Impact of number of induction courses to achieve complete remission in patients with AML prior to allo-HSCT

Induction chemotherapy is often administered to induce complete remission (CR) in patients with acute myeloid leukemia, prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Many patients who do not achieve CR after the first induction course (IND1) will go on to achieve CR after a second induction course (IND2). However, outcomes of patients who achieved CR with IND1 vs IND2 have yet to be compared.

Here, we summarize the key results published by Loke et al.¹ in Cancer from a registry-based study aiming to identify the prognostic value of the number of induction courses required to achieve CR, as well as which prognostic factors influence outcomes in patients requiring IND2 to achieve CR prior to allo-HSCT.

Study design¹

• A registry-based Acute Leukemia Working Party study from the European Society for Blood and Marrow Transplantation.
• Patients with acute myeloid leukemia who received allo-HSCT in the first CR from 2010–2020 were included.
• Patients received a human leukocyte antigen matched sibling donor, or a human leukocyte antigen 10/10 or 9/10 matched unrelated donor.

Key findings

• A total of 4,995 patients were included in the study
  • 3,839 patients required IND1 to achieve CR
  • 1,116 patients required IND2 to achieve CR
• The median follow-up period was 43.5 months.
• Patients requiring IND2 experienced poor overall survival (OS), leukemia-free survival and an increased risk of relapse vs those requiring IND1 (Figure 1).

Allo-HSCT, allogeneic hematopoietic stem cell transplant; CIR, cumulative incidence of relapse; IND1, one induction course; IND2, two induction course; OS, overall survival.
*Adapted from Loke, et al.¹

 

• Multivariate analysis showed IND2 to be an independent adverse prognostic factor for relapse (hazard ratio [HR] 1.38, p = 0.0003) and death (HR, 1.27, p = 0.002).
• The presence of FLT3-ITD mutation and adverse cytogenetics increased the risk of relapse and reduced OS in patients requiring IND2 vs IND1.
• Measurable residual disease prior to allo-HSCT remained a prognostic factor for relapse risk and OS regardless of the number of induction courses required for CR (Figure 2).
• In patients receiving IND2, chronic graft-versus-host disease was associated with a reduction in relapse risk (HR 0.64, p = 0.039) and an improved OS (HR 0.60, p = 0.04).

Allo-HSCT, allogeneic hematopoietic stem cell transplant; IND1, one induction course; IND2, two induction courses; MRD, measurable residual disease; OS, overall survival.
*Adapted from Loke, et al.¹

 

Key learnings

Patients requiring IND2 experienced an increased risk of death, but no increase in non-relapse mortality vs those requiring IND1. The reduced impact of IND2 on non-relapse mortality suggests that the inferior outcomes are associated with chemo resistant disease. In addition, adverse cytogenetics is a major prognostic factor influencing the outcomes of patients who required IND2 to achieve CR.