Treatment Experience of Patients with Acute Myeloid Leukemia in the Era of Novel Therapies: A Longitudinal Electronic Patient-Reported Outcomes Study

Background: Since 2017, novel therapies for acute myeloid leukemia (AML) have emerged as options for patients unfit for high-intensity induction chemotherapy. However, much of our current understanding of the symptom burden that patients with AML face stems from studies prior to 2017, and few studies have measured symptoms longitudinally. Understanding patterns in symptom burden in this era of novel therapies can help optimize treatment decisions and supportive care for patients with AML. In this prospective, observational study, we used a symptom monitoring app to compare symptom burden, quality of life, and symptom bother between patients on high- and low-intensity treatment regimens.

Methods: We enrolled 186 adults with AML (of any genomic signature, de novo/secondary status, and line of therapy) across 7 sites nationally from 9/21/2020 to 2/27/2024. We excluded patients not on active treatment or whose recorded regimen was erroneous. High-intensity regimens included 7+3 (an anthracycline plus cytarabine), cytarabine plus a purine analog (e.g., FLAG-/CLAG-based regimens), or high-dose cytarabine alone. Low-intensity regimens included low-dose cytarabine, hypomethylating agents, or targeted therapies (e.g., inhibitors of FLT3, IDH1/2, etc.) Patients received weekly symptom monitoring surveys from the Carevive Patient-Reported Outcomes mobile platform (PROmpt™). They were asked whether they experienced any of 16 common cancer-related symptoms and rated severity as “mild”, “moderate”, “severe”, or “very severe”. We compared between high- and low-intensity regimens the proportion of survey responses where patients experienced >1 moderate to very severe (MOD-VS) symptom using a multivariable generalized linear mixed model (GLMM). Covariates included line of therapy, regimen type (induction, consolidation, maintenance), age, Charlson Comorbidity Index (CCI), and 2022 European LeukemiaNet risk category; p-values below are for regimen intensity. Patients also rated “I am bothered by treatment side effects” (FACT-GP5) as “not at all”, “a little bit”, “somewhat”, “quite a bit”, or “very much”; we defined high symptom bother as “somewhat”, “quite a bit”, or “very much”. We compared between regimen intensities the proportion of survey responses where patients endorsed high symptom bother using a GLMM as described. We also compared between regimen intensities mean “overall quality of life over the past week” (EORTC QLQ-C30 Item 30; 0 [very poor] to 7 [excellent]) using a GLMM.

Results: Among 186 patients, mean (SD) age was 62.7 (14.5) years; 83 (44.6%) were female, 148 (79.6%) White, and 5 (2.7%) Hispanic/Latino. Mean (SD) CCI was 3.3 (2.2). AML was de novo in 87 patients (46.8%), secondary in 36 (19.4%), and unknown in 63 (33.9%). Where recorded, mutations in FLT3-ITD or -TKD were present in 36 patients (25.4%), IDH1/2 in 39 (27.5%), TP53 in 15 (10.6%), NPM1 in 25 (17.6%), and RUNX1 in 24 (16.9%); inv(16) was present in 5 (3.5%). Out of 2852 surveys, 631 (22.1%) were skipped. The most common MOD-VS symptoms were decreased appetite (endorsed ≥1 time by 45.9% of patients), fatigue (43.2%), general pain (35.1%), constipation (33.5%), and shortness of breath (31.9%). Fatigue was most often rated as the most bothersome symptom (27.3% of survey responses). Following exclusions, 125 patients remained, encompassing 457 and 1535 survey responses across high- and low-intensity regimens, respectively. The proportion of weeks where >1 MOD-VS symptom was endorsed was 26.8% and 30.3% among patients on high- and low-intensity regimens, respectively (p=0.964). The proportion of survey responses where high symptom bother was endorsed was 25.7% and 33.1% across high- and low-intensity regimens, respectively (p=0.552). Mean (SD) quality of life was 5.5 (1.1) and 5.1 (1.2) across high- and low-intensity regimens, respectively (p=0.787).

Conclusion: Albeit limited by a discrepancy in survey responses between regimen intensities and crossover in regimen intensity for a few patients, our study did not reveal significant differences in symptom burden, quality of life, or symptom bother between regimen intensities in the era of novel AML therapies. While evidence demonstrates the benefit of low-intensity regimens for patients with advanced age or comorbidities, our findings also suggest that patients on low-intensity regimens have significant unmet symptom management needs that warrant attention.