Treatment selection and functional outcomes in treatment-related acute myeloid leukemia (tAML) and AML with myelodysplasia-related changes (MRC): A multicenter prospective cohort study

Abstract

Abstract Introduction: Liposomal encapsulated daunorubicin/cytarabine (L-dauno/ara-C) is FDA approved for adults with tAML and AML MRC based on survival advantage compared with traditional cytarabine and anthracycline (7+3). Since venetoclax plus low intensity chemotherapy is approved for upfront treatment of AML in patients 75 years and older and in those unfit for intensive induction, L-dauno/ara-C may not be utilized in every patient within its approved indications. We studied how patients' multidimensional functional status may influence treatment selection in tAML and AML MRC, and their functional outcomes. Methods: We enrolled patients ≥18 years with newly diagnosed tAML or AML MRC in a prospective cohort study across 6 US centers. Multidimensional study assessments including measures of physical function, cognitive function, depression, comorbidity burden, and health-related quality of life (HRQOL) were completed at baseline, and at 1 and 3 months. Instruments included Katz activities of daily living (ADL), Lawton instrumental ADL (IADL), Blessed Orientation-Memory-Concentration (BOMC), Patient Health Questionnaire (PHQ)-9, hematopoietic cell transplantation comorbidity index (HCT CI), Charlson comorbidity index, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Therapy selection was left to the discretion of the treating physician. Patients were followed for up to a year for disease status and survival. Results: Between February 2020-January 2024, 80 patients were consented with 3 deemed screen failures. Baseline characteristics included a median age of 66 years with 25% >70 years, 43% female, 97% white, and a median KPS of 80. ELN 2017 genetic risk categories included adverse (66%), intermediate (30%), and good-risk AML (4%). The most common comorbidities included obesity with BMI ≥ 30 (39%), depression/anxiety (23%), prior solid malignancies (23%), cardiovascular (22%), arrhythmia (16%), and diabetes (11%). About one-third had impaired physical function measured by ADL (33%) and IADL (35%), whereas 21% had abnormal depression screen (per PHQ-9). Only 5.5% had impaired cognition measured by BOMC (a score of ≥7). Whereas 18.9% had no functional impairments, 47.3% had one impairment, and over 33.8% had ≥2 impairments. Impairments in these multidimensional assessments were noted even in patients with KPS 80-100. A total of 54% patients received low-intensity chemotherapy: azacitidine or decitabine in combination with venetoclax (44%), and other (10%). Other patients received intensive chemotherapy (46%): L-dauno/ara-C (38%) or 7+3 regimen (8%) with or without additional agent. 85% started first cycle of chemotherapy in the hospital. 34% underwent allogeneic stem cell transplantation; 77% of these transplant recipients had received prior intensive chemotherapy. Survival at 30 days from diagnosis was 94.4% and at 1 year was 52.2%. Patients who received low-intensity chemotherapy vs. intensive chemotherapy were more likely to have impaired ADL (46.9% vs. 15%, p=0.034), and IADL (48.6% vs. 20.7%, p=0.035) at diagnosis but did not differ based on KPS, PHQ-9 and BOMC. Among survivors evaluated at baseline and 3 months, most showed either stabilization or improvement in ADL (71%), IADL (59%), PHQ-9 (81%) and BOMC (76%), using the widely-accepted cutoffs for minimal clinically important difference in functional changes. Stabilization or improvement were noted in HRQOL domains: global health status (80%), physical function (69%), social function (57%), cognitive function (66%), and fatigue (51%). Functional changes were not statistically different based on treatment intensity. Conclusions: To our knowledge, this is the first multicenter prospective multidimensional characterization of adults with newly diagnosed tAML and AML MRC. One-third of participants had impaired physical function, as measured by ADL or IADL. Patients with impaired ADL/IADL were more likely to be treated with low-intensity vs. intensive chemotherapy (usually L-dauno/ara-C). Despite the high burden of functional impairments at baseline, many survivors had either stabilization or improvement in functional and HRQOL measures by 3 months. This highlights that patients with tAML/AML MRC including those with functional impairments at diagnosis can benefit from treatment of AML and can have stable or improved functional outcomes.