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2024-06-03T10:21:37.000Z

Salvage chemotherapy to induce remission prior to allo-HSCT vs immediate transplant in patients with R/R AML

Jun 3, 2024
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Learning objective: After reading this article, learners will be able to cite a new clinical development in the treatment of acute myeloid leukemia.

Allogeneic hematopoietic stem cell transplant (allo-HSCT) is currently the only treatment that offers long-term disease-free survival in patients with relapsed/refractory acute myeloid leukemia. However, the impact of therapeutic interventions to induce complete remission prior to allo-HSCT has never been fully evaluated in randomized trials. 

Recently, Stelljes et al.1 published results from the phase III ASAP trial (NCT02461537) in Lancet Hematology, comparing disease control strategies and immediate allo-HSCT vs standard salvage chemotherapy to induce remission prior to allo-HSCT. We summarize the key results below.

Study design1 

  • In this open-label, multicenter, randomized controlled trial, patients in the remission induction group received high-dose cytarabine (3g/m2 twice daily on Days 13) and mitoxantrone (10mg/m2 on Days 35); patients in the disease control group proceeded to allo-HSCT as soon as possible. 

  • The primary endpoint was the rate of treatment success, defined as complete remission on Day 56 post allo-HSCT. 

  • The key secondary endpoint was overall survival from randomization. 

Key findings1 

  • A total of 281 patients were enrolled: 

  • 141 in the remission induction group; and 

  • 140 in the disease control group. 

  • The median follow up was 37 months. 

  • In the per-protocol population (n = 272), treatment success was achieved by more patients in the disease control group than in the remission induction group (84% vs 81%; p = 0.047). 

  • Survival outcomes were comparable in the intent-to-treat population for patients treated with remission induction or disease control (Figure 1). 

Figure 1. Survival outcomes for patients with relapsed/refractory AML treated with salvage chemotherapy before allo-HSCT or disease control and immediate allo-HSCT (intention-to-treat population)*  

AML, acute myeloid leukemia; allo-HSCT, allogeneic hematopoietic stem cell transplant; CIR, cumulative incidence of relapse; CR, complete remission; LFS leukemia-free survival; NRM, non-relapse mortality; OS, overall survival. 
*Adapted from Stelljes, et al.1 
Estimated difference in treatment success was 3.4%.  
Non-inferiority could not be shown at the 2.5% significance level. 

 Safety 

  • Non-hematological Grade 3 adverse events were more frequent in the remission induction group vs the disease control group (61% vs 21%; p<0.0001). 

  • The most common event across both groups was infection (55% vs 16%; p <0.0001). 

  • The cumulative incidence of Grade 24 acute graft-versus-host disease at Day 120 post HSCT was comparable between the induction remission and disease control groups in the per-protocol population (21% vs 22%, p = 0.74). 

  • Within 28 days, 6 patients died in the remission induction group and 8 patients from the disease control group (p = 0.65). 

Key learnings 

  • In this study, non-inferiority of disease control and immediate allo-HSCT was not shown, and remission induction with salvage chemotherapy prior to HSCT did not improve the rate of treatment success. 

  • Overall, the results suggest that if a donor is available, salvage chemotherapy could be omitted in fit patients with relapsed/refractory AML without compromising long-term disease-free survival; however, more randomized controlled trials are needed. 

  1. Stelljes M, Middeke J, Bug G, et al. Remission induction versus immediate allogeneic hematopoietic stem cell transplantation for patients with relapsed or poor responsive acute myeloid leukemia (ASAP): a randomized, open-label, phase 3, non-inferiority trial. Lancet Hematol. 2024. Online ahead of print. DOI: 10.1016/S2352-3026(24)00065-6  

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