Measurable residual disease as predictor of post-day +100 relapses after allografting in adult AML
Naveed Ali1,2, Megan Othus3, Eduardo Rodríguez-Arbolí4,5
1Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
Abstract:
Measurable residual disease (MRD) by multiparametric flow cytometry (MFC) before allogeneic hematopoietic cell transplantation (HCT) identifies patients at high risk of acute myeloid leukemia (AML) relapse, often occurring early after allografting. To examine the role of MFC MRD testing to predict later relapses, we examined 935 adults with AML or myelodysplastic neoplasm/AML transplanted in first or second morphologic remission who underwent bone marrow restaging studies between day 70 and 100 after HCT and were alive and without relapse by day +100. Of 935 adults, 136 (15%) had MRD before HCT, whereas only 11 (1%) had MRD at day +70 to +100. In day +100 landmark analyses, pre-HCT and day +70 to +100 MFC MRD were both associated with relapse (both P < .001), relapse-free survival (RFS; both P < .001) overall survival (OS; both P < .001), and, for post-HCT MRD, nonrelapse mortality (P = .001) after multivariable adjustment. Importantly, although 126/136 patients (92%) with MRD before HCT tested negative for MRD at day +70 to +100, their outcomes were inferior to those without MRD before HCT and at day +70 to +100, with 3-year relapse risk of 40% vs 15% (P < .001), 3-year RFS of 50% vs 72% (P < .001), and 3-year OS of 56% vs 76% (P < .001), whereas 3-year nonrelapse mortality estimates were similar (P = .53). Thus, despite high MRD conversion rates, outcomes MRD positive/MRD negative (MRDneg) patients are inferior to those of MRDneg/MRDneg patients, suggesting all patients with pre-HCT MRD should be considered for preemptive therapies after allografting.
Insights
Measurable residual disease (MRD) testing using multiparametric flow cytometry (MFC) before allogeneic hematopoietic cell transplantation (HCT) predicts relapse in acute myeloid leukemia (AML). Even if MRD is cleared post-HCT, pre-HCT MRD positivity indicates poorer outcomes, suggesting preemptive therapy.
Area of Science:
- Hematology
- Oncology
- Transplantation Immunology
Background:
- Measurable residual disease (MRD) detected by multiparametric flow cytometry (MFC) before allogeneic hematopoietic cell transplantation (HCT) is a significant risk factor for early acute myeloid leukemia (AML) relapse.
- The predictive value of MFC MRD testing for later relapses after HCT requires further investigation.
Purpose of the Study:
- To evaluate the role of MFC MRD testing in predicting both early and late relapse risks in patients undergoing HCT for AML or myelodysplastic neoplasm/AML.
- To assess the impact of pre-HCT and post-HCT MRD status on relapse-free survival (RFS), overall survival (OS), and non-relapse mortality (NRM).
Main Methods:
- A cohort of 935 adult patients with AML or myelodysplastic neoplasm/AML in remission undergoing HCT were analyzed.
- Bone marrow restaging studies were performed between day 70 and 100 post-HCT. Patients alive and in remission by day +100 were included.
- Statistical analyses, including multivariable adjustment, were used to assess the association between MRD status and clinical outcomes.
Main Results:
- Fifteen percent of patients had MRD before HCT, while only 1% had MRD between days 70-100 post-HCT.
- Both pre-HCT and post-HCT MRD were significantly associated with increased relapse risk, decreased RFS, and decreased OS.
- Patients with MRD before HCT but negative MRD post-HCT had inferior outcomes compared to those consistently MRD-negative, with higher relapse rates (40% vs. 15%) and lower RFS (50% vs. 72%) and OS (56% vs. 76%) at 3 years.
Conclusions:
- Pre-HCT MFC MRD is a critical predictor of relapse in AML patients undergoing HCT.
- Even with MRD clearance post-HCT, a history of pre-HCT MRD positivity is linked to inferior survival outcomes.
- Consideration of preemptive therapies for all patients with pre-HCT MRD is warranted to improve outcomes after allografting.
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