Chronic myelomonocytic leukemia

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

• Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel. (2017) 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

Chemotherapy

• Azacitidine (Vidaza) 75 mg/m² IV or SC once per day on days 1 to 7

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

• 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

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. PANTHER_MDS: 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

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

• 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

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

• Decitabine (Dacogen) 20 mg/m² IV over 60 minutes once per day on days 1 to 5

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

• Decitabine and cedazuridine (Inqovi) 35/100 mg PO once per day on days 1 to 5

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

• Hydroxyurea (Hydrea) 1000 to 4000 mg/day PO

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

• Azacitidine (Vidaza) 60 mg/m² SC once per day on days 1 to 5

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