Findings from a phase 3 trial published in JAMA Oncology suggest allo-HCT may not provide an OS benefit for patients with intermediate-risk acute myeloid leukemia during first complete remission.
Allogeneic hematopoietic cell transplantation (alloHCT) did not correlate with superior overall survival (OS) vs consolidation chemotherapy in patients aged 60 years or younger with intermediate-risk acute myeloid leukemia (AML) during first complete remission (CR), according to findings from a phase 3 study (NCT01246752).1
The median follow-up among patients was 50 months (interquartile range, 48-66). In the intention-to-treat analysis, the OS at 2 years was 74% (95% CI, 62%-83%) after primary alloHCT and 84% (95% CI, 73%-92%) after consolidation chemotherapy (P = .22).
At 2 years, disease-free survival (DFS) after HCT was 69% (95% CI, 57%-80%) vs 40% (95% CI, 28%-53%) after consolidation chemotherapy (P = .001). The cumulative incidence of relapse at 2 years was 20% (95% CI, 13%-31%) among patients given alloHCT during the first CR vs 58% with consolidation chemotherapy (95% CI, 47%-71%; P < .001).
The investigator-initiated, open-label, 2-armed, phase 3 randomized trial sought to assess the optimal therapy for patients with intermediate-risk AML after first complete remission. Patients were evaluated across 16 hospitals in Germany from February 2, 2011, until July 1, 2018.
Those included in the trial were patients aged 18-60 years with cytogenetically defined intermediate-risk AML according to Medical Research Council classification, first CR or CR with incomplete blood cell count recovery after conventional induction therapy, and availability of a human leukocyte antigen-matched sibling or unrelated donor who was fit for alloHCT.2
The trial enrolled 143 patients with a mean age of 48.2 years, and a total of 81 (57%) patients were male. Patients were randomized in a 1:1 ratio to receive alloHCT or high-dose cytarabine for consolidation and salvage HCT only in case of relapse.1
The primary end point of the trial was OS, and secondary end points were DFS, cumulative incidence of relapse, treatment-related mortality, and quality-of-life measured according to the Medical Outcomes Study 36-Item Short-Form Health Survey.
Additional findings showed that non relapse mortality at 2 years was 9% (95% CI, 5%-19%) after primary alloHCT and 2% (95% CI, 0%-11%) after consolidation chemotherapy (P = .005). All 41 patients relapsed after consolidation chemotherapy, including 36 hematologic, 4 molecular, and 1 extramedullary, proceeded to alloHCT.
Additionally, there were no significant differences in health-related quality-of-life measures between groups.
For safety, any-grade serious adverse events were seen in 74% of both groups, and the median hospital stay was 42.5 days (IQR, 31.0-62.0 days) among patients who underwent alloHCT vs 106.0 days (IQR, 72.0-143.0 days) with consolidation chemotherapy (P <.001).
Overall, findings suggest that though patients treated with alloHCT had improved DFS vs in the conventional consolidation chemotherapy group, alloHCT may not provide an OS benefit for patients with intermediate-risk AML during first CR.