Outcomes of older patients with secondary AML according to treatment strategy

This month, in an article published in Cancer, Prajwal Chaitanya Boddu from The University of Texas MD Anderson Cancer Center (MDACC), Houston, and colleagues aimed to identify the most suitable treatment strategy for older patients with Secondary Acute Myeloid Leukemia (sAML).

The authors retrospectively evaluated 931 newly diagnosed sAML patients (median age = 68 years, range 60–70 years) treated at the MDACC between 1990–2015. Patients were grouped into five cohorts according to treatment regimen; patients receiving high-intermediate dose cytarabine-based Intensive Chemotherapy (IC, n = 396), patients receiving a Hypomethylating Agent (HMA) or HMA combinations (n = 220), patients receiving CPX-351, a liposomal formulation of cytarabine and daunorubicin (n = 20), patients receiving Low-Dose cytarabine (LDAC, n = 186) and patients receiving other Investigational (INV) agents (n = 109).

The key results of the study were:

• Complete Remission (CR) rate were significantly lower in patients receiving HMA (36%) and INV (16%) compared to IC (46%), LDAC (43%) and CPX-351(45%); P < 0.001
• Eight-week mortality rate in the IC, HMA, CPX-351, LDAC and INV group were 23%, 12%, 10%, 19% and 27% respectively
• Median Overall Survival (OS) in the IC, HMA, CPX-351, LDAC and INV group; 5.4 vs 6.7 vs 7.6 vs 7.1 vs 4.6 months, P = 0.002
• Median OS in patients receiving less intensive (HMA- and LDAC- based) and IC- based regimen; 6.9 vs 5.4 months, P = 0.048

In summary, “lower-intensity strategies such as HMA and LDAC-based regimens are associated with lower early mortality rates and improved OS in comparison to intensive regimen”. However, the outcomes of patients treated with agents were poor.

The authors concluded by suggesting that the poor outcomes obtained using INV agents “underscores the need for more effective therapies” to be developed for older high-risk AML patients.

Abstract

BACKGROUND

The development of newer strategies to improve outcomes for older patients with secondary acute myeloid leukemia (s-AML) is a critical unmet need. Establishing baseline metrics for evaluating newer approaches is important.

METHODS

s-AML was defined as 1 or more of the following: a history of an antecedent hematologic disorder (AHD), a diagnosis of therapy-related acute myeloid leukemia (AML), and AML with karyotype abnormalities characteristic of myelodysplastic syndrome. Newly diagnosed s-AML patients aged 60 to 75 years were grouped into 5 treatment cohorts: 1) patients receiving high- or intermediate-dose cytarabine–based intensive chemotherapy (IC), 2) patients receiving a hypomethylating agent (HMA) or HMA combinations, 3) patients receiving low-dose cytarabine (LDAC) combinations, 4) patients receiving CPX-351, and 5) patients receiving investigational (INV) agents. Nine hundred thirty-one patients met the age and s-AML criteria.

RESULTS

Complete remission rates were statistically lower in the HMA group (36%) versus the IC (46%), CPX-351 (45%), and LDAC groups (43%). Patients receiving less intensive regimens (the HMA and LDAC groups combined) had superior overall survival (OS) in comparison with patients receiving IC-based regimens (median 6.9 vs 5.4 months; P = .048). Only 4.3% of the IC patients proceeded to transplantation, whereas 10.3% of the patients on lower intensity regimens did (P = .001). There was no difference in median survival between patients treated with CPX-351 and patients treated with conventional lower intensity approaches (P = .75). Age > 70 years, an adverse karyotype, and a prior AHD were associated with decreased OS in a multivariate analysis.

CONCLUSIONS

Lower intensity approaches are associated with lower early mortality rates and improved OS in comparison with intensive regimens. OS is poor with currently available therapies with a median OS of 6 months (5.4-7.6 months across regimens). Unsatisfactory outcomes with other INV agents underscore the need for more effective therapies