Efficacy of combined immunosuppression with or without eltrombopag in children with newly diagnosed aplastic anemia

Abstract

We compared the efficacy and safety of eltrombopag (ELTR) combined with immunosuppressive therapy (IST) and IST alone in treatment-naïve children with severe (SAA) and very severe (vSAA) aplastic anemia. Ninety-eight pediatric patients were randomized to receive horse antithymocyte globulin and cyclosporin A with (n=49) or without (n=49) ELTR. The primary endpoint was the overall response rate (ORR) at 4 months. After 4 months, nonresponders were crossed over to the alternative group. In all patients, the ORR in ELTR+IST and IST groups was similar (65% vs. 53%, p=0.218); however, the complete response (CR) rate was significantly higher in ELTR+IST group (31% vs. 12%, p=0.027). In severity subgroups, the ORR was 89% vs. 57% (p=0.028) in favor of IST+ELTR in SAA, but it did not differ in patients with vSAA (52% vs. 50%, p=0.902). At 6 months after the crossover, 61% of initial ELTR(-) patients achieved a response compared to 17% of initial ELTR(+) patients (p=0.016). No significant difference in ELTR+IST and IST groups was observed in the 3-year OS (89% vs. 91%, p=0.673) or the 3-year EFS (53% vs. 41%, p=0.326). There was no unexpected toxicity related to ELTR. Adding ELTR to standard IST was well tolerated and increased the CR rate. The greatest benefit from ELTR combined with IST was observed in patients with SAA, but not in those with vSAA. The second course of IST resulted in a high ORR in initial ELTR(-) patients who added ELTR and had limited efficacy among patients who received ELTR upfront. Clinicaltrials.gov #NCT03413306.

A single-center historical control study of eltrombopag combined with immunosuppressive therapy for severe aplastic anemia in children

“…EFS at 1432.5 days (median follow-up time in the eltrombopag group) in 6-month responders was significantly lower in the eltrombopag group (57%) compared with the IST group (69%) [14] . However, other pediatric studies showed no significant differences in relapse rate and EFS between the eltrombopag and control groups [15][16] . In this study, the OS rates were 97.0% in the eltrombopag group and 96.0% in the control group.…”

“…The potential toxicity of eltrombopag includes thrombocytosis, thrombosis, reversible bone marrow fibrosis, rebound thrombocytopenia, cataract formation, and reversible hepatic dysfunction [20] . Many studies have reported that eltrombopag shows satisfactory safety in children [4] [11] [14][15][16] . Eltrombopag was not discon-tinued because of adverse events in any patient in this study, showing that eltrombopag is well tolerated in children with SAA.…”

“…]2 years as frontline treatment for SAA. Although the application of eltrombopag for SAA treatment in adults is relatively mature [11][12][13] , reports on eltrombopag use in pediatric SAA are still scarce, with conflicting findings [14][15][16] . Therefore, we conducted a historical control study to evaluate the efficacy and safety of eltrombopag combined with IST for SAA in children.…”

Efficacy of eltrombopag with immunosuppressive therapy for children with acquired aplastic anemia

“…Studies of EPAG with IST as a first-line therapy have been conducted primarily with adults in the past decade, while clinical evidence for the benefit of adding EPAG to standard IST in children remains limited and conflicting ( Supplementary Table S1 ) ( 12 – 20 ). According to a retrospective study performed by the NIH, it seems that the addition of EPAG to IST did not provide the same benefit in children as that observed in adults with SAA ( 16 ).…”

“…According to a retrospective study performed by the NIH, it seems that the addition of EPAG to IST did not provide the same benefit in children as that observed in adults with SAA ( 16 ). Notably, a multicenter prospective trial recently found that EPAG combined with IST increased the complete response (CR) rate but not the overall response (OR) rate in pediatric patients ( 12 ). Due to the controversial results in different studies worldwide, more clinical evidence is needed to ascertain the rational use of EPAG with IST in children with SAA ( 21 ).…”