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.
The ASAP trial (ClinicalTrials.gov 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.