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Quizartinib with low-intensity treatment in AML
Table 5. Incidence of common treatment-emergent adverse events in all patients. Quizartinib/AZA
Quizartinib/LDAC (n=33) Grade 1-2
N (%)
10 (30)
8 (24)
6 (18)
9(27) 0
Adverse events
Non-hematologic toxicities
Hypomagnesemia Hyperbilirubinemia Hypokalemia Hypocalcemia Increased ALT Hyponatremia Febrile neutropenia Elevated creatinine Hypophosphatemia Pneumonia
Nausea
Fatigue
Diarrhea Hypoalbuminemia Vomiting
Rash
Hyperkalemia
Lower limb edema Generalized weakness Oral mucositis Anorexia
Constipation Dizziness
Abdominal pain Hypotension
Atrial fibrillation Headache
Pleural effusion
Back pain
QTc prolongation Sinus tachycardia Sinus bradycardia
Hematologic toxicities
Total
27 (68) 25 (63) 24 (60) 23 (58) 23 (58) 17 (43) 16 (40) 13 (33) 12 (30) 11 (28) 10 (25) 9 (23) 8 (20) 8 (20) 6 (15) 6 (15) 5 (13) 5 (13) 5 (13) 5 (13) 4 (10) 4 (10) 4 (10) 4 (10) 4 (10) 2 (5) 1(3)
1 (3) 1 (3) 1 (3) 1 (3)
(n=40) Grade 1-2 N (%)
26 (65) 19 (48) 11 (28) 16 (40) 19 (48) 12 (30) 0
13 (33) 5 (13) 0
9 (23) 8 (20) 5 (13) 6 (15) 6 (15) 4 (10) 3 (8) 5 (13) 4 (10) 4 (10) 3 (8) 4 (10) 4 (10) 1 (3) 1 (3) 0 1(3) 1 (3) 1 (3) 0
0
Grade 3-5
1 (3) 6 (15) 13 (33) 7 (18) 4 (10) 5 (13) 16 (40) 0
7 (18) 11 (28) 1 (3) 1 (3) 3 (8) 2 (5) 0
2 (5) 2 (5) 0
1 (3) 1 (3) 1 (3) 0
0
3 (8) 3 (8) 2 (5)
Total
10 (30) 9 (27) 9 (27) 9 (27) 15 (45) 8 (24) 12 (36) 7 (21) 3 (9) 19 (58) 14 (42) 10 (30) 13 (39) 7 (21) 10 (30) 9 (27) 4 (12) 4 (12) 5 (15) 8 (24) 5 (15) 5 (15) 6 (18) 8 (24) 12 (36) 3 (9)
Grade 3-5
000
0 6(18) 3(9)
0
0
1 (3) 1 (3)
5 (15) 10 (30) 4 (12) 2 (6) 3 (9)
4 (12) 9 (27) 3 (9) 2 (6) 3 (9)
13 (39) 5 (15) 0
7 (21) 2 (6) 3 (9) 12 (36) 7 (21) 10 (30) 7 (21) 8 (24) 8 (24) 4 (12) 4 (12) 3 (9) 7 (21)
2 (6)
3 (9) 12 (36) 0
1 (3) 16 (48) 2 (6) 3 (9) 3 (9) 0
2 (6) 1 (3) 0
0
2 (6) 1 (3)
5(15) 0
5 (15) 5 (15) 7 (21) 4 (12) 2 (6)
0
1 (3) 1 (3) 8 (24) 1 (3) 3(9) 1 (3) 1 (3) 1 (3) 0
0
0
1 (3) 3 (9)
Thrombocytopenia
Leukopenia
Neutropenia
Anemia 1(3) 1(3) 0 5(15) 0 5(15) Leukocytosis 0 0 0 2(6) 0 2(6)
6 (15) 3 (8) 3 (8)
1 (3) 1 (3) 1 (3)
0 0 0
particularly with AZA, might improve the probability of response and the response duration in these patients. Prospective randomized studies are warranted to validate our results.
Disclosures
No conflicts of interest to disclose.
Contributions
JC and HK designed the study; MS, JC, VG, SP, MRP and LX collected and analyzed the data, and performed the statistical analysis; MS and JC wrote the manuscript. All the authors reviewed the manuscript and approved the version for submission.
Funding
The study was supported in part by a Cancer Center Support Grant (NCI grant P30 CA016672).
5 (13) 2 (5) 2 (5)
10 (30) 14 (42) 14 (42)
10 (30) 14 (42) 14 (42)
AZA: azacitidine; LDAC, low-dose cytarabine; ALT: alanine transaminase.
Online Supplementary Table S5). Recently, Levis and his col- leagues showed that among patients with FLT3-mutated R/R AML treated with gilteritinib monotherapy, patients with NPM1 co-mutation had significantly better survival outcomes.34 Similarly, NPM1 co-mutation was associated with non-significantly better CRc rates and longer overall survival in our R/R patients (Online Supplementary Figure S2 and Online Supplementary Table S4). In general, these asso- ciations follow the same direction as those found in our series, but the small number of patients preclude firm con- clusions. These possible interactions remain to be con- firmed in larger series.
In conclusion, our study demonstrated that quizartinib, in combination with AZA or LDAC, can be administered safely to patients with FLT3-mutated AML, whether as initial therapy or as first salvage treatment. Our prelimi- nary observations suggest that the combination therapy,
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