Table 1.
Selected clinical trials of HMA monotherapy.
| Drug | Phase | Patient population | Intervention | Outcomes | Ref. |
|---|---|---|---|---|---|
| Azacitidine | III |
n = 358 higher-risk MDS |
1:1 randomization AZA (75 mg/m2 per day for 7 days every 28 days) or conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy per choice of investigators before randomization) | (1) median OS 24.5 months for AZA versus
15.0 months for conventional care group
(p = 0.0001) (2) 2-year OS, 50.8% (95% CI 42.1–58.8) for AZA versus 26.2% (18.7–34.3) for conventional care group (p < 0.0001) |
Fenaux et al.11 |
| Decitabine | III |
n = 170 MDS pts |
1:1 randomization to DEC (15 mg/m2 IV every 8 h for 3 days repeated every 6 weeks, or best supportive care. | (1) ORR: 17% (9% CR) with DEC versus 0%
with supportive care (0%)
(p < 0.001). (2) Responses were durable (median, 10.3 months) and prolonged AML progression time (12.1 months versus 7.8 months [p = 0.16]) |
Kantarjian et al.30 |
| Guadectiabine | I/II | n = 105 intermediate-1-risk, intermediate-2-risk, or high-risk MDS or CMML (28 pts treatment-naive, 27 R/R disease after previous HMA treatment) | Open-label, 1:1 randomization to subcutaneous guadecitabine 60 or 90 mg/m2 on D1-5 of a 28 days treatment cycle. | (1) Response independent of dose groups [21 of 53 with
60 mg/m2 and 27 of 49 (55%, 95% CI 40–69)
with 90 mg/m2
p = 0.16] (2) ORR: 51% in pts who were treatment-naive and 43% in relapsed or refractory disease. |
Garcia-Manero et al.31 |
| ASTX727 (combination of oral Decitabine with cytidine deaminase inhibitor Cedazuridine) | II | n = 50 intermediate or high risk MDS or CMML | Randomized 1:1 to either 5 days of IV-DEC or 5 days of ASTX727, followed by a cross-over to the other in cycle 2. Cycles 3 forward only ASTX727 | ORR: 62% [32 pts, with 8 (16%) CR, 14 (28%) mCR, and 9 (18%) HI] | Garcia-Manero et al.32 |
| CC-486 (oral azacitidine) | II |
n = 31 (MDS n = 18, CMML n = 4, and AML n = 9) |
CC-486 300 mg once-daily for 21 days of repeated 28 days cycles | (1) ORR: 32% in MDS/CMML subgroups, 22% in AML (2) Red blood cell transfusion independence rates 33% in MDS/CMML and 25% in AML |
Savona et al.33 |
AML, acute myeloid leukemia; AZA, azacytidine; CMML, chronic myelomonocytic leukemia; CR, complete remission; DEC, decitabine; HI, hematologic improvement; HMA, hypomethylating agents; MDS, myelodysplastic syndrome; mCR, marrow CR; ORR, overall response rate; OS, overall survival; Ref, reference; RR, relapsed/refractory.