Efficacy and safety of avatrombopag in combination with standard immunosuppressive therapy for severe aplastic anemia

Exp Hematol. 2024 Dec:140:104670. doi: 10.1016/j.exphem.2024.104670. Epub 2024 Nov 5.

Abstract

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. The addition of eltrombopag to immunosuppressive therapy (IST) improves the response rate, but its hepatotoxicity is concerning. Avatrombopag (AVA), a small-molecule thrombopoietin-receptor agonist without hepatotoxicity, has unknown efficacy in SAA treatment. This retrospective study assessed the efficacy and safety of AVA added to IST 42 SAA patients compared to a historical cohort of 84 patients receiving IST alone, using propensity score matching. The median age was 31.5 (6.0-67.0 years) years old in group A and 26 (16.0-45.0 years) years old in group B. At 3 months, group A showed higher complete response (CR) and overall response (OR) rates than group B (CR: 19.0% vs. 4.8%, p = 0.024; OR: 54.8% vs. 39.3%, p = 0.145). Higher CR and OR rates were also found at 6 months in group A than in group B (CR: 31.0% vs. 14.3%, p = 0.145; OR 71.4% vs. 51.2%, p = 0.048). In multivariate analysis of group A, a shorter interval from disease onset to antithymocyte globulin (ATG) treatment (≤6 months) (p = 0.005) predicted better responses rate at 6 months. Event-free survival was also improved in group A (60.7% vs. 49.6%). AVA was well-tolerated, with no hepatic injury observed during treatment, even in those with pre-existing hepatic impairment. The addition of AVA to IST improves both the response rate and response quality in patients with SAA while ensuring safety.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anemia, Aplastic* / drug therapy
  • Child
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydrazines / administration & dosage
  • Hydrazines / adverse effects
  • Hydrazines / therapeutic use
  • Hydrazones / adverse effects
  • Hydrazones / therapeutic use
  • Immunosuppressive Agents* / adverse effects
  • Immunosuppressive Agents* / therapeutic use
  • Male
  • Middle Aged
  • Pyrazoles* / adverse effects
  • Pyrazoles* / therapeutic use
  • Receptors, Thrombopoietin / agonists
  • Retrospective Studies
  • Thiazoles
  • Thiophenes
  • Treatment Outcome
  • Young Adult

Substances

  • Immunosuppressive Agents
  • avatrombopag
  • Pyrazoles
  • Receptors, Thrombopoietin
  • Hydrazines
  • Hydrazones
  • Thiazoles
  • Thiophenes