Safety and efficacy of immunosuppressive therapy for elderly patients with severe aplastic anaemia

Uncertainty remains regarding the safety and tolerability of immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG) and cyclosporine (CSA) in older patients. We retrospectively analysed two prospective clinical trials of IST in treatment-naïve severe aplastic anaemia (SAA) to assess safety in older compared to younger patients. Patients ≥18 years of age who had received IST with ATG and CSA +/- eltrombopag (EPAG) were included. Pre-treatment baseline characteristics and co-morbidities were assessed as predictors of therapy-related complications in younger (<60 years) versus older (≥60 years) patients. Out of 245 eligible patients, 54 were older and 191 were younger. Older patients had a similar frequency of SAEs, ICU admissions and hospital length of stay compared to younger patients. Older patients had a higher frequency of cardiac events related to IST, but none resulted in death. Older patients had worse long-term overall survival, and more relapse and clonal evolution post-IST. However, older patients who responded to IST had a similar survival at a median follow-up to younger patients. Disease-related factors and limited therapeutic options in refractory disease likely contribute to poorer outcomes in older patients, not complications of upfront IST. Therefore, IST should be considered first-line therapy for most older SAA patients.