Efficacy and Safety of Avatrombopag on Thrombocytopenia after Chemotherapy in Acute Leukaemia

Background: Thrombocytopenia following chemotherapy is a common and serious complication that leads to an increased risk of bleeding and poor prognosis for patients with acute leukaemia. Current therapeutic strategies consist of platelet transfusion, recombinant human interleukin-11(rhIL-11) and recombinant human thrombopoietin (rhTPO) injection, but these strategies are not satisfactory for some patients and the treatment remains challenging. Avatrombopag is a novel thrombopoietin receptor agonist, which had been approved for thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a surgery in the USA, Europe, and China, and in patients with chronic immune thrombocytopenia who were unresponsive to previous treatments in the USA and Europe. This study aims to determine the efficacy and safety of avatrombopag on thrombocytopenia after chemotherapy of acute leukaemia, and to increase the evidence for clinical use of avatrombopag.

Methods: The clinical data of 24 acute leukaemia patients with grade 3/4 chemotherapy-induced thrombocytopenia (CIT) for 3-28 days were collected from February 2022 to February 2023. All patients received avatrombopag orally at a dose of 40 mg / day. Platelet (PLT) transfusion was allowed when the platelet level was less than 20×10 ⁹/L or with bleeding events. If platelet count increased to 100 ×10 ⁹/L or 50 ×10 ⁹/L more than baseline, which was defined as complete response (CR), treatment of avatrombopag was stopped.

Results: The median age of 24 patients with CIT was 38 (range 17‒69) years, with 14 patients diagnosed with acute myeloid leukemia (AML), 9 patients diagnosed with acute lymphoblastic leukemia (ALL), and 1 patient diagnosed with mixed phenotype acute leukemia (MPAL). Chemotherapy regiments for patients with AML included decitabine combined with venetoclax (n=5), decitabine combined with arabinoside (n=3), arsenic trioxide combined with retinoic acid (n=3), azacytidine combined with venetoclax (n=2), azacytidine combined with medium-dose arabinoside (n=1). Chemotherapy regiments for patients with ALL included CD19 specific CAR-T cells (n=3), decitabine (n=2), blinatumomab (n=2), IVP (idarubicin, vindesine, and prednisone) (n=1), azacytidine combined with venetoclax and chidamide (n=1). Chemotherapy regiment for the patient with MPAL was decitabine combined with venetoclax (n=1). At baseline, 10 patients experienced grade 3 thrombocytopenia after chemotherapy, while 14 patients experienced grade 4 thrombocytopenia after chemotherapy. The median lowest platelet count was 19×10 ⁹/L (range 1-47×10 ⁹/L). During the treatment period, 14 patients received platelet transfusion. The median time to reach the CR standard was 6 (range 3-26) days, and no patients stopped treatment due to side effect or drug intolerance. Compared with using avatrombopag before, the levels of platelet count were significantly increased ( P=0.000 1). The optimal platelet count of 22 patients reached the standard of CR after 7 days of drug withdrawal.

Conclusion: Avatrombopag is effective on increasing platelet counts in patients with acute leukaemia after chemotherapy, with a good safety profile. It is a suitable therapeutic option for thrombocytopenia after chemotherapy.