Conference Coverage

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


 

AT ASH 2022

Investigators confessed to being “astonished” by results of a randomized trial showing that patients with acute myeloid leukemia (AML) who have a poor response after induction therapy do just as well proceeding straight to immediate allogeneic transplant as they would if they had received an intensive salvage induction regimen to get them into remission before transplant.

The results come from the phase 3 ASAP Trial and were presented at the annual meeting of the American Society of Hematology.

“We selected this to be in the plenary because it completely changes how we’ve traditionally thought about acute myeloid leukemia,” commented press briefing moderator Mikkael A. Sekeres, MD, from the University of Miami, who also serves as chair of the ASH Committee on Communications.

“When we have a patient who has relapsed or refractory AML, that person is in a very, very difficult situation, and the mortality among those sort of patients is incredibly high,” Dr. Sekeres commented. “So traditionally we’ve given them very high doses of chemotherapy to try to reduce the tumor burden – at least that’s been the theory – to then get them successfully to a transplant.”

This new finding “completely upends that, if these results hold,” he said. The clinical implication is that “we no longer have to hospitalize these patients and give them very aggressive chemotherapy ... [and] we don’t introduce all the morbidity from giving them very high dose chemotherapy, which can actually prevent a transplant from happening if they get sick enough, and we can get them to a transplant quicker.”

The ASAP trial was conducted in patients with an unfavorable risk AML who either had a poor response to first induction therapy or a relapse after first induction therapy.

They were randomly assigned to either a remission-induction strategy aiming for a better response prior to an allogeneic hematopoietic stem cell transplant (alloHCT), or a disease-control strategy consisting primarily of watchful waiting with low-dose cytarabine and single doses of mitoxantrone as needed, followed by sequential conditioning and alloHCT.

The results after 4 years of follow-up showed no differences in either leukemia-free survival or overall survival between patients who underwent additional chemotherapy with the remission-induction strategy and those who went straight to transplant, reported Johannes Schetelig, MD, MSc, from the Clinical Trials Unit at DKMS, Dresden, Germany.

“We expected non-inferiority – this was what we tested, and of course this was based on an assumption that we could get close or even somewhat better with respect to the primary endpoint, disease-free survival, after transplantation,” he said.

“What we did not expect is that the early success, [complete response] on day 56 after transplantation, also translates into equal long-term benefit, so this is what I was really astonished about,” Dr. Schetelig said at a press briefing prior to his presentation.

Less intensive approach

Dr. Schetelig explained that the rationale for the study was previous work by his group and others showing that alloHCT in patients with residual aplasia after first induction is feasible, with favorable outcomes, compared with standard of care. Additionally, the impetus for the research was evidence that sequential conditioning based on high-dose cytarabine or melphalan plus reduced-intensity conditioning and alloHCT resulted in long-term control for relapsed or refractory AML.

Pages

Recommended Reading

AML’s seasonal peak suggests viral or environmental etiology
MDedge Hematology and Oncology
First drug therapy approved for childhood GVHD
MDedge Hematology and Oncology
Bias and other barriers to HSCT access
MDedge Hematology and Oncology
Pivotal trials in blood cancers don’t mirror patient populations
MDedge Hematology and Oncology
`Wonder Woman’ launches myelofibrosis research foundation
MDedge Hematology and Oncology
Drug combo holds promise of better AML outcomes
MDedge Hematology and Oncology
Worldwide trial seeks to revolutionize pediatric leukemia care
MDedge Hematology and Oncology
FDA approves olutasidenib for some AML patients
MDedge Hematology and Oncology
ASH 2022: New clinical data challenge long-held assumptions
MDedge Hematology and Oncology
Global effort needed to widen access to HSCT
MDedge Hematology and Oncology