Impact of KRAS and NRAS mutations on outcomes in acute myeloid leukemia

Figures & data

Table 1. Unadjusted baseline characteristics of patients with RAS-mutated and wild-type AML.

	Wild-type AML	RAS-mutated AML			p-Value
		KRAS	NRAS	KRAS/NRAS
General demographics
Patients, n (%)	196 (82)	11 (5)	25 (10)	7 (3)
Age, mean ± SD, years	63.2 ± 14.7	64.3 ± 19.1	64.6 ± 10.6	60.6 ± 27.0	0.94
Age, median (IQR), years	64.5 (56.2–74.0)	68.0 (59.1–76.6)	67.8 (58.3–69.9)	72.0 (38.0–76.7)	NC
Female, n (%)	83 (42)	4 (36)	10 (40)	2 (29)	0.88
BMI, mean ± SD	28.6 ± 7.2	28.9 ± 8.2	26.2 ± 5.3	36.2 ± 15.0	0.49
Variant allele frequencyt
KRAS, mean ± SD, %	0	26.7 ± 12.6	0	11.1 ± 13.3	-
NRAS, mean ± SD, %	0	0	20.1 ± 14.6	14.1 ± 14	-
Blood counts at diagnosis, mean ± SD
White blood cells, K/µL	37.1 ± 71.1	66.4 ± 67.8	55.0 ± 55.9	41.7 ± 34.8	0.35
Hemoglobin, g/dL	8.1 ± 2.1	8.1 ± 1.8	8.5 ± 2.6	8.0 ± 1.8	0.91
Platelets, K/µL	90.6 ± 231	52.1 ± 39.7	76.6 ± 98.4	24.0 ± 15.1	<0.001
Blasts, %	48.3 ± 24.5	50.2 ± 26.1	53.2 ± 23.1	51.0 ± 7.7	0.81
Ethnicity, n (%)					0.43
Caucasian	129 (66)	10 (91)	19 (76)	3 (43)
Other	66 (34)	1 (9)	6 (24)	4 (57)
Unknown	1 (1)	0 (0)	0 (0)	0 (0)
Comorbidities, n (%)
Cardiovascular disease	53 (27)	1 (9)	4 (16)	1 (14)	0.33
Diabetes mellitus	37 (19)	1 (9)	7 (28)	2 (29)	0.51
Hypertension	92 (47)	4 (36)	10 (40)	3 (43)	0.84
CKD stage III–V or ESRD	11 (6)	1 (9)	0 (0)	0 (0)	0.52
Active cancer	5 (3)	1 (9)	1 (4)	0 (0)	0.60
AML type, n (%)					0.17
De novo AML	121 (62)	3 (27)	13 (52)	3 (43)
AML with MDS changes	42 (21)	5 (46)	9 (36)	3 (43)
AML with MPN changes	12 (6)	0 (0)	2 (8)	0 (0)
Therapy-related AML	21 (11)	3 (27)	1 (4)	1 (14)
Not performed	7 (4)	0 (0)	0 (0)	0 (0)
ELN 2022 cytogenetic category, n (%)					0.04
Favorable risk	8 (4)	1 (9)	5 (20)	2 (29)
Intermediate risk	156 (80)	10 (91)	18 (72)	4 (57)
Unfavorable risk	25 (13)	0 (0)	2 (8)	1 (14)
Not performed	7 (4)	0 (0)	0 (0)	0 (0)
FLT3-ITD mutational status, n (%)					0.93
Mutated, 1–49%	23 (12)	0 (0)	2 (8)	0 (0)
Mutated, 50–100%	12 (6)	1 (9)	1 (4)	0 (0)
Unmutated	160 (82)	10 (91)	22 (88)	7 (100)
Unmeasured	1 (1)	0 (0)	0 (0)	0 (0)
FLT3-TKD mutational status, n (%)					0.29
Mutated	30 (15)	3 (27)	5 (20)	3 (43)
Unmutated	145 (74)	7 (64)	15 (60)	4 (57)
Untested	21 (11)	1 (9)	5 (20)	0 (0)
Other mutations, n (%)
ASXL1 mutated	30 (15)	3 (27)	5 (20)	1 (14)	0.71
CEBPA mutated	18 (09)	1 (09)	1 (04)	0 (0)	0.70
NPM1 mutated	44 (22)	2 (18)	5 (20)	0 (0)	0.54
RUNX1 mutated	37 (19)	1 (9)	6 (24)	2 (29)	0.68
TP53 mutated	48 (24)	0 (0)	2 (8)	2 (29)	0.07
ECOG status, n (%)					0.02
ECOG status I/II	177 (90)	11 (100)	23 (92)	4 (57)
ECOG status III/IV	18 (9)	0 (0)	2 (8)	3 (43)
ECOG status unknown	1 (1)	0 (0)	0 (0)	0 (0)
Type of first-line treatment, n (%)					0.67
Anthracycline-based	80 (41)	5 (46)	12 (48)	3 (43)
Non-anthracycline-based	108 (55)	5 (46)	13 (52)	3 (43)
HMA	45 (23)	3 (27)	6 (24)	1 (14)
HMA plus venetoclax	29 (15)	1 (9)	6 (24)	1 (14)
Other	34 (17)	1 (9)	1 (4)	1 (14)
None	8 (4)	1 (9)	0 (0)	1 (14)

SD: standard deviation; IQR: interquartile range; NC: not calculable; BMI: body mass index; CKD: chronic kidney disease; ESRD: end-stage renal disease; MDS: myelodysplastic syndrome; MPN: myeloproliferative neoplasm; ELN: European LeukemiaNet; FLT3: fms-like tyrosine kinase 3; ITD: internal tandem duplication; TKD: tyrosine kinase domain; HMA: hypomethylating agent.

Figure 1. A) Heat map of co-occurring mutations in RAS-mutated AML of co-occurring mutations in RAS-mutated and wild-type AML tested through next-generation sequencing with variant allele frequency estimation, ranging from zero to 100 percent.

Figure 2. Propensity score-adjusted overall survival (A) and event-free survival (B) for patients with KRAS-mutated vs. NRAS-mutated AML.

Data availability statement

The data that support the findings of this study are available from MMA upon reasonable request.