Tacrolimus Is Effective Immunosuppressive Therapy in Aplastic Anemia

Introduction: For patients with aplastic anemia (AA) who are ineligible or unsuited for hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy (IST) with cyclosporine A (CsA) and horse antithymocyte globulin (ATG) remains the standard therapeutic regimen of choice. However, CsA has notable side effects including hirsutism and gingival hyperplasia that may limit the overall duration and effective dosage of this therapy. In both renal and heart transplant patients, tacrolimus has shown an improved toxicity profile when compared to CsA, however the use of tacrolimus as an alternative to CsA in AA has not been systematically examined. We report our experience using tacrolimus plus horse ATG as first- and second-line IST in a diverse ethnic cohort of patients with acquired AA at two urban hospitals. Methods: We conducted a retrospective chart review of patients with AA treated at the University of Southern California (USC) Norris Cancer Hospital from 2008 to 2017 and the LAC+USC Medical Center from 2015 to 2017. Out of a cumulative 197 AA patients meeting inclusion criteria, 23 patients were identified who had received tacrolimus-based IST in either the first- or second-line setting. In these patients, tacrolimus was combined with horse ATG, glucocorticoids and more recently, eltrombopag. Demographic data as well as 3, 6, and 12 month overall response rate (ORR), time to last transfusion, time to transplant and toxicity were assessed. The Camitta criteria were used to categorize the severity of AA based on bone marrow cellularity and peripheral cell count. Criteria for complete response (CR) were ANC>1000, HGB>10 g/dL, and PLT >100,000. Partial response (PR) was defined as no longer meeting criteria for severe AA, or if moderate AA, transfusion independence or an increase in ANC by 500, HGB by 3 g/dL, and/or PLTs by 20,000. Results: Among the 23 patients in our cohort treated with tacrolimus IST, mean age at diagnosis was 40, 65% were female, 47.8% were Latino and 34.7% were Caucasian. 12 patients (52%) received tacrolimus as front-line immunosuppression. Of these patients, 4 (33%) had moderate AA and the rest (66%) had severe or very severe AA. The ORR was 75% at 3 months (3 CR + 6 PR), 80% at 6 months (1 CR + 7 PR) and 100% in those evaluable at 12 months (4 PR). Among those with severe disease, ORR were 75%, 71% and 27% at 3, 6 and 12 months respectively, with 2 receiving subsequent HSCT. 11 patients received tacrolimus in the second-line setting due to cyclosporine toxicity or incomplete response to cyclosporine IST. Prior to starting tacrolimus, 73% had moderate AA and 18% had severe or very severe AA. ORR was 55% (1CR + 4 PR) at 3 months, 36% (2 CR + 2 PR) at 6 months and 45% (4 CR + 1 PR) at 12 months. All responses were in patients with moderate AA. Conclusion: Front-line tacrolimus IST with horse ATG demonstrated in the treatment of AA with an overall favorable safety profile. For patients who are transplant ineligible, tacrolimus should be considered a suitable alternative to CsA as part of an IST front-line regimen. More strikingly, tacrolimus in the second-line IST setting can achieve significant responses in patients that continue to have moderate AA despite initial cyclosporine-based IST. Disclosures Weitz: Alexion Pharmaceuticals: Speakers Bureau.