Association Between Measurable Residual Disease in Patients With Intermediate-Risk Acute Myeloid Leukemia and First Remission, Treatment, and Outcomes

Abstract

IMPORTANCE Measurable residual disease (MRD) is widely used as a therapy-stratification factor for acute myeloid leukemia (AML), but the association of dynamic MRD with postremission treatment (PRT) in patients with intermediate-risk AML (IR-AML) has not been well investigated. OBJECTIVE To investigate PRT choices based on dynamic MRD in patients with IR-AML. DESIGN, SETTING, AND PARTICIPANTS This cohort study examined 549 younger patients with de novo IR-AML in the South China Hematology Alliance database during the period from January 1, 2012, to June 30, 2016, including 154 who received chemotherapy, 116 who received an autologous stem cell transplant (auto-SCT), and 279 who received an allogeneic SCT (allo-SCT). Subgroup analyses were performed according to dynamic MRD after the first, second, and third courses of chemotherapy. The end point of the last follow-up was August 31, 2020. Statistical analysis was performed from December 1, 2019, to September 30, 2020. EXPOSURES Receipt of chemotherapy, auto-SCT, or allo-SCT. MAIN OUTCOMES AND MEASURESThe primary end points were 5-year cumulative incidence of relapse and leukemia-free survival. RESULTS Subgroup analyses were performed for 549 participants (314 male participants [57.2%]; median age, 37 years [range, 14-60 years]) according to the dynamics of MRD after 1, 2, or 3 courses of chemotherapy. Comparable cumulative incidences of relapse, leukemia-free survival, and overall survival were observed among participants who had no MRD after 1, 2, or 3 courses of chemotherapy.Participants who underwent chemotherapy and those who underwent auto-SCT had better graftvs-host disease-free, relapse-free survival (GRFS) than those who underwent allo-SCT

Dynamic assessment of measurable residual disease in favorable-risk acute myeloid leukemia in first remission, treatment, and outcomes

“…Cytogenetic and molecular analyses were routinely performed at initial diagnosis [ 25 ]. After CR, MRD in bone marrow was assessed by eight-color multiparameter flow cytometry (MFC) after induction and each course of PRT and then at two-month intervals within the 1st year, three-month intervals within the 2nd year, four-month intervals within the 3rd year, and half-year intervals from the 4th to 5th year post-treatment [ 26 , 27 ].…”

“…According to our practical guidelines, patients are generally scheduled for “3 + 7” induction therapy consisting of daunorubicin 60 mg/m2 or idarubicin 10–12 mg/m2 on days 1-3 and cytarabine 200 mg/m2 per day for 7 days. For those who failed to achieve CR after the first induction, a second induction consisting of daunorubicin 60 mg/m 2 or idarubicin 10 mg/m 2 per day on days 1–3 and cytarabine 2.0 g/m 2 twice daily on days 1–3 (“3 + 3” regimen), or the same regimen as the first induction was administered [ 25 ]. After CR, usually four courses of cytarabine-based consolidation chemotherapy, three courses of chemotherapy followed by auto-SCT, or two courses followed by allo-SCT were administered based on MRD status and donor availability.…”

“…OS was evaluated from the start of therapy to death or censored at the last follow-up. CR, GVHD, NRM, and GRFS were defined according to previous literature [ 25 ]. MRD1, MRD2, and MRD3 were defined as MRD by MFC after one, two, and three courses, respectively.…”

“…But when is the best timepoint making decisions on PRT is still inconclusive [ 19 , 20 , 23 , 24 ]. Recently, our multicenter, large-sample study demonstrated that treatment based on dynamic MRD by multiparameter flow cytometry (MFC) was associated with improved outcomes for intermediate-risk AML [ 25 ]. Whether dynamic MRD would play an analogous role in FR-AML is unclear.…”

The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update

“…In a prospective trial comparing HID-HSCT and chemotherapy as consolidation therapy in 147 patients with int-risk AML CR1 in the absence of MSDs or URDs, HID-HSCT was an independent risk factor for a reduced cumulative incidence of relapse (CIR) (adjusted hazard ratio (HR) 0.161; p = 0.001), improved DFS (HR 0.360; p = 0.011) and overall survival (OS, HR 0.361, p = 0.017) [ 11 ]. Yu et al reported that in a multicenter study of 549 patients with int-risk AML, allo-HSCT had superior CIR, LFS and OS compared with chemotherapy in patients with any positive MRD after 1, 2, or 3 courses of chemotherapy [ 12 ].…”