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J. Lambert et al.
Table 1. Event-free survival (EFS) results (mITT population) by the investigator-assessed and blinded independent review methods.
EFS
Events, n (%)
Induction failure Relapse
Death
Censored patients
Median time to event, months [95% CI]*
HR† [95% CI]
P-value‡
Probability of being event-free [95% CI]§
At 2 years
At 3 years
GO n=135
73 (54.1)
17 (12.6)
44 (32.6)
12 (8.9)
62 (45.9) 17.3 [13.4−30.0] 0.56 [0.42−0.76] 0.0002
42.1 [32.9−51.0]
39.8 [30.2−49.3]
Control n=136
102 (75.0) 29 (21.3) 58 (42.6) 15 (11.0) 34 (25.0) 9.5 [8.1−12.0]
18.2 [11.1−26.7]
13.6 [5.8−24.8]
GO n=135
78 (57.8)
25 (18.5)
43 (31.9)
10 (7.4)
57 (42.2) 13.6 [9.0−19.2] 0.66 [0.49−0.89] 0.006
38.5 [29.6−47.3]
36.5 [27.3–45.7]
Control n=136
100 (73.5) 34 (25.0) 50 (36.8) 16 (11.8) 36 (26.5) 8.5 [7.5−12.0]
18.1 [11.1−26.5]
13.6 [5.8–24.7]
Investigator assessed
Blinded independent review
Control: 3+7 daunorubicin + cytarabine (DA); GO: gemtuzumab ozogamicin + 3+7 DA; HR: hazard ratio; mITT: modified intent to treat; n: number. *Median estimated by Kaplan- Meier method; Confidence Interval (CI) based on the Brookmeyer-Crowley method with log-log transformation. †Based on the Cox proportional hazards model. ‡Two-sided P-value from the log-rank test. §Estimated from Kaplan-Meier curve. Probability (%) calculated by the product-limit method; CI calculated from the log-log transformation of sur- vival probability using a normal approximation and back transformation, and two-sided CIs for the estimates were computed using the Greenwood formula.
Table 2. Post-study treatment (mITT population).
Patients with ≥1 follow-up therapy, n (%)
Patients receiving GO as a component of follow-up therapy, n (%) Patients with HSCT, n ( %)
Timing of HSCT, n (%)
In first remission for responder patients
After induction failure
After relapse
GO n=135
96 (71.1)
2 (1.5) 32 (23.7)
17 (12.6)
2 (1.5)
13 (9.6)
Control n=136
109 (80.1)
30 (22.1) 53 (39.0)
22 (16.2)
9 (6.6)
22 (16.2)
Data are number (n) (%) unless otherwise indicated.Control:3+7 daunorubicin + cytarabine (DA);GO:gemtuzumab ozogamicin + 3+7 DA;HSCT:hematopoietic stem cell trans- plant; mITT: modified intent to treat.
Of interest, it did not appear that low CD33 expression (<30% of blasts positive) had an influence on the EFS ben- efit with GO; however, few enrolled patients (13.7%) had low CD33 expression. Similarly, analysis using a Cox pro- portional hazards model incuding treatment and CD33 expression as a continuous variable did not show any effect of CD33 expression on EFS.
Relapse-free survival
Relapse-free survival (RFS) was significantly longer for patients in the GO arm compared with control (Online Supplementary Figure S3). Median RFS was 28.0 months (95%CI: 16.3-not estimable) in the GO arm and 11.4 months (95%CI: 10.0-14.4) in the control arm, correspon- ding to a 47% reduction in the risk of an event for patients in the GO arm compared with those in the control arm.
Post-study treatment
The majority of patients [96 (71.1%) in the GO arm and 109 (80.1%) in the control arm] (Table 2) received at least 1 subsequent therapy for AML following study treatment. Overall, 32 patients (23.7%) in the GO arm and 53 (39.0%) in the control arm received a hematopoietic stem cell transplant (HSCT) either in first remission or after induction failure or relapse. All transplants were allogene-
ic, except one autologous transplant in the control arm. This included 17 patients (12.6%) in the GO arm and 22 (16.2%) in the control arm who received HSCT in first remission. Additional analysis of OS censoring the patients at the time of transplant showed no impact on the OS results (P=0.240). The other patients received rescue therapy after either induction failure or relapse, including 30 patients (22.1%) in the chemotherapy arm who subse- quently received GO as rescue therapy as part of a com- passionate use program.
Safety
A summary of treatment-emergent AEs of special inter- est is shown in Table 3. Overall, 208 (77.6%) patients experienced a severe (grade ≥3) infection; the incidence was similar between arms [GO arm, 102 (77.9%); control arm, 106 (77.4%)]. Hemorrhage of any grade occurred in the majority of patients in both treatment arms [225 (84.0%)]; the rate was significantly higher (P=0.008) among patients in the GO arm [118 (90.1%)] than the con- trol arm [107 (78.1%)]. Grade ≥3 hemorrhages were reported in 30 (22.9%) patients in the GO arm and 13 (9.5%) patients in the control arm. Six (4.6%) patients in the GO arm and 2 (1.5%) patients in the control arm expe- rienced veno-occlusive disease (VOD; P=0.165) (Table 3
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