Chronic myelomonocytic leukemia
Jump to navigation
Jump to search
| 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 |
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
- 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 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
- 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
- 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
- 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
- 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
- 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
- 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 |
References
- 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 |
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