Eltrombopag added to immunosuppression for children with treatment‐naïve severe aplastic anaemia

Abstract

Acquired severe aplastic anaemia (SAA) has an immune pathogenesis, and immunosuppressive therapy (IST) with anti-thymocyte globulin and cyclosporine is effective therapy. Eltrombopag (EPAG) added to standard IST was associated with higher overall and complete response rates in patients with treatment-na€ ıve SAA compared to a historical IST cohort. We performed a paediatric subgroup analysis of this trial including all patients aged <18 years who received EPAG plus standard IST (n = 40 patients) compared to a historical cohort (n = 87) who received IST alone. Response, relapse, clonal evolution, event-free survival (EFS), and overall survival were assessed. There was no significant difference in either the overall response rate (ORR) or complete response rate at 6 months (ORR 70% in EPAG group, 72% in historical group, P = 0Á78). Adults (≥18 years) had a significantly improved ORR of 82% with EPAG compared to 58% historically (P < 0Á001). Younger children had lower response rates than did adolescents. The trend towards relapse was higher and EFS significantly lower in children who received EPAG compared to IST alone. Addition of EPAG added to standard IST did not improve outcomes in children with treatment-na€ ıve SAA. EPAG in the paediatric population should not automatically be considered standard of care. Registration: clinicaltrials.gov (NCT01623167).

Thrombopoietin Receptor Agonists (TPO-RAs): Drug Class Considerations for Pharmacists

“…Notably, the overall response rate (complete and partial response) at month 6 in cohort 3 was 80%, which was significantly higher than the 66% overall response rate observed in a historical cohort of 102 patients with SAA who received antithymocyte globulin and cyclosporine alone [71]. Although eltrombopag is approved for use in combination with standard immunosuppressive therapy in adults and children aged 2 years and older with severe aplastic anemia, a recent subgroup analysis of 40 pediatric patients receiving eltrombopag plus immunosuppressive therapy versus a historical cohort of 87 children receiving immunosuppressive therapy alone did not identify a significant improvement in overall response rates (70% with eltrombopag plus immunosuppressive therapy versus 72% in the historical cohort of children receiving immunosuppressive therapy alone; p = 0.78) [30,72].…”

Acquired severe aplastic anaemia: how medical therapy evolved in the 20th and 21st centuries

“…A subgroup analysis of 40 patients <18 years of age who received ACE was compared to a historical cohort (n = 87) of paediatric patients treated with IST only. 218 The overall haematologic response rate was 70% in the eltrombopag group, which did not differ from that in the comparator cohort (72%; P = 0Á78). Relapses and clonal evolution rates occurred at similar rates in the ACE and historical groups.…”

“…A smaller proportion of patients in the NIH ACE study was children. A subgroup analysis of 40 patients <18 years of age who received ACE was compared to a historical cohort ( n = 87) of paediatric patients treated with IST only 218 . The overall haematologic response rate was 70% in the eltrombopag group, which did not differ from that in the comparator cohort (72%; P = 0·78).…”

Fludarabine–Cyclophosphamide-Based Conditioning with Antithymocyte Globulin Serotherapy Is Associated with Durable Engraftment and Manageable Infections in Children with Severe Aplastic Anemia

“…Our results show that a median time to transplantation of 4.5 months leaves a window of opportunity for a nontransplant strategy before the availability of the alternative donor. The chance of improving IS results can be seen in using new drugs, such as thrombopoietin receptor antagonists, which have been shown to stimulate the proliferation of autologous hematopoietic stem cells, resulting in the licensing of eltrombopag in SAA in adults and children over 12 years of age, but studies in children have not confirmed the efficacy of SAA upfront therapy [ 58 , 59 ].…”