The effect of eltrombopag in managing thrombocytopenia associated with tyrosine kinase therapy in patients with chronic myeloid leukemia and myelofibrosis.

Abstract

Approximately 20-50% patients with chronic phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs) or with myelofibrosis (MF) treated with ruxolitinib develop grade ≥3 thrombocytopenia needing treatment interruptions and dose reductions. We conducted a non-randomized, phase II, single-arm study to determine the efficacy of eltrombopag for patients with CML or MF with persistent thrombocytopenia while on TKI or ruxolitinib. Eltrombopag was initiated at 50 mg/day, with dose escalation up to 300 mg daily allowed every 2 weeks. Twenty-one patients were enrolled (CML=15, MF=6); median age 60 years (range, 31-97 years). The median platelet count was 44x109/L (range, 3-49x109/L) in CML and 62x109/L (range, 21-75x109/L) in MF. After a median of 18 months (range, 5-77 months), 12/15 patients with CML achieved complete platelet response. The median peak platelet count among responders was 154x109/L (range, 74-893x109/L). Among CML patients 5 could re-escalate the TKI dose and 9 improved their response. None of the 6 patients with MF had a sustained response. Therapy was generally well tolerated. One patient discontinued therapy due to toxicity (elevated transaminases). One patient with CML developed significant thrombocytosis (>1000x109/L). Another CML patient developed non occlusive deep venous thrombosis in the right upper extremity without thrombocytosis, and one MF patient had myocardial infarction. Eltrombopag may help improve platelet counts in CML patients receiving TKI with recurrent thrombocytopenia. Further studies are warranted.

• Authors: Mahran Shoukier, Gautam Borthakur, Elias Jabbour, Farhad Ravandi, Guillermo Garcia-Manero, Tapan Kadia, Jairo Matthews, Lucia Masarova, Kiran Naqvi, Koji Sasaki, Srdan Verstovsek, Jorge Cortes
• Journal: Haematologica (Haematologica) Vol. 106 Issue 11 Pg. 2853-2858 (11 01 2021) ISSN: 1592-8721 [Electronic] Italy
• PMID: 33054123 (Publication Type: Journal Article)

Chemical References

• Benzoates
• Hydrazines
• Protein Kinase Inhibitors
• Pyrazoles
• Protein-Tyrosine Kinases
• eltrombopag

Topics

• Benzoates
• Humans
• Hydrazines
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy)
• Middle Aged
• Primary Myelofibrosis (drug therapy)
• Protein Kinase Inhibitors (adverse effects)
• Protein-Tyrosine Kinases
• Pyrazoles
• Thrombocytopenia (drug therapy)
• Treatment Outcome