Chronic myelomonocytic leukemia

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

Note: many trials consider CMML to be a subtype of MDS; please check the MDS page for additional relevant studies.

Last updated on 2024-07-23:
7 regimens on this page
10 variants on this page


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.

EBMT


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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 to not reported 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 to not reported 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed content property of HemOnc.org


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