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Quizartinib with low-intensity treatment in AML
Table 2. Summary of responses in the intention-to-treat population (n=73).
Frontline
Responses Overall Quizartinib/ Quizartinib/ Overall
Relapsed/Refractory Quizartinib/ AZA
(n=25)
Quizartinib/ LDAC (n=14)
CR
CRi
CRp
CRc
PR
ORR
NR
9(26) 8(53) 1(5) 3(8) 2(8) 1(7)
12 (35) 4 (27) 8 (42) 14 (36) 12 (48) 2 (14) 6(18) 1(7) 5(26) 3(8) 2(8) 1(7) 27 (79) 13 (87) 14 (74) 20 (51) 16 (64) 4 (29)
0 0 0 2(5) 0 2(14) 27 (79) 13 (87) 14 (74) 22 (56) 16 (64) 6 (43) 5(15) 1(7) 4(21) 16(41) 8(32) 8(57)
(n=34) AZA LDAC (n=39) (n=15) (n=19)
N (%)
AZA: azacitidine; LDAC: low-dose cytarabine; CR: complete response; CRi: CR with incomplete hematologic recovery; CRp: CR without platelet recovery; CRh: CR with partial hematologic recovery; CRc: composite response rate (CR+CRi+CRp); PR: partial response; ORR: overall response rate (CRc+PR); NR:, no response.
Table 3. Summary of responses in evaluable patients*(n=70).
Frontline
Responses Quizartinib/AZA Quizartinib/LDAC
(n=14) (n=18)
Relapsed/Refractory Quizartinib/AZA Quizartinib/LDAC (n=24) (n=14)
CR 8(57) 1(6) 2(8) 1(7)
CRi 4 (29) 8 (44) 12 (50) 2 (14) CRp 1(7) 5(28) 2(8) 1(7) CRh 0000
N (%) or [range]
CRc
PR
ORR
NR
Time to best response, months Duration of responseb, months
CRp 0 1(33) 0 0 Time to MRD negativity prior to SCT, months 4.7 [1-5.9] 0.9 [0.9-3] 2 [0.9-4.8] 1.4 [0.9-1.9]
AZA: azacitidine; LDAC: low-dose cytarabine; CR: complete response; CRi: CR with incomplete hematologic recovery; CRp: CR without platelet recovery; CRh: CR with partial hematologic recovery; CRc: composite response rate (CR+CRi+CRp+CRh); PR: partial response; ORR: overall response rate (CRc+PR); NR:, no response; MRD: minimal residual disease; SCT: stem cell transplantation. aOnly patients who completed at least one course of study treatment were included in the per-protocol response assessment (1 patient in the AZA cohort died early and 1 in each cohort did not complete a course of study treatment due to SCT in 1 case and atrial fibrillation in the other). bPatients proceeded to SCT were censored at the date of SCT. One patient treated frontline in quizartinib/LDAC and as first salvage in quizartinib/AZA cohort has an ongoing response. cMRD was assessed by multicolor flow cytometry. dCensored patients who achieved MRD negativity after SCT in the group treated frontline (n=4; AZA – 3, LDAC -1) and in those with relapsed/refractory disease (AZA – 3).
13 (93) 14 (78) 16 (67) 4 (29) 0 0 0 2(14) 13 (93) 14 (78) 16 (67) 6 (43) 1(7) 4(22) 8(33) 8(57)
MRDc
MRD assessed in responders MRD negatived
3.2 [0.9-6.3] 4.2 [0.2-30]
11 (85) 5 (45)
1.5 [0.9-3] 3.7 [0.2-17]
12 (86) 3 (25)
1 [0.9-4.8] 2.5 [0.1-19.4]
13 (81) 6 (46)
1 [0.9-8.7] 2.4 [0.5-7.2]
3 (50)
2 (67) CR 4(80) 1(33) 1(17) 1(50) CRi 1(20) 1(33) 5(83) 1(50)
70 (38 in the quizartinib/AZA cohort, 32 in the quizar- tinib/LDAC cohort) completed at least one cycle of study treatment and were included for per-protocol response assessment. Three patients were not evaluable for per- protocol response: one proceeded to a stem-cell transplant (SCT) after 14 days of treatment, one developed atrial fib- rillation on day 4 (prior to receiving quizartinib), and one died early on day 7 of multi-organ failure secondary to sepsis from an unknown organism. Among the ITT popu- lation treated frontline, the CRc rate (CR + CRi + CRp + CRh) was 87% (n=13/15 patients: 8 CR, 4 CRi, 1 CRp) (Table 2) in those treated with quizartinib/AZA and 74% (n=14/19 patients: 1 CR, 8 CRi, 5 CRp) in those treated with quizartinib/LDAC. The per-protocol response data are shown in Table 3. The median duration of response (time from best response to death/disease
progression/date of SCT or last follow-up/off treatment) was 4.2 months (range, 0.2 - 30 months) among patients treated with quizartinib/AZA and 3.7 months (range, 0.2 - 17 months) among those treated with quizartinib/LDAC. Among responders, MRD was assessed in 11 patients (85%) in the quizartinib/AZA cohort and 12 (86%) in the quizartinib/LDAC cohort. MRD was undetectable in five (45%) patients treated with quizartinib/AZA and three (25%) with quizartinib/LDAC (excluding patients who achieved MRD-negative status following SCT). Four patients (29%) treated with quizartinib/AZA and one (6%) with quizartinib/LDAC proceeded to SCT after achieving CRc. MRD was assessed in all responders before SCT, and only one of them (treated with quizar- tinib/AZA) was MRD-negative before undergoing the transplant. With regard to the ITT population with R/R
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