Abstract
Introduction There has been a rapid evolution in diagnostic and management evaluation for AML, associated with the introduction of new therapies, some of which target specific mutations, over the past decade. The Connect ® Myeloid Registry (NCT01688011) is a multicenter, prospective, observational cohort study that began enrollment in December 2013 and represents a rich source of information to evaluate changes in disease course and outcomes over time in patients with myeloid diseases. We evaluated 10-year longitudinal data from patients with AML treated in real-world clinical practice at community and academic institutions to understand the evolution of diagnosis and treatment of patients with this myeloid condition. Methods Patients in the AML cohort were ≥ 55 years of age and newly diagnosed with AML according to the 2008 revised World Health Organization criteria and were grouped by year of diagnosis: 2013-2016 (Group 1; before commercial availability of numerous novel therapies including venetoclax, midostaurin, ivosidenib, enasidenib, gemtuzumab ozogamicin, and others), and 2017-2022 (Group 2; after availability of new therapies). Baseline demographic and clinical characteristics, treatment patterns, and outcomes were evaluated by group. Overall survival (OS) from the date of diagnosis was estimated by the Kaplan-Meier method. Results A total of 773 patients with AML (Group 1, n = 292; Group 2, n = 481) were assessed. Median (range) age was 70.0 years (55.0-91.0) in Group 1, and 71.0 years (55.0-97.0) in Group 2. Median OS was 11.0 months (95% confidence interval [CI]: 9.0-14.0) in Group 1, and 16.0 months (13.0-18.0) in Group 2 ( P = 0.039; Figure). A higher percentage of patients in Group 2 survived to 60 months compared with Group 1 ( Figure). Improved survival over time was primarily observed in patients < 75 years of age at diagnosis; median (95% CI) OS among patients < 75 years of age increased over time from 14.0 months (11.0-17.0) in Group 1 to 20.0 months (17.0-24.0) in Group 2 ( P = 0.022) but remained unchanged over time among patients ≥ 75 years of age (9.0 months [6.0-10.0] in Group 1; 9.0 months [6.0-13.0] in Group 2; P = NS). Rates of transplant increased significantly over time for younger patients; among those < 75 years of age at diagnosis, 45/201 (22%) in Group 1 received a transplant, compared with 99/318 (31%) in Group 2( P = 0.035). The proportion of patients receiving molecular testing increased over time from 68.8% in Group 1 to 86.9% in Group 2. The mean (standard deviation) number of mutations tested among those who underwent molecular testing also increased over time, from 6.1 (5.9) in Group 1 to 11.8 (7.4) in Group 2. Longer median (95% CI) OS was observed in patients who received molecular testing compared with those who did not: 14.0 months (11.0-17.0) versus 9.0 months (7.0-11.0) in Group 1; 16.0 months (13.0-19.0) versus 13.0 months (6.0-17.0) in Group 2. The proportion of patients receiving first-line treatment with intensive chemotherapy (IC) regimens was similar in the 2 time periods (Group 1, 51.0%; Group 2, 47.1%). Among patients not receiving IC, those in Group 2 increasingly received targeted therapies and venetoclax-based regimens and less-frequent low-intensity chemotherapy and supportive care. Conclusions In the AML cohort of Connect ® Myeloid, one of the longest-running US registries of myeloid diseases, we observed that patient characteristics at diagnosis were similar from 2013-2022. A statistically significant increase in median OS was observed over time. The increased rate of transplant, higher rates of molecular testing, and uptake of novel, targeted, treatments may have contributed to the improvement in survival. These results demonstrate the need for long-running, prospective observational studies to continue to understand rapidly changing treatment algorithms, combinations, and outcomes in AML.
