Salvage chemotherapy before allogeneic hematopoietic stem cell transplant (allo-HSCT) does not improve outcomes in patients with relapsed/refractory acute myeloid leukemia (AML), according to results of the phase 3 ASAP trial.

Intensive remission-induction chemotherapy followed by allo-HSCT did not improve disease-free survival (DFS) or overall survival (OS) when compared with allo-HSCT given after conditioning without an attempt to induce a complete remission (CR) before transplant.

These results were presented at the 2022 ASH Annual Meeting by Johannes Schetelig, MD, of University Hospital TU Dresden in Germany.

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The ASAP trial ( Identifier: NCT02461537) enrolled adults with AML who had a poor response after first induction or a first untreated relapse. They were randomly assigned to a remission-induction arm or a disease-control arm. 

Patients in the remission-induction arm received cytarabine (3 g/m2 if ≤60 years or 1 g/m2 if >60 years) twice daily on days 1-3 plus mitoxantrone (10 mg/m2) on days 3-5, followed by conditioning and allo-HSCT. Patients in the disease-control arm underwent watchful waiting or received low-dose cytarabine and single doses of mitoxantrone for disease control when necessary, followed by sequential conditioning and allo-HSCT. 

The intent-to-treat population included 276 patients — 137 in the remission-induction arm and 139 in the disease-control arm. The per-protocol population included 272 patients — 134 in the remission-induction arm and 138 in the disease-control arm.

At the data lock date, 76% of patients in the disease-control arm were kept on watchful waiting until the start of sequential conditioning. The remaining 24% of patients needed disease control measures.  

In the remission-induction arm, 46% of patients achieved a CR. Five patients received a second course of intensive chemotherapy. The remaining patients underwent allo-HSCT with no additional attempt to induce a CR. 

The median time to allo-HSCT was 4 weeks in the disease-control arm and 8 weeks in the remission-induction arm. From randomization, 97% of patients in the disease-control arm had been transplanted by week 16, and 93% of patients in the remission-induction arm had been transplanted by week 17. 

The primary endpoint was DFS at day 56 after allo-HSCT. In the per-protocol population, the DFS rate at day 56 was 84.1% in the disease-control arm and 81.3% in the remission-induction arm (P for noninferiority =.047). In the intent-to-treat population, the DFS rate at day 56 was 83.5% and 81.0%, respectively (P for noninferiority =.054). 

Among patients who met the primary endpoint, there was no significant difference between the remission-induction and disease-control arms for leukemia-free survival from day 56 (P =.61). In the intent-to treat population, there was no significant difference between the arms for OS from randomization (P =.47). The median follow-up from randomization was 37 months.

The rate of grade 3 or higher adverse events was 64% in the remission-induction arm and 23% in the disease-control arm (P <.001). Patients in the remission-induction arm also spent more than twice as long in the hospital (mean, 42 days vs 19 days; P <.001).

“Watchful waiting and sequential conditioning prior to allogeneic transplantation results in comparable CR rates and overall survival and may be the preferred option whenever a stem cell donor is readily available,” Dr Schetelig said. 

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.  


Stelljes M, Middeke JM, Bug G, et al. In patients with relapsed/refractory AML sequential conditioning and immediate allogeneic stem cell transplantation (allo-HCT) results in similar overall and leukemia-free survival compared to intensive remission induction chemotherapy followed by allo-HCT: Results from the randomized phase III ASAP trial. Presented at ASH 2022. December 10-13, 2022. Abstract 4.