‘Astonishing’ results: Skip salvage chemo, proceed to HSCT

Dr. Schetelig also gave details of the two treatment arms of the ASAP trial. The remission-inducing arm consisted of cytarabine (3 g/m² for younger patients or 1 g/m² for patients over age 60) twice daily on days 1-3 plus 10 mitoxantrone mg/m² on days 3-5 and subsequent alloHCT. In the other group – disease control prior to sequential conditioning and alloHCT – watchful waiting was recommended, but low-dose cytarabine (LDAC) and single doses of mitoxantrone were permitted for disease control.

Although, as Dr. Schetelig noted, the statistical goal of the study was to show non-inferiority of the disease control arm, this less intensive strategy exceeded expectations for meeting the primary endpoint of disease-free survival (DFS; a maintained complete response) by day 56 after alloHCT.

In an intention-to-treat and per-protocol analysis, the respective rates of DFS at 56 days in the disease control group were 83.5% and 84.1%. In comparison, the respective rates in the remission-induction group were 81% and 81.3%.

Further, after a median follow-up from randomization of 37 months, there were no differences in either leukemia-free survival or overall survival out to 4 years after DFS at day 56.

The disease-control strategy was also associated with significantly fewer adverse events grade 3 or greater (23% vs. 64%, P < .001), and fewer days in hospital prior to transplant (mean 19 vs. 42, P < .001). There were no significant differences between the trial arms in either deaths within 28 days of randomization or time to discharge from hospital (28 days in each arm).

“These data support sequential conditioning and alloHCT without prior remission-induction chemotherapy whenever a stem cell donor is readily available,” the researchers concluded.

“These results underline the importance of facilitating alloHCT as [the] most effective anti-leukemic therapy in patients with [relapsed or refractory] AML and stress the need for starting donor search at diagnosis,” they added.

The study was sponsored by DKMS gemeinnützige GmbH. Dr. Schetelig disclosed honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Sekkeres reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.