Table 4.
Use of hypomethylating agents in chronic myelomonocytic leukemia (CMML)
| Reference | Number of patients |
Median Age (years, range) |
Phase of Study |
Treatment Regimen | Response Rates | Toxicity | Median Survival |
Progression to Acute Myeloid Leukemia |
|---|---|---|---|---|---|---|---|---|
| Aribi (2007)59 | 19 | 66 (44–82) | II | Decitabine 100 mg/m2 per course in three different schedules, repeated every 4 weeks | CR: 58% HI: 11% |
Myelosuppression associated complications: 8% | 19 months | NR |
| Wijermans (2008)65 | 31 | 71 (53–81) | II | Decitabine 15 mg/m2 over 4 hours IV three times per day on three consecutive days, with a total dose of 135 mg/m2 per course, every 6 weeks | CR: 10% PR: 16% HI: 19% |
Nausea, vomiting, pneumonia, mortality due to sepsis: 3% | 15 months | NR |
| Costa (2010)61 | 38 | 70 (36–83) | II | Azacitidine 75 mg/m2/day for 7 days or 100 mg/m2/day for 5 days every 4 weeks | CR: 11% PR: 3% HI: 25% |
Pneumonia, mortality due to sepsis: 3% | 12 months | NR |
| Garcia-Manero (2011)63 | 41 (4 with CMML) | 70 (31–91) | I | 1 cycle of subcutaneous azacitidine 75 mg/m2 on the first 7 days of cycle 1, followed by oral azacitidine daily,120 to 600 mg, on the first 7 days of each additional 28-day cycle | ORR: 35% in previously treated patients and 73% in previously untreated patients | diarrhea, nausea, vomiting, febrile neutropenia, fatigue | NR | NR |
| Braun (2011)60 | 39 | 71 (54–88) | II | Decitabine 20 mg/m2 per day intravenously for 5 days every 28 days | CR: 10% PR: 20% HI: 8% ORR: 38% |
Neutropenia and thrombocytopenia (36%), severe infection (20%) | 18 months | NR |
| Thorpe (2012)64 | 10 | 66 (41–76) | II | Azacitidine 75 mg/m2 for 7 days or azacitidine 100 mg/m2 for 5 days every 28 days | CR: 20% HI: 40% ORR: 60% |
Thrombocytopenia, pneumonia (20%) | 29 months | NR |
| Ades (2013)58 | 76 | 70 (33–85) | II | Azacitidine 75 mg/m2 for 5–7 days every 28 days | CR: 17% PR: 1% Marrow CR: 8% HI: 17% ORR: 43% |
NR | 29 months | 31% after 1.2 years from azacitidine initiation |
| Wong (2013)66 | 11 | 65 (42–80) | II | Azacitidine 75 mg/m2 for 7 days every 28 days | CR: 9% Marrow CR: 27% PR: 9% HI: 9% ORR: 55% |
Local skin reactions (55%), nausea (36%), infection (73%) | 17 months | 18% |
| Fianchi (2013)62 | 31 | 69 (53–84) | II | Azacitidine 50–75 mg/m2 for 7 days in 22 patients, and 100 mg flat dose for 5–7 days in 9 patients | CR: 45% PR: 3% HI: 6% ORR: 54% |
Grade 4 thrombocytopenia (6%), grade 4 anemia (6%) | 37 months | 16% after 12.7 months |
| Santini (2013) | 44 | 71 (42–84) | II | Decitabine 20 mg/m2 for 5 days, every 28 days | CR: 14% PR: 2% Marrow CR: 17% ORR: 33% |
Severe infections (17%) | 19 months | NR |
| Pleyer (2014) | 48 | 71 (38–87) | II | Azacitidine 75 mg/m2 for 7 days in 42 patients, and 100 mg flat dose for 5–7 days in 6 patients | CR/marrow CR: 13% HI: 50% ORR: 54% |
Grade 3–4 cardiac events (21%) | 12.6 months | 4% after 9 months |
| Drummond (2014) | 32 | 70 (57–85) | II | Azacitidine 75 mg/m2 for 7 days, every 28 days | CR: 7% PR: 0 Marrow CR: 7% HI:3% ORR: 17% |
NR | 16 months | 33% after 13 months |
| Sekeres (2017) | 53 with CMML | 70 (28–93) | Randomized phase II | Azacitidine (75 mg/m2/day on days 1 to 7 of a 28–day cycle); Azacitidine plus lenalidomide (10 mg/day on days 1 to 21); or Azacitidine plus vorinostat (300 mg twice daily on days 3 to 9). |
ORR: 38% (68% in the azacitidine and lenalidomide arm) | Azacitidine plus lenalidomide associated with higher incidence of skin rashes, while azacitidine and vorinostat with a higher incidence of Gastrointestinal side effects | Not reached | NR |
| Santini (2018) | 43 | 71.5 (42–84) | II | Decitabine 20 mg/m2 for 5 days, every 28 days | CR: 16% PR: 2.4% Marrow CR: 19% HI: 9.5% ORR: 47.6% |
Thrombocytopenia (64%) Anemia (52%) Gastrointestinal side effects (23.8%) |
17 months | 57.5%after 51.5 months |
Abbreviations Used:
CR: complete remission; PR: partial remission; HI: hematologic improvement; ORR: overall response rate; NR: not reported; CMML: chronic myelomonocytic leukemia.