Association Seen Between MRD and First Remission/Outcomes in Intermediate-Risk Acute Myeloid Leukemia

Clinical decision-making based on minimal residual disease may be associated with improved therapy satisfaction and optimized post-remission treatment for patients with intermediate-risk acute myeloid leukemia.

Clinical decision-making based on minimal residual disease (MRD) may be associated with improved therapy satisfaction and optimized post-remission treatment for patients with intermediate-risk acute myeloid leukemia (IR-AML), according to findings from a study published in JAMA Network Open.

Patients who were treated with chemotherapy (HR, 0.35; 95% CI, 0.14-0.90), as well as those who were treated with autologous stem cell transplant (HR, 0.07; 95% CI, 0.01-0.58; P = .01) had better graft-versus-host disease, relapse-free survival (GRFS). Patients who were MRD positive after 1 course of chemotherapy but were MRD negative after 2 to 3 courses, and those who underwent autologous (HR, 0.08; 95% CI, 0.02-0.24; P <.001) and allogenic stem cell transplant (HR, 0.25; 95% CI, 0.08-0.78; P = .01) had a lower cumulative incidence of relapse vs chemotherapy alone. Additionally, better leukemia-free survival (LFS; autologous: HR, 0.26; 95% CI, 0.10-0.64; P = .004; allogenic: HR, 0.21; 95% CI, 0.09-0.46; P <.001), and overall survival (OS; autologous: HR, 0.22; 95% CI, 0.08-0.64; P = .005; allogenic: HR, 0.25; 95% CI, 0.11-0.59; P = .001) were lower among those who also received stem cell transplant vs chemotherapy alone.

“It remains a challenge for practitioners to choose the optimal [post-remission treatment] for patients with IR-AML because different conclusions have been drawn in previous reports. On the one hand, some studies have suggested that patients with IR-AML might benefit from [allogenic-stem cell transplant]. For instance, [matched sibling donors stem cell transplants] or matched unrelated donor [stem cell transplant] might be superior to chemotherapy or auto-[stem cell transplant]. In addition, some investigators have reported that haploidentical donor–[stem cell transplant] also achieved more favorable survival outcomes than chemotherapy or auto-[stem cell transplant] owing to significantly lower cumulative incidence of relapse and acceptable transplant-related mortality,” the authors wrote.

The registry-based cohort study examined patients with de novo AML who were either intermediate risk, CR1, or between the ages of 14 to 60 years. Patients who had been diagnosed with acute promyelocytic leukemia, had an NPM1 variant with a FLT3 internal tandem duplication, did not achieve a complete response (CR) after 2 cycles of induction chemotherapy, had less than 3 cycles of consolidation chemotherapy, and lacked MRD parameters were not eligible to enroll on the study.

Induction chemotherapy regimens generally included 60 mg/m2 of daunorubicin hydrochloride or 10 to 12 mg/m2 of idarubicin hydrochloride on days 1 through 3, as well as cytarabine (200 mg/m2) once per day for 1 week. Those who were not able to achieve a CR following first induction chemotherapy received a second induction regimen that included 60 mg/m2 of daunorubicin hydrochloride or 10 mg/m2 of idarubicin hydrochloride on days 1 through 3 and 2.0 g/m2 of cytarabine twice daily on days 1 to 3; some patients also received the first induction regimen a second time. After achieving a CR, patients received 4 courses of treatment with consolidation cytarabine, 3 courses of chemotherapy, and autologous transplant or 2 courses of chemotherapy followed by allogenic transplant based on MRD status and available of donors.

The primary end points of the trial included relapse, survival, and transplant-related mortality.

A total of 549 patients were included on the study, 154 of whom were allocated to the chemotherapy arm, 116 to the autologous transplant arm, and 279 to the allogenic transplant arm.

Additional findings indicated that autologous stem cell transplant yielded an improved GRFS over allogenic stem cell transplant (HR, 0.45; 95% CI, 0.21-0.98; P = .04). Patients who were positive for MRD following 1 to 2 courses of chemotherapy but MRD negative after 3 and underwent treatment with allogenic transplant experienced a superior cumulative incidence of relapse (HR, 0.10; 95% CI, 0.06-0.94; P = .04) and LFS (HR, 0.18; 95% CI, 0.05-0.68; P = .01) vs chemotherapy alone. However, investigators did not identify an advantage in cumulative incidence of relapse (HR, 0.15; 95% CI, 0.02-1.42; P = .10) and LFS (HR, 0.23; 95% CI, 0.05-1.08; P = .06) compared with autologous stem cell transplant.

Those who tested positive for MRD following 3 courses of treatment with chemotherapy followed by autologous stem cell transplant appeared to have superior incidence of relapse (HR, 0.16; 95% CI, 0.08-0.33; P <.001), LFS (HR, 0.19; 95% CI, 0.10-0.35; P <.001), OS (HR, 0.29; 95% CI, 0.15-0.55; P <.001) compared with chemotherapy, as well as autologous transplant (relapse: HR, 0.25; 05% CI, 0.12-0.53; P <.001; LFS: HR, 0.35; 95% CI, 0.18-0.73; P = .004; OS: HR, 0.54; 95% CI, 0.26-0.94; P = .04). Additionally, among those with recurrent MRD, allogenic stem cell transplant was associated with cumulative incidence of relapse (HR, 0.12; 95% CI, 0.04-0.33; P <.001), LFS (HR, 0.24; 95% CI, 0.10-0.56; P = .001) and OS (HR, 0.31; 95% CI, 0.13-0.75; P = .01) compared with both chemotherapy and autologous transplant (relapse: HR, 0.28; 95% CI, 0.9-0.81; P = .02; LFS: HR, 0.20; 95% CI, 0.12-0.76; P = .01; OS: HR, 0.26; 95% CI, 0.10-0.70; P = .007).

After a median follow up of 48.1 months (range, 5.4-94.7) following CR1, a total of 394 patients survived and 155 died. The 5-year cumulative incidence of transplant-related mortality was 1.3% in the chemotherapy arm, 3.4% in the autologous arm, and 10.4% in the allogenic arm. Additionally, the 5-year LFS rate was 49.3%, 69.0%, and 76.0% in the 3 arms, respectively. Investigators also noted a 5-year OS rate of 57.6%, 75.0%, and 78.1% in the 3 cohorts, respectively.

Reference

Yu S, Fan Z, Ma L, et al. Association between measurable residual disease in patients with intermediate-risk acute myeloid leukemia and first remission, treatment, and outcomes. JAMA Netw Open. 2021;4(7):e2115991. doi:10.1001/jamanetworkopen.2021.15991