Avatrombopag Use in Patients with Persistent Thrombocytopenia Secondary to Intensive Chemotherapy Treatment

INTRODUCTION AND OBJECTIVES:

Thrombocytopenia after intensive chemotherapy treatment or after allogeneic hematopoietic stem cell transplantation (alloHSCT) can lead to an increase in the morbidity and mortality of patients, increasing the bleeding risk, requiring periodic platelet transfusions and/or reducing the intensity of chemotherapy doses. Therefore, new prevention and treatment strategies are required.

Avatrombopag (AVA) is a thrombopoietin receptor agonist, whose function is to mimic the biological effects of thrombopoietin (TPO), stimulating the development and maturation of megakaryocytes and increasing the platelet count.

Our objective was to describe and analyze the experience of treatment with AVA in adult patients with persistent thrombocytopenia secondary to intensive chemotherapy or alloHSCT in our hospital.

MATERIAL AND METHODS:

This retrospective, descriptive study examines 14 patients aged over 18 years who experienced persistent thrombocytopenia after undergoing intensive chemotherapy. The data were collected from cases treated between December 2023 and July 2024. We collected clinical-biological variables, diagnosis and previous chemotherapy treatment, platelet counts, AVA administered dose, response rate, time to response, platelets transfusions received and secondary adverse effects as well.

AVA was initiated at a dose of 20 mg/day, with dose adjustment to achieve platelet recovery to >30 × 10⁹/L (partial response, PR) or >100 × 10⁹/L (complete response, CR) without transfusion during 7 consecutive days.

RESULTS:

A total of 14 patients were analyzed, 9 of them (64%) were men, with a median age of 64 years [21-72] and an ECOG of 1 [0-2]. 4 patients were diagnosed of diffuse large B cell lymphoma, 2 primary mediastinal lymphoma, 2 severe bone marrow aplasia, 2 primary myelofibrosis, 1 HTLV1-associated adult T leukemia/lymphoma, 1 tricholeukemia, 1 acute myeloid leukemia and 1 multiple myeloma.

Persistent thrombocytopenia was secondary to intensive chemotherapy in 8 patients (57%), 4 patients after alloHSCT (29%) and 2 patients after CAR-T cell therapy (14%). Eight patients (57%) initially presented hemorrhagic symptoms: cutaneous-mucosal hemorrhage in 5 patients, upper gastrointestinal bleeding in 2 patients and subarachnoid hemorrhage in 1 patient.

Avatrombopag administered dose was 20 mg/day (140 mg/week), needing to increase to 40 mg/day (280 mg/week) in 4 patients (29%) and maintaining the initial dose in the rest. After starting AVA treatment, weekly blood count monitoring was conducted. The median platelet count was: 11x10⁹/L at the beginning, 22.1x10⁹/L in the first week of treatment, 39x10⁹/L after two weeks, 55.3x10⁹/L in the third and 86.1x10⁹/L in the fourth week.

Twelve patients achieved an overall response rate of 86%, with 6 achieving CR (43%) and 6 PR (43%). However, the 2 patients who received CAR-T therapy (14%) did not show any improvement. Treatment lasted a median of 43 [18-116] days, considering that 5 patients are currently taking the drug. The treatment with AVA was well tolerated with only three patients (21%) presenting nausea, vomiting and asthenia. No associated thrombotic events were observed in any of the patients.

In total, 7 patients (50%) did not require any platelet transfusions during this period and the other 7 patients (50%) received a median of 6 [0-27] platelet transfusions. None of them presented new hemorrhagic events or bleeding complications.

The median of hospitalization days were 23 days [range 0-168], and 5 patients (36%) were managed exclusively in outpatient care, without requiring hospital admission.

CONCLUSIONS:

- In our experience, Avatrombopag was effective in increasing platelet count after intensive chemotherapy in 86% of analyzed patients, with few associated adverse events.

- Avatrombopag use could decrease bleeding complications, platelets transfusions needs and the number of hospitalization days; however, further studies are needed to confirm this effect.

Bento De Miguel:Kite/Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Abbvie: Consultancy; Takeda: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Lilly: Consultancy; Incyte: Honoraria, Speakers Bureau. Fernández de Larrea:Pfizer: Honoraria; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Takeda: Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria, Other: Travel Expenses; Cellectar Biosciences: Research Funding; GSK: Consultancy, Honoraria. Canaro Hinryk:Novo Nordisk, Takeda, Roche, Pfizer, Octapharma, Amgen, Novartis, CSL Behring and Sobi: Speakers Bureau; Novo Nordisk, Takeda, Roche, Pfizer, Octapharma, Amgen, Novartis, CSL Behring and Sobi: Honoraria.