Treatment patterns in patients with acute myeloid leukemia in the United States: a cross-sectional, real-world survey

Figures & data

Table 1. Patient clinical and demographic characteristics according to treatment intensity.

		Treatment intensity		p
Characteristic	All patients (N = 284)	High (n = 170)	Low (n = 114)
Median age at diagnosis, years (range)	60 (19–91)	55 (19–90)	67 (24–91)	<.0001
IQR	69–50	65–45	77–57
Male, n (%)	161 (57)	96 (56)	65 (57)	1.00
Median time since diagnosis, months (range)^a	4.0 (0–70.0)	5.0 (0–70.0)	4.0 (0–40.0)	.0165
IQR	9.0–2.0	12.0–2.0	6.0–2.0
ECOG performance status at diagnosis, n (%)				<.0001
0	54 (19)	26 (15)	28 (25)
1	110 (39)	85 (50)	25 (22)
2	92 (32)	42 (25)	50 (44)
3	22 (8)	15 (9)	7 (6)
4	6 (2)	2 (1)	4 (4)
AML origin, n (%)				.0095
De novo	254 (89)	159 (94)	95 (83)
Secondary^b	30 (11)	11 (6)	19 (17)
White blood cell count at diagnosis, n (%)				.0228
≥100,000	100 (35)	69 (41)	31 (27)
<100,000	184 (65)	101 (59)	83 (73)
Risk category at diagnosis, n (%)^c	N = 275	N = 168	N = 107	.2599
Favorable	88 (32)	58 (35)	30 (28)
Intermediate	128 (47)	79 (47)	49 (46)
Adverse/poor	59 (21)	31 (18)	28 (26)
Concomitant conditions prior to diagnosis^d, n (%)	N = 272	N = 164	N = 108
Hypertension	67 (25)	39 (24)	28 (26)	.3738
Hyperlipidemia	48 (18)	28 (17)	20 (19)	.2568
COPD	36 (13)	18 (11)	18 (17)	.203
Anxiety	34 (13)	23 (14)	11 (10)	.4965
Depression	34 (13)	27 (16)	7 (6)	.0149
Uncomplicated diabetes	33 (12)	20 (12)	13 (12)	.7373
Obesity	31 (11)	24 (15)	7 (6)	.05
Cerebrovascular disease	21 (7)	6 (4)	15 (14)	.0042
Osteoporosis	12 (4)	4 (2)	8 (7)	.0701
Prior stroke/TIA	11 (4)	3 (2)	8 (7)	.0293
Chronic kidney disease (moderate)	10 (4)	1 (1)	9 (8)	.0014
Peripheral vascular disease	9 (3)	2 (1)	7 (6)	.032
Congestive heart failure	5 (2)	0	5 (5)	.0095

Abbreviations. AML, Acute myeloid leukemia; COPD, Chronic obstructive pulmonary disease; ECOG, Eastern Cooperative Oncology Group; IQR, Interquartile range; TIA, Transient ischemic attack.

^a The mean time since diagnosis was 7.0 months (standard deviation 8.5 months), consistent with some patients being included who had been diagnosed for ≥5 years, thereby skewing the mean.

^b Secondary to pre-existing hematologic disorder (n = 30): chronic myeloid leukemia (n = 1; 3%), essential thrombocytopenia (n = 2; 7%), Fanconi anemia (n = 3; 10%), myelodysplastic syndrome (n = 22; 73%), other condition (n = 3; 10%).

^c Physician-perceived risk status.

^d Comorbidities occurring in >10% of patients or at statistically significantly different rates in high-intensity or low-intensity treated patients.

Table 2. Treatment regimens prescribed in the front-line induction setting according to patient age.

Regimen	All patients	Age		p
	(n = 284)	<60 years (n = 139)	≥60 years (n = 145)
High intensity	N = 170	N = 101	N = 69	.1138
Cytarabine + anthracycline^a	111 (65)	64 (63)	47 (68)
Cytarabine monotherapy	14 (8)	9 (9)	5 (7)
Cladribine containing	11 (6)	7 (7)	4 (6)
Cytarabine + anthracycline + other	9 (5)	6 (6)	3 (4)
Arsenic trioxide containing	7 (4)	7 (7)	0
Cyclophosphamide containing	4 (2)	1 (1)	3 (4)
Anthracycline monotherapy	3 (2)	1 (1)	2 (3)
Cytarabine + fludarabine	3 (2)	3 (3)	0
Clofarabine containing	3 (2)	2 (2)	1 (1)
Other combination therapy	5 (3)	1 (1)	4 (6)
Low intensity	N = 114	N = 38	N = 76	.0012
Low-dose cytarabine	35 (31)	8 (21)	27 (36)
Azacitidine monotherapy	29 (25)	6 (16)	23 (30)
Decitabine monotherapy	22 (19)	7 (18)	15 (20)
Anthracycline monotherapy	9 (8)	7 (18)	2 (3)
Clofarabine containing	3 (3)	2 (5)	1 (1)
Fludarabine	4 (4)	4 (11)	0
Vincristine sulfate	3 (3)	2 (5)	1 (1)
Azacitidine combination	3 (3)	2 (5)	1 (1)
Other combination therapy	2 (2)	0	2 (3)
Other monotherapy	4 (4)	0	4 (5)

^a Includes daunorubicin hydrochloride, doxorubicin, idarubicin and mitoxantrone.

Table 3. Patient characteristics considered by physicians when choosing high- or low-intensity treatment in AML (n = 61 physicians).

Factor involved in prescribing decisions, no. of physicians (%)	Considered suitable for
	High-intensity treatment	Low-intensity treatment
Patient age
<65 years	41 (67)	10 (16)
≥65 years	10 (16)	41 (67)
ECOG performance status
Good (0/1)	39 (64)	10 (16)
Very poor/poor (≥2)	8 (13)	38 (62)
Concomitant conditions
No	37 (61)	11 (18)
Yes	9 (15)	38 (62)
Leukemia cells in CNS
No	27 (44)	17 (28)
Yes	29 (48)	15 (25)
Prior MDS or pre-existing hematologic blood disorders
No	31 (51)	14 (23)
Yes	24 (39)	18 (30)
Prior cancer/exposure to radiation therapy or chemotherapy
No	27 (44)	13 (21)
Yes	17 (28)	23 (38)
High white blood cell count (>100,000 cells/µL)
No	25 (41)	13 (21)
Yes	30 (49)	11 (18)
Patient has normal cytogenetics	28 (46)	17 (28)
Chromosome abnormalities
Favorable^a	28 (46)	16 (26)
Unfavorable^b	29 (48)	11 (18)
Genetic mutation
FLT3 gene	32 (52)	10 (16)
NPM1 gene	29 (48)	10 (16)
CEBRA gene	33 (54)	6 (10)
DNMT3A, NRAS, c-KIT, IDH1, or IDH2 genes	32 (52)	8 (13)
Markers on leukemia cells
None	25 (41)	15 (25)
CD34 protein and/or P-glycoprotein	25 (41)	11 (18)
Patient eligible for SCT
Yes	33 (54)	8 (13)
No	22 (36)	23 (38)
Access to medication/reimbursement (Medicare)
Yes	33 (54)	11 (18)
No	22 (36)	20 (33)

Abbreviations. AML, Acute myeloid leukemia; CNS, Central nervous system; ECOG, Eastern Cooperative Oncology Group; MDS, Myelodysplastic syndrome; SCT, Stem cell transplant.

^a t(8;21), inv(16;16), t(16;16), t(15;17).

^b −5, −7, t(3;3), t(6;9), t(9;22), 11q23, complex >3 clonal chromosomal abnormalities.

Table 4. Clinical and demographic characteristics according to patient age.

		Age		p
Characteristic	All patients (N = 284)	<60 years (n = 139)	≥60 years (n = 145)
Median age at diagnosis, years (range)	60 (19–91)	50 (19–59)	68 (60–91)	<.0001
IQR	69–50	55–41	76–65
Male, n (%)	161 (57)	82 (59)	79 (54)	.4735
Median time since diagnosis, months (range)	4.0 (0–70.0)	5.0 (0–38.0)	3.0 (0–70.0)	.0012
IQR	9.0–2.0	12.0–2.0	7.0–1.0
ECOG performance status, n (%)				<.0001
0	54 (19)	38 (27)	16 (11)
1	110 (39)	56 (40)	54 (37)
2	92 (32)	29 (21)	63 (43)
3	22 (8)	15 (11)	7 (5)
4	6 (2)	1 (1)	5 (3)
Tests most commonly used to diagnose AML, n (%)
Bone marrow aspiration/biopsy	229 (81)	103 (74)	126 (87)	.007
Complete blood count	199 (70)	98 (71)	101 (70)	.8975
Biochemical profile	184 (65)	100 (72)	84 (58)	.018
Cytogenetic analysis	158 (56)	86 (62)	72 (50)	.0427
Bone biopsy	136 (48)	69 (50)	67 (46)	.6347
FISH	125 (44)	68 (49)	57 (39)	.1203
Molecular tests/PCR	116 (41)	55 (40)	61 (42)	.7177
Morphology	111 (39)	61 (44)	50 (34)	.1148
Immunophenotyping	106 (37)	60 (43)	46 (32)	.0504
CT scan	93 (33)	58 (42)	35 (24)	.0023
AML origin, n (%)				.0002
De novo	254 (89)	134 (96)	120 (83)
Secondary^a	30 (11)	5 (4)	25 (17)
White blood cell count at diagnosis, n (%)				.5345
≥100,000	100 (35)	46 (33)	54 (37)
<100,000	184 (65)	93 (67)	91 (63)
Risk category at diagnosis, n (%)^b	N = 274	N = 136	N = 139	<.0001
Favorable	88 (32)	61 (45)	27 (19)
Intermediate	128 (47)	56 (41)	72 (52)
Adverse/poor	59 (21)	19 (14)	40 (29)
Concomitant conditions prior to diagnosis, n (%)	N = 272	N = 134	N = 138
Hypertension	67 (25)	19 (14)	48 (35)	<.0001
Hyperlipidemia	48 (18)	17 (13)	31 (22)	.0211
COPD	36 (13)	11 (8)	25 (18)	.0198
Anxiety	34 (13)	17 (13)	17 (12)	.855
Depression	34 (13)	15 (11)	19 (14)	.5852
Uncomplicated diabetes	33 (12)	12 (9)	21 (15)	.0779

Abbreviations. AML, Acute myeloid leukemia; COPD, Chronic obstructive pulmonary disease; CT, Computed tomography; ECOG, Eastern Cooperative Oncology Group; FISH, Fluorescent in situ hybridization; IQR, Interquartile range; PCR, Polymerase chain reaction.

^a Secondary to pre-existing hematologic disorder (n = 30): chronic myeloid leukemia (n = 1; 3%), essential thrombocytopenia (n = 2; 7%), Fanconi anemia (n = 3; 10%), myelodysplastic syndrome (n = 22; 73%), other condition (n = 3; 10%).

^b Physician-perceived risk status.

Table 5. Clinical and demographic characteristics of patients who relapsed after, or were considered refractory to, previous therapy according to current treatment intensity.

Characteristic	All patients (N = 32)	Current treatment intensity
		High (n = 22)	Low (n = 10)
Median age at diagnosis, years (range)	56 (28–91)	55.5 (28–91)	61.5 (54–79)
IQR	64.5–51	63–48	68–55
<60 years, n (%)	18 (56)	14 (64)	4 (40)
≥60 years, n (%)	14 (44)	8 (36)	6 (60)
Male, n (%)	16 (50)	8 (36)	4 (40)
ECOG performance status at diagnosis, n (%)
0	7 (22)	5 (24)	2 (20)
1	14 (44)	10 (45)	4 (40)
2	8 (25)	5 (23)	3 (30)
3	1 (3)	0	1 (10)
4	2 (6)	2 (9)	0
Family history of AML, n (%)^a	3 (10)	3 (14)	0
Current concomitant conditions, n (%)^b
Anxiety	4 (13)	3 (14)	1 (10)
Obesity	6 (19)	4 (18)	2 (20)
Uncomplicated diabetes	5 (16)	4 (18)	1 (10)
Depression	5 (16)	4 (18)	1 (10)
Hypertension	4 (13)	1 (5)	3 (30)
Osteoarthritis	3 (9)	2 (9)	1 (10)
COPD	3 (9)	0	3 (10)
Intensity of induction therapy, n (%)
High	25 (78)	19 (86)	6 (60)
Low	7 (22)	3 (14)	4 (40)

Abbreviations. AML, Acute myeloid leukemia; COPD, Chronic obstructive pulmonary disease; ECOG, Eastern Cooperative Oncology Group; IQR, Interquartile range.

^a Data not available for 2 patients.

^b Comorbidities occurring in >10% of patients.

Table 6. Current treatment regimens for patients with disease considered relapsed or refractory to prior AML drug therapy.

Regimen, n (%)	All patients (N = 32)	Current treatment intensity
		High (n = 22)	Low (n = 10)
Cytarabine monotherapy	7 (22)	7 (32)	0
Cyclophosphamide containing	4 (13)	4 (18)	0
Clofarabine containing	3 (9)	2 (9)	1 (10)
Cladribine containing	2 (6)	2 (9)	0
Cytarabine + anthracycline	1 (3)	1 (5)	0
Cytarabine + anthracycline + other	1 (3)	1 (5)	0
Decitabine	2 (6)	0	2 (20)
Azacitidine	3 (9)	0	3 (30)
Vincristine sulfate	1 (3)	0	1 (10)
Fludarabine	2 (6)	0	2 (20)
Other combination therapy	5 (9)	4 (18)	1 (10)
Other monotherapy	2 (6)	1 (5)	1 (5)

Abbreviation. AML, Acute myeloid leukemia.

Data availability statement

The authors confirm that the questions relating directly to the analysis will be made available to scientific researchers (on request) by Adelphi Real World as a supplementary document. Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under “Sponsor Specific Details for Astellas”.