Table.
Refractory Group | R6–12 Group | LFR Group | P Valueb | Additional Cases for Clearance Assessment |
|
---|---|---|---|---|---|
Patients in cohort, No. | 34 | 12 | 25 | 25 | |
Age at study entry, mean (95% CI), y | 51.6 (46.4–56.9) | 48.7 (39.0–58.3) | 50.6 (45.4–55.8) | .82 | 57.4 (53.1–61.8) |
Male sex, No. (%) | 15 (44.1) | 5 (41.7) | 14 (56.0) | .59 | 12 (48.0) |
Bone marrow blasts at diagnosis, mean (95% CI), % | 72.5 (65.8–79.2) | 63.1 (50.2–76.0) | 75.4 (69.5–81.3) | .15 | 56.4 (47.5–65.4) |
White cell count at diagnosis, mean (95% CI), per mm3 | 52 600 (37 400–67 700) | 75 900 (27 600–124 200) | 44 800 (17 700–71 900) | .18 | 33 940 (21 040–46 830) |
Median (IQR) | 47 100 (12 000–80 500) | 51 900 (15 400–118 200) | 19 800 (5 000–59 300) | 21 700 (7500–21 700) | |
Event-free survival, median (95% CI), mo | 3.0 (2.2–3.7) | 8.2 (6.4–10.2) | 20.6 (16.6–40.4) | <.001 | 10.7 (9.5–17.3) |
Overall survival, median (95% CI), mo | 7.5 (5.7–9.3) | 11.7 (7.9–16.4) | 42.3 (24.8-NE) | <.001 | 20.4 (15.1–22.2) |
Normal cytogenetic profile, No. (%) | 13 (38.2) | 8 (66.7) | 20 (80.0) | .02 | 12 (48.0) |
Cytogenetic risk group, No. (%) | |||||
Favorable | 0 | 0 | 0 | 6 (24.0) | |
Intermediate | 19 (55.9) | 10 (83.3) | 23 (92.0) | 14 (56.0) | |
Unfavorable | 13 (38.2) | 2 (16.7) | 2 (8.0) | 5 (20.0) | |
Missing data | 2 (5.9) | 0 | 0 | 0 | |
Total coding mutations, mean (95% CI)c | 21.8 (17.7–25.9) | 20.8 (14.6–27.1) | 16.0 (12.1–19.9) | .06 | 11.8 (9.7–13.9) |
Median (IQR) | 20.0 (14.0–27.0) | 19.5 (15.0–25.5) | 14.0 (9.0–20.0) | 12.0 (8.5–14.0) | |
Common AML somatic mutations, No. (%) | |||||
NPM1 | 7 (20.6) | 6 (50.0) | 15 (60.0) | .005 | 8 (32.0) |
DNMT3A | 8 (23.5) | 5 (41.7) | 10 (40.0) | .31 | 5 (20.0) |
FLT3 | 13 (38.2) | 6 (50.0) | 10 (40.0) | .77 | 10 (40.0) |
TP53 | 7 (20.6) | 2 (16.7) | 1 (4.0) | .19 | 1 (4.0) |
IDH1 and/or IDH2 | 10 (29.4) | 1 (8.3) | 10 (40.0) | .13 | 4 (16.0) |
KRAS and/or NRAS | 6 (17.7) | 2 (16.7) | 5 (20) | >.99 | 11 (44.0) |
WT1 | 6 (17.7) | 3 (25) | 1 (4.0) | .16 | 1 (4.0) |
RUNX1 | 5 (14.7) | 0 (0.0) | 0 (0.0) | .08 | 2 (8.0) |
NF1 | 4 (11.8) | 0 (0.0) | 0 (0.0) | .16 | 0 |
WGS cases, samples | 29 | 12 | 17 | ||
Total variants, mean (95% CI) | 411.2 (336.2–486.3) | 422.9 (306.6–539.3) | 375.1 (284.6–465.6) | .78 | |
Median (IQR) | 435.0 (282.0–509.0) | 414.5 (268.0–583.5) | 378.0 (287.0–439.0) | ||
Subclones, mean (95% CI) | 1.2 (0.9–1.5) | 1.3 (0.6–2.1) | 1.4 (0.9–1.9) | .78 | |
Median (IQR) | 1.0 (1.0–2.0) | 1.0 (0.5–2.5) | 1.0 (1.0–2.0) |
Abbreviations: AML, acutemyeloid leukemia; IQR, interquartile range; LFR, long first remission; R6–12, relapsed between 6 and 12 months from the initiation of therapy;WGS, whole-genome sequencing.
Percentages may not total 100 because of rounding.
P values are based on a comparison of the 3 different outcome groups.
Coding variants for the 71 refractory, R6–12, or LFR cases are based on the number of coding variants from the WGS or exome sequencing data; for the 25 additional cases for clearance assessment, this number is based on the total number of variants identified by exome sequencing. Common AML somatic mutations are the numbers of cases with any somatic mutation in DNMT3A, TP53 (including deletions), WT1, RUNX1, or NF1, and canonical mutations in IDH1, IDH2, KRAS, NRAS, or FLT3.