Abstract
BACKGROUND: Acute myeloid leukemia (AML) and therapy for patients with AML represent a striking example of age-related outcome disparity in oncology. Older patients experience shorter overall survival, have usually more comorbidities, and are at greater risk for treatment-related mortality. Consequently, a substantial portion of older patients are considered "unfit" for standard intensive chemotherapy and are offered less intensive regimens or best supportive care. In recent years, hypomethylating agents (HMAs), namely azacitidine (AZA) and decitabine (DEC), have emerged as standards of care for patients with AML unfit for intensive chemotherapy. The objective of this study was to identify and describe HMA utilization in older patients with AML (≥65 years) not receiving intensive chemotherapy in a real-world claims database.
METHODS: AML patients were retrospectively identified in the MarketScan® Research Database (Truven Health) including both Commercial and Medicare Supplemental claims databases between 01/2011 to 07/2016. Patients ≥ 65 years old with a minimum of two claims with an AML diagnosis, ≥ 1 bone marrow procedure (the first AML diagnosis following the bone marrow diagnosis procedure was defined as the index date), and ≥ 12 months of continuous eligibility (baseline period) prior to the index date were included. Exclusion criteria were the following: ≥ 1 diagnosis for AML relapse or remission on or before the bone marrow diagnosis procedure, ≥ 2 diagnoses for another blood cancer, ≥ 1 allogeneic hematopoietic stem cell transplantation before the bone marrow diagnosis procedure, or ≥ 1 claim for intensive chemotherapy at any time. We recorded the percentages of HMA usage (AZA and DEC) among patients treated with ≥ 1 antineoplastic agent (excluding hormonal therapy agents) overall and in first and second lines of therapy, and treatment duration (i.e., cumulative duration of AZA- or DEC-based lines of therapy) along with the corresponding number of 28-day treatment cycles obtained by dividing the treatment duration by 28. In patients using HMAs in first- or second-line therapy, the percentages of monotherapy and blood transfusion use were tabulated and the proportion of patients who initiated a subsequent line of therapy was recorded.
RESULTS: After applying the selection criteria, 1,492 patients were identified for inclusion in our study population. Mean (standard deviation [SD]) patient age was 76.8 (7.0) years, 36.6% were ≥ 80 years old, and 61.0% were male. The mean (SD) Quan-Charlson Comorbidity Index (CCI) was 3.4 (2.4), with 33.5% of patients having a prior diagnosis of myelodysplastic syndrome. Among 610 (40.9%) patients treated with an antineoplastic agent, 449 (73.6%) patients received HMAs at any time during the observation period: 250 (55.7%; Table 1) of them used AZA (mean [SD] age = 77.3 [6.4] years; 59.6% male; mean [SD] CCI = 3.2 [2.3]) and 230 (51.2%; Table 1) used DEC (mean [SD] age = 76.5 [6.3] years; 60.0% male; mean [SD] CCI = 3.4 [2.4]). Mean (SD) total treatment duration was 134.8 (150.6) days with AZA and 139.8 (128.6) days with DEC, which is equivalent to a mean (SD) number of 28-day treatment cycles of 4.8 (5.5) for AZA and 4.9 (4.6) for DEC (Table 1). Among the 436 (71.5%) patients that received HMAs in first line, 232 (53.2%) used AZA, 204 (46.8%) used DEC, 395 (90.6%) used them in monotherapy, 379 (86.9%) had ≥ 1 blood transfusion during the first line of therapy, and 91 (20.9%) initiated a second line of therapy (Table 1). Of 120 (19.7%) patients with a second-line therapy, 65 (54.2%) received HMAs. Among them, 28 (43.1%) used AZA, 39 (60.0%) used DEC, 38 (58.5%) used them as monotherapy, 54 (83.1%) had ≥ 1 blood transfusion during the second line of therapy, and 10 (15.4%) patients proceeded to a third line of therapy (Table 1).
CONCLUSION: This study confirms that HMAs are commonly used in older (≥65 years) patients with AML who did not receive intensive chemotherapy, following National Comprehensive Cancer Network guideline recommendations. Utilization and treatment patterns were similar between both HMAs. A large proportion of patients received blood supportive products during their therapy and few of them initiated a subsequent line of therapy suggesting the need for additional treatment options. Additional studies with detailed evaluation of HMA use (including sequencing) are needed to further evaluate the important unmet need in the management of older patients with AML.
Sundaram: Johnson & Johnson, LLC: Equity Ownership; Janssen: Employment. Lafeuille: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd: Research Funding; Janssen Scientific Affairs, LLC: Research Funding. Hoehn: Johnson & Johnson, LLC: Equity Ownership; Janssen: Employment. Emond: Janssen Scientific Affairs, LLC: Research Funding. Romdhani: Janssen Scientific Affairs, LLC: Research Funding. Lefebvre: Janssen Scientific Affairs, LLC: Research Funding.
