Combo worsens platelet recovery in MDS
Sixty-three of the 177 AEs in the eltrombopag group were suspected to be treatment-related, compared to 42 of 173 AEs in the placebo group.
One hundred twenty-eight (72%) serious AEs occurred in the eltrombopag arm, compared to 100 (56%) in the placebo arm.
Fifteen percent of the serious AEs were suspected to be related to eltrombopag treatment, compared to 4% of the serious AEs in the placebo group.
At the final analysis, 108 patients had died—57 (32%) in the eltrombopag group and 51 (29%) in the placebo group (hazard ratio [HR] 1.42; 95% CI 0.97, 2.08; nominal P=0.164).
The main causes of death were disease progression (28 in the eltrombopag group and 21 in the placebo group) and sepsis (18 in the eltrombopag group and 13 in the placebo group).
Efficacy
The study’s primary endpoint was the proportion of patients free of platelet transfusions during cycles one to four of azacitidine therapy.
At the final analysis, there were fewer patients in the eltrombopag arm than in the placebo arm who had achieved platelet transfusion independence—16% (28/179) and 31% (55/177), respectively. The odds ratio (OR) was 0.37 (95% CI 0.21, 0.65; two-sided P value=0.001).
Secondary efficacy endpoints included overall survival, disease response, duration of response, progression to AML, progression-free survival, and hematologic improvement.
The investigators pointed out that no formal statistical tests were performed for the secondary endpoints. Therefore, “statistical interpretation should be made with caution,” they wrote.
Overall response by IWG criteria occurred in 20% of patients in the eltrombopag group and 35% of those in the placebo group, according to investigator assessment (OR=0.51; 95% CI 0.30, 0.86; nominal P=0.005).
There was no significant difference in hematologic improvement, overall survival, or progression-free survival between the treatment arms.
The investigators found a higher rate of progression to AML in the eltrombopag arm than in the placebo arm—15% and 9%, respectively (OR=1.59; 95% CI 0.81, 3.14; nominal P=0.079).
They pointed out that these results contrasted with those of recent clinical studies of eltrombopag monotherapy1,2,3,4 in patients with MDS.
“[T]he findings of this trial were unexpected,” the investigators wrote.
They hypothesized that eltrombopag inhibits the effects of azacitidine when the drugs are given concomitantly. The issue is being studied further with ongoing research, they said.
The authors acknowledged financial support for medical editorial assistance provided by Novartis Pharmaceuticals Corporation.
Dr. Dickinson disclosed relationships with Celgene, Novartis, Janssen, Pfizer, and Roche. Senior study author Uwe Platzbecker, MD, disclosed relationships with Amgen, Celgene, GlaxoSmithKline, and Novartis.
1. Platzbecker U, et al Lancet Haematol. 2015;2(10):e417-e426. DOI: https://doi.org/10.1016/S2352-3026(15)00149-0
2. Oliva EN, et al. Lancet Haematol. 2017;4(3):e127-e136. DOI: https://doi.org/10.1016/S2352-3026(17)30012-1
3. Mittelman M, et al. Lancet Haematol. 2017;5(1):e34-e43. DOI: https://doi.org/10.1016/S2352-3026(17)30228-4
4. Buckstein R. Lancet Haematol. 2015;2(10):e396-e397. DOI: https://doi.org/10.1016/S2352-3026(15)00200-8
