Chronic myelomonocytic leukemia
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Section editor | |
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Sanjay R. Mohan, MD, MSCI Vanderbilt University Nashville, TN |
7 regimens on this page
10 variants on this page
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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 |
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
- 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 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 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 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
- 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
- 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