Efficacy outcomes in the treatment of older or medically unfit patients with acute myeloid leukaemia: A systematic review and meta-analysis.

Older and medically unfit patients with acute myeloid leukaemia (AML) who are unsuitable for standard induction therapy have limited treatment options. A meta-analysis was performed with two objectives: 1) to describe outcomes for patients treated with hypomethylating agents, either decitabine or azacitidine, or low-dose cytarabine (LDAC) and 2) to describe the effect of age (<75 vs ≥75) on the remission rates. Thirteen published multi-centre studies in 1822 patients were identified where patients were treated with hypomethylating agents or LDAC. A random effects meta-analysis was performed to provide a pooled estimate of efficacy for the following endpoints: complete remission (CR), overall response rate (CR + complete remission with incomplete white blood cell recovery [CRi]), relapse free survival (RFS), overall survival (OS), and 60-day mortality. For all endpoints apart from RFS, there was significant unexplained between-trial variability (I2 > 64%). The pooled estimates of average outcome across studies were 15% (95% CI: 12%-19%) for CR; 22% (95% CI: 18%-26%) for overall response rate; 8.8 months (95% CI: 7.7 m-10.0 m) for median RFS; 6.3 months (95% CI: 5.3 m-7.4 m) for median OS and 21% (95% CI: 18%-25%) for 60-day mortality. The odds of response were 1.85 times higher (95% CI: 1.3-2.7) among patients who were <75 compared to those who were older.