Demographic and disease characteristics in the MRD-evaluable cohort, stratified by MRD status at baseline and by randomized treatment arm
| . | Baseline MRD+ . | Baseline MRD− . | ||||
|---|---|---|---|---|---|---|
| Characteristic . | Oral azacitidine (n = 103) . | Placebo (n = 116) . | Total (n = 219) . | Oral azacitidine (n = 133) . | Placebo (n = 111) . | Total (n = 244) . |
| Age, years, median (range) | 68 (55-84) | 69 (56-82) | 69 (55-84) | 68 (56-86) | 68 (55-79) | 68 (55-86) |
| Sex, n (%) | ||||||
| Male | 50 (49) | 60 (52) | 110 (50) | 67 (50) | 64 (58) | 131 (54) |
| Female | 53 (51) | 56 (48) | 109 (50) | 66 (50) | 47 (42) | 113 (46) |
| WHO AML classification, n (%) | ||||||
| Recurrent genetic abnormalities | 17 (17) | 19 (16) | 36 (16) | 22 (17) | 24 (22) | 46 (19) |
| Myelodysplasia-related changes | 19 (18) | 26 (22) | 45 (21) | 29 (22) | 14 (13) | 43 (18) |
| Therapy-related | 2 (2) | 0 | 2 (0.9) | 0 | 0 | 0 |
| Not otherwise specified | 65 (63) | 71 (61) | 136 (62) | 82 (62) | 72 (65) | 154 (63) |
| Missing | 0 | 0 | 0 | 0 | 1 (0.9) | 1 (0.4) |
| Type of AML, n (%) | ||||||
| De novo | 90 (87) | 106 (91) | 196 (89) | 122 (92) | 103 (93) | 225 (92) |
| Secondary | 13 (13) | 10 (9) | 23 (11) | 11 (8) | 8 (7) | 19 (8) |
| Prior history of MDS/CMML, n (%) | 10 (10) | 9 (8) | 19 (9) | 11 (8) | 8 (7) | 19 (8) |
| Cytogenetic risk at diagnosis, n (%) | ||||||
| Intermediate | 87 (84) | 97 (84) | 184 (84) | 114 (86) | 100 (90) | 214 (88) |
| Poor | 16 (16) | 19 (16) | 35 (16) | 19 (14) | 11 (10) | 30 (12) |
| Response following induction, n (%) | ||||||
| CR | 89 (86) | 93 (80) | 182 (83) | 96 (72) | 97 (87) | 193 (79) |
| CRi | 14 (14) | 23 (20) | 37 (17) | 37 (28) | 14 (13) | 51 (21) |
| Received consolidation therapy, n (%) | ||||||
| Yes | 82 (80) | 90 (78) | 172 (79) | 103 (77) | 96 (86) | 199 (82) |
| 1 cycle | 51 (50) | 52 (45) | 103 (47) | 58 (44) | 49 (44) | 107 (44) |
| 2 cycles | 28 (27) | 32 (28) | 60 (27) | 42 (32) | 40 (36) | 82 (34) |
| 3 cycles | 3 (3) | 6 (5) | 9 (4) | 3 (2.3) | 7 (6) | 10 (4) |
| No | 21 (20) | 26 (22) | 47 (22) | 30 (23) | 15 (14) | 45 (18) |
| Total number of chemotherapy cycles received (induction + consolidation), median (range) | 2 (1-7) | 2 (1-6) | 2 (1-7) | 2 (1-6) | 2 (1-5) | 2 (1-6) |
| Response at randomization, n (%) | ||||||
| CR | 85 (83) | 87 (75) | 172 (79) | 97 (73) | 85 (77) | 182 (75) |
| CRi | 16 (16) | 23 (20) | 39 (18) | 33 (25) | 20 (18) | 53 (22) |
| No longer in CR/CRi | 2 (2) | 5 (4) | 7 (3) | 3 (2) | 6 (5) | 9 (4) |
| Missing | 0 | 1 (0.9) | 1 (0.5) | 0 | 0 | 0 |
| Time from diagnosis to randomization, months, median (range) | 4.2 (1.7-9.2) | 4.1 (1.5-7.6) | 4.1 (1.5-9.2) | 4.2 (1.5-9.1) | 4.3 (1.4-10.9) | 4.3 (1.4-10.9) |
| Time from induction to randomization, months, median (range) | 4.0 (1.5-7.8) | 3.9 (1.5-15.1) | 4.0 (1.5-15.1) | 3.9 (1.4-8.8) | 4.0 (1.3-10.2) | 4.0 (1.3-10.2) |
| Time from achievement of CR/CRi to randomization, days, median (range)* | 81 (7-130) | 80 (7-134) | 81 (7-134) | 85 (8-154) | 87 (11-263) | 86 (8-263) |
| ECOG performance status score, n (%) | ||||||
| 0 | 56 (54) | 57 (49) | 113 (52) | 59 (44) | 52 (47) | 111 (46) |
| 1 | 40 (39) | 49 (42) | 89 (41) | 61 (46) | 52 (47) | 113 (46) |
| 2-3 | 7 (7) | 10 (9) | 17 (8) | 13 (10) | 7 (6) | 20 (8) |
| Reason ineligible for HSCT, n (%)† | ||||||
| Age | 68 (66) | 78 (67) | 146 (67) | 85 (64) | 69 (62) | 154 (63) |
| Comorbidities | 28 (27) | 24 (21) | 52 (24) | 24 (18) | 23 (21) | 47 (19) |
| Performance status | 6 (6) | 4 (3) | 10 (5) | 7 (5) | 4 (4) | 11 (5) |
| No available donor | 12 (12) | 19 (16) | 31 (14) | 25 (19) | 16 (14) | 41 (17) |
| Patient decision | 4 (4) | 13 (11) | 17 (8) | 15 (11) | 19 (17) | 34 (14) |
| Unfavorable cytogenetics | 2 (2) | 2 (2) | 4 (2) | 4 (3) | 8 (7) | 12 (5) |
| Other | 13 (13) | 8 (7) | 21 (10) | 14 (11) | 11 (10) | 25 (10) |
| Bone marrow blasts, %, median (range)‡ | 2.5 (0.0-5.0) | 2.0 (0.0-6.5) | 2.5 (0.0-6.5) | 1.5 (0.0-4.5) | 2.0 (0.0-4.5) | 2.0 (0.0-4.5) |
| Hemoglobin, g/L, median (range) | 113 (86-159) | 109 (77-149) | 111 (77-159) | 115 (75-149) | 109 (81-140) | 111 (75-149) |
| Platelets, 109/L, median (range)‡ | 163 (29-735) | 184 (23-636) | 174 (23-735) | 145 (22-801) | 173 (21-626) | 160 (21-801) |
| Platelet count <50 ×109/L, n (%) | 4 (4) | 9 (8) | 13 (6) | 8 (6) | 7 (6) | 15 (6) |
| ANC, 109/L, median (range)‡ | 3.4 (0.6-15.6) | 2.6 (0.5-9.6) | 3.1 (0.5-15.6) | 2.6 (0.3-15.9) | 3.0 (0.6-9.1) | 2.8 (0.3-15.9) |
| ANC <1.0 ×109/L, n (%) | 4 (4) | 8 (7) | 12 (6) | 3 (2) | 10 (9) | 13 (5) |
| WBC, 109/L, median (range) | 5.3 (1.5-18.0) | 4.5 (1.7-12.6) | 4.9 (1.5-18.0) | 4.6 (0.8-18.7) | 4.5 (1.3-12.2) | 4.5 (0.8-18.7) |
| . | Baseline MRD+ . | Baseline MRD− . | ||||
|---|---|---|---|---|---|---|
| Characteristic . | Oral azacitidine (n = 103) . | Placebo (n = 116) . | Total (n = 219) . | Oral azacitidine (n = 133) . | Placebo (n = 111) . | Total (n = 244) . |
| Age, years, median (range) | 68 (55-84) | 69 (56-82) | 69 (55-84) | 68 (56-86) | 68 (55-79) | 68 (55-86) |
| Sex, n (%) | ||||||
| Male | 50 (49) | 60 (52) | 110 (50) | 67 (50) | 64 (58) | 131 (54) |
| Female | 53 (51) | 56 (48) | 109 (50) | 66 (50) | 47 (42) | 113 (46) |
| WHO AML classification, n (%) | ||||||
| Recurrent genetic abnormalities | 17 (17) | 19 (16) | 36 (16) | 22 (17) | 24 (22) | 46 (19) |
| Myelodysplasia-related changes | 19 (18) | 26 (22) | 45 (21) | 29 (22) | 14 (13) | 43 (18) |
| Therapy-related | 2 (2) | 0 | 2 (0.9) | 0 | 0 | 0 |
| Not otherwise specified | 65 (63) | 71 (61) | 136 (62) | 82 (62) | 72 (65) | 154 (63) |
| Missing | 0 | 0 | 0 | 0 | 1 (0.9) | 1 (0.4) |
| Type of AML, n (%) | ||||||
| De novo | 90 (87) | 106 (91) | 196 (89) | 122 (92) | 103 (93) | 225 (92) |
| Secondary | 13 (13) | 10 (9) | 23 (11) | 11 (8) | 8 (7) | 19 (8) |
| Prior history of MDS/CMML, n (%) | 10 (10) | 9 (8) | 19 (9) | 11 (8) | 8 (7) | 19 (8) |
| Cytogenetic risk at diagnosis, n (%) | ||||||
| Intermediate | 87 (84) | 97 (84) | 184 (84) | 114 (86) | 100 (90) | 214 (88) |
| Poor | 16 (16) | 19 (16) | 35 (16) | 19 (14) | 11 (10) | 30 (12) |
| Response following induction, n (%) | ||||||
| CR | 89 (86) | 93 (80) | 182 (83) | 96 (72) | 97 (87) | 193 (79) |
| CRi | 14 (14) | 23 (20) | 37 (17) | 37 (28) | 14 (13) | 51 (21) |
| Received consolidation therapy, n (%) | ||||||
| Yes | 82 (80) | 90 (78) | 172 (79) | 103 (77) | 96 (86) | 199 (82) |
| 1 cycle | 51 (50) | 52 (45) | 103 (47) | 58 (44) | 49 (44) | 107 (44) |
| 2 cycles | 28 (27) | 32 (28) | 60 (27) | 42 (32) | 40 (36) | 82 (34) |
| 3 cycles | 3 (3) | 6 (5) | 9 (4) | 3 (2.3) | 7 (6) | 10 (4) |
| No | 21 (20) | 26 (22) | 47 (22) | 30 (23) | 15 (14) | 45 (18) |
| Total number of chemotherapy cycles received (induction + consolidation), median (range) | 2 (1-7) | 2 (1-6) | 2 (1-7) | 2 (1-6) | 2 (1-5) | 2 (1-6) |
| Response at randomization, n (%) | ||||||
| CR | 85 (83) | 87 (75) | 172 (79) | 97 (73) | 85 (77) | 182 (75) |
| CRi | 16 (16) | 23 (20) | 39 (18) | 33 (25) | 20 (18) | 53 (22) |
| No longer in CR/CRi | 2 (2) | 5 (4) | 7 (3) | 3 (2) | 6 (5) | 9 (4) |
| Missing | 0 | 1 (0.9) | 1 (0.5) | 0 | 0 | 0 |
| Time from diagnosis to randomization, months, median (range) | 4.2 (1.7-9.2) | 4.1 (1.5-7.6) | 4.1 (1.5-9.2) | 4.2 (1.5-9.1) | 4.3 (1.4-10.9) | 4.3 (1.4-10.9) |
| Time from induction to randomization, months, median (range) | 4.0 (1.5-7.8) | 3.9 (1.5-15.1) | 4.0 (1.5-15.1) | 3.9 (1.4-8.8) | 4.0 (1.3-10.2) | 4.0 (1.3-10.2) |
| Time from achievement of CR/CRi to randomization, days, median (range)* | 81 (7-130) | 80 (7-134) | 81 (7-134) | 85 (8-154) | 87 (11-263) | 86 (8-263) |
| ECOG performance status score, n (%) | ||||||
| 0 | 56 (54) | 57 (49) | 113 (52) | 59 (44) | 52 (47) | 111 (46) |
| 1 | 40 (39) | 49 (42) | 89 (41) | 61 (46) | 52 (47) | 113 (46) |
| 2-3 | 7 (7) | 10 (9) | 17 (8) | 13 (10) | 7 (6) | 20 (8) |
| Reason ineligible for HSCT, n (%)† | ||||||
| Age | 68 (66) | 78 (67) | 146 (67) | 85 (64) | 69 (62) | 154 (63) |
| Comorbidities | 28 (27) | 24 (21) | 52 (24) | 24 (18) | 23 (21) | 47 (19) |
| Performance status | 6 (6) | 4 (3) | 10 (5) | 7 (5) | 4 (4) | 11 (5) |
| No available donor | 12 (12) | 19 (16) | 31 (14) | 25 (19) | 16 (14) | 41 (17) |
| Patient decision | 4 (4) | 13 (11) | 17 (8) | 15 (11) | 19 (17) | 34 (14) |
| Unfavorable cytogenetics | 2 (2) | 2 (2) | 4 (2) | 4 (3) | 8 (7) | 12 (5) |
| Other | 13 (13) | 8 (7) | 21 (10) | 14 (11) | 11 (10) | 25 (10) |
| Bone marrow blasts, %, median (range)‡ | 2.5 (0.0-5.0) | 2.0 (0.0-6.5) | 2.5 (0.0-6.5) | 1.5 (0.0-4.5) | 2.0 (0.0-4.5) | 2.0 (0.0-4.5) |
| Hemoglobin, g/L, median (range) | 113 (86-159) | 109 (77-149) | 111 (77-159) | 115 (75-149) | 109 (81-140) | 111 (75-149) |
| Platelets, 109/L, median (range)‡ | 163 (29-735) | 184 (23-636) | 174 (23-735) | 145 (22-801) | 173 (21-626) | 160 (21-801) |
| Platelet count <50 ×109/L, n (%) | 4 (4) | 9 (8) | 13 (6) | 8 (6) | 7 (6) | 15 (6) |
| ANC, 109/L, median (range)‡ | 3.4 (0.6-15.6) | 2.6 (0.5-9.6) | 3.1 (0.5-15.6) | 2.6 (0.3-15.9) | 3.0 (0.6-9.1) | 2.8 (0.3-15.9) |
| ANC <1.0 ×109/L, n (%) | 4 (4) | 8 (7) | 12 (6) | 3 (2) | 10 (9) | 13 (5) |
| WBC, 109/L, median (range) | 5.3 (1.5-18.0) | 4.5 (1.7-12.6) | 4.9 (1.5-18.0) | 4.6 (0.8-18.7) | 4.5 (1.3-12.2) | 4.5 (0.8-18.7) |
ANC, absolute neutrophil count; CMML, chronic myelomonocytic leukemia; ECOG, Eastern Cooperative Oncology Group; HSCT, hematopoietic stem cell transplant; MDS, myelodysplastic syndromes; WBC, white blood cell count; WHO, World Health Organization.
4 patients were enrolled beyond the 4-month (plus or minus 7 days) inclusion window (protocol violations).
Patients may have been accounted for in multiple categories.
Patients may have had multiple visits between screening and randomization. All patients met relevant eligibility criteria at their screening visit.