Treatment with ATGAM leads to enduring haematological responses and 3-year survival probability of 84% in adult acquired aplastic anaemia patients in the Netherlands
Acquired aplastic anaemia(AA) is characterized by bone marrow failure. First-line treatment is either allogeneic stem cell transplantation(alloSCT) or intensive immunosuppressive therapy(IST) consisting of horse-derived Anti-Thymocyte globulin(ATGAM) and ciclosporin. Patients who are refractory 6 months after first-line treatment with IST can be treated with second-line alloSCT, rabbit-derived ATG(Thymoglobulin) or Eltrombopag, a Thrombopoietin-mimetic. In 2013, a national registry was started in which seven university hospitals and two large non-academic hospitals collect data on all consecutive adult AA patients, that received ATGAM and ciclosporin as first-line treatment. We present the outcomes of 103 patients from this registry.
Data on adults with AA who received ISTas first-line treatment was collected in the LUMC, A-UMC, UMCG, UMCU, RadboudUMC, Erasmus MC, Medisch spectrum Twente and Antonius Ziekenhuis Nieuwegein. The data included baseline-characteristics and follow-up data at 3, 6, 9 and 12 months. After 12 months, follow-up data was collected yearly. Response was defined as transfusion independency and neutrophil count >0.5 x 109/L. Overall survival(OS) was evaluated with the Kaplan-Meier method.
In October 2020, 103 patients treated with first-line IST consisting of ATGAM and ciclosporin were registered. Median age at start of treatment was 56 years (18-83). Median follow-up time was 30 months. OS probability at 36 months was 84% (CI 76-91%). Three patients died within six months after start of treatment and for 5 patients follow up time was less than 6 months. Of 95 evaluable patients, response rate at 6 months was 61% (CI 51-70%). From 37 non responding(NR) patients at 6 months, 11 continued ciclosporin without additional treatment of whom 9 became transfusion independent up to 16 months after ATGAM treatment. 26 NR patients received second-line treatment with alloSCT (n=7), Thymoglobulin (n=6), Eltrombopag (n=12) or Danazol (n=1) and 17 of them responded. Eight of the 9 patients without response to second-line treatment died. Among the 58 patients with initial response at 6 months, AA relapsed in 15. Three relapsing patients were treated with supportive care and in 3 patients ciclosporin was reintroduced (2 responses). Nine patients received second-line treatment (3 alloSCT, 6 eltrombopag) of whom 4 had a response and 4 of the NR patients died.
First-line treatment with ATGAM and ciclosporin in adult AA patients leads to a 6 month response rate of 61%. The majority of patients with refractory or relapsing disease do respond to second-line treatment). However, 12 of the 14 patients without a response to second-line therapy died as a result of bone marrow failure or treatment related toxicity. Future recommendations should aim to improve the outcome of second-line treatment in AA patients.