Treatment Patterns and FLT3 Mutation Testing Among Patients with Acute Myeloid Leukemia in China: A Retrospective Observational Study

Figures & data

Table 1 Demographics and Disease Characteristics of Patients with (a) ND and (b) R/R AML in the NICHE-AML Registry

(a)
Characteristic	All ND AML Patients N = 853	FLT3^WT N = 432	FLT3^MUT N = 109	Unknown FLT3 Mutation Status^a N = 312
Follow-up duration, days	573.4 (475.9)	494.8 (364.2)	399.8 (328.1)	742.9 (592.6)
Age at diagnosis, y	42.5 (12.8)	43.1 (12.8)	44.0 (12.5)	41.3 (12.8)
Male, n (%)	448 (52.5)	244 (56.5)	51 (46.8)	153 (49.0)
Known mutation status at diagnosis, n (%)	541 (63.4)	432 (100)	109 (100)	-
FLT3	109 (20.1)	0	109 (100)	-
NPM1	109 (20.1)	66 (15.3)	43 (39.4)	-
CEBPA	103 (19.0)	89 (20.6)	14 (12.8)	-
IDH1	38 (7.0)	32 (7.4)	6 (5.5)	-
Other acquired mutation	533 (98.5)	428 (99.1)	105 (96.3)	-
Cytogenetic status, n (%)	832 (97.5)	421 (97.5)	105 (96.3)	306 (98.1)
Abnormal karyotype	416 (50.0)	235 (55.8)	42 (40.0)	139 (45.4)
FAB classification,^Citation23 n (%)	650 (76.2)	345 (79.9)	77 (70.6)	228 (73.1)
M0	3 (0.5)	2 (0.6)	0	1 (0.4)
M1	6 (0.9)	2 (0.6)	1 (1.3)	3 (1.3)
M2	253 (38.9)	158 (45.8)	20 (26.0)	75 (32.9)
M4	113 (17.4)	54 (15.7)	12 (15.6)	47 (20.6)
M5	265 (40.8)	126 (36.5)	44 (57.1)	95 (41.7)
M6	6 (0.9)	1 (0.3)	0	5 (2.2)
M7	1 (0.2)	0	0	1 (0.4)
Type of AML
De novo	849 (99.5)	428 (99.1)	109 (100)	312 (100)
Secondary	4 (0.5)	4 (0.9)	0	0
Risk stratification^Citation7	746 (87.5)	427 (98.8)	108 (99.1)	211 (67.6)
Favorable	283 (37.9)	200 (46.8)	82 (75.9)	1 (0.5)
Intermediate	423 (56.7)	227 (53.2)	26 (24.1)	170 (80.6)
Adverse	40 (5.4)	0	0	40 (19.0)
(b)
Characteristic	All R/R AML Patients N = 289	FLT3^WT N = 58	FLT3^MUT N = 14	Unknown FLT3 Mutation Status^b N = 217
Follow-up duration, days	562.7 (438.3)	606.2 (371.7)	479.2 (261.3)	556.4 (463.2)
Age at diagnosis, y	43.6 (13.5)	43.5 (13.1)	44.4 (15.4)	43.6 (13.6)
Male, n (%)	154 (53.3)	32 (55.2)	9 (64.3)	113 (52.1)
Known mutation status at diagnosis, n (%)	183 (63.3)	45 (77.6)	9 (64.3)	129 (59.4)
FLT3	29 (15.8)	3 (6.7)	4 (44.4)	22 (17.1)
NPM1	30 (16.4)	8 (17.8)	3 (33.3)	19 (14.7)
CEBPA	45 (24.6)	20 (44.4)	1 (11.1)	24 (18.6)
IDH1	15 (8.2)	2 (4.4)	2 (22.2)	11 (8.5)
Other acquired mutation	182 (99.5)	44 (97.8)	9 (100)	129 (100)
Cytogenetic status, n (%)	285 (98.6)	56 (96.6)	14 (100)	215 (99.1)
Abnormal karyotype	135 (47.4)	21 (37.5)	2 (14.3)	112 (52.1)
FAB classification,^Citation23 n (%)	229 (79.2)	56 (96.6)	11 (78.6)	162 (74.7)
M0	0	0	0	0
M1	2 (0.9)	2 (3.6)	0	0
M2	87 (38.0)	30 (53.6)	1 (9.1)	56 (34.6)
M4	34 (14.8)	5 (8.9)	2 (18.2)	27 (16.7)
M5	103 (45.0)	19 (33.9)	7 (63.6)	77 (47.5)
M6	2 (0.9)	0	1 (9.1)	1 (0.6)
M7	0	0	0	0
Type of AML
De novo	287 (99.3)	58 (100)	14 (100)	215 (99.1)
Secondary	2 (0.7)	0	0	2 (0.9)
Risk stratification^Citation7c	254 (87.9)	55 (94.8)	14 (100)	185 (85.3)
Favorable	88 (34.6)	31 (56.4)	5 (35.7)	52 (28.1)
Intermediate	152 (59.8)	23 (41.8)	9 (64.3)	120 (64.9)
Adverse	14 (5.5)	1 (1.8)	0	13 (7.0)

Notes: Data are mean (SD), unless otherwise stated. ^aGenetic testing results were not available for patients with unknown FLT3 mutation status at initial AML diagnosis; ^bGenetic testing results at initial diagnosis were summarized among patients with relevant information at initial diagnosis; ^cEach patient was classified into only one risk category.

Abbreviations: AML, acute myeloid leukemia; CEBPA, CCAAT enhancer binding protein alpha; FAB, French-American-British; FLT3, FMS-like tyrosine kinase-3; IDH, isocitrate dehydrogenase; MUT, mutated; ND, newly diagnosed; NPM1, nucleophosmin 1; R/R, relapsed or refractory; SD standard deviation, WT, wild-type, y, years.

Figure 1 Flow of patients through the study. *All patients had newly diagnosed AML at entry to the NICHE-AML historical database.

Abbreviations: AML, acute myeloid leukemia; FLT3, FMS-like tyrosine kinase-3; MUT, mutated; R/R, relapsed/refractory; WT, wild type.

Table 2 Prevalence, Method, and Outcome of FLT3 Mutation Testing for Patients with AML

Key Epidemiologic Characteristic, n (%)	All ND AML Patients N = 853	All R/R AML Patients N = 289
Progression from ND to R/R AML	289 (33.9)	–
Relapsed after initial treatment	234 (27.4)	–
Refractory to initial treatment	55 (6.4)	–
FLT3 mutation testing
At initial AML diagnosis	541 (63.4)	–
At first R/R diagnosis	–	72 (24.9)
NGS testing method	541 (100)	72 (100)
Other testing method	0	0
FLT3^MUT positivity among tested patients^a
At initial AML diagnosis	109 (20.1)	–
FLT3-ITD mutation	53 (48.6)	–
FLT3-TKD mutation	32 (29.4)	–
Unspecified FLT3 mutation	26 (23.9)	–
At first R/R AML diagnosis	–	14 (19.4)
FLT3-ITD mutation	–	9 (64.3)
FLT3-TKD mutation	–	6 (42.9)
Unspecified FLT3 mutation	–	1 (7.1)
FLT3 testing at both initial AML and first R/R diagnoses		54 (18.7)
Lost FLT3 mutation at first R/R	–	3 (5.6)
Gained FLT3 mutation at first R/R	–	5 (9.3)
FLT3-ITD vs FLT3-TKD mutation switch at first R/R	–	3 (5.6)
From FLT3-ITD to FLT3-TKD	–	1 (33.3)
From FLT3-TKD to FLT3-ITD	–	2 (66.7)

Notes: ^aPatients could harbor both FLT3-ITD and FLT3-TKD mutations, therefore, the percentages of each FLT3 mutation type may not add up to 100%.

Abbreviations: AML, acute myeloid leukemia; FLT3, FMS-like tyrosine kinase-3; ITD, internal tandem duplication; MUT, mutated; ND, newly diagnosed; NGS, next generation sequencing; R/R, relapsed or refractory; TKD, tyrosine kinase domain.

Table 3 (a) First-Line Treatments Recorded for Patients with ND AML and (b) Treatments Recorded Prior to First Diagnosis of R/R AML in Patients with R/R AML

(a)
Therapy	All Patients with ND AML (N = 853)		FLT3^WT at Initial Diagnosis (N = 432)		FLT3^MUT at Initial Diagnosis (N = 109)		Unknown FLT3 Mutation Status (N = 312)
	Patients,^a n (%)	Mean (SD) Ara-C Dose (mg/m^2), Cycles	Patients, n (%)	Mean (SD) Ara-C Dose (mg/m^2), Cycles	Patients, n (%)	Mean (SD) Ara-C Dose (mg/m^2), Cycles	Patients, n (%)	Mean (SD) Ara-C Dose (mg/m^2), Cycles
Induction	853 (100)		432 (100)		109 (100)		312 (100)
DA^b	602 (70.6)	166.1 (289.5), 1.0 (0.1)	341 (78.9)	154.3 (232.3), 1.0 (0.0)	91 (83.5)	147.8 (222.4), 1.0 (0.1)	170 (54.5)	199.3 (401.5), 1.0 (0.0)
IA^c	133 (15.6)	118.8 (16.5), 1.1 (0.3)	92 (21.3)	117.9 (15.7), 1.1 (0.3)	26 (23.9)	119.9 (18.6), 1.1 (0.4)	15 (4.8)	122.8 (18.1), 1.0 (0.0)
HAD	126 (14.8)	233.1 (362.9), 1.0 (0.2)	4 (0.9)	120.7 (8.6), 1.0 (0.0)	2 (1.8)	119.3 (3.1), 1.0 (0.0)	120 (38.5)	238.7 (370.9), 1.0 (0.2)
MA	61 (7.2)	107.4 (22.8), 1.0 (0.0)	30 (6.9)	106.6 (25.6), 1.0 (0.0)	5 (4.6)	126.2 (10.3), 1.0 (0.0)	26 (8.3)	104.7 (19.7), 1.0 (0.0)
Other^d	140 (16.4)	–	83 (19.2)	–	25 (22.9)	–	40 (12.8)	–
Consolidation	743 (87.1)		371 (85.9)		97 (89.0)		275 (88.1)
HiDAC	469 (63.1)	6004.0 (323.3), 2.6 (0.6)	245 (66.0)	6021.1 (322.7), 2.6 (0.7)	62 (63.9)	6042.8 (235.0), 2.6 (0.7)	162 (58.9)	5964.4 (348.5), 2.7 (0.6)
MA	236 (31.8)	495.4 (979.4), 1.9 (0.8)	78 (21.0)	140.5 (303.3), 1.4 (0.6)	14 (14.4)	229.9 (445.7), 1.4 (0.5)	144 (52.4)	659.5 (1134.4), 2.1 (0.9)
DA	216 (29.1)	582.8 (1083.4), 1.6 (0.5)	92 (24.8)	138.1 (250.6), 1.8 (0.5)	20 (20.6)	119.0 (15.1), 1.7 (0.5)	104 (37.8)	1131.6 (1416.8), 1.5 (0.5)
MiDAC	124 (16.7)	2346.1 (799.6), 1.9 (0.5)	71 (19.1)	2314.8 (811.5), 2.0 (0.6)	13 (13.4)	2395.0 (805.6), 1.8 (0.4)	40 (14.5)	2386.9 (785.5), 1.9 (0.4)
HA	108 (14.5)	112.9 (36.2), 1.7 (0.6)	52 (14.0)	113.1 (48.8), 1.7 (0.5)	7 (7.2)	119.3 (10.6), 1.7 (0.5)	49 (17.8)	111.8 (19.8), 1.8 (0.6)
Ara-C+HDAC	67 (9.0)	5851.6 (526.5), 2.0 (0.7)	41 (11.1)	5921.0 (404.8), 1.8 (0.7)	8 (8.2)	6044.8 (149.9), 1.9 (0.8)	18 (6.5)	5651.0 (729.2), 2.2 (0.7)
Decitabine	62 (8.3)	-, 2.5 (1.5)	33 (8.9)	-, 2.5 (1.6)	5 (5.2)	-, 3.4 (1.7)	24 (8.7)	-, 2.1 (1.0)
IA	62 (8.1)	183.8 (325.9), 1.1 (0.2)	47 (12.7)	167.1 (266.5), 1.0 (0.2)	8 (8.2)	116.5 (18.5), 1.0 (0.0)	7 (2.5)	351.3 (663.1), 1.2 (0.5)
AA	60 (8.1)	105.8 (45.3), 1.5 (0.5)	34 (9.2)	113.1 (52.5), 1.5 (0.5)	6 (6.2)	115.8 (23.1), 1.7 (0.5)	20 (7.3)	90.1 (32.7), 1.5 (0.5)
Other^d	234 (31.5)	-	117 (31.5)	-	20 (20.6)	-	75 (27.3)	-
HSCT
Allogeneic	62 (7.3)	-	32 (7.4)	-	12 (11.0)	-	18 (5.8)	-
Autologous	1 (0.1)	-	1 (0.2)	-	0	-	0	-
(b)
Therapy	All Patients with R/R AML (N = 289)		FLT3^WT at R/R Diagnosis (N = 58)		FLT3^MUT at R/R Diagnosis (N = 14)		Unknown FLT3 Mutation Status (N = 217)
	Patients,^a n (%)	Mean (SD) Ara-C Dose (mg/m^2), Cycles	Patients, n (%)	Mean (SD) Ara-C Dose (mg/m^2), Cycles	Patients, n (%)	Mean (SD) Ara-C Dose (mg/m^2), Cycles	Patients, n (%)	Mean (SD) Ara-C Dose (mg/m^2), Cycles
Induction	289 (100)		58 (100)		14 (100)		217 (100)
DA^b	213 (73.7)	182 (355.3), 1.0 (0.0)	48 (82.8)	201.8 (332.5), 1.0 (0.0)	10 (71.4)	121.1 (8.1), 1.0 (0.0)	155 (71.4)	180.6 (373.8), 1.0 (0.0)
IA^c	50 (17.3)	116.6 (15.3), 1.2 (0.4)	7 (12.1)	112.0 (6.0), 1.2 (0.5)	2 (14.3)	121.7 (8.0), 1.0 (0.0)	41 (18.9)	117.2 (16.6), 1.2 (0.4)
HAD	43 (14.9)	199.3 (308.8), 1.0 (0.2)	3 (5.2)	104.4 (8.2), 1.0 (0.0)	2 (14.3)	111.0 (9.7), 1.0 (0.0)	38 (17.5)	208.7 (323.2), 1.1 (0.2)
MA	30 (10.4)	109.8 (20.1), 1.0 (0.0)	6 (10.3)	110.9 (17.9), 1.0 (0.0)	1 (7.1)	104.1 (-), 1.0 (-)	23 (10.6)	109.7 (21.5), 1.0 (0.0)
D-AA	16 (5.5)	48.5 (16.7), 1.1 (0.3)	0	-	0	-	16 (7.4)	48.5 (16.7), 1.1 (0.3)
Other^d	33 (11.4)	-	4 (6.9)	-	1 (7.1)	-	26 (12.0)	-
Consolidation	230 (79.6)		55 (94.8)		12 (85.7)		163 (75.1)
HiDAC	134 (58.3)	5979.1 (325.1), 2.7 (0.6)	35 (63.6)	5980.4 (315.4), 2.7 (0.6)	8 (66.7)	5985.1 (301.4), 2.8 (0.4)	91 (55.8)	5977.9 (332.5), 2.6 (0.7)
MA	80 (34.8)	528.0 (1015.6), 1.8 (0.8)	14 (25.5)	273.6 (662.1), 1.7 (0.9)	4 (33.3)	112.6 (9.2), 1.4 (0.5)	62 (38.0)	592.0 (1079.9), 1.8 (0.7)
DA^b	68 (29.6)	655.5 (1146.5), 1.6 (0.6)	15 (27.3)	250.3 (589.8), 1.6 (0.5)	0	-	53 (32.5)	768.1 (1238.0), 1.6 (0.6)
MiDAC	43 (18.7)	2175.4 (724.6), 1.9 (0.5)	10 (18.2)	1961.5 (172.2), 2.1 (0.4)	1 (8.3)	4165.8 (-), 2.0 (-)	32 (19.6)	2185.4 (759.5), 1.8 (0.5)
HA	34 (14.8)	121.8 (37.7), 1.7 (0.6)	9 (16.4)	148.5 (50.7), 1.9 (0.3)	1 (8.3)	117.8 (-), 2.0 (-)	24 (14.7)	111.0 (26.0), 1.6 (0.6)
Decitabine	20 (8.7)	-, 1.9 (1.1)	3 (5.5)	-, 1.0 (0.0)	1 (8.3)	-, 3.0 (-)	16 (9.8)	-, 1.8 (1.1)
Ara-C+HDAC	18 (7.8)	5915.5 (397.5), 1.8 (0.6)	2 (3.6)	5613.8 (284.9), 1.0 (0.0)	1 (8.3)	6095.8 (-), 1.0 (-)	15 (9.2)	5932.4 (406.3), 1.9 (0.6)
AA	17 (7.4)	106.3 (52.8), 1.6 (0.5)	3 (5.5)	175.4 (49.4), 1.8 (0.4)	0	-	14 (8.6)	88.1 (36.7), 1.5 (0.5)
IA^c	14 (6.1)	135.5 (61.1), 1.0 (0.0)	4 (7.3)	187.5 (50.1), 1.0 (0.0)	0	-	10 (6.1)	114.7 (53.7), 1.0 (0.0)
Other^d	60 (26.1)	-	11 (20.0)	-	1 (8.3)	-	34 (20.9)	-
HSCT	-
Allogeneic	12 (4.2)	-	1 (1.7)	-	2 (14.3)	-	9 (4.1)	-
Autologous	0	-	0	-	0	-	0	-

Notes: ^aTreatment information was summarized for each regimen and categorized by therapy type. This column summarizes the number of patients who ever received a specific treatment regimen. A patient receiving multiple treatment regimens under one treatment type would be counted for each received treatment regimen; therefore, the percentages under each treatment type may not add up to 100%; ^bDA regimen included DA 7+3, DA 5+2, and other DA. DA 7+3 refers to cytarabine daily for 7 days and daunorubicin daily for 3 days. DA 5+2 refers to cytarabine daily for 5 days and daunorubicin daily for 2 days; ^cIA regimen included IA 7+3, IA 5+2, and other IA. IA 7+3 refers to cytarabine daily for 7 days and idarubicin daily for 3 days. IA 5+2 refers to cytarabine daily for 5 days and idarubicin daily for 2 days; ^dOther refers to a combined group of individual regimens used by <5% of patients.

Abbreviations: AA, cytarabine and aclarubicin; AML, acute myeloid leukemia; Ara-C, cytarabine; Ara-C+HDAC, cytarabine and histone deacetylase; DA, daunorubicin and cytarabine; D-AA, decitabine, cytarabine, and aclarubicin; FLT3, FMS-like tyrosine kinase-3; HA, homoharringtonine and cytarabine; HAD, homoharringtonine, cytarabine, and daunorubicin; HSCT, hematopoietic stem-cell transplantation; HiDAC, high-dose cytarabine; IA, idarubicin and cytarabine; MA, cytarabine and mitoxantrone; MiDAC, mid-dose cytarabine; MUT, mutated; ND, newly diagnosed; SD, standard deviation; WT, wild type.

Table 4 First-Line Treatment Response Among (a) Patients with Newly Diagnosed AML and (b) All Patients with R/R AML, and Those with R/R AML and FLT3^WT, FLT3^MUT, and Unknown FLT3 Mutation Status

(a)
Therapy	All newly Diagnosed Patients (N = 853)
	Patients Who Received Treatment(s), n (%)	Treatment Response, n (%)		Relapsed, n (%)	Refractory, n (%)
		CR/CRi Not Yet Achieved/Observed	Ever Achieved CR/CRi
Induction therapy	853 (100)	102 (12.0)	751 (88.0)	234 (27.4)	55 (6.4)
Consolidation therapy	743 (87.1)	61 (8.2)	682 (91.8)
HSCT	63 (7.4)	9 (14.3)	54 (85.7)
(b)
Therapy	All R/R diagnosed patients (N = 289)
	Patients who received treatment(s), n (%)	Treatment response, n (%)		Time from treatment initiation to first relapse after initial treatment (days), mean (SD) [median (IQR)]	Time from first documented CR/CRi to first relapse after initial treatment (days), mean (SD) [median (IQR)]
		CR/CRi not yet achieved/observed	Ever achieved CR/CRi
Induction therapy	289 (100)	59 (20.4)	230 (79.6)	358.0 (241.5) [306.5 (254.2)]	314.3 (242.6) [252.0 (268.0)]
Consolidation therapy	230 (79.6)	29 (12.6)	201 (87.4)
HSCT	12 (4.2)	4 (33.3)	8 (66.7)
Therapy	FLT3^WT (N = 58)
	Patients who received treatment(s), n (%)	Treatment response, n (%)		Time from treatment initiation to first relapse after initial treatment (days), mean (SD), [median (IQR)]	Time from the first documented CR/CRi to the first relapse after the initial treatment (days), mean (SD) [median (IQR)]
		CR/CRi not yet achieved/observed	Ever achieved CR/CRi
Induction therapy	58 (100)	3 (5.2)	55 (94.8)	366.9 (220.3) [331.5 (235.8)]	321.8 (220.1) [291.0 (212.8)]
Consolidation therapy	55 (94.8)	4 (7.3)	51 (92.7)
HSCT	1 (1.7)	0 (0)	1 (100)
Therapy	FLT3^MUT at R/R (N = 14)
	Patients who received treatment(s), n (%)	Treatment response, n (%)		Time from treatment initiation to first relapse after initial treatment (days), mean (SD), [median (IQR)]	Time from first documented CR/CRi to first relapse after initial treatment (days), mean (SD), [median (IQR)]
		CR/CRi not yet achieved/observed	Ever achieved CR/CRi
Induction therapy	14 (100)	2 (14.3)	12 (85.7)	320.0 (172.5) [294.0 (123.8)]	271.0 (174.3) [242.0 (126.0)]
Consolidation therapy	12 (85.7)	1 (8.3)	11 (91.7)
HSCT	2 (14.3)	2 (100)	0 (0)
Therapy	Unknown FLT3 mutation status at R/R (N = 217)
	Patients who received treatment(s), n (%)	Treatment response, n (%)		Time from treatment initiation to first relapse after initial treatment (days), mean (SD), [median (IQR)]	Time from first documented CR/CRi to first relapse after initial treatment (days), mean (SD), [median (IQR)]
		CR/CRi not yet achieved/observed	Ever achieved CR/CRi
Induction therapy	217 (100)	54 (24.9)	163 (75.1)	357.8 (252.7) [293.0 (283.0)]	314.9 (254.3) [235.0 (292.0)]
Consolidation therapy	163 (75.1)	24 (14.7)	139 (85.3)
HSCT	9 (4.1)	2 (22.2)	7 (77.9)

Abbreviations: AML, acute myeloid leukemia; CR, complete remission; CRi, complete remission with incomplete hematologic recovery; HSCT, hematopoietic stem-cell transplantation; FLT3, FMS-like tyrosine kinase-3; HSCT, hematopoietic stem-cell transplantation; MUT, mutated; R/R, relapsed/refractory; SD, standard deviation; WT, wild type.

Cheson BD, Cassileth PA, Head DR, et al. Report of the national cancer institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol. 1990;8(5):813–819. doi:10.1200/JCO.1990.8.5.813

 PubMed Web of Science ®Google Scholar

Leukemia & Lymphoma Group, Chinese Society of Hematology, Chinese Medical Association. Chinese guidelines for the diagnosis and treatment of adult acute myeloid leukemia (not APL) (2021). Zhonghua Xue Ye Xue Za Zhi. 2021;42(8):617–623. doi:10.3760/cma.j.issn.0253-2727.2021.08.001

 PubMedGoogle Scholar