Efficacy of Low Dose Generic Antithymocyte Globulin and Cyclosporine in Idiopathic Aplastic Anemia

Background: In transplant ineligible idiopathic aplastic anemia (IAA) patients, immunosuppressant therapy (IST) with equine Anti-thymocyte globulin (eATG) and cyclosporine is a standard treatment option. In resource constraint settings, where cost is an indisputable determinant of care, haematologists perennially face challenges to come forward with economical yet effective treatment strategies to ensure wider affordability. To explore cost-effective therapeutic options for this under addressed patient population, we studied the efficacy of a lower dose of generic eATG.

Methods: Transplant ineligible AA patients (age > 12 years) treated with generic eATG (Thymogam) and cyclosporine from January 2010 to December 2016 were retrospectively analysed. Efficacy of low dose generic eATG (25 mg/kg/d for 4 days) was analysed and compared with standard dose of generic eATG (40 mg/kg/d for 4 days). The choice of eATG dose was based on affordability of the patient. The patients who had completed eATG therapy and followed up at 3 months and 6 months were included in efficacy analysis. Overall response rate (ORR) [including complete response (CR) and partial response (PR)] at 3 months and 6 months were analysed.

Results: Thirty-four AA patients treated with generic eATG and cyclosporine were analysed. Mean age was 23.74 years (range 13-45 years); 22 (64.7%) were males. PNH clone was present in 13 (38.2%) patients. Median duration of follow up was 21.1 months (range 3-42 months). Out of 34 patients included in the study, one patient died on day 15 of therapy due to febrile neutropenia, 32 followed up at 3 months and 30 completed 6 months follow up. ORR in the study population was 48.8% at 3 months and 60.6% at 6 months. Difference between ORR at 3 months with low dose (42.9%, CR 0, PR 6) and standard dose eATG (47.3%, CR 0, PR 9) was not significantly significant (p = 0.8). Similarly, difference in ORR at 6 months was not statistically significant between low dose (53.8%, CR 0, PR 7) and standard dose (61.1%, CR 1, PR 10) eATG (p = 0.537). Serious adverse events were observed in three patients in low dose group [non-fatal febrile neutropenia 1; seizure 1; acute kidney injury (AKI) 1] and 7 patients in standard dose group [death due to febrile neutropenia 1; non-fatal febrile neutropenia 2; intracranial bleed 1; AKI 2; flash pulmonary edema 1]. On multivariate analysis for ORR at 6 months, none of the expected variables (age, absolute neutrophil count, absolute lymphocyte count, interval between onset of symptoms to initiation of therapy) could reach statistical significance. Two patients relapsed (after 30 months and 36 months, respectively) after receiving low dose ATG and three patients relapsed after receiving standard dose ATG (after 18 months, 26 months and 38 months, respectively).

Conclusion: We found that efficacy of low dose generic eATG was similar to the standard dose generic eATG. We conclude that IST with low dose generic eATG and cyclosporine is an efficacious and economical approach that can potentially enhance treatment affordability in IAA patients. However, prospective studies with larger number of patients are needed to further validate these results.