Should we use intensive chemotherapy prior to allo-HCT in relapsed/refractory AML? 

In the phase 3 ASAP trial, intensive chemotherapy in advance of allogeneic haematopoietic cell transplantation (allo-HCT) did not lead to improved outcomes or survival benefits compared with watchful waiting followed by sequential conditioning and allo-HCT in patients with relapsed or refractory acute myeloid leukaemia (AML). 

A complete remission (CR) in advance to allo-HCT is an advantageous factor for patients with AML. Thus far, it has not been thoroughly investigated whether intensive chemotherapy, with the goal to induce remission, before allo-HCT results in better outcomes than sequential conditioning and allo-HCT in patients with relapsed/refractory AML. To assess this matter, the EATL3-ASAP trial (NCT02461537) randomised 182 patients with relapsed/refractory AML who were eligible for intensive chemotherapy and allo-HCT 1:1 to either:

• High-dose cytarabine and mitoxantrone, followed by allo-HCT; or
• Disease control: recommended watchful waiting but permission of low-dose cytarabine (LDAC) and single doses of mitoxantrone, followed by sequential conditioning, and allo-HCT.

The primary outcome was the CR rate at day 56 after allo-HCT. Prof. Matthias Stelljes (University of Muenster, Germany) presented the results [1].

In total, 76% of the participants in the disease-control arm did not need disease-control measures until the start of sequential conditioning. The primary endpoint did not reveal a significant difference between the disease control arm and the chemotherapy arm, with 84.1% and 81.3% of the participants achieving a CR at day 56 after allo-HCT, respectively (non-inferiority P=0.047). Moreover, the 1-year leukaemia-free survival rates following CR at day 56 were 71.5% in the disease-control arm and 69.9% in the chemotherapy arm (P=0.8). Finally, the 3-year overall survival rates were comparable, with 51.0% in the disease control arm and 54.2% in the chemotherapy arm (log-rank P=0.47). The disease control strategy resulted in fewer grade ³3 adverse events than the chemotherapy arm (23% vs 64%; P<0.001). Also, the number of days spent in the hospital prior to allo-HCT was significantly reduced in the disease-control arm compared with the chemotherapy arm (19 vs 42; P<0.001).

In conclusion, the current study showed that patients with relapsed or refractory AML did not achieve improved long-term outcomes if they received salvage chemotherapy in advance of allo-HCT, suggesting that a minimal disease burden is not necessarily a pre-requisite for good outcomes after allo-HCT.

1. Stelljes M, 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 ByAllo-HCT: Results from the Randomized Phase III ASAP Trial. Abstract 4, ASH 64^th Annual Meeting, 10–13 December 2022, New Orleans, LA, USA.

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Posted on 20 February 202327 March 2024