HSCT During First CR Yields Non-Superior OS vs Consolidation Chemo in AML

Although the use of allogeneic hematopoietic cell transplantation (allo-HCT) during first complete remission (CR) yielded improved disease-free survival (DFS), overall survival (OS) was not superior compared with consolidation chemotherapy plus allo-HCT only in case of relapse for patients with intermediate-risk acute myeloid leukemia (AML), according to findings from a phase 3 trial (NCT01246752).

"The results of this randomized clinical trial support the notion that patients 60 years or younger with intermediate-risk AML, as defined by Medical Research Council cytogenetic criteria, despite an improved DFS, do not benefit from allo-HCT during first CR with regard to OS," according to the study authors.

The probability of survival at 2 years was 74% (95% CI, 62%-83%) following primary allo-HCT and 84% (95% CI, 73%-92%) after consolidation chemotherapy (P = .22). The differences in proportional OS was 6.7% (95% CI, –10% to 25%) after 2 years and 7.1% (95% CI, –14% to 25%) after 4 years in each respective treatment group. Data from a post hoc analysis indicated that OS was not superiority in the allo-HCT arm vs the chemotherapy arm; the 2-year OS rates were 76% (95% CI, 67%-86%) and 83% (95% CI, 75%-93%) in each respective group.

The 2-year DFS rate was 69% (95% CI, 57%-80%) with primary allo-HCT vs 40% (95% CI, 28%-53%) with conventional consolidation chemotherapy (P = .001). Findings from a post hoc analysis highlighted a 2-year DS rate of 70% vs 39% in each respective treatment cohort (P = .02).

“The results of this randomized clinical trial support the notion that patients 60 years or younger with intermediate-risk AML, as defined by Medical Research Council cytogenetic criteria, despite an improved DFS, do not benefit from allo-HCT during first CR with regard to OS,” the study authors stated. “The early identification of a suitable donor allows timely rescuing of those patients with relapse after conventional consolidation chemotherapy.”

Investigators of this open-label, randomized phase 3 trial assessed patients with intermediate-risk AML at 16 hospitals in Germany from February 2, 2011 to July 1, 2018. Patients were randomly assigned 1:1 to either receive allo-HCT or high-dose cytarabine plus salvage HCT only in the event of a relapse. Investigators stratified patients based on age, NPM1 and CEBPA variant status, and donor type.

The primary end point of the trial was OS. Secondary end points included DFS, cumulative incidence of relapse, treatment-related mortality, and quality of life as determined with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36).

Patients 18 to 60 years old with cytogenetically defined intermediate-risk AML based on Medical Research Council criteria were eligible for enrollment on the trial. Additional inclusion criteria included having first CR or CR with incomplete blood cell count recovery following induction of consolidation chemotherapy and availability of a human leukocyte antigen-matched sibling or unrelated donor.

Of 143 enrolled patients, 76 were randomly assigned to the allo-HCT arm vs 67 to the consolidation chemotherapy arm. The mean patient age was 48.2 years (standard deviation, 9.8), and 57% of patients were male. In the allo-HCT and consolidation chemotherapy groups, respectively, most patients had normal karyotypes (71% vs 82%), had NPM1 and FLT3-ITD wild-type disease (51% vs 53%), and matched unrelated donors (67% vs 52%).

Twelve of 76 patients in the allo-HCT group received 1 course of high-dose consolidation cytarabine after achieving CR to bridge until allo-HCT, and all other patients received allo-HCT directly following induction therapy. In the consolidation therapy cohort, all but 1 patient received between 1 and 3 cycles of cytarabine with a median of 3 cycles (range, 2-3).

The non-relapse mortality rate at 2 years was 9% (95% CI, 5%-19%) in the allo-HCT group vs 2% (95% CI, 0%-11%) in the consolidation chemotherapy group (P = .005). Additionally, the 2-year cumulative relapse incidence rate was 20% (95% CI, 13%-31%) vs 58% (95% CI, 47-71%) in each respective group (P <.001). All 41 patients who relapsed in the chemotherapy group underwent allo-HCT directly (n = 20) or following salvage therapy (n = 21).

There was 1 patient who died in the consolidation chemotherapy group following salvage HCT due to early post-transplant complications.

Investigators noted that results based on the SF-36 scales did not differ significantly between the allo-HCT and consolidation chemotherapy cohorts. Additionally, the median duration of in-hospital stay was 42.5 days (interquartile range [IQR], 31.0-62.0) for patients in the allo-HCT group, vs 106 days (IQR, 72.0-143.0; P <.001) for patients in the consolidation chemotherapy group.

Reference

Bornhäuser M, Schliemann C, Schetelig J, et al. Allogeneic hematopoietic cell transplantation vs standard consolidation chemotherapy in patients with intermediate-risk acute myeloid leukemia: a randomized clinical trial. JAMA Oncol. Published online February 9, 2023. doi:10.1001/jamaoncol.2022.7605