Randomized trials in higher-risk MDS
| Trial name . | Phase . | Investigational arm . | Control arm* . | Patient population . | Eligibility . | Primary endpoint . | Results of primary endpoint . | Secondary endpoint . | Reference # . |
|---|---|---|---|---|---|---|---|---|---|
| SWOG S1117 | 2 | azacitidine + lenalidomide (10 mg/day days 1-21) | azacitidine | HR-MDS/CMML | Blasts ≥5%; IPSS ≥1.5 | ↑ ORR 20% (CR/PR/HI) | 49% vs 38% (P = 0.16) | No improvement in OS | 27 |
| SWOG S1117 | 2 | azacitidine + vorinostat (300 mg twice daily on days 3-9) | azacitidine | HR-MDS/CMML | Blasts ≥5%; IPSS ≥1.5 | ↑ ORR 20% (CR/PR/HI) | 27% vs 38%; (P = 0.16) | 11.6 versus 16.7 months (p = 0.74) | 27 |
| E1905 Study | 2 | azacitidine + entinostat (4 mg/m2/day on days 3 and 10) | azacitidine | Therapy-related MDS/AML | Any IPSS | CR, PR, or trilineage HI | 17% vs 46% | OS versus 13 months | 28 |
| FUSION-AML-001 (MDS Cohort) | 2 | azacitidine + durvalumab (1500 mg IV q 4 weeks) | azacitidine | Int to very high MDS | IPSS-R int to very high | ORR (CR, mCR, HI) | 61.9% vs 47.6% (P = 0.18) | No Increase PDL1 on BM Blasts | 29 |
| SUPPORT | 3 | azacitidine + eltrombopag (200 mg/day, up to 300 mg/day) | azacitidine | Int to HR-MDS | int-1, int-2, high IPSS | Platelet transfusion-free interval | 16% vs 31% (P = 0.001) | ORR 20% vs 35% | 25 |
| NCT02610777 | 2 | azacitidine + pevonedistat (20 mg/m2 IV days 1,3,5) | azacitidine | HR-MDS/CMML/ oligoblastic AML | IPSS-R int to very high | OS | 21.8 vs 19.0 months (P = 0.334) | EFS 20.2 vs 14.8 months (p = 0.045) for HR-MDS | 34 |
| NCT03745716 | 3 | azacitidine + eprenetapopt (4.5 g IV days 1-4) | azacitidine | TP53 mutant HR-MDS | IPSS-R int to very high | CR | 34.6% vs 22.4%; P = 0.13 | NA | NA |
| PANTHER | 3 | azacitidine + pevonedistat (20 mg/m2 IV days 1,3,5) | azacitidine | HR-MDS/CMML/ oligoblastic AML | IPSS-R int to very high | EFS | 17.7 months vs 15.7 months (P = 0.447) | OS 21.6 vs17.5 (0.293) in HR-MDS | 26 |
| STIMULUS-MDS1 | 2 | azacitidine/decitabine + sabatolimab (400 mg day 8 and 22) | azacitidine/ decitabine | Int to very high MDS | IPSS-R int to very high | CR and PFS | PFS 11.1 vs 8.5 months (P = 0.102); CR 21.5% vs 17.7% (P = 0.769) | Lower risk and <10% blasts with improved PFS | 30 |
| STIMULUS-MDS2 | 3 | azacitidine + sabatolimab (800 mg day 8) | azacitidine | Int to very high MDS/CMML-2 | IPSS-R int to very high | OS | |||
| ENHANCE | 3 | azacitidine + magrolimab (priming/loading over C1-2; C3 + 30 mg/kg days 1 and 15) | azacitidine | Int to very high MDS | IPSS-R int to very high | CR and OS | |||
| VERONA | 3 | azacitidine + venetoclax (400 mg days 1-14) | azacitidine | Int to very high MDS; excludes t-MDS | IPSS-R int to very high | OS |
| Trial name . | Phase . | Investigational arm . | Control arm* . | Patient population . | Eligibility . | Primary endpoint . | Results of primary endpoint . | Secondary endpoint . | Reference # . |
|---|---|---|---|---|---|---|---|---|---|
| SWOG S1117 | 2 | azacitidine + lenalidomide (10 mg/day days 1-21) | azacitidine | HR-MDS/CMML | Blasts ≥5%; IPSS ≥1.5 | ↑ ORR 20% (CR/PR/HI) | 49% vs 38% (P = 0.16) | No improvement in OS | 27 |
| SWOG S1117 | 2 | azacitidine + vorinostat (300 mg twice daily on days 3-9) | azacitidine | HR-MDS/CMML | Blasts ≥5%; IPSS ≥1.5 | ↑ ORR 20% (CR/PR/HI) | 27% vs 38%; (P = 0.16) | 11.6 versus 16.7 months (p = 0.74) | 27 |
| E1905 Study | 2 | azacitidine + entinostat (4 mg/m2/day on days 3 and 10) | azacitidine | Therapy-related MDS/AML | Any IPSS | CR, PR, or trilineage HI | 17% vs 46% | OS versus 13 months | 28 |
| FUSION-AML-001 (MDS Cohort) | 2 | azacitidine + durvalumab (1500 mg IV q 4 weeks) | azacitidine | Int to very high MDS | IPSS-R int to very high | ORR (CR, mCR, HI) | 61.9% vs 47.6% (P = 0.18) | No Increase PDL1 on BM Blasts | 29 |
| SUPPORT | 3 | azacitidine + eltrombopag (200 mg/day, up to 300 mg/day) | azacitidine | Int to HR-MDS | int-1, int-2, high IPSS | Platelet transfusion-free interval | 16% vs 31% (P = 0.001) | ORR 20% vs 35% | 25 |
| NCT02610777 | 2 | azacitidine + pevonedistat (20 mg/m2 IV days 1,3,5) | azacitidine | HR-MDS/CMML/ oligoblastic AML | IPSS-R int to very high | OS | 21.8 vs 19.0 months (P = 0.334) | EFS 20.2 vs 14.8 months (p = 0.045) for HR-MDS | 34 |
| NCT03745716 | 3 | azacitidine + eprenetapopt (4.5 g IV days 1-4) | azacitidine | TP53 mutant HR-MDS | IPSS-R int to very high | CR | 34.6% vs 22.4%; P = 0.13 | NA | NA |
| PANTHER | 3 | azacitidine + pevonedistat (20 mg/m2 IV days 1,3,5) | azacitidine | HR-MDS/CMML/ oligoblastic AML | IPSS-R int to very high | EFS | 17.7 months vs 15.7 months (P = 0.447) | OS 21.6 vs17.5 (0.293) in HR-MDS | 26 |
| STIMULUS-MDS1 | 2 | azacitidine/decitabine + sabatolimab (400 mg day 8 and 22) | azacitidine/ decitabine | Int to very high MDS | IPSS-R int to very high | CR and PFS | PFS 11.1 vs 8.5 months (P = 0.102); CR 21.5% vs 17.7% (P = 0.769) | Lower risk and <10% blasts with improved PFS | 30 |
| STIMULUS-MDS2 | 3 | azacitidine + sabatolimab (800 mg day 8) | azacitidine | Int to very high MDS/CMML-2 | IPSS-R int to very high | OS | |||
| ENHANCE | 3 | azacitidine + magrolimab (priming/loading over C1-2; C3 + 30 mg/kg days 1 and 15) | azacitidine | Int to very high MDS | IPSS-R int to very high | CR and OS | |||
| VERONA | 3 | azacitidine + venetoclax (400 mg days 1-14) | azacitidine | Int to very high MDS; excludes t-MDS | IPSS-R int to very high | OS |
*Azacitidine 75 mg/m2 in all studies with exception of E19905 study, which used 50 mg/m2 × 10 days).
BM, bone marrow; CMML , chronic myelomonocytic leukemia; HI, hematologic improvement; Int , intermediate; IPSS-R, revised International Prognostic Scoring System; mCR, marrow CR; PR , partial remission.