by Isabell Arndt, DKMS

Credit: Unsplash/CC0 Public Domain

Results of a recently published long-term follow-up of the ASAP trial, which was conducted at universities and clinics across Germany, show that the genetic risk of disease, not remission status, determines overall survival of patients with high-risk acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, there is no benefit of remission induction with standard salvage chemotherapy prior to allo-HSCT.

The selection of patients for allo-HSCT and the best approach to bridging patients to transplantation is continuously discussed by experts. The first results of the ASAP study (ASAP standing for "as soon as possible"), publishedin 2024, have already attracted considerable attention.

ASAP questions existing treatment standards for AML and was the first randomized controlled trial to compare remission induction with salvage chemotherapy prior to allo-HSCT—which represents the current standard of care (SOC)—against an alternative approach of immediate transplantation after intensified conditioning combined with non-intensive disease control strategies such as less aggressive chemotherapy or simple monitoring of leukemic proliferation. These two groups are referred to as the SOC arm and the alternative treatment arm, respectively.

The long-term analysis, nowpublishedin the journalBlood, supports the initial results of the ASAP trial. The findings suggest that a transplantation as soon as possible yields comparable treatment outcomes as remission induction—with shorter hospital stays and reduced exposure to chemotherapy.

"The results question the international standard of leukemia treatment. We no longer need to give all patients a very aggressive chemotherapy to reduce the tumor burden ahead of transplantation when regimens with good anti-leukemic activity are used for conditioning on the days prior to stem cell transplantation," says Prof. Dr. Johannes Schetelig, co-author of the study.

The results were based on a median follow-up of 61 months in the patient cohort: The induction of remission in the SOC arm (5-year OS: 47.5%) compared to immediate transplantation in the alternative treatment arm (5-year OS: 46.1%) showed no overall survival (OS) advantage in AML patients, which were poorly responsive to initial treatment or with untreated relapse.

Since non-inferiority could not be demonstrated formally, immediate transplantation will not replace the common SOC but can be considered more often today.

One argument in favor of proceeding directly to transplantation without remission induction is that patients who received intensive salvage chemotherapy in the SOC arm spent one month longer in hospital and experienced more adverse events.

The long-term follow-up of ASAP additionally analyzed treatment success according to risk classification and genetic subgroups. Both age and AML genetics were identified as the most important baseline risk factors influencing survival. AML genetics were classified according to the ELN 2022 criteria.

The overall survival probabilities at 5 years (5-year OS) from randomization in the different risk groups independent from treatment arm were:

When both the ELN risk and the treatment were taken into account, the 3-year overall survival was 77% for patients with favorable/intermediate AML with watchful waiting in the alternative treatment arm (N = 49) versus 66% for patients transplanted with complete remission in the SOC arm in the same risk group (N = 49).

"In summary, it can be concluded that survival after allo-HSCT in AML patients is less influenced by remission induction or bridging strategies and more influenced by intrinsic disease biology," concludes Prof. Schetelig. Interestingly, reducing the pre-transplant leukemia burden did not translate into improved survival when intensive cytotoxic regimens were used, challenging a common assumption in treatment planning.

The uncertain benefits of inducingremissionprior to allo-HSCT are in contrast to the fundamental impact of AML genetics. Favorable risk AML was associated with higher survival rates compared to adverse risk AML. These findings are consistent with previous reports on the prognostic impact of the ELN 2022 classification in patients undergoing allogeneic stem cell transplantation.

"But the data of the ASAP trial also demonstrate that tolerable novel bridging therapies and posttransplant maintenance for more personalized strategies are urgently warranted, especially for adverse risk AML, to improve outcomes after allo-HSCT," summarizes Prof. Schetelig.

"These findings open the door for future research to identify specific AML subgroups—a key step toward precision medicine in transplantation."

More information: Matthias Stelljes et al, Disease risk but not remission status determines transplant outcomes in AML: long-term outcomes of the ASAP trial, Blood (2025). DOI: 10.1182/blood.2025028730 Journal information: Blood

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