manuscript PubMed NCT01235117
- SWOG S1117: Sekeres MA, Othus M, List AF, Odenike O, Stone RM, Gore SD, Litzow MR, Buckstein R, Fang M, Roulston D, Bloomfield CD, Moseley A, Nazha A, Zhang Y, Velasco MR, Gaur R, Atallah E, Attar EC, Cook EK, Cull AH, Rauh MJ, Appelbaum FR, Erba HP. Randomized phase II study of azacitidine alone or in combination with lenalidomide or with vorinostat in higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia: North American Intergroup Study SWOG S1117. J Clin Oncol. 2017 Aug 20;35(24):2745-2753. Epub 2017 May 9. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01522976
- PANTHERMDS: Adès L, Girshova L, Doronin VA, Díez-Campelo M, Valcárcel D, Kambhampati S, Viniou NA, Woszczyk D, De Paz Arias R, Symeonidis A, Anagnostopoulos A, Munhoz EC, Platzbecker U, Santini V, Fram RJ, Yuan Y, Friedlander S, Faller DV, Sekeres MA. Pevonedistat plus azacitidine vs azacitidine alone in higher-risk MDS/chronic myelomonocytic leukemia or low-blast-percentage AML. Blood Adv. 2022 Sep 13;6(17):5132-5145. link to original article contains dosing details in manuscript link to PMC article PubMed NCT03268954
Azacitidine & Lenalidomide
Regimen variant #1, 7 days of azacitidine
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sekeres et al. 2017 (SWOG S1117) | 2012-2014 | Randomized Phase 2, fewer than 20 pts in subgroup (E-esc) | 1. Azacitidine | Seems to have superior ORR (primary endpoint) |
2. Azacitidine & Vorinostat | Not reported |
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 IV or SC once per day on days 1 to 7
Targeted therapy
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
28-day cycles
Regimen variant #2, 5-2-2 azacitidine
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sekeres et al. 2017 (SWOG S1117) | 2012-2014 | Randomized Phase 2, fewer than 20 pts in subgroup (E-esc) | 1. Azacitidine | Seems to have superior ORR (primary endpoint) |
2. Azacitidine & Vorinostat | Not reported |
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 IV or SC once per day on days 1 to 5, 8 & 9
Targeted therapy
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
28-day cycles
References
- SWOG S1117: Sekeres MA, Othus M, List AF, Odenike O, Stone RM, Gore SD, Litzow MR, Buckstein R, Fang M, Roulston D, Bloomfield CD, Moseley A, Nazha A, Zhang Y, Velasco MR, Gaur R, Atallah E, Attar EC, Cook EK, Cull AH, Rauh MJ, Appelbaum FR, Erba HP. Randomized phase II study of azacitidine alone or in combination with lenalidomide or with vorinostat in higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia: North American Intergroup Study SWOG S1117. J Clin Oncol. 2017 Aug 20;35(24):2745-2753. Epub 2017 May 9. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01522976
Azacitidine & Vorinostat
Regimen variant #1, 7 days of azacitidine
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sekeres et al. 2017 (SWOG S1117) | 2012-2014 | Randomized Phase 2, fewer than 20 pts in subgroup (E-esc) | 1. Azacitidine | Did not meet primary endpoint of ORR |
2. Azacitidine & Lenalidomide | Not reported |
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 IV or SC once per day on days 1 to 7
Targeted therapy
- Vorinostat (Zolinza) 300 mg PO twice per day on days 3 to 9
28-day cycles
Regimen variant #2, 5-2-2 azacitidine
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sekeres et al. 2017 (SWOG S1117) | 2012-2014 | Randomized Phase 2, fewer than 20 pts in subgroup (E-esc) | 1. Azacitidine | Did not meet primary endpoint of ORR |
2. Azacitidine & Lenalidomide | Not reported |
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 IV or SC once per day on days 1 to 5, 8 & 9
Targeted therapy
- Vorinostat (Zolinza) 300 mg PO twice per day on days 3 to 9
28-day cycles
References
- SWOG S1117: Sekeres MA, Othus M, List AF, Odenike O, Stone RM, Gore SD, Litzow MR, Buckstein R, Fang M, Roulston D, Bloomfield CD, Moseley A, Nazha A, Zhang Y, Velasco MR, Gaur R, Atallah E, Attar EC, Cook EK, Cull AH, Rauh MJ, Appelbaum FR, Erba HP. Randomized phase II study of azacitidine alone or in combination with lenalidomide or with vorinostat in higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia: North American Intergroup Study SWOG S1117. J Clin Oncol. 2017 Aug 20;35(24):2745-2753. Epub 2017 May 9. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01522976
Decitabine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Santini et al. 2017 (DECI2009) | 2010-04 to 2011-10 | Phase 2 | ORR: 48% | |
Garcia-Manero et al. 2020 (ASTX727-01-B) | 2014-NR | Randomized Phase 2, fewer than 20 pts in this subgroup (C) | Oral decitabine | Not reported |
Itzykson et al. 2023 (DACOTA) | 2014-10 to 2019-09 | Phase 3 (E-switch-ooc) | Hydroxyurea | Did not meet primary endpoint of EFS |
Note: ASTX727-01-B was a randomized crossover trial examining PK/PD, and was not designed to compare efficacy.
Chemotherapy
- Decitabine (Dacogen) 20 mg/m2 IV over 60 minutes once per day on days 1 to 5
28-day cycles
References
- DECI2009: Santini V, Allione B, Zini G, Gioia D, Lunghi M, Poloni A, Cilloni D, Sanna A, Masiera E, Ceccarelli M, Abdel-Wahab O, Terenzi A, Angelucci E, Finelli C, Onida F, Pelizzari A, Ferrero D, Saglio G, Figueroa M, Levis A. A phase II, multicentre trial of decitabine in higher-risk chronic myelomonocytic leukemia. Leukemia. 2018 Feb;32(2):413-418. Epub 2017 Jun 13. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01251627
- ASTX727-01-B: Garcia-Manero G, Griffiths EA, Steensma DP, Roboz GJ, Wells R, McCloskey J, Odenike O, DeZern AE, Yee K, Busque L, O'Connell C, Michaelis LC, Brandwein J, Kantarjian H, Oganesian A, Azab M, Savona MR. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood. 2020 Aug 6;136(6):674-683. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02103478
- DACOTA: Itzykson R, Santini V, Thepot S, Ades L, Chaffaut C, Giagounidis A, Morabito M, Droin N, Luebbert M, Sapena R, Nimubona S, Goasguen J, Wattel E, Zini G, Torregrosa Diaz JM, Germing U, Pelizzari AM, Park S, Jaekel N, Metzgeroth G, Onida F, Navarro R, Patriarca A, Stamatoullas A, Goetze K, Puttrich M, Mossuto S, Solary E, Gloaguen S, Chevret S, Chermat F, Platzbecker U, Fenaux P. Decitabine Versus Hydroxyurea for Advanced Proliferative Chronic Myelomonocytic Leukemia: Results of a Randomized Phase III Trial Within the EMSCO Network. J Clin Oncol. 2023 Apr 1;41(10):1888-1897. Epub 2022 Dec 1. link to original article contains dosing details in abstract PubMed NCT02214407
Decitabine and cedazuridine monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Garcia-Manero et al. 2020 (ASTX727-01-B) | 2014-NR | Randomized Phase 2, fewer than 20 pts in this subgroup (E-RT-switch-ic) | Decitabine | Not reported |
Note: this was a randomized crossover trial examining PK/PD, and was not designed to compare efficacy.
Chemotherapy
- Decitabine and cedazuridine (Inqovi) 35/100 mg PO once per day on days 1 to 5
28-day cycles
References
- ASTX727-01-B: Garcia-Manero G, Griffiths EA, Steensma DP, Roboz GJ, Wells R, McCloskey J, Odenike O, DeZern AE, Yee K, Busque L, O'Connell C, Michaelis LC, Brandwein J, Kantarjian H, Oganesian A, Azab M, Savona MR. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood. 2020 Aug 6;136(6):674-683. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02103478
Hydroxyurea monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Itzykson et al. 2023 (DACOTA) | 2014-10 to 2019-09 | Phase 3 (C) | Decitabine | Did not meet primary endpoint of EFS |
References
- DACOTA: Itzykson R, Santini V, Thepot S, Ades L, Chaffaut C, Giagounidis A, Morabito M, Droin N, Luebbert M, Sapena R, Nimubona S, Goasguen J, Wattel E, Zini G, Torregrosa Diaz JM, Germing U, Pelizzari AM, Park S, Jaekel N, Metzgeroth G, Onida F, Navarro R, Patriarca A, Stamatoullas A, Goetze K, Puttrich M, Mossuto S, Solary E, Gloaguen S, Chevret S, Chermat F, Platzbecker U, Fenaux P. Decitabine Versus Hydroxyurea for Advanced Proliferative Chronic Myelomonocytic Leukemia: Results of a Randomized Phase III Trial Within the EMSCO Network. J Clin Oncol. 2023 Apr 1;41(10):1888-1897. Epub 2022 Dec 1. link to original article contains dosing details in abstract PubMed NCT02214407
Maintenance after first-line therapy
Azacitidine monotherapy
Regimen
Study | Evidence |
---|---|
Grövdal et al. 2010 | Phase 2 |
References
- Grövdal M, Karimi M, Khan R, Aggerholm A, Antunovic P, Astermark J, Bernell P, Engström LM, Kjeldsen L, Linder O, Nilsson L, Olsson A, Holm MS, Tangen JM, Wallvik J, Oberg G, Hokland P, Jacobsen SE, Porwit A, Hellström-Lindberg E. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. Br J Haematol. 2010 Aug;150(3):293-302. Epub 2010 May 20. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org