DAC-BuCy vs BuCy in KMT2A-rearranged leukaemia

Background

Phase 3, open-label, randomized trial at 8 transplant centres in China. N=130. Patients aged 14-65 y, ECOG 0-2, with KMT2A-rearranged leukaemia undergoing allogeneic HSCT. Question: does adding the hypomethylating agent decitabine to myeloablative BuCy reduce relapse.

Results

Interventions and follow up: Arm A: DAC-BuCy: decitabine 20 mg/m2 IV days -14 to -10 + busulfan 3.2 mg/kg IV days -7 to -4 + cyclophosphamide 60 mg/kg IV days -3 to -2 (n=65)
Arm B: BuCy: same busulfan and cyclophosphamide (n=65)
Primary endpoint: 2-year cumulative incidence of relapse (ITT)
mFollow up: 34.7 mo (IQR 30.2-52.5)
Results: 2-yr relapse (CIR): 12% (6-22) vs 29% (19-41); HR 0.41 (0.20-0.87); P=.017
OS/PFS: NR in abstract

Adverse events

Infections (G3-5): 42% vs 38%
Acute GVHD (G3-5): 35% vs 34%
GI disorders (G3-5): 22% vs 23%
Deaths from AEs: 6% vs 8% (2 regimen-related toxicity deaths overall)

Conclusions

Adding decitabine to BuCy conditioning reduced relapse risk with an acceptable safety profile in adults with KMT2A-rearranged leukaemia undergoing allo-HSCT.

Key Limitations

Open-label, modest sample (N=130) with a relapse primary endpoint; survival benefit is not reported in the abstract. Heterogeneous KMT2A-rearranged population (AML and ALL) and transplant platforms, Chinese centres only, and conditioning-only comparison (no maintenance or post-transplant strategy control). Wide CIs; needs external validation.

Clinical Context

Myeloablative BuCy or Flu-Bu/TBI-based regimens are standard conditioning; KMT2A-rearranged leukaemia has high post-transplant relapse. This trial supports incorporating a hypomethylating agent into conditioning but is a single-country phase 3 without OS benefit shown; guideline adoption is not established.

References