Dynamic MRD Can Drive Clinical Decisions in AML

Clinicians may be able to optimize postremission treatment (PRT) and improve therapy stratification using dynamic measurable residual disease (MRD) in patients with intermediate-risk acute myeloid leukemia (AML), according to a study published in JAMA Network Open.

The researchers used the South China Hematology Alliance database to evaluate 549 patients between the ages of 14 and 60 years with intermediate-risk AML. Of these patients, 154 received chemotherapy, 116 received an autologous stem cell transplant (auto-SCT), and 279 received an allogeneic SCT (allo-SCT).

While most younger patients with AML can achieve complete remission (CR) after induction chemotherapy, further PRT consisting of either a SCT or cytarabine-based consolidation chemotherapy is necessary to prevent a relapse, the authors explained. Although allo-SCT is more effective than auto-SCT when it comes to preventing relapse, it has a higher risk of transplant-related mortality.

“Currently, decisions for PRT depend mainly on risk stratification based on cytogenetics and molecular markers, but it remains controversial, particularly for patients with intermediate-risk AML,” they wrote.

MRD was assessed after induction therapy, each cycle of PRT, at 2-month intervals the first year, at 3-month intervals the second year, at 4-month intervals the third year, and finally half-year intervals during years 4 and 5 after PRT. The end point of the last follow up was August 31, 2020.

At the last follow up, 146 patients had relapsed, and the median time from first CR to relapse was 10.9 months. For patients receiving chemotherapy, the median time from first CR to relapse was 9.9 months; for patients receiving auto-SCT, 10.9 months; and for patients receiving allo-SCT, 13.0 months.

The study also found:

• 76 patients receiving chemotherapy relapsed; 58 received further treatment and 13 survived at the last follow-up
• 32 patients receiving auto-SCT relapsed; 26 received further treatment and 7 survived at last follow-up
• 38 patients receiving allo-SCT relapsed; 29 received salvage treatment and 6 survived at the last follow-up

The 5-year relapse rate was 49.4% (95% CI, 41.2%-57.0%) for patients on chemotherapy, 27.6% (95% CI, 19.8%-36.0%) for patients receiving auto-SCT, and 13.6% (95% CI, 9.9%-17.9%) for patients receiving allo-SCT. The 5-year cumulative incidence of transplant-related mortality was 1.3% (95% CI, 0.3%-4.2%) for chemotherapy, 3.4% (95% CI, 1.1%-8.0%) for auto-SCT, and 10.4% (95% CI, 7.2%-14.3%) for allo-SCT.

The 5-year overall survival (OS) and leukemia-free survival rates were higher for the SCT groups compared with the chemotherapy group. Both rates were comparable between the 2 SCT groups.

During subgroup analyses, patients were classified into 5 subgroups based on the dynamics of MRD after 1, 2, and 3 courses of chemotherapy:

1. Subgroup A was persistently MRD negative for all 3 courses. The 3 different PRT groups had comparable cumulative incidence of relapse, leukemia-free survival, and OS.
2. Subgroup B was persistently MRD positive after all 3 courses. The allo-SCT group had better leukemia-free survival and OS compared with the chemotherapy and auto-SCT groups, as well as a lower cumulative incidence of relapse.
3. Subgroup C was defined as being recurrent MRD positive after being MRD negative. The allo-SCT group had better leukemia-free survival and OS compared with the chemotherapy and auto-SCT groups, as well as a lower cumulative incidence of relapse.
4. Subgroup D was MRD negative after 2 courses of chemotherapy. Patients who received allo-SCT had significantly lower cumulative incidence of relapse, better leukemia-free survival, and better OS than patients in the other 2 groups.
5. Subgroup E was MRD negative after 3 courses of chemotherapy. Patients who received allo-SCT had a lower cumulative incidence of relapse and better leukemia-free survival, but a comparable OS compared with chemotherapy. Compared with auto-SCT, patients who received allo-SCT did not have a lower cumulative incidence of relapse, better leukemia-free survival, or difference in OS.

“Based on these results, we suggest that chemotherapy and auto-SCT might be preferable for patients who are persistently MRD negative, and allo-SCT should be recommended for patients who are persistently MRD positive and patients with recurrent MRD,” the authors concluded. “Auto-SCT prior to allo-SCT might be recommended for patients who are MRD negative after 2 cycles of chemotherapy. Allo-SCT might be preferable for patients who are MRD negative after 3 cycles of chemotherapy.”

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.