Baseline demographics and disease characteristics (full analysis population)
| Parameter . | Monotherapy OLU∗ (n = 6) . | Combination OLU + AZA (n = 16) . | Pooled (N = 22) . |
|---|---|---|---|
| Age, median (range), y | 77 (66-87) | 72 (59-82) | 74 (59-87) |
| <65 y, n (%) | 0 | 3 (19) | 3 (14) |
| 65 to <75 y, n (%) | 2 (33) | 7 (44) | 9 (41) |
| ≥75 y, n (%) | 4 (67) | 6 (38) | 10 (45) |
| Sex, n (%) | |||
| Male | 4 (67) | 9 (56) | 13 (59) |
| Female | 2 (33) | 7 (44) | 9 (41) |
| Race, n (%) | |||
| White | 6 (100) | 13 (81) | 19 (86) |
| Not specified/other | 0 | 3 (19) | 3 (14) |
| Region | |||
| North America | 6 (100) | 11 (69) | 17 (77) |
| EU | 0 | 2 (13) | 2 (9) |
| Asia Pacific | 0 | 3 (19) | 3 (14) |
| MDS disease, n (%) | |||
| R/R | 4 (67) | 11 (69) | 15 (68) |
| TN | 2 (33) | 5 (31) | 7 (32) |
| MDS risk category per IPSS-R, n (%) | |||
| Intermediate, >3 to 4.5 | 0 | 3 (19) | 3 (14) |
| High, >4.5 to 6 | 5 (83) | 10 (63) | 15 (68) |
| Very high, >6 | 1 (17) | 3 (19) | 4 (18) |
| ECOG performance status, n (%) | |||
| 0 | 0 | 4 (25) | 4 (18) |
| 1 | 4 (67) | 11 (69) | 15 (68) |
| 2 | 2 (33) | 1 (6) | 3 (14) |
| Bone marrow blast percentage, median (range) | 6.5 (0-16) | 7.5 (0-16) | 7.5 (0-16) |
| Renal function, n (%) | |||
| Normal, ≥90 mL/min | 2 (33) | 3 (19) | 5 (23) |
| Mildly impaired, 60-89 mL/min | 2 (33) | 9 (56) | 11 (50) |
| Moderately impaired, 30-59 mL/min | 2 (33) | 4 (25) | 6 (27) |
| Prior number of regimens, n (%) | |||
| 0 | 2 (33) | 5 (31) | 7 (32) |
| 1 | 3 (50) | 5 (31) | 8 (36) |
| 2 | 0 | 5 (31) | 5 (23) |
| ≥3 | 1 (17) | 1 (6) | 2 (9) |
| Prior HMA, n (%) | 4 (67) | 10 (63) | 14 (64) |
| Prior HSCT, n (%) | 0 | 1 (6) | 1 (5) |
| IDH1 mutation type | |||
| R132C | 3 (50) | 4 (25) | 7 (32) |
| R132H | 2 (33) | 10 (63) | 12 (55) |
| R132G | 1 (17) | 1 (6) | 2 (9) |
| Unknown | 0 | 1 (6) | 1 (5) |
| Cytogenetic risk classification, n (%) | |||
| Good | 1 (17) | 9 (56) | 10 (45) |
| Intermediate | 1 (17) | 3 (19) | 4 (18) |
| Poor | 0 | 2 (13) | 2 (9) |
| Very poor | 2 (33) | 0 | 2 (9) |
| Unknown | 2 (33) | 2 (13) | 4 (18) |
| Cytogenetic result, n (%) | |||
| Normal | 1 (17) | 8 (50) | 9 (41) |
| Abnormal | 3 (50) | 6 (38) | 9 (41) |
| Complex (≥3 abnormalities) | 2 (33) | 1 (6) | 3 (14) |
| Unknown | 2 (33) | 2 (13) | 4 (18) |
| No. of comutations, n (%) | |||
| None | 1 (17) | 0 | 1 (5) |
| 1-3 | 4 (67) | 10 (63) | 14 (64) |
| 4-7 | 1 (17) | 3 (19) | 4 (18) |
| Not done | 0 | 3 (19) | 3 (14) |
| Parameter . | Monotherapy OLU∗ (n = 6) . | Combination OLU + AZA (n = 16) . | Pooled (N = 22) . |
|---|---|---|---|
| Age, median (range), y | 77 (66-87) | 72 (59-82) | 74 (59-87) |
| <65 y, n (%) | 0 | 3 (19) | 3 (14) |
| 65 to <75 y, n (%) | 2 (33) | 7 (44) | 9 (41) |
| ≥75 y, n (%) | 4 (67) | 6 (38) | 10 (45) |
| Sex, n (%) | |||
| Male | 4 (67) | 9 (56) | 13 (59) |
| Female | 2 (33) | 7 (44) | 9 (41) |
| Race, n (%) | |||
| White | 6 (100) | 13 (81) | 19 (86) |
| Not specified/other | 0 | 3 (19) | 3 (14) |
| Region | |||
| North America | 6 (100) | 11 (69) | 17 (77) |
| EU | 0 | 2 (13) | 2 (9) |
| Asia Pacific | 0 | 3 (19) | 3 (14) |
| MDS disease, n (%) | |||
| R/R | 4 (67) | 11 (69) | 15 (68) |
| TN | 2 (33) | 5 (31) | 7 (32) |
| MDS risk category per IPSS-R, n (%) | |||
| Intermediate, >3 to 4.5 | 0 | 3 (19) | 3 (14) |
| High, >4.5 to 6 | 5 (83) | 10 (63) | 15 (68) |
| Very high, >6 | 1 (17) | 3 (19) | 4 (18) |
| ECOG performance status, n (%) | |||
| 0 | 0 | 4 (25) | 4 (18) |
| 1 | 4 (67) | 11 (69) | 15 (68) |
| 2 | 2 (33) | 1 (6) | 3 (14) |
| Bone marrow blast percentage, median (range) | 6.5 (0-16) | 7.5 (0-16) | 7.5 (0-16) |
| Renal function, n (%) | |||
| Normal, ≥90 mL/min | 2 (33) | 3 (19) | 5 (23) |
| Mildly impaired, 60-89 mL/min | 2 (33) | 9 (56) | 11 (50) |
| Moderately impaired, 30-59 mL/min | 2 (33) | 4 (25) | 6 (27) |
| Prior number of regimens, n (%) | |||
| 0 | 2 (33) | 5 (31) | 7 (32) |
| 1 | 3 (50) | 5 (31) | 8 (36) |
| 2 | 0 | 5 (31) | 5 (23) |
| ≥3 | 1 (17) | 1 (6) | 2 (9) |
| Prior HMA, n (%) | 4 (67) | 10 (63) | 14 (64) |
| Prior HSCT, n (%) | 0 | 1 (6) | 1 (5) |
| IDH1 mutation type | |||
| R132C | 3 (50) | 4 (25) | 7 (32) |
| R132H | 2 (33) | 10 (63) | 12 (55) |
| R132G | 1 (17) | 1 (6) | 2 (9) |
| Unknown | 0 | 1 (6) | 1 (5) |
| Cytogenetic risk classification, n (%) | |||
| Good | 1 (17) | 9 (56) | 10 (45) |
| Intermediate | 1 (17) | 3 (19) | 4 (18) |
| Poor | 0 | 2 (13) | 2 (9) |
| Very poor | 2 (33) | 0 | 2 (9) |
| Unknown | 2 (33) | 2 (13) | 4 (18) |
| Cytogenetic result, n (%) | |||
| Normal | 1 (17) | 8 (50) | 9 (41) |
| Abnormal | 3 (50) | 6 (38) | 9 (41) |
| Complex (≥3 abnormalities) | 2 (33) | 1 (6) | 3 (14) |
| Unknown | 2 (33) | 2 (13) | 4 (18) |
| No. of comutations, n (%) | |||
| None | 1 (17) | 0 | 1 (5) |
| 1-3 | 4 (67) | 10 (63) | 14 (64) |
| 4-7 | 1 (17) | 3 (19) | 4 (18) |
| Not done | 0 | 3 (19) | 3 (14) |
ECOG, Eastern Cooperative Oncology Group; OLU, olutasidenib.
During phase 1 dose escalation with OLU monotherapy, 3 patients received a suboptimal dose that was ≤50% of the approved dose of OLU. One patient received 100 mg daily, and 2 patients received 150 mg daily.