In the phase II FIGARO trial reported in the Journal of Clinical Oncology, Craddock et al found that intensified reduced-intensity conditioning with fludarabine/amsacrine/cytarabine–busulfan (FLAMSA-Bu) did not improve outcomes following allogeneic stem cell transplantation vs standard fludarabine-based reduced-intensity conditioning in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
Study Details
In the multicenter open-label trial, 244 patients (median age = 59 years) with high-risk AML (n = 164) or MDS (n = 80) recruited between October 2013 and February 2017 were randomly assigned to FLAMSA-Bu (n = 122) or a fludarabine-based reduced-intensity conditioning regimen (control group, n = 122). The primary endpoint was overall survival in the intention-to treat population. Outcomes were analyzed according to pretransplantation measurable residual disease (MRD) monitored by flow cytometry. T-cell lineage chimerism was assessed at regular intervals post-transplantation.
Key Findings
At 2 years, overall survival was 58.8% in the control group vs 60.9% in the FLAMSA-Bu group (hazard ratio [HR] = 1.05, 85% confidence interval [CI] = 0.80–1.38, P = .81), event-free survival was 48.7% vs 54.2% (HR = 0.96, 95% CI = 0.68–1.35, P = .82), and cumulative incidence of relapse was 30% vs 27% (HR = 0.94, 95% CI = 0.60–1.46, P = .81).
Two-year overall and event-free survival were similar in both groups in a per-protocol sensitivity analysis; no benefit of FLAMSA-Bu was observed in AML or MDS subgroups, subgroups with AML according to cytogenetic risk category, or patients older or younger than 60 years.
Pretransplantation MRD monitored by flow cytometry was associated increased 2-year cumulative incidence of relapse in the entire population (41.0% vs 20.0%, P = .01), but no difference between groups was observed for relapse or survival according to MRD status.
Among all patients, acquisition of full donor T-cell chimerism at 3 months was associated with reduced risk of relapse (13% vs 45%) and improved overall survival (68% vs 52%) at 2 years. MRD-positive patients with full donor T-cell chimerism at 3 months had outcomes similar to those observed among MRD-negative patients.
The investigators concluded, “…FLAMSA-Bu did not improve outcomes in adults transplanted for high-risk AML or MDS regardless of pretransplant MRD status. 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.”
Charles Craddock, MD, of the Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Blood Cancer UK, Cure Leukemia, Pierre Fabre, and Eurocept. For full disclosures of the study authors, visit ascopubs.org.
