Difference between revisions of "Chronic myelomonocytic leukemia"

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search
m
m (Text replacement - "http://hemonc.org" to "https://hemonc.org")
(99 intermediate revisions by 3 users not shown)
Line 1: Line 1:
−
'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]].'''
+
<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">
−
Is there a regimen missing from this list?  Would you like to share a different dosage/schedule or an additional reference for a regimen?  Have you noticed an error?  Do you have an idea that will help the site grow to better meet your needs and the needs of many others?  You are [[How_to_contribute|invited to contribute to the site]].
+
[[#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: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
+
|<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: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} 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>
 
|}
 
|}
 +
<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==
−
*[http://www.bloodjournal.org/content/129/13/1753.long Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel. (2017)] [https://www.ncbi.nlm.nih.gov/pubmed/28096091 PubMed]
+
*[http://www.bloodjournal.org/content/129/13/1753.long Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel. (2017)] [https://pubmed.ncbi.nlm.nih.gov/28096091/ PubMed]
−
 
 
 
==NCCN==
 
==NCCN==
−
*[https://www.nccn.org/professionals/physician_gls/pdf/mds.pdf NCCN Guidelines - Myelodysplastic Syndromes]
+
*''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].''
  
−
=Primary Treatment=
+
=First-line therapy=
 +
==Azacitidine monotherapy {{#subobject:3235e3|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 7 days {{#subobject:bad5a2|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]]
 +
|-
 +
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ Sekeres et al. 2017 (SWOG S1117)]
 +
|rowspan=2|2012-2014
 +
|rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, fewer than 20 pts in subgroup (C)
 +
|1. [[#Azacitidine_.26_Lenalidomide|Azacitidine & Lenalidomide]]
 +
| style="background-color:#fc8d59" |Seems to have inferior ORR
 +
|-
 +
|2. [[#Azacitidine_.26_Vorinostat|Azacitidine & Vorinostat]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7
 +
'''28-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 5-2-2 {{#subobject:38dc01|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/10.1038/leu.2014.85 Drummond et al. 2014 (CTRU-CMML-201)]
 +
|2010
 +
|style="background-color:#91cf61"|Phase 2
 +
|style="background-color:#d3d3d3"|
 +
|style="background-color:#d3d3d3"|
 +
|-
 +
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ Sekeres et al. 2017 (SWOG S1117)]
 +
|rowspan=2|2012-2014
 +
|rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, fewer than 20 pts in subgroup (C)
 +
|1. [[#Azacitidine_.26_Lenalidomide|Azacitidine & Lenalidomide]]
 +
| style="background-color:#fc8d59" |Seems to have inferior ORR
 +
|-
 +
|2. [[#Azacitidine_.26_Vorinostat|Azacitidine & Vorinostat]]
 +
|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====
 +
*[[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'''
 +
</div></div>
 +
===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 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 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<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}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 7 days of azacitidine {{#subobject:dbee1c|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]]
 +
|-
 +
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ Sekeres et al. 2017 (SWOG S1117)]
 +
|rowspan=2|2012-2014
 +
|rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, fewer than 20 pts in subgroup (E-esc)
 +
|1. [[#Azacitidine_monotherapy|Azacitidine]]
 +
| style="background-color:#91cf60" |Seems to have superior ORR (primary endpoint)
 +
|-
 +
|2. [[#Azacitidine_.26_Vorinostat|Azacitidine & Vorinostat]]
 +
|style="background-color:#d3d3d3"|Not reported
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> 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'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 5-2-2 azacitidine {{#subobject:8be395|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]]
 +
|-
 +
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ Sekeres et al. 2017 (SWOG S1117)]
 +
|rowspan=2|2012-2014
 +
|rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, fewer than 20 pts in subgroup (E-esc)
 +
|1. [[#Azacitidine_monotherapy|Azacitidine]]
 +
| style="background-color:#91cf60" |Seems to have superior ORR (primary endpoint)
 +
|-
 +
|2. [[#Azacitidine_.26_Vorinostat|Azacitidine & Vorinostat]]
 +
|style="background-color:#d3d3d3"|Not reported
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> 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'''
 +
</div></div>
 +
===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 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}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 7 days of azacitidine {{#subobject:68c3a6|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]]
 +
|-
 +
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ Sekeres et al. 2017 (SWOG S1117)]
 +
|rowspan=2|2012-2014
 +
|rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, fewer than 20 pts in subgroup (E-esc)
 +
|1. [[#Azacitidine_monotherapy|Azacitidine]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 +
|-
 +
|2. [[#Azacitidine_.26_Lenalidomide|Azacitidine & Lenalidomide]]
 +
|style="background-color:#d3d3d3"|Not reported
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> 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'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 5-2-2 azacitidine {{#subobject:fbb1d5|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]]
 +
|-
 +
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5562170/ Sekeres et al. 2017 (SWOG S1117)]
 +
|rowspan=2|2012-2014
 +
|rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, fewer than 20 pts in subgroup (E-esc)
 +
|1. [[#Azacitidine_monotherapy|Azacitidine]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 +
|-
 +
|2. [[#Azacitidine_.26_Lenalidomide|Azacitidine & Lenalidomide]]
 +
|style="background-color:#d3d3d3"|Not reported
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> 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'''
 +
</div></div>
 +
===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 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}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:fbeb38|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://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808077/ Santini et al. 2017 (DECI2009)]
 +
|2010-04 to 2011-10
 +
|style="background-color:#91cf61"|Phase 2
 +
|style="background-color:#d3d3d3"|
 +
|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://doi.org/10.1200/JCO.22.00437 Itzykson et al. 2023 (DACOTA)]
 +
|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====
 +
*[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 +
'''28-day cycles'''
 +
</div></div>
 +
===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://www.nature.com/articles/leu2017186 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]
  
−
==Azacitidine (Vidaza) {{#subobject:3235e3|Regimen=1}}==
+
==Decitabine and cedazuridine monotherapy {{#subobject:c98ugac|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:5ocu131c|Variant=1}}===
 +
{| class="wikitable sortable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
−
 
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
===Regimen {{#subobject:e6184|Variant=1}}===
+
!style="width: 20%"|Study
−
{| border="1" style="text-align:center;" !align="left"  
+
!style="width: 20%"|Dates of enrollment
−
|'''Study'''
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[http://www.nature.com/leu/journal/v28/n7/full/leu201485a.html Drummond et al. 2014]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7414597/ Garcia-Manero et al. 2020 (ASTX727-01-B)]
−
|style="background-color:#EEEE00"|Phase II
+
|2014-NR
 +
| style="background-color:#91cf61" |Randomized Phase 2, fewer than 20 pts in this subgroup (E-RT-switch-ic)
 +
|[[#Decitabine_monotherapy|Decitabine]]
 +
| style="background-color:#d3d3d3" |Not reported
 
|-
 
|-
 
|}
 
|}
 +
''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====
−
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 5 and days 8 & 9 (5-2-2 schedule)
+
*[[Decitabine and cedazuridine (Inqovi)]] 35/100 mg PO once per day on days 1 to 5
−
 
+
'''28-day cycles'''
−
'''28-day cycle for at least 6 cycles, then continued for responders or SD until progression or intolerance.'''
+
</div></div>
−
 
 
 
===References===
 
===References===
−
# 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. [http://www.nature.com/leu/journal/v28/n7/full/leu201485a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24569776 PubMed]
+
#'''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}}==
−
=Maintenance=
+
<div class="toccolours" style="background-color:#eeeeee">
−
 
+
===Regimen {{#subobject:fbhc38|Variant=1}}===
−
==Azacitidine (Vidaza) {{#subobject:2471cc|Regimen=1}}==
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
!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
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
 +
<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}}===
 
===Regimen {{#subobject:8044|Variant=1}}===
−
{| border="1" style="text-align:center;" !align="left"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
|'''Study'''
+
!style="width: 25%"|Study
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2010.08235.x/full Grövdal et al. 2010]
+
|[https://doi.org/10.1111/j.1365-2141.2010.08235.x Grövdal et al. 2010]
−
|style="background-color:#EEEE00"|Phase II
+
|style="background-color:#91cf61"|Phase 2
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Azacitidine (Vidaza)]] 60 mg/m<sup>2</sup> SC once per day on days 1 to 5
 
*[[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. [http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2010.08235.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20497178 PubMed] content property of [http://hemonc.org HemOnc.org]
+
# 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 leukemiaregimens]]
+
[[Category:Chronic myelomonocytic leukemia regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
−
[[Category:Disease index]]
+
[[Category:Myeloproliferative neoplasms]]

Revision as of 19:28, 23 June 2024

Back to Top

Section editor
Sanjay mohan.png
 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

NCCN

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

Chemotherapy

28-day cycles


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

28-day cycle for at least 6 cycles

References

  1. 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
  2. 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
  3. 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

Targeted therapy

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

Targeted therapy

28-day cycles

References

  1. 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

Targeted therapy

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

Targeted therapy

28-day cycles

References

  1. 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

28-day cycles

References

  1. 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
  2. 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
  3. 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

28-day cycles

References

  1. 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

Chemotherapy

28-day cycles

References

  1. 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

Chemotherapy

28-day cycles

References

  1. 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
Retrieved from "https://hemonc.org/w/index.php?title=Chronic_myelomonocytic_leukemia&oldid=86555"