Amplified RIC Regimen Does Not Improve Post-Transplant Outcomes in AML

In a study of adults transplanted for high-risk acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), an intensified reduced-intensity conditioning (RIC) regimen did not improve outcomes, regardless of pretransplant minimal residual disease (MRD) status (J Clin Oncol. 2020 Dec 29. Epub ahead of print).

According to lead investigator Charles Craddock, MD, Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, United Kingdom, and colleagues, RIC regimens have prolonged the curative potential of allogeneic stem-cell transplantation in older adults with high-risk AML and MDS, but are tied to a high risk for relapse. Therefore, strategies to reduce recurrence are needed.

“Registry data have demonstrated improved outcomes using a sequential transplant regimen, fludarabine/amsacrine/cytarabine-busulphan (FLAMSA-Bu), but the impact of this intensified conditioning regimen has not been studied in randomized trials,” wrote Dr Craddock and co-investigators, who randomized 244 patients (median age, 59 years) with high-risk AML (n = 164) or MDS (n = 80) in a 1:1 ratio to receive FLAMSA-Bu or a fludarabine-based RIC regimen (control).

The researchers used flow cytometry (MFC-MRD) to monitor pretransplant MRD, and correlated that against the outcome.

Findings showed that there was no difference in 2-year overall survival (hazard ratio [HR], 1.05; 85% CI, 0.80-1.38; P = .81) or cumulative incidence of relapse (CIR; HR, 0.94; 95%CI, 0.60-1.46; P = .81) between recipients of the control or FLAMSA-Bu.

Detectable pretransplant MFC-MRD was shown to be tied to an increased CIR (2-year CIR, 41% vs 20%; P = .01) in the overall trial cohort, with a comparable impact on prognosis when measured by an unsupervised analysis approach.

Of note, the researchers reported no evidence of interaction between MRD status and conditioning regimen intensity for relapse or survival. Furthermore, attainment of full donor T-cell chimerism at 3 months nullified the adverse effect of pretransplant MRD on CIR and overall survival.

“The intensified RIC conditioning regimen, FLAMSA-Bu, did not improve outcomes in adults transplanted for high-risk AML or MDS regardless of pretransplant MRD status,” Dr Craddock et al wrote.

“Our data instead support the exploration of interventions with the ability to accelerate acquisition of full donor T-cell chimerism as a tractable strategy to improve outcomes in patients allografted for AML,” they concluded.—Hina Porcelli