Real-world use of thrombopoietin receptor agonists in older patients with primary immune thrombocytopenia

Blood. 2021 Aug 19;138(7):571-583. doi: 10.1182/blood.2021010735.

Abstract

The efficacy and safety of thrombopoietin receptor agonists (TRAs) in older patients with primary immune thrombocytopenia (ITP) are unknown. We investigated TRA response and switch, thrombotic/hemorrhagic risk, and sustained responses off-treatment (SROTs) in 384 patients with ITP aged ≥60 years. After 3 months, 82.5% and 74.3% of eltrombopag- and romiplostim-treated patients, respectively, achieved a response; 66.7% maintained the response (median follow-up, 2.7 years). Eighty-five (22.2%) patients switched to the alternative TRA; although no cross-toxicity was observed, 83.3% of resistant patients had a response after the switch. Thirty-four major thromboses (3 fatal) and 14 major hemorrhages (none fatal) occurred in 18 and 10 patients, respectively, while on TRAs and were associated with thrombosis history (subdistribution hazard ratio, 2.04, P = .05) and platelet count <20 × 109/L (subdistribution hazard ratio, 1.69; P = .04), respectively, at TRA start. A recurrent event occurred in 15.6% of patients surviving thrombosis, in all cases but 1 during persisting TRA treatment (incidence rate, 7.7 per 100 patient-years). All recurrences occurred in the absence of adequate antithrombotic secondary prophylaxis. Sixty-two (16.5%) responding patients discontinued TRAs; 53 (13.8%) patients maintained SROTs, which were associated with TRA discontinuation in complete response (P < .001). Very old age (≥75 years; 41.1%) was associated with the more frequent start of TRAs in the persistent/acute phase but not with response or thrombotic/hemorrhagic risk. TRAs are effective in older patients with ITP, with no fatal hemorrhages and with SROTs in a significant portion of patients. Caution is warranted in patients with a history of thrombosis, and a careful risk/benefit balance should be considered.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Benzoates* / administration & dosage
  • Benzoates* / adverse effects
  • Female
  • Follow-Up Studies
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Hydrazines* / administration & dosage
  • Hydrazines* / adverse effects
  • Male
  • Middle Aged
  • Purpura, Thrombocytopenic, Idiopathic* / drug therapy
  • Purpura, Thrombocytopenic, Idiopathic* / mortality
  • Pyrazoles* / administration & dosage
  • Pyrazoles* / adverse effects
  • Receptors, Fc* / administration & dosage
  • Receptors, Thrombopoietin / antagonists & inhibitors*
  • Recombinant Fusion Proteins* / administration & dosage
  • Recombinant Fusion Proteins* / adverse effects
  • Retrospective Studies
  • Thrombopoietin* / administration & dosage
  • Thrombopoietin* / adverse effects
  • Thrombosis* / chemically induced
  • Thrombosis* / mortality

Substances

  • Benzoates
  • Hydrazines
  • Pyrazoles
  • Receptors, Fc
  • Receptors, Thrombopoietin
  • Recombinant Fusion Proteins
  • MPL protein, human
  • Thrombopoietin
  • romiplostim
  • eltrombopag