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

Abstract

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.

Keywords: aplastic anaemia; elderly patients; immunosuppression.

Figure 1.. Schematic of Patients included in Current Study.

Patients aged ≥18 were included from two clinical trials (NCT00260689: hATG+CSA versus rATG+CSA and NCT01623167: hATG+CSA + EPAG) and split into two cohorts: older (≥ 60 years old) and younger (aged 18–59 years old). Treatment specific toxicities were assessed, as were long-term outcomes.

Figure 2.. Relapse and Clonal Evolution by Age.

(A) Cumulative incidence of relapse from 6 months by age, ≥60 (red), 18–59 (blue) (B) Cumulative incidence of clonal evolution by age, ≥60 (red), 18–59 (blue).

Figure 3.. Overall Survival and Survival stratified by age and response.

(A) KM curve of survival by age group, ≥60 (red), 18–59 (blue). (B) KM curve of survival by age group and 6-month response. Non-Response (NR) 18–59 (orange), NR ≥60 (green), Response (R) ≥60 (purple), (R) 18–59 (blue).