Postremission Survival Influenced by Choice of Induction Therapy in AML
Conducting a clinical trail
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Induction therapy with FLAG-Ida (fludarabine, cytarabine, and granulocyte-colony stimulating factor, with or without idarubicin) results in better postremission survival in patients with nonfavorable National Comprehensive Cancer Network (NCCN) risk acute myeloid leukemia (AML) who achieve a first complete remission (CR1), compared with those who received induction therapy with 3+7 (anthracycline plus cytarabine). These results were presented at the 2018 American Society of Hematology (ASH) Annual Meeting and Exposition.
The MRC AML 15 trial compared 2 induction courses of FLAG-Ida with 3+7 with etoposide (ADE). Study results showed relapse-free survival was higher among patients who received FLAG-Ida. However, one course of induction therapy followed by consolidation if patients achieve remission is used by many US oncologists.
Therefore, researchers at the Blood and Marrow Transplant Program at Northside Hospital, in Atlanta, Georgia, sought to determine the impact of these induction regimens on postremission survival in patients with nonfavorable (intermediate or high) NCCN risk AML. In their single-center study, the outcomes of 306 consecutive patients with AML initially treated at the facility between January 2009 and July 2017 were assessed. The treatment algorithm at this center is to offer consolidation therapy with allogeneic hematopoietic stem cell transplantation (HSCT) to all patients with nonfavorable NCCN risk AML who achieve CR1 and are considered transplant candidates.
For this study, 218 patients received FLAG-Ida and 88 received 3+7. Patients were median age 58 (range, 19 to 75), 55% were male, 12% were FLT3-internal tandem duplication (ITD) positive, NCCN risk was intermediate (49%) or poor (51%), and 45% had normal cytogenetics. Patients in the FLAG-Ida group were younger at diagnosis (59 years vs 66 years; P< .001); other baseline characteristics were similar.
A total of 240 (78%) patients achieved CR1, with similar rates between the 2 groups (79% in the FLAG-IDA group [167 patients] and 76% in the 3+7 group [67 patients]). Those in the FLAG-Ida group were more likely to achieve CR1 after 1 course of induction therapy (74% vs 62%, P< .001) and achieved CR1 in fewer days (30 days vs 37.5 days, P< .001) compared with those in the 3+7 arm. Complete remission was achieved in 84% of patients with intermediate NCCN risk disease and 73% of patients with poor NCCN risk disease.
HSCT was performed in 172 patients (72% of the 240 patients who achieved CR1). No significant difference in transplant rates were noted between the FLAG-Ida and 3+7 groups.
Among those who achieved CR1, time from diagnosis to transplant was significantly shorter after FLAG-Ida compared with 3+7 (115 days vs 144 days; P< .001). After a median follow up of 41 months, 3-year postremission overall survival (OS) and disease-free survival (DFS) was significantly better in the FLAG-Ida group than in the 3+7 group (54% vs 39% and 49% vs 32%, respectively; P= .01 for both end points).