Chronic myelomonocytic leukemia

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

7 regimens on this page 10 variants on this page

Guidelines

International expert panel

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

NCCN

• NCCN Guidelines - Myelodysplastic Syndromes

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

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	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

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 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 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 not superior
			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 not superior
			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 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	Seems not superior
			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	Seems not superior
			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 PubMed NCT01522976

Decitabine monotherapy

Regimen

Study	Evidence	Efficacy
Santini et al. 2017	Phase 2	ORR: 48%

Chemotherapy

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

28-day cycles

References

1. 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

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

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

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