Disease risk but not remission status determines transplant outcomes in AML: long-term outcomes of the ASAP trial Open Access

• No benefit of remission induction with standard salvage chemotherapy prior to alloHCT for poorly responsive AML or first untreated relapse

• AML genetics, not remission status, determines overall survival after allogeneic hematopoietic cell transplantation

Attempting to induce a complete remission (CR) prior to allogeneic hematopoietic cell transplantation (alloHCT) is current practice in patients with AML. A benefit of remission induction prior to alloHCT, however, has never been proven in a prospective trial. Potent conditioning regimens exist which allow for successful alloHCT in patients with active AML. Therefore, the ASAP trial was conducted to test remission induction by salvage chemotherapy prior to alloHCT against immediate transplantation after intensified conditioning. In total 281 patients with AML with poor response after first induction or untreated first relapse were randomized 1:1 to remission induction (RIST) with high-dose cytarabine plus mitoxantrone versus immediate alloHCT with sequential conditioning after non-intensive disease control measures (DisC) preferentially watchful waiting only. Overall survival (OS) at 5 years from randomization analyzed according to ITT was 46.1% for DisC versus 47.5% for RIST (p=0.82). In multivariable Cox regression analysis, genetic AML risk according to ELN (p<0.0001), age (p=0.001) and comorbidities (p=0.046) predicted survival, but not treatment arm (HR 1.08 for DisC versus RIST, p=0.67). In conclusion, long-term follow-up of the ASAP trial showed no survival advantage for standard salvage chemotherapy prior to alloHCT as opposed to immediate alloHCT. The trial results question the general concept of remission induction with intensive standard salvage therapy prior to alloHCT for all patients, since immediate alloHCT may reduce time in hospital and health care expenses. Well tolerable novel bridging therapies and post-transplant maintenance with targeted drugs are urgently warranted, especially for adverse-risk AML, to improve outcome after alloHCT. NCT02461537