Results from a CIBMTR study of patients with MLL-rearranged AML

Translocations at chromosome 11q23 involving the MLL gene are present in 3%–4% of patients with acute myeloid leukemia (AML). Because adult cases of AML with 11q23 abnormalities are rare, there are a lack of studies evaluating the impact of these translocations on patient outcomes.¹ During the 2020 Transplantation & Cellular Therapy (TCT) Meeting, Kamal Menghrajani, Memorial Sloan Kettering Cancer Center,  New York, US, presented the results of a study by Center for International Blood and Marrow Transplant Research (CIBMTR)  evaluating the impact of MLL-rearranged AML on post-transplant outcomes as compared to intermediate- and adverse-risk disease.²

Methods²

• 8,709 adult patients with AML from the CIBMTR database were included
• Patients transplanted in first complete remission (CR1) were stratified by presence of 11q23 rearrangement, intermediate- or adverse-risk disease
• Relapse, non-relapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) were analyzed
• Of the 8,709 eligible patients, 3,779 were selected based on disease and donor type, HSCT in CR1, and availability of data, of these:
  • 426 patients had an 11q23 translocation:
    • t(9;11): 26% (n = 112)
    • t(11;19): 15% (n = 62)
    • t(6;11): 10% (n = 41)
    • t(10;11): 7% (n = 28)
    • 11% (n = 47) had other translocation partners
    • For 32% (n = 136) no translocation partner was provided
  • 2,384 patients had intermediate-risk disease
  • 969 patients had adverse-risk disease

Results²

• DFS was lowest in adverse-risk patients, hazard ratio (HR) for death:
  • adverse- risk, 1.47 (p < 0.001)
  • MLL, 1.26 (p = 0.002)
• OS was shorter for the MLL- and adverse-risk groups:
  • adverse-risk, HR = 1.45 (p < 0.001)
  • MLL, HR = 32 (p < 0.001)
• NRM was worse for patients with adverse-risk disease, with an HR of 1.17 (p = 0.05)
• Relapse risk was higher for adverse-risk patients:
  • adverse risk, HR = 1.71 (p < 0.001)
  • MLL, HR = 1.27 (p = 0.01)
• Relapse rates were similar for all translocation partners
• For patients with measurable residual disease (MRD)-positivity:
  • HR for relapse, 1.23 (p < 0.006)
  • For DFS, HR for death, 1.13 (p = 0.04)

Conclusions²

In adult patients with MLL-rearranged AML, transplanted in CR1:

• DFS and OS are very similar to patients with adverse-risk disease
• MRD was a predictor of relapse and DFS, but not of NRM or OS
• All translocation partners showed very similar relapse rates

All together these results demonstrated that adult patients with MLL-rearranged AML had a poor outcome, similar to patients with adverse-risk disease. New therapeutic approaches are needed for this population.