Association Between Measurable Residual Disease in Patients With Intermediate-Risk Acute Myeloid Leukemia and First Remission, Treatment, and Outcomes
Authors: Sijian Yu, Zhiping Fan, Liping Ma, Yu Wang, Fen Huang, Qing Zhang, Jiafu Huang, Shunqing Wang, Na Xu, Li Xuan, Mujun Xiong, Lijie Han, Zhiqiang Sun, Hongyu Zhang, Hui Liu, Guopan Yu, Pengcheng Shi, Jun Xu, Meiqing Wu, Ziwen Guo, Yiying Xiong, Chongyang Duan, Jing Sun, Qifa Liu, Yu Zhang
Journal: JAMA Network Open (2021)

<h3>Importance</h3> 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. <h3>Objective</h3> To investigate PRT choices based on dynamic MRD in patients with IR-AML. <h3>Design, Setting, and Participants</h3> 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. <h3>Exposures</h3> Receipt of chemotherapy, auto-SCT, or allo-SCT. <h3>Main Outcomes and Measures</h3> The primary end points were 5-year cumulative incidence of relapse and leukemia-free survival. <h3>Results</h3> 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 graft-vs-host disease–free, relapse-free survival (GRFS) than those who underwent allo-SCT (chemotherapy: hazard ratio [HR], 0.35 [95% CI, 0.14-0.90];<i>P</i> = .03; auto-SCT: HR, 0.07 [95% CI, 0.01-0.58];<i>P</i> = .01). Among participants with MRD after 1 course of chemotherapy but no MRD after 2 or 3 courses, those who underwent auto-SCT and allo-SCT showed lower cumulative incidence of relapse (auto-SCT: HR, 0.25 [95% CI, 0.08-0.78];<i>P</i> = .01; allo-SCT: HR, 0.08 [95% CI, 0.02-0.24];<i>P</i> &lt; .001), better leukemia-free survival (auto-SCT: HR, 0.26 [95% CI, 0.10-0.64];<i>P</i> = .004; allo-SCT: HR, 0.21 [95% CI, 0.09-0.46];<i>P</i> &lt; .001), and overall survival (auto-SCT: HR, 0.22 [95% CI, 0.08-0.64];<i>P</i> = .005; allo-SCT: HR, 0.25 [95% CI, 0.11-0.59];<i>P</i> = .001) vs chemotherapy. In addition, auto-SCT showed better GRFS than allo-SCT (HR, 0.45 [95% CI, 0.21-0.98];<i>P</i> = .04) in this group. Among participants with MRD after 1 or 2 courses of chemotherapy but no MRD after 3 courses, allo-SCT had superior cumulative incidence of relapse (HR, 0.10 [95% CI, 0.06-0.94];<i>P</i> = .04) and leukemia-free survival (HR, 0.18 [95% CI, 0.05-0.68];<i>P</i> = .01) compared with chemotherapy, but no advantageous cumulative incidence of relapse (HR, 0.15 [95% CI, 0.02-1.42];<i>P</i> = .10) and leukemia-free survival (HR, 0.23 [95% CI, 0.05-1.08];<i>P</i> = .06) compared with auto-SCT. Among participants with MRD after 3 courses of chemotherapy, allo-SCT had superior cumulative incidences of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.16 [95% CI, 0.08-0.33];<i>P</i> &lt; .001; leukemia-free survival: HR, 0.19 [95% CI, 0.10-0.35];<i>P</i> &lt; .001; overall survival: HR, 0.29 [95% CI, 0.15-0.55];<i>P</i> &lt; .001) and auto-SCT (relapse: HR, 0.25 [95% CI, 0.12-0.53];<i>P</i> &lt; .001; leukemia-free survival: HR, 0.35 [95% CI, 0.18-0.73];<i>P</i> = .004; overall survival: HR, 0.54 [95% CI, 0.26-0.94];<i>P</i> = .04). Among participants with recurrent MRD, allo-SCT was also associated with advantageous cumulative incidence of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.12 [95% CI, 0.04-0.33];<i>P</i> &lt; .001; leukemia-free survival: HR, 0.24 [95% CI, 0.10-0.56];<i>P</i> = .001; overall survival: HR, 0.31 [95% CI, 0.13-0.75];<i>P</i> = .01) and auto-SCT (relapse: HR, 0.28 [95% CI, 0.09-0.81];<i>P</i> = .02; leukemia-free survival: HR, 0.30 [95% CI, 0.12-0.76];<i>P</i> = .01; overall survival: HR, 0.26 [95% CI, 0.10-0.70];<i>P</i> = .007). <h3>Conclusions and Relevance</h3> This study suggests that clinical decisions based on dynamic MRD might be associated with improved therapy stratification and optimized PRT for patients with IR-AML. Prospective multicenter trials are needed to further validate these findings.