Comparable Long-Term Outcomes of Low-Dose Versus Standard-Dose Equine Anti-Thymocyte Globulin with Cyclosporine in Aplastic Anemia

Background: Immunosuppressant therapy (IST) with equine anti-thymocyte globulin (eATG) and cyclosporine is the current standard treatment for transplant-ineligible aplastic anemia (AA) patients. Recently eltrombopag has been added to this IST backbone. The standard dose of eATG is 40mg/kg/day, however, the ideal dose of eATG is not known. We studied the efficacy of 25 mg/kg/day x 4 days (low-dose) with standard-dose eATG in transplant-ineligible AA patients at our tertiary care centre.

Methods: AA patients (age >12 years) who received eATG and cyclosporine from 2003 to 2021 were retrospectively analysed.The choice of eATG dose was based on patients'finances. Patients developing nephrotoxicity with cyclosporine were switched to oral mycophenolate mofetil. Overall response rates (ORR) [complete response (CR) and partial response (PR)] were analysed at 3 months, 6 months and 12 months after eATG.Kaplan-Meier survival analyses were performed to analyse overall survival (OS) and event free survival (EFS).

Results: Ninety-three AA patients received eATG during the study period. Their median age was 30 years (range 13-65 years); 60 (64.5%) were males. PNH clone was present in 33 (35.5%) patients. Median duration from symptom onset to diagnosis was 3 months (range 1-100 months). 62 patients (66.7%) received low-dose eATG; 31 patients (33.3%) received standard-dose eATG. 17 patients (18.3%) received eltrombopag in addition to eATG plus cyclosporine. The number of patients eligible for response assessment at 3 months, 6 months and 12 months were 93 (100%), 86 (92.4%) and 80 (86%), respectively. ORRs in the total study population at 3 months, 6 months, and 12 months were 49.5%, 66.3%, and 72.5%, respectively; respective CR rates were 5.4%, 14% and 20%. The differences between ORRs among low-dose versus standard-dose eATG groups at 3 months (50% vs 48.4%; p = 0.88), 6 months (63.8% vs 71.4%; p = 0.67) and 12 months (69.6% vs 79.2%; p = 0.167) were statistically insignificant. Median duration of oral cyclosporine after eATG was 25 months (range 3-144 months); 23 patients (24.7%) who were having suboptimal response at 6 months (PR 15, NR 8) and 12 months (PR 18, NR 5) achieved CR after 12 months with the continuation of cyclosporine. The median duration of follow up was 52 months (range 3-229 months). 11 patients (11.8%) relapsed after eATG (7 in low-dose group, 4 in standard-dose group) after a median duration of 32 months (range 12-84 months). Two patients (2.1%) underwent clonal evolution to AML and MDS-EB2 at 83 months and 35 months, respectively (both in standard-dose group). 15 patients (16.1%) died during follow up and 18 (19.3%) were lost to follow up. 10-year OS and 10-year EFS of the total study population were 80% and 64%, respectively. There was no significant difference between low-dose and standard-dose groups in terms of 10-year OS (82.4% vs 74.8%; p = 0.43) and 10-year EFS (64.5% vs 63.1%; p = 0.64), respectively.

Conclusion: This study revealed that low-dose eATG and standard dose eATG have comparable response rates and long-term survival. CR rates continue to improve with continuation of oral cyclosporine beyond 12 months in patients who have partial or no response at 6 and 12 months.

No relevant conflicts of interest to declare.