Background
Methods
Study design and participants
Procedures
Outcomes
Statistical analysis
Results
Patients and disposition
Characteristics | All patients (n = 96) | Refractory AML (n = 37) | Relapsed AML after chemotherapy (n = 16) | Relapsed AML after allo-HSCT (n = 43) | P |
---|---|---|---|---|---|
Age, median (IQR), y | 45 (33–55) | 48 (38–57) | 45.5 (33–64) | 41 (32–52) | |
Gender, No (%) | 0.47 | ||||
Male | 51 (53.1) | 21 (56.8) | 10 (62.5) | 20 (46.5) | |
Female | 45 (46.9) | 16 (43.2) | 6 (37.5) | 23 (53.5) | |
Prior hypomethylating agent†, No (%) | 0.06 | ||||
Yes | 36 (37.5) | 9 (24.3) | 9 (56.3) | 18 (41.9) | |
No | 60 (62.5) | 28 (75.7) | 7 (43.8) | 25 (58.1) | |
Cytogenetics‡, No (%) | 0.55 | ||||
Favorable | 6 (6.3) | 4 (10.8) | 0 (0) | 2 (4.7) | |
Intermediate | 53 (55.2) | 18 (48.7) | 10 (62.5) | 25 (58.1) | |
Poor | 27 (28.1) | 12 (32.4) | 3 (18.8) | 12 (27.9) | |
Unknown | 10 (10.4) | 3 (8.1) | 3 (18.8) | 4 (9.3) | |
ELN classification, No (%) | 0.68 | ||||
Favorable | 17 (17.7) | 7 (18.9) | 2 (12.5) | 8 (18.6) | |
Intermediate | 22 (22.9) | 10 (27.0) | 5 (31.3) | 7 (16.3) | |
Adverse | 57 (59.4) | 20 (54.1) | 9 (56.3) | 28 (65.1) | |
Number of VEN cycles, No (%) | 0.01 | ||||
One | 45 (46.9) | 25 (67.6) | 6 (37.5) | 14 (32.6) | |
Two | 42 (43.7) | 12 (32.4) | 8 (50.0) | 22 (51.2) | |
Three | 9 (9.4) | 0 (0) | 2 (12.5) | 7 (16.3) | |
Patients bridge to Allo-HSCT, No (%) | 40 (41.7) | 26 (70.3) | 7 (43.8) | 7 (16.3) | < 0.01 |
Molecular abnormalities, No (%) | |||||
NPM1 | 11 (11.5) | 3 (8.1) | 2 (12.5) | 6 (14.0) | 0.71 |
AML1-ETO | 6 (6.3) | 4 (10.8) | 0 (0) | 2 (4.7) | 0.28 |
CEBPA | 10 (10.4) | 3 (8.1) | 2 (12.5) | 5 (11.6) | 0.84 |
TET2 | 41 (42.7) | 13 (35.1) | 7 (43.8) | 21 (48.8) | 0.46 |
DNMT3A | 18 (18.8) | 9 (24.3) | 2 (12.5) | 7 (16.3) | 0.51 |
IDH1/2 | 14 (14.6) | 8 (21.6) | 3 (18.8) | 3 (7.0) | 0.16 |
FLT3 | 19 (19.8) | 7 (18.9) | 2 (12.5) | 10 (23.3) | 0.64 |
ASXL1 | 22 (22.9) | 7 (18.9) | 4 (25.0) | 11 (25.6) | 0.76 |
RUNX1 | 22 (22.9) | 6 (16.2) | 3 (18.8) | 13 (30.2) | 0.30 |
TP53 | 7 (7.3) | 4 (10.8) | 0 (0) | 3 (7.0) | 0.38 |
MLL | 7 (7.3) | 2 (5.4) | 3 (18.8) | 2 (4.7) | 0.15 |
EZH2 | 6 (6.3) | 1 (2.7) | 1 (6.3) | 4 (9.3) | 0.48 |
BCL6 | 7 (7.3) | 1 (2.7) | 1 (6.3) | 5 (11.6) | 0.31 |
BCOR | 7 (7.3) | 6 (16.2) | 0 (0) | 1 (2.3) | 0.03 |
GATA2 | 5 (5.2) | 1 (2.7) | 0 (0) | 4 (9.3) | 0.25 |
RAS | 9 (9.4) | 6 (16.2) | 1 (6.3) | 2 (4.7) | 0.19 |
CD101 | 8 (8.3) | 2 (5.4) | 1 (6.3) | 5 (11.6) | 0.57 |
Efficacy
All(n = 96) | Refractory AML (n = 37) | Relapsed AML after chemotherapy (n = 16) | Relapsed AML after allo-HSCT (n = 43) | P | |
---|---|---|---|---|---|
CRc (CR + CRi), No. (% [95% CI]) | 68 (70.8[60.8–79.2]) | 29 (78.4[61.9–89.0]) | 10 (62.5[36.6–82.8]) | 29 (67.4[51.9–79.9]) | 0.407 |
CR, No. (%) | 40 (41.7) | 19 (51.4) | 8 (50.0) | 13 (30.2) | |
CRi, No. (%) | 28 (29.2) | 10 (27.0) | 2 (12.5) | 16 (37.2) | |
MRD- CRc, No. (%)† | 40 (58.8) | 17 (58.6) | 5 (50.0) | 18 (62.1) | 0.799 |
PR, No. (%) | 7 (7.3) | 1 (2.7) | 1 (6.3) | 5 (11.6) | |
NR, No. (%) | 21 (21.9) | 7 (18.9) | 5 (31.3) | 9 (20.9) | |
ORR, No. (% [95% CI]) | 75 (78.1[68.6–85.4]) | 30 (81.1[64.8–90.9]) | 11 (68.8[42.1–86.9]) | 34 (79.1[64.0–88.9]) | 0.596 |
CRc at Cycle 1, No. (% [95% CI]) | 56 (58.3[48.1–67.9]) | 27 (73.0[56.2–85.0]) | 7 (43.8[21.7–68.6]) | 22 (51.2[36.2–65.9]) | 0.062 |
ORR at Cycle 1, No. (% [95% CI]) | 69 (71.9[61.9–80.1]) | 30 (81.1[64.8–90.9]) | 9 (56.3[31.4–78.3]) | 30 (69.8[54.2–81.8]) | 0.167 |
EFS | |||||
Median, months (95% CI) | 14.3 (7.0 to NE) | Not reached | 7.8 (2.0 to NE) | 6.0 (2.3 to NE) | 0.182 |
12-months, % (95% CI) | 51.0 (40.7–60.5) | 64.9 (47.3–77.9) | 43.8 (19.8–65.6) | 41.9 (27.1–55.9) | 0.099 |
Estimated 24-months, % (95% CI) | 46.0 (34.0–57.2) | 54.1 (32.8–71.2) | 43.8 (19.8–65.6) | 41.9 (27.1–55.9) | 0.182 |
OS | |||||
Median, months (95% CI) | 22.1 (12.7 to NE) | Not reached | 22.1 (3.0 to NE) | 15.4 (6.8 to NE) | 0.114 |
12-months, % (95% CI) | 61.5 (51.0–70.4) | 70.3 (52.8–82.3) | 56.3 (29.5–76.2) | 55.8 (39.9–69.1) | 0.345 |
Estimated 24-months, % (95% CI) | 47.2 (33.3–59.8) | 63.2 (41.9–78.6) | 37.5 (8.4–67.8) | 34.3 (14.6–56.4) | 0.114 |
Cytogenetic and molecular response
Survival
Adverse events
Grade 1–2 | Grade 3 | Grade 4 | Grade 5 | |
---|---|---|---|---|
Adverse event (n = 96) | ||||
Anemia | 16 (16.7) | 62 (64.6) | 2 (2.1) | 0 |
Neutropenia | 6 (6.3) | 60 (62.5) | 19 (19.8) | 0 |
Thrombocytopenia | 8 (8.3) | 14 (14.6) | 58 (60.4) | 0 |
Febrile neutropenia | 0 | 25 (26.0) | 10 (10.4) | 1 (1.0) |
Pneumonia | 1 (1.0) | 15 (15.6) | 6 (6.3) | 1 (1.0) |
Sepsis | 0 | 0 | 10 (10.4) | 1 (1.0) |
Nausea | 20 (22.9) | 3 (3.1) | 0 | 0 |
Constipation | 12 (12.5) | 0 | 0 | 0 |
Diarrhea | 11 (11.5) | 0 | 0 | 0 |
Vomiting | 10 (10.4) | 2 (2.1) | 0 | 0 |
Decreased appetite | 22 (22.9) | 2 (2.1) | 0 | 0 |
Hypokalemia | 13 (13.5) | 5 (5.2) | 1 (1.0) | 0 |
Peripheral edema | 10 (10.4) | 1 (1.0) | 0 | 0 |
Fatigue | 23 (24.0) | 2 (2.1) | 0 | 0 |
Mucositis | 8 (8.3) | 4 (4.2) | 0 | 0 |
Colitis | 5 (5.2) | 1 (1.0) | 0 | 0 |
Cough | 11 (11.5) | 1 (1.0) | 0 | 0 |
Muscle weakness | 0 | 1 (1.0) | 0 | 0 |
Hyperbilirubinemia | 9 (9.4) | 3 (3.1) | 0 | 0 |
ALT or AST elevation | 12 (12.5) | 4 (4.2) | 0 | 0 |
Allergic reaction | 3 (3.7) | 1 (1.0) | 0 | 0 |
Heart failure | 1 (1.0) | 2 (2.1) | 1 (1.0) | 1 (1.0) |
Renal failure | 0 | 0 | 1 (1.0) | 0 |
Tumor lysis syndrome | 0 | 1 (1.0) | 1 (1.0) | 0 |