Uptake of Novel Therapies Into First-Line Treatment for Acute Myeloid Leukemia Patients: EU4 + UK Perspective

Figures & data

Table 1. Patient characteristics.

	All N = 2040	Novel agents n = 604	Ref.
Median age, years (range)	60–64	65–69
Sex ratio, M/F %	58/41	57/43
ECOG at diagnosis, %
0	14.9	11.4
1	45.6	47.2
2	19.7	21.7
3	4.6	5.3
4	0.8	1
Unknown	14.5	13.3
Co-morbidities, n (%)
Cardiac disease (arrhythmias, heart failure, ischemia)	359 (17.7)	99 (16.4)
Cerebrovascular disease	78 (3.8)	23 (3.8)
Peripheral vascular disease	88 (4.3)	32 (5.3)
Chronic pulmonary disease	182 (8.9)	54 (8.9)
Diabetes	270 (13.2)	78 (12.9)
Hyperlipidaemia	283 (13.9)	90 (14.9)
Hypertension	722 (35.4)	213 (35.3)
Obesity	127 (6.2)	35 (5.8)
Liver cirrhosis (w/w portal hypertension, bleeding varices)	58 (2.8)	12 (2)
Chronic renal failure (creatinine ≥3 mg/dL)	187 (9.1)	54 (8.9)
Severe renal failure (on dialysis, renal transplant)	24 (1.2)	5 (0.8)
Peptic ulcer disease	58 (2.8)	16 (2.6)
AIDS (not just HIV positive)	5 (0.2)	2 (0.3)
None of the above	591 (29)	175 (29)
Unknown	28 (1.4)	7 (1.2)
Molecular Profile, n (%)
FLT3-ITD	698 (34.2)	302 (50.0)
FLT3-TKD	515 (25.2)	207 (34.3)
NPM1	287 (14.1)	105 (17.4)
DNMT3A	317 (15.5)	88 (14.6)
CEBPA	141 (6.9)	39 (6.5)
IDH1	182 (8.9)	44 (7.3)
IDH2	185 (9.1)	55 (9.1)
TP53	202 (9.9)	52 (8.6)
AXL	165 (8.1)	57 (9.4)
CD33	253 (12.4)	91 (15.1)
Cytogenetic abnormalities, n (%)
inv(16) or t(16;16)	128 (6.3)	18 (3.0)
t(8;21)	155 (7.6)	37 (6.1)
t(15;17)	109 (5.3)	29 (4.8)
+8 alone	72 (3.5)	20 (3.3)
t(9;11)	152 (7.5)	48 (7.9)
-5, 5q, -7, 7q	119 (5.8)	30 (5.0)
Rearrangement of 11q23 - non t(9,11)	48 (2.4)	15 (2.5)
t(6;9)	66 (3.2)	14 (2.3)
t(9;22)	45 (2.2)	8 (1.3)
Complex karyotype	298 (14.6)	96 (15.9)
Monosomal karyotype	46 (2.3)	17 (2.8)
Normal cytogenetics	728 (35.7)	244 (40.4)
Unknown/not tested	206 (10.1)	42 (7.0)
Molecular and genetic risk stratification			[9]
Favorable Risk	557 (27.3)	105 (17.4)
Intermediate Risk	782 (38.3)	252 (41.3)
Adverse Risk	577 (28.3)	221 (36.6)
Not tested	65 (3.2)	10 (1.7)
Unknown	59 (2.9)	16 (2.7)
Treatment Program
Clinical trial	108 (5.3)	46 (7.6)
Compassionate use program	82 (4.0)	38 (6.3)
Neither of them	1850 (90.7)	520 (86.1)

ECOG: Eastern Cooperative Oncology Group.

Figure 1. Frequency of molecular profiles (EU4 + UK).

EU4: France, Germany, Italy, Spain.

Table 2. Use of novel agents in first-line acute myeloid leukemia patients by type of regimen.

Treatment regimen	Use of novel agents (n = 2040 patients)
	No	Yes/combo	Yes/monotherapy
Intensive	946	337	2
Non-intensive	490	261	4
Total (%)	1436 (70.3)	598 (29.3)	6 (0.3)

Table 3. Novel agents in combination administered in first-line treatment acute myeloid leukemia patients.

Treatment regimen	Use of novel agents in combination (n = 604 patients)
	Chemotherapy + novel agent	HMA + novel agent	LDAC + novel agent
Intensive	316 (91.8%)	20 (8.3%)	1 (8.3%)
Non-intensive	28 (8.2%)	222 (91.7%)	11 (91.7%)
Total (%)	344 (57.5)	242 (40.5)	12 (2.0)

HMA: Hypomethylating agents; LDAC: Low dose cytarabine.

Table 4. Use of novel agents across time.

Novel agent	Novel agents across time, in first-line
	January–March 2020		December 2020–February 2021
	Patients (n)	Freq. (%)	Patients (n)	Freq. (%)
No	709	70.0	727	70.7
Yes/combo	298	29.4	300	29.2
Yes/monotherapy	5	0.5	1	0.09
Total	1012		1028

Table 5. Different treatments combination with novel agents across time.

Treatment	Type of treatment with novel agents across time, in first-line
	January–March 2020		December 2020–February 2021
	Patients (n)	Freq. (%)	Patients (n)	Freq. (%)
Chemo regimen + Novel Agent	198	65.4	146	48.5
HMA + Novel Agent	100	33.0	142	47.2
LDAC + Novel Agent	0	0	12	4.0
Novel Agent monotherapy	5	1.65	1	0.3
Total	303		301

HMA: Hypomethylating agents; LDAC: Low dose cytarabine.

Table 6. Treatment response.

Novel agent	No	Yes/combo	Yes/monotherapy
First-line-intensive regimen, n = 752	556	195	1
Overall Response (CR + PR)	458 (82.3)	163 (83.5)	1 (100)
CR	372 (66.9)	141 (72.3)	1 (10.0)
PR	86 (15.4)	22 (11.28)	0
Progressive Disease	67 (12.0)	17 (8.7)	0
SD	31 (5.5)	15 (7.6)	0
First-line-non-intensive regimen n = 272	197	75	0
Overall Response (CR + PR)	70 (35,.5)	31 (41.3)	0 (0)
CR	27 (13.7)	10 (13.3)	0
PR	43 (21.8)	21 (28.0)	0
Progressive Disease	87 (44.0)	36 (48.0)	0
SD	40 (20.0)	8 (10.6)	0
Total (n = 1024)	753	270	1

All data is expressed as n(%).

CR: Complete Response; PR: Partial Response; SD: Stable Disease.

Figure 2. Duration of induction in newly diagnosed acute myeloid leukemia patients receiving an intensive regimen.

LOT: Line of treatment.

Table 7. Probability of still being treated across time in newly diagnosed acute myeloid leukemia patients receiving intensive regimens.

% of still being treated under first-line intensive regimen	% Remaining in therapy
	All	Novel agents
3 months	50.2	49.0
6 months	26.6	22.5
12 months	11.8	10.5

Figure 3. Duration of induction in newly diagnosed acute myeloid leukemia patients receiving a non-intensive regimen.

LOT: Line of treatment.

Table 8. Probability of still being treated across time in newly diagnosed acute myeloid leukemia patients receiving non-intensive regimens.

% of still being treated under first-line intensive regimen	% Remaining in therapy
	All	Novel agents
3 months	75.4	80.5
6 months	58.5	65.8
12 months	35.6	44.8

Döhner H, Estey E, Grimwade D et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4), 424–447 (2017).

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