Evaluation of bone marrow reticulin in patients with chronic immune thrombocytopenia treated with eltrombopag: Data from the EXTEND study

Abstract

Thrombopoietin receptor agonists, which raise platelet counts in patients with chronic immune thrombocytopenia, may be associated with increases in bone marrow (BM) reticulin. Patients with chronic immune thrombocytopenia participating in the Eltrombopag Extended Dosing (EXTEND) study underwent BM biopsies to identify clinically relevant BM fibrosis‐related increases. Specimens were centrally reviewed by 2 hematopathologists. Two hundred thirty‐two biopsy specimens were collected from 117 patients treated for ≤5.5 years. Moderate to marked reticulin fibrosis was found in 2 patients. After withdrawing from the study, the biopsy of 1 patient reverted to normal. There were no other pathologic changes identified among on‐treatment specimens, and no pattern of abnormal reticulin deposition associated with eltrombopag treatment was evident. Am. J. Hematol. 90:598–601, 2015. © 2015 Wiley Periodicals, Inc.

Eltrombopag for use in children with immune thrombocytopenia

“…The Eltrombopag Extended Dosing Study (EXTEND), which started in 2006, is a recently completed, open-label trial that assessed adult patients with chronic ITP who were being treated with eltrombopag for bone marrow reticulin fibrosis. 31 Initial results from this trial were published in 2015 and showed moderate to marked fibrosis in only 2 patients. 31 One patient's marrow findings reversed after the patient withdrew from the study.…”

“…31 Initial results from this trial were published in 2015 and showed moderate to marked fibrosis in only 2 patients. 31 One patient's marrow findings reversed after the patient withdrew from the study. 31 The final results of the study (published in December 2017) showed data from 356 biopsy specimens collected from 166 patients treated for up to 7 years with eltrombopag.…”

How we manage immune thrombocytopenia in the elderly

“…The distinction between bone marrow samples in early MDS and ITP may be difficult. Abnormal megakaryocyte morphology and, sometimes, fine fibres of reticulin deposits can be observed in ITP (Brynes et al, 2015;Rivi ere et al, 2015). A frequent situation is the presence of some features of dyserythropoiesisis and/or dysgranulopoiesis in the blood smear, which are insufficient to ascertain MDS (<10% dysplasia of myeloid lineage and blast proportion <5%), sometimes considered to be idiopathic cytopenia of undetermined significance (ICUS) (Valent et al, 2012;Kwok et al, 2015).…”

Management of newly diagnosed immune thrombocytopenia: can we change outcomes?

“…The most concerning side effects are thrombocytosis, thrombosis, transaminitis with eltrombopag, and bone marrow reticulin changes. [38][39][40] Eltrombopag was associated with cataract formation in early preclinical studies; however, in clinical trials the risk does not appear to be increased. It is unclear whether any additional risks would be increased with concomitant corticosteroid use or any new safety signals will be discovered.…”