Impact of Choice of Induction Regimen on Overall Survival and Post-Remission Survival Among Older Adults with Acute Myeloid Leukemia

Older patients make up the majority of those diagnosed with acute myeloid leukemia (AML), however, many of these patients are not able to tolerate intense induction chemotherapy regimens. The use of lower intensity induction such as hypomethylating agents (HMA) with or without venetoclax or other targeted therapies has widened the scope of patients who are able to receive induction chemotherapy and move towards a hematopoietic stem cell transplant. Recent data from the Center of International Blood and Marrow Transplant research showed that patients aging >64 years accounted for 26% of all allogeneic transplantations in 2019 compared to only 9% in 2009. We have previously published a report showing that induction with FLAG +/- Idarubicin (FLAG+ IDA) results in better post remission survival than '7+3'induction (Solh et al, Leuk res 2020). In order to determine how induction chemotherapy affects post-remission outcomes among older patients with AML, 289 patients over the age of 55 year who received either FLAG±IDA, 7+3, or HMA based induction at a single institution were analyzed. Median follow up was 48 months. Patient and disease characteristics were as follows: Median age 64 (55,83) years, secondary AML (10%), abnormal cytogenetics (49%), and NCCN non-favorable risk (76%). Induction regimens included FLAG+/- Ida (n=208, 72%), 7+3 (n=60, 21%) and HMA based (n=21, 7%). A total of 248 patients (86%) achieved CR/Cri after induction with a median time from induction to CR of 28 days. Patients who received induction with FLAG±IDA reached a higher rate of CR after one cycle (92% vs 75% vs 62%) and had a shorter time to CR (27 vs 33vs 55 days) compared to '7+3' or HMA based therapy (p<0.001 for both). FLAG±IDA had better overall survival and DFS 3 years post-remission compared to '7+3' and HMA OS (50%, 45%, 22%, p=0.021) and DFS (45%, 37%, 8% p=0.01) respectively. A total of 133 patients received allogeneic transplantation. Transplant rate was similar between FLAG+/- IDA (n=100) and 7+3 (n=29) at 48% and was significantly better than HMA-based induction 19% (n=4) (p=0.03). Post-transplant survival and DFS was not significantly different between FLAG+/-Ida and 7+3, however both were better compared to HMA based induction with OS (54%, 44%, 25%) and DFS (51%, 44%, 25%) . On multivariate analysis on post remission survival and disease free survival, NCCN risk and age were both associated with OS ( high risk NCCN vs others HR 3.63, P<0.001; Age per 5 year increment HR 1.16, p=0.049) and NCCN risk was the only factor associated with worse DFS ( high vs others HR 2.4, p<0.0001). The choice of induction regimen did not significantly impact post-remission survival outcomes.

In conclusion, Older patients with AML achieve higher rates of complete remission, shorter time to remission and better post-remission survival with FLAG+/-IDA than 7+3 or HMA-based induction.