NEW ORLEANS — Investigators confessed to being "astonished" by results of a randomized proceedings showing that patients with acute myeloid leukemia who person a mediocre effect pursuing induction therapy bash conscionable arsenic good going connected to contiguous allogeneic transplant arsenic they would if they had received an intensive salvage induction regimen to get them into remission earlier transplant.
The results travel from the signifier 3 ASAP Trial and were presented present astatine the American Society of Hematology yearly meeting.
"We selected this to beryllium successful the plenary due to the fact that it wholly changes however we've traditionally thought astir acute myeloid leukemia," commented property briefing moderator Mikkael A. Sekeres, MD, from the University of Miami Miller School of Medicine, who besides serves arsenic seat of the ASH Committee connected Communications.
"When we person a diligent who has relapsed oregon refractory AML, that idiosyncratic is successful a very, precise hard situation, and the mortality among those benignant of patients is incredibly high," Sekeres commented. "So traditionally we've fixed them precise precocious doses of chemotherapy to effort to trim the tumor load — astatine slightest that's been the mentation — to past get them successfully to a transplant."
This caller uncovering "completely upends that, if these results hold," helium said. The objective accusation is that "we nary longer person to hospitalize these patients and springiness them precise assertive chemotherapy…[and] we don't present each the morbidity from giving them precise precocious dose chemotherapy, which tin really forestall a transplant from happening if they get sick enough, and we tin get them to a transplant quicker."
The ASAP proceedings was conducted successful patients with an unfavorable hazard AML who either had a mediocre effect to archetypal induction therapy oregon a relapse aft archetypal induction therapy.
They were randomly assigned to either a remission-induction strategy aiming for a amended effect anterior to an allogeneic hematopoietic stem compartment transplant (alloHCT), oregon a disease-control strategy consisting chiefly of watchful waiting with low-dose cytarabine and azygous doses of mitoxantrone arsenic needed, followed by sequential conditioning and alloHCT.
The results aft 4 years of follow-up showed nary differences successful either leukemia-free endurance oregon wide endurance betwixt patients who underwent further chemotherapy with the remission-induction strategy and those who went consecutive to transplant, reported Johannes Schetelig, MD, MSc, from the Clinical Trials Unit astatine DKMS successful Dresden, Germany.
"We expected non-inferiority — this was what we tested, and of people this was based connected an presumption that we could get adjacent oregon adjacent somewhat amended with respect to the superior endpoint, disease-free survival, aft transplantation," helium said.
"What we did not expect is that the aboriginal success, [complete response] connected time 56 aft transplantation, besides translates into adjacent semipermanent benefit, truthful this is what I was truly astonished about," Schetelig said astatine a property briefing anterior to his presentation.
Less Intensive Approach
Schetelig explained that the rationale for the survey was erstwhile enactment by his radical and others showing that alloHCT successful patients with residual aplasia aft archetypal induction is feasible, with favorable outcomes compared with modular of care, and besides connected grounds that sequential conditioning based connected high-dose cytarabine oregon melphalan positive reduced-intensity conditioning and alloHCT resulted successful semipermanent power for relapsed oregon refractory AML.
He besides gave details of the 2 attraction arms of the ASAP trial. The remission-inducing limb consisted of cytarabine (3 g/m2 for younger patients oregon 1 g/m2 for patients implicit property 60) doubly regular connected days 1-3 positive 10 mitoxantrone mg/m2 connected days 3-5 and consequent alloHCT. In the different radical — illness power anterior to sequential conditioning and alloHCT — watchful waiting was recommended, but low-dose cytarabine (LDAC) and azygous doses of mitoxantrone were permitted for illness control.
Although, arsenic Schetelig noted, the statistical extremity of the survey was to amusement non-inferiority of the illness power arm, this little intensive strategy succeeded expectations for gathering the superior endpoint of disease-free endurance (DFS; a maintained implicit response) by time 56 aft alloHCT.
In an intention-to-treat and per-protocol analysis, the respective rates of DFS astatine 56 days successful the illness power radical were 83.5% and 84.1%. In comparison, the respective rates successful the remission-induction radical were 81% and 81.3%.
In addition, aft a median follow-up from randomization of 37 months, determination were nary differences successful either leukemia-free endurance oregon wide endurance retired to 4 years aft DFS astatine time 56.
The disease-control strategy was besides associated with importantly less adverse events people 3 oregon greater (23% vs 64%, P < .001), and less days successful infirmary anterior to transplant (mean 19 vs. 42, P < .001). There were nary important differences betwixt the proceedings arms successful either deaths wrong 28 days of randomization oregon clip to discharge from infirmary (28 days successful each arm).
"These information enactment sequential conditioning and alloHCT without anterior remission-induction chemotherapy whenever a stem compartment donor is readily available," the researchers concluded.
"These results underline the value of facilitating alloHCT arsenic [the] astir effectual anti-leukemic therapy successful patients with [relapsed oregon refractory] AML and accent the request for starting donor hunt astatine diagnosis," they added.
The survey was sponsored by DKMS gemeinnützige GmbH. Schetelig disclosed honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Sekkeres reported nary applicable fiscal relationships.
American Society of Hematology (ASH) 2022 Annual Meeting: Abstract 4. Presented December 10, 2022.
Neil Osterweil, an award-winning aesculapian journalist, is simply a long-standing and predominant contributor to Medscape.
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