Predicting AML Outcomes by Monitoring Minimal Residual Disease

Minimal residual disease (MRD) is a powerful predictor of outcomes, but the science of targeting MRD remains unclear. A new abstract presented at the 60th American Society of Hematology (ASH) Annual Meeting & Exposition analyzed responses in patients with acute myeloid leukemia (AML) who underwent induction chemotherapy and were monitored for MRD.¹

The researchers studied 163 patients at Memorial Sloan Kettering Cancer Center who received anthracycline and cytarabine. These patients had baseline next-generation sequencing followed by serial immunophenotypic monitoring for MRD after induction. Patients were considered MRD+ if they had any level of residual disease. Patients in the study were 58.3% male, with a median age of 60.8 years.

After induction and prior to further therapy, 153 of the patients had a bone marrow biopsy; of those patients, 124 underwent flow cytometry after induction. Approximately half (52.4%; 65/124) achieved complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) after induction alone with another 25% (31/124) MRD+ CR/CRi, and 27.4% (34/124) achieved CR/CRi without any MRD (MRD—).

The results showed that patients with specific molecular mutations, such as RNX1, SF3B1, and TP53, are unlikely to achieve MRD— CR/CRi. A posttransplant analysis revealed that most patients who enter transplant with AML or MRD+ are clear of MRD after the transplant (69.7%; 30/43).

“Our results suggest that development of MRD-eradicating therapies after AML induction has the potential to improve post-transplant outcomes,” the authors concluded.

In a second abstract² presented at ASH, researchers studied the potential predictors of induction failure and first complete response duration in patients with FLT3-ITD—mutated AML. The analyzed 235 patients with a median age of 64 years.

Using cytogenetic data of 166 patients available at diagnosis, the identified 33 (20%) as having favorable risk, 117 (70%) having intermediate risk, and 16 (10%) having adverse risk. A total of 166 (71%) of the 235 total patients achieved CR/CRi and 69 (29%) failed induction.

The researchers found that achieving CR instead of CRi and MRD— were both associated with first CR that lasted 6 or more months. MRD–, CR versus CRi, receiving a high dose cytarabine–based induction, or receiving allogeneic cell transplant at first CR were also associated with longer relapse-free survival.

References

1. Goldberg AD, Famulare C, Devlin SM, et al. Molecular predictors and current management of minimal residual disease (MRD) following induction chemotherapy for acute myeloid leukemia (AML). Presented at: 60th American Society of Hematology Annual Meeting & Exposition; December 2, 2018; San Diego, CA. Abstract 292.
2. Yalniz F, Kantarjian HM, Borthakur G, et al. Potential predictors of induction failure and complete remission duration in FLT3-ITD mutated acute myeloid leukemia. Presented at: 60th American Society of Hematology Annual Meeting & Exposition; December 3, 2018; San Diego, CA. Abstract 3996.