Background
Methods
Patients
Efficacy endpoints
Safety
Statistical methods
Results
Baseline demographic and disease characteristics
All patients with AML-MRC (N = 262) | LDAC-preselected patients with AML-MRC (n = 160) | |||
---|---|---|---|---|
Azacitidine (n = 129) | CCR (n = 133) | Azacitidine (n = 81) | LDAC (n = 79) | |
Age (years), median (min, max) | 76 (64, 90) | 75 (65, 87) | 76 (64, 90) | 75 (65, 87) |
Age ≥ 75 years, n (%) | 77 (60) | 69 (52) | 55 (68) | 41 (52) |
Male gender, n % | 81 (63) | 78 (59) | 42 (52) | 43 (54) |
Prior history of MDS*, n (%) | 44 (34) | 35 (26) | 32 (40) | 20 (25) |
ECOG PS, n (%) | ||||
0–1 | 94 (73) | 104 (78) | 56 (69) | 64 (81) |
2 | 35 (27) | 29 (22) | 25 (31) | 15 (19) |
Cytogenetic risk, n (%) | ||||
Intermediate | 63 (49) | 61 (46) | 47 (58) | 33 (42) |
Poor | 66 (51) | 72 (54) | 34 (42) | 46 (58) |
No. of dysplastic lineages, n (%) | ||||
0–1 | 57 (44) | 52 (39) | 36 (44) | 35 (44) |
2–3 | 72 (56) | 81 (61) | 45 (56) | 44 (56) |
% BM blasts, median (min, max) | 65.0 (27, 99) | 70.0 (26, 100) | 66.0 (27, 99) | 69.0 (31, 100) |
Haematology, median (min, max) | ||||
ANC (109/L) | 0.4 (0.0, 11.6) | 0.3 (0.0, 8.7) | 0.4 (0.0, 11.6) | 0.3 (0.0, 8.7) |
Platelets (109/L) | 56 (3, 585) | 55 (6, 244) | 58 (7, 585) | 55 (6, 244) |
WBC (109/L) | 3.2 (0.6, 26.5) | 2.4 (0.4, 22.6) | 2.6 (0.6, 26.5) | 2.3 (0.4, 13.5) |
Hgb (g/dL) | 9.5 (5.0, 13.4) | 9.3 (5.0, 14.4) | 9.4 (5.0, 11.8) | 9.4 (5.6, 14.4) |
Survival: All AML-MRC patients
All patients with AML-MRC (N = 262) | |||||||||
---|---|---|---|---|---|---|---|---|---|
N
| Median OS, months (95%CI) | Difference, months | Hazard ratio (95% CI) | K-M Estimated 1-Year survival | Difference | ||||
AZA | CCR | AZA | CCR | AZA | CCR | ||||
Overall | 129 | 133 | 8.9 (6.9, 12.9) | 4.9 (3.8, 6.5) | 4.0 |
0.74 (0.57, 0.97)
| 44.3% | 26.9% | 17.4% |
Cytogenetic risk | |||||||||
Intermediate | 63 | 61 | 16.4 (12.9, 19.7) | 8.9 (5.4, 13.7) | 7.5 | 0.73 (0.48, 1.10) | 65.1% | 42.4% | 22.7% |
Poor | 66 | 72 | 5.0 (3.6, 7.2) | 3.2 (2.2, 4.7) | 1.8 | 0.79 (0.55, 1.11) | 23.9% | 13.7% | 10.2% |
Age | |||||||||
65–74 years | 52 | 64 | 14.2 (10.8, 18.7) | 7.3 (4.8, 11.3) | 6.9 |
0.64 (0.42, 0.97)
| 59.6% | 32.5% | 27.2% |
≥75 years | 77 | 69 | 5.9 (4.5, 9.2) | 3.8 (2.6, 5.1) | 2.1 | 0.77 (0.54, 1.09) | 33.8% | 21.4% | 12.3% |
LDAC-preselected patients with AML-MRC (n = 160) | |||||||||
N
| Median OS, months (95%CI) | Difference, months | Hazard ratio (95% CI) | K-M Estimated 1-Year survival | Difference | ||||
AZA | LDAC | AZA | LDAC | AZA | LDAC | ||||
Overall | 81 | 79 | 9.5 (5.9, 14.1) | 4.6 (3.3, 6.4) | 4.9 | 0.77 (0.55, 1.09) | 45.3% | 23.5% | 21.8% |
Cytogenetic risk | |||||||||
Intermediate | 47 | 33 | 14.1 (8.9, 17.6) | 6.4 (3.8, 14.2) | 7.7 | 0.90 (0.54, 1.50) | 57.4% | 34.4% | 23.0% |
Poor | 34 | 46 | 5.6 (2.2, 9.5) | 3.7 (2.2, 5.1) | 1.9 | 0.83 (0.52, 1.33) | 28.1% | 15.8% | 12.3% |
Age | |||||||||
65–74 years | 26 | 38 | 14.9 (9.0, 19.6) | 5.2 (3.5, 10.0) | 9.7 | 0.68 (0.39, 1.18) | 61.5% | 26.3% | 35.2% |
≥75 years | 55 | 41 | 8.8 (4.5, 12.9) | 4.0 (2.8, 6.4) | 4.8 | 0.78 (0.50, 1.22) | 37.5% | 20.8% | 16.7% |
Survival: LDAC preselection subgroup
Response
All patients with AML-MRC (N = 262)
| ||||
---|---|---|---|---|
AZA (n = 129) | CCR (n = 133) | |||
n (%) | ||||
Overall Response Rate (CR + CRi) | 32 (24.8) | 23 (17.3) | ||
CR | 25 (19.4) | 20 (15.0) | ||
CRi | 7 (5.4) | 3 (2.3) | ||
Partial remission | 1 (0.8) | 2 (1.5) | ||
Stable disease | 46 (35.7) | 38 (28.6) | ||
Progressive disease | 11 (8.5) | 16 (12.0) | ||
AML-MRC patients with Intermediate-risk cytogenetics | AML-MRC patients with Poor-risk cytogenetics | |||
AZA (n = 63) | CCR (n = 61) | AZA (n = 66) | CCR (n = 72) | |
n (%) | ||||
Overall Response Rate (CR + CRi) | 21 (33.3) | 15 (24.6) | 11 (16.7) | 8 (11.1) |
CR | 18 (28.6) | 13 (21.3) | 7 (10.6) | 7 (9.7) |
CRi | 3 (4.8) | 2 (3.3) | 4 (6.1) | 1 (1.4) |
Partial remission | 1 (1.6) | 1 (1.6) | 0 | 1 (1.4) |
Stable disease | 25 (39.7) | 18 (29.5) | 21 (31.8) | 20 (27.8) |
Progressive disease | 6 (9.5) | 5 (8.2) | 5 (7.6) | 11 (15.3) |
AML-MRC patients ages 65–74 years | AML-MRC patients ages ≥ 75 years | |||
AZA (n = 52) | CCR (n = 64) | AZA (n = 77) | CCR (n = 69) | |
n (%) | ||||
Overall Response Rate (CR + CRi) | 15 (28.8) | 16 (25.0) | 17 (22.1) | 7 (10.1) |
CR | 11 (21.2) | 14 (21.9) | 14 (18.2) | 6 (8.7) |
CRi | 4 (7.7) | 2 (3.1) | 3 (3.9) | 1 (1.4) |
Partial remission | 0 | 2 (3.1) | 1 (1.3) | 0 |
Stable disease | 20 (38.5) | 24 (37.5) | 26 (33.8) | 14 (20.3) |
Progressive disease | 5 (9.6) | 6 (9.4) | 6 (7.8) | 10 (14.5) |
Patients with AML-MRC preselected to receive LDAC (n = 160) | ||||
---|---|---|---|---|
AZA (n = 81) | LDAC (n = 79) | |||
n (%) | ||||
Overall Response Rate (CR + CRi) | 22 (27.2) | 11 (13.9) | ||
CR | 17 (21.0) | 10 (12.7) | ||
CRi | 5 (6.2) | 1 (1.3) | ||
Partial remission | 1 (1.2) | 1 (1.3) | ||
Stable disease | 30 (37.0) | 30 (38.0) | ||
Progressive disease | 4 (4.9) | 11 (13.9) | ||
LDAC-preselected Intermediate-risk cytogenetics | LDAC-preselected Poor-risk cytogenetics | |||
AZA (n = 47) | LDAC (n = 33) | AZA (n = 34) | LDAC (n = 46) | |
n (%) | ||||
Overall Response Rate (CR + CRi) | 15 (31.9) | 6 (18.2) | 7 (20.6) | 5 (10.9) |
CR | 12 (25.5) | 6 (18.2) | 5 (14.7) | 4 (8.7) |
CRi | 3 (6.4) | 0 | 2 (5.9) | 1 (2.2) |
Partial remission | 1 (2.1) | 1 (3) | 0 | 0 |
Stable disease | 19 (40.4) | 15 (45.5) | 11 (32.4) | 15 (32.6) |
Progressive disease | 4 (8.5) | 2 (6.1) | 0 | 9 (19.6) |
LDAC-preselected age 65–74 years | LDAC-preselected age ≥ 75 years | |||
AZA (n = 26) | LDAC (n = 38) | AZA (n = 55) | LDAC (n = 41) | |
n (%) | ||||
Overall Response Rate (CR + CRi) | 10 (38.5) | 7 (18.4) | 12 (21.8) | 4 (9.8) |
CR | 7 (26.9) | 6 (15.8) | 10 (18.2) | 4 (9.8) |
CRi | 3 (11.5) | 1 (2.6) | 2 (3.6) | 0 |
Partial remission | 0 | 1 (2.6) | 1 (1.8) | 0 |
Stable disease | 9 (34.6) | 18 (47.4) | 21 (38.2) | 12 (29.3) |
Progressive disease | 2 (7.7) | 4 (10.5) | 2 (3.6) | 7 (17.1) |
Safety
Preferred term | Azacitidine (n = 128) n (%) | CCR (n = 130) n (%) |
---|---|---|
Any grade 3–4 TEAE | 111 (87) | 113 (87) |
Thrombocytopenia | 33 (26) | 27 (21) |
Febrile neutropenia | 29 (23) | 43 (33) |
Neutropenia | 28 (22) | 25 (19) |
AML* | 25 (20) | 23 (18) |
Pneumonia | 24 (19) | 18 (14) |
Anaemia | 19 (15) | 21 (16) |
Pyrexia | 13 (10) | 9 (7) |
Hypokalaemia | 9 (7) | 10 (8) |
Leukopenia | 8 (6) | 10 (8) |
Sepsis | 7 (6) | 9 (7) |
Decreased appetite | 6 (5) | 2 (2) |
Dyspnoea | 6 (5) | 4 (3) |
Preferred term | Cycles 1–2 | Cycles 3–4 | Cycles 5–6 | Cycles 7+ | ||||
---|---|---|---|---|---|---|---|---|
AZA (N = 128) | CCR (N = 130) | AZA (n = 89) | CCR (n = 61) | AZA (n = 75) | CCR (n = 25) | AZA (n = 57) | CCR (n = 17) | |
Any Grade 3–4 TEAE, n (%) | 83 (65) | 99 (76) | 47 (53) | 35 (57) | 33 (44) | 8 (32) | 37 (65) | 13 (77) |
Febrile Neutropenia, n (%) | 23 (18) | 34 (26) | 7 (8) | 7 (12) | 4 (5) | 3 (12) | 3 (5) | 2 (12) |
Thrombocytopenia, n (%) | 24 (19) | 26 (20) | 11 (12) | 8 (13) | 8 (11) | 0 | 9 (16) | 0 |
Neutropenia, n (%) | 16 (13) | 20 (15) | 10 (11) | 9 (15) | 3 (4) | 2 (8) | 12 (21) | 5 (29) |
Anaemia, n (%) | 17 (13) | 21 (16) | 3 (3) | 3 (5) | 1 (1) | 0 | 5 (9) | 0 |