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Efficacy and Immunomodulating Properties of Eltrombopag in Aplastic Anemia following Autologous Stem Cell Transplant: Case Report and Review of the Literature.

ABSTRACT: Thrombopoietin receptor agonists (TPO-RA) are currently indicated for the treatment of chronic immune thrombocytopenia and relapsed refractory aplastic anemia. However, the off-label use of these drugs is more and more frequent, including in the setting of aplasia secondary to chemotherapy and hemopoietic stem cell transplant (SCT). Growing evidence suggests that mechanisms of action of TPO-RA go beyond the TPO-receptor stimulation and point at the immunomodulating properties of these drugs. Here, we present a case of prolonged bone marrow aplasia secondary to autologous SCT treated with eltrombopag. We describe the clinical efficacy and the immunomodulating effect of this drug on inflammatory cytokine profile and bone marrow histology. Furthermore, we provide a review of the most recent literature highlighting the efficacy and safety of TPO-RA after SCT and chemotherapy for hematologic conditions.

SUBMITTER: Bortolotti M

PROVIDER: S-EPMC9032708 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Efficacy and Immunomodulating Properties of Eltrombopag in Aplastic Anemia following Autologous Stem Cell Transplant: Case Report and Review of the Literature.

Bortolotti Marta M Pettine Loredana L Zaninoni Anna A Croci Giorgio Alberto GA Barcellini Wilma W Fattizzo Bruno B

Pharmaceuticals (Basel, Switzerland) 20220330 4

Thrombopoietin receptor agonists (TPO-RA) are currently indicated for the treatment of chronic immune thrombocytopenia and relapsed refractory aplastic anemia. However, the off-label use of these drugs is more and more frequent, including in the setting of aplasia secondary to chemotherapy and hemopoietic stem cell transplant (SCT). Growing evidence suggests that mechanisms of action of TPO-RA go beyond the TPO-receptor stimulation and point at the immunomodulating properties of these drugs. Her ...[more]

PMID: 35455416

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Project description:BackgroundAcquired aplastic anemia results from immune-mediated destruction of bone marrow. Immunosuppressive therapies are effective, but reduced numbers of residual stem cells may limit their efficacy. In patients with aplastic anemia that was refractory to immunosuppression, eltrombopag, a synthetic thrombopoietin-receptor agonist, led to clinically significant increases in blood counts in almost half the patients. We combined standard immunosuppressive therapy with eltrombopag in previously untreated patients with severe aplastic anemia.MethodsWe enrolled 92 consecutive patients in a prospective phase 1-2 study of immunosuppressive therapy plus eltrombopag. The three consecutively enrolled cohorts differed with regard to the timing of initiation and the duration of the eltrombopag regimen (cohort 1 received eltrombopag from day 14 to 6 months, cohort 2 from day 14 to 3 months, and cohort 3 from day 1 to 6 months). The cohorts were analyzed separately. The primary outcome was complete hematologic response at 6 months. Secondary end points included overall response, survival, relapse, and clonal evolution to myeloid cancer.ResultsThe rate of complete response at 6 months was 33% in cohort 1, 26% in cohort 2, and 58% in cohort 3. The overall response rates at 6 months were 80%, 87%, and 94%, respectively. The complete and overall response rates in the combined cohorts were higher than in our historical cohort, in which the rate of complete response was 10% and the overall response rate was 66%. At a median follow-up of 2 years, the survival rate was 97%; one patient died during the study from a nonhematologic cause. Marked increases in bone marrow cellularity, CD34+ cell number, and frequency of early hematopoietic progenitors were noted. Rates of relapse and clonal evolution were similar to our historical experience. Severe rashes occurred in two patients, resulting in the early discontinuation of eltrombopag.ConclusionsThe addition of eltrombopag to immunosuppressive therapy was associated with markedly higher rates of hematologic response among patients with severe aplastic anemia than in a historical cohort. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT01623167 .).

Project description:Few therapeutic options are available for patients with aplastic anemia who are ineligible for transplantation or refractory to immunosuppressive therapy. Eltrombopag was recently shown to produce trilineage responses in refractory patients. However, the effects of real-life use of this drug remain unknown. This retrospective study (2012-2016) was conducted by the French Reference Center for Aplastic Anemia on patients with relapsed/refractory aplastic anemia, and patients ineligible for antithymocyte globulin or transplantation, who received eltrombopag for at least 2 months. Forty-six patients with aplastic anemia were given eltrombopag without prior antithymocyte globulin treatment (n=11) or after antithymocyte globulin administration (n=35) in a relapsed/refractory setting. Eltrombopag (median daily dose 150 mg) was introduced 17 months (range, 8-50) after the diagnosis of aplastic anemia. At last followup, 49% were still receiving treatment, 9% had stopped due to a robust response, 2% due to toxicity and 40% due to eltrombopag failure. Before eltrombopag treatment, all patients received regular transfusions. The overall rates of red blood cell and platelet transfusion independence were 7%, 33%, 46% and 46% at 1, 3, 6 months and last follow-up. Responses were slower to develop in antithymocyte treatment-naïve patients. In patients achieving transfusion independence, hemoglobin concentration and platelet counts improved by 3 g/dL (interquartile range, 1.4-4.5) and 42×109/L (interquartile range, 11-100), respectively. Response in at least one lineage (according to National Institutes of Health criteria) was observed in 64% of antithymocyte treatment-naïve and 74% of relapsed/refractory patients, while trilineage improvement was observed in 27% and 34%, respectively. We found high rates of hematologic improvement and transfusion independence in refractory aplastic anemia patients but also in patients ineligible for antithymocyte globulin receiving first-line treatment. In conclusion, elderly patients unfit for antithymocyte globulin therapy may benefit from eltrombopag.

Dataset Information

Efficacy and Immunomodulating Properties of Eltrombopag in Aplastic Anemia following Autologous Stem Cell Transplant: Case Report and Review of the Literature.

Publications

Efficacy and Immunomodulating Properties of Eltrombopag in Aplastic Anemia following Autologous Stem Cell Transplant: Case Report and Review of the Literature.

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