Difference between revisions of "Chronic myelomonocytic leukemia"
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==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://pubmed.ncbi.nlm.nih.gov/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] | ||
| − | |||
==[https://www.nccn.org/ NCCN]== | ==[https://www.nccn.org/ NCCN]== | ||
*[https://www.nccn.org/professionals/physician_gls/pdf/mds.pdf NCCN Guidelines - Myelodysplastic Syndromes] | *[https://www.nccn.org/professionals/physician_gls/pdf/mds.pdf NCCN Guidelines - Myelodysplastic Syndromes] | ||
| − | |||
=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;" | ||
| Line 36: | Line 33: | ||
!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 2, <20 pts in subgroup (C) | |rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, <20 pts in subgroup (C) | ||
| Line 46: | Line 43: | ||
|- | |- | ||
|} | |} | ||
| + | <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;" | ||
| Line 65: | Line 63: | ||
|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 2, <20 pts in subgroup (C) | |rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, <20 pts in subgroup (C) | ||
| Line 81: | Line 79: | ||
|- | |- | ||
|} | |} | ||
| + | <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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24569776 PubMed] NCT01235117 | # '''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] 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://pubmed.ncbi.nlm.nih.gov/28486043 PubMed] NCT01522976 | + | # '''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] 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://pubmed.ncbi.nlm.nih.gov/35728048/ PubMed] 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://pubmed.ncbi.nlm.nih.gov/35728048/ PubMed] 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;" | ||
| Line 101: | Line 98: | ||
!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 2, <20 pts in subgroup (E-esc) | |rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, <20 pts in subgroup (E-esc) | ||
| Line 111: | Line 108: | ||
|- | |- | ||
|} | |} | ||
| + | <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;" | ||
| Line 126: | Line 124: | ||
!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 2, <20 pts in subgroup (E-esc) | |rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, <20 pts in subgroup (E-esc) | ||
| Line 136: | Line 134: | ||
|- | |- | ||
|} | |} | ||
| + | <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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28486043 PubMed] NCT01522976 | + | # '''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] 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;" | ||
| Line 156: | Line 153: | ||
!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 2, <20 pts in subgroup (E-esc) | |rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, <20 pts in subgroup (E-esc) | ||
| Line 166: | Line 163: | ||
|- | |- | ||
|} | |} | ||
| + | <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;" | ||
| Line 181: | Line 179: | ||
!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 2, <20 pts in subgroup (E-esc) | |rowspan=2 style="background-color:#91cf61"|Randomized Phase 2, <20 pts in subgroup (E-esc) | ||
| Line 191: | Line 189: | ||
|- | |- | ||
|} | |} | ||
| + | <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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28486043 PubMed] NCT01522976 | + | # '''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] 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: 60%; text-align:center;" | {| class="wikitable" style="width: 60%; text-align:center;" | ||
| Line 214: | Line 211: | ||
|- | |- | ||
|} | |} | ||
| + | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5 | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
| − | |||
'''28-day cycles''' | '''28-day cycles''' | ||
| − | + | </div></div> | |
===References=== | ===References=== | ||
# 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] | # 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] | ||
| − | |||
=Maintenance after first-line therapy= | =Maintenance after first-line therapy= | ||
| − | |||
==Azacitidine monotherapy {{#subobject:2471cc|Regimen=1}}== | ==Azacitidine monotherapy {{#subobject:2471cc|Regimen=1}}== | ||
| − | + | <div class="toccolours" style="background-color:#eeeeee"> | |
| − | |||
===Regimen {{#subobject:8044|Variant=1}}=== | ===Regimen {{#subobject:8044|Variant=1}}=== | ||
{| class="wikitable" style="width: 40%; text-align:center;" | {| class="wikitable" style="width: 40%; text-align:center;" | ||
| Line 236: | Line 230: | ||
|- | |- | ||
|} | |} | ||
| + | <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. [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 [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 [http://hemonc.org HemOnc.org] | ||
| − | |||
==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}}=== | ||
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''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.'' | ||
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====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 | ||
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'''28-day cycles''' | '''28-day cycles''' | ||
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===References=== | ===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] NCT02103478 | #'''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] NCT02103478 | ||
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[[Category:Chronic myelomonocytic leukemia regimens]] | [[Category:Chronic myelomonocytic leukemia regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Myeloproliferative neoplasms]] | [[Category:Myeloproliferative neoplasms]] | ||
Revision as of 14:34, 24 February 2023
| Section editor | |
|---|---|
 |
Sanjay R. Mohan, MD, MSCI Vanderbilt University Nashville, TN |
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
International expert panel
- Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel. (2017) PubMed
NCCN
First-line therapy
Azacitidine monotherapy
Regimen variant #1, 7 days
| Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Sekeres et al. 2017 (SWOG S1117) | 2012-2014 | Randomized Phase 2, <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 | Years 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, <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 PubMed NCT03268954
Azacitidine & Lenalidomide
Regimen variant #1, 7 days of azacitidine
| Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Sekeres et al. 2017 (SWOG S1117) | 2012-2014 | Randomized Phase 2, <20 pts in subgroup (E-esc) | 1. Azacitidine | Seems to have superior ORR |
| 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Sekeres et al. 2017 (SWOG S1117) | 2012-2014 | Randomized Phase 2, <20 pts in subgroup (E-esc) | 1. Azacitidine | Seems to have superior ORR |
| 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Sekeres et al. 2017 (SWOG S1117) | 2012-2014 | Randomized Phase 2, <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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Sekeres et al. 2017 (SWOG S1117) | 2012-2014 | Randomized Phase 2, <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 | Evidence | Efficacy |
|---|---|---|
| Santini et al. 2017 | Phase 2 | ORR: 48% |
References
- 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
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
Decitabine and cedazuridine monotherapy
Regimen
| FDA-recommended dose |
| Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Garcia-Manero et al. 2020 (ASTX727-01-B) | 2014-NR | Randomized Phase 2, <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