source: The American Society of Pediatric Hematology/Oncology Conference

year: 2018

authors: Julie Kanter Washko, Abdullah Kutlar, Darla Liles, Rodolfo Cançado, Michael Shi, Zewen Zhu, Kenneth I. Ataga

Background:

In the 52-week SUSTAIN study, crizanlizumab 5.0 mg/kg significantly reduced the frequency of SCPCs versus placebo (1.6 vs 3.0, P=0.01) and increased the time to first on-treatment SCPC (4.1 vs 1.4 months, P=0.001) in patients with sickle cell disease (SCD).

Objectives:

To evaluate time to first SCPC in SUSTAIN study subgroups and the likelihood of not experiencing SCPC for the duration of the trial using post hoc analyses.

Design/Method:

SUSTAIN was a randomized, double-blind, placebo-controlled, phase 2 study (NCT01895361). Inclusion criteria were: SCD patients aged 16-65 years; 2-10 SCPCs in previous 12 months; concomitant hydroxyurea use permitted if ≥6 months and stable dose for ≥3 months. Patients were randomized 1:1:1 to receive intravenous crizanlizumab 5.0 mg/kg, 2.5 mg/kg, or placebo.

Study treatments were administered on days 1 and 15, then every 4 weeks to week 50, with the final assessment at week 52. Median time to first SCPC after first dose was summarized for crizanlizumab 5.0 mg/kg or placebo in these subgroups: 2-4 or 5-10 SCPCs in previous 12 months; SCD genotype; and hydroxyurea use at baseline. Hazard ratios (HRs) for crizanlizumab 5.0 mg/kg versus placebo were calculated based on Cox regression analysis, with treatment as a covariate. Descriptive statistics were used to summarize the frequency of patients who were SCPC event-free for the duration of the study by prior SCPC events, SCD genotype, and hydroxyurea use at baseline.

Results:

67 patients received crizanlizumab 5.0 mg/kg and 65 received placebo. There was a meaningful delay in time to first SCPC with crizanlizumab 5.0 mg/kg versus placebo observed in the entire study population. The effect was present in both SCPC subgroups, and the largest treatment difference was observed in HbSS SCD versus other genotypes (4.1 vs 1.1 months; HR: 0.50). In patients taking hydroxyurea who experienced 2-10 SCPCs in the previous year, time to first on-study SCPC was longer with crizanlizumab 5.0 mg/kg versus placebo (2.4 vs 1.2 months; HR: 0.58).

A greater proportion of patients treated with crizanlizumab 5.0 mg/kg were SCPC event-free versus placebo in each of the analyzed subgroups. One third of patients who were taking hydroxyurea and treated with crizanlizumab 5.0 mg/kg were SCPC event-free during the study versus 17.5% with placebo, possibly suggesting an additive effect.

Conclusion:

With crizanlizumab 5.0 mg/kg, there was a clinically meaningful delay in time to first SCPC and an increased likelihood of being SCPC-free versus placebo in all subgroups investigated.

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