Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach

Abstract

BACKGROUND Developing newer strategies to improve outcomes in older patients with secondary AML is a critical unmet need. Establishing baseline metrics from which to evaluate newer approaches is important. METHODS Secondary AML was defined by one or more of the following: history of antecedent hematological disorder; the diagnosis of therapy related AML; AML with karyotype abnormalities characteristic of MDS. Newly diagnosed secondary AML (s-AML) patients aged 60–75 years were grouped into 5 treatment cohorts: 1) high/intermediate intensity chemotherapy (IC), 2) hypomethylating agent (HMA)/HMA combinations, 3) low dose Ara-c combinations (LDAC), 4) CPX-351, 5) investigational (INV). 931 patients met the criteria of age and s-AML. RESULTS Complete remission rates were statistically lower in the HMA (36%) when compared with IC (46%), CPX-351 (45%) and LDAC (43%). Patients receiving less intensive regimens [HMA and LDAC based, combined] had superior OS compared with IC-based regimens (6.9m vs. 5.4; P=0.048). Only 4.3% of IC patients proceeded to transplant as compared with 10.3% of patients on lower intensity regimens (p=0.001). There was no difference in median survival in patients treated with CPX-351 compared with conventional lower-intensity approaches (p=0.75). Age >70yrs, adverse karyotype, and prior AHD were associated with a decreased OS on multivariate analysis. CONCLUSIONS Lower-intensity approaches are associated with lower early mortality and improved OS when compared with intensive regimens. Overall survival is poor with currently available therapies, with average OS of 6 months (across regimens, 5.4–7.6 mo). Unsatisfactory outcomes using other investigational agents (INV) underscores the need for more effective therapies.

Genetic alteration patterns and clinical outcomes of elderly and secondary acute myeloid leukemia

“…Consistent with previous studies, we observed that both e‐AML and s‐AML were associated with lower CR rate and a short duration of EFS and OS. Although some new therapeutic agents were applied to these high‐risk AML patients, the treatment of e/s‐AML remains a challenge, and there is no consensus on this controversial issue.…”

Outcome of patients aged 60‐75 years with newly diagnosed secondary acute myeloid leukemia: A single‐institution experience

“…Until recently, therapeutic strategies did not really differ from de novo AML. Patients are offered induction chemotherapy and allogeneic stem‐cell transplantation if deemed fit for intensive therapies, those considered unfit for such treatment receive hypomethylating agents (HMA), low dose cytarabine or supportive care …”

“…Patients are offered induction chemotherapy and allogeneic stem-cell transplantation if deemed fit for intensive therapies, those considered unfit for such treatment receive hypomethylating agents (HMA), low dose cytarabine or supportive care. 3,4,7 The CPX-351 trial has been specifically designed for older patients with secondary or high-risk AML and demonstrated the superiority of the dual-drug liposomal encapsulation of daunorubicin and cytarabine (CPX-351) over the conventional "7 + 3" cytarabine-daunorubicin regimen. 8 This phase 3 study represents a unique example of prospective data in this rare AML subgroup providing a solid basis for comparison with real life data.…”

How I treat older patients with acute myeloid leukemia

“…The main risk factor for the development of AML is increasing age, and although there rarely are other identifiable predisposing factors, there is an increasing number of AML cases after exposure to chemotherapy or radiotherapy (collectively referred to as “therapy‐related AML” [t‐AML]). There also is a distinct high‐risk category of secondary AML (s‐AML) after antecedent hematological disorders, such as myelodysplastic syndromes (MDS) or myeloproliferative neoplasms . Outcomes of AML in older adults (aged >60 years) are dismal, with survival rates reported to be <10% at 3 years and <5% at 5 years .…”

“…There also is a distinct highrisk category of secondary AML (s-AML) after antecedent hematological disorders, such as myelodysplastic syndromes (MDS) or myeloproliferative neoplasms. 2 Outcomes of AML in older adults (aged >60 years) are dismal, with survival rates reported to be <10% at 3 years and <5% at 5 years. 3,4 Therapeutic challenges include both a more aggressive biology of the disease as well as a patient that is more susceptible to the toxic effects of chemotherapy.…”