Eltrombopag, oral immunosuppressant and androgen combination therapy in twelve patients with refractory severe aplastic anemia

Abstract

Objective: Eltrombopag monotherapy or eltrombopag combined with immunosuppressant has achieved robust hematologic responses in severe aplastic anemia (SAA). In patients with refractory SAA, for whom hematopoietic stem cell transplantation is unavailable, we attempted to combine eltrombopag with oral immunosuppressant and androgen, to further improve hematologic response. Methods: We collected and analyzed data retrospectively from twelve refractory SAA cases who had received combination therapy of eltrombopag, oral immunosuppressant and androgen. All these patients had received intensive immunosuppressive treatment (IST) for more than 6 months and were evaluated as nonresponders. Results: A total of 12 SAA patients were treated with a combination of eltrombopag, an oral immunosuppressant (cyclosporine, N = 9; tacrolimus, N = 3) and androgen. The median maximum dose of eltrombopag was 75 mg/day (range, 75-150). After a median follow-up of 8.5 months (7-23), the overall response rate (ORR) was 42% (5/12, including trilineage, N = 4; hemoglobin + platelet, N = 1). Two of 5 responders reached normal blood counts. Optimal hematological response rates were reached at 6 months. The median increase in neutrophil, hemoglobin and platelet count were 1.64 × 10 9 /L (0.71-2.66), 53 g/L (25-66.5) and 25 × 10 9 /L (14-230), respectively. In general, the combination therapy was well tolerated; however, two patients suffered from non-lethal upper extremity venous thrombosis when they were platelet transfusion-dependent. Conclusion: Eltrombopag, oral immunosuppressant and androgen combination therapy in patients with IST-refractory SAA is feasible and could restore multi-lineage hematopoiesis. Thrombosis risk of eltrombopag still needs to be monitored.

Use of Cyclosporine A and danazol in treatment of aplastic anemia: A real-world data from a teaching hospital in South India

“…In a study by Gao et al, they observed that, in total of 12 patients, overall response rate was 42%. 10 In the present study, it was also observed that 73% patients were lost to follow-up (Figure 1). High incidence of AA in India is linked to lower socioeconomic status.…”

“…9 Eltrombopag is added to this combination if the patient affords this treatment. 10 However, there are limited data published in the literature from India, which highlights the utility of cyclosporine and anabolic steroids. Hence, this study was conducted to know the effect of these medications in patients with AA.…”

Long-term Prophylaxis with Androgens in the management of Hereditary Angioedema (HAE) in emerging countries

“…Despite having been shown to increase C1-INH mRNA expression, upregulate C1-INH protein levels and promote accelerated degradation of bradykinin to alleviate the symptoms of angioedema, the exact mechanism of androgens requires further study [ 13 , 14 ]. In the last decade, androgens are considered to be effective and commonly used for HAE and other diseases, such as aplastic anemia, testicular insufficiency, and anorchidism [ 15 – 17 ].…”

Table_1.pdf

“…Aged patients usually exhibit poor response to treatment when compared with the younger ones, for either IST or HSCT (35)(36)(37). Under this circumstance, we found that EPAG+IST had a very similar ORR (lower in absolute number) than the haplo-HSCT (81% in the EPAG+IST group and 86% in the haplo-HSCT group, p = 0.23).…”

“…However, there was a non-significant higher OS and less death rate, probably due to the small number of patients. These findings imply that EPAG+IST has comparable efficacy and OS with haplo-HSCT, even for younger patients, who are the right candidates for haplo-HSCT (35). So far, there was no head-to-head comparison for the frontline treatment of either EPAG+IST with MSD or EPAG+IST with haplo-HSCT.…”