Impact of Adverse Events on Health-Related Quality of Life in Patients with Chronic Myeloid Leukemia (CML) Treated with Tyrosine Kinase Inhibitors (TKIs) - Early Results of the Survey on Humanistic Burden of Intolerance to First or Second TKIs (SHIFT) Study

INTRODUCTION:

Patients with chronic phase CML (CP-CML) treated with first- (1G) or second-generation (2G) TKIs as their first or second treatment often experience TKI-associated adverse events (AEs) leading to changing medications, treatment cessation, or reduced quality of life (QoL). The SHIFT study aims to provide a better understanding of how AEs impact health-related QoL in patients with CML in US real-world settings.

METHODS:

The SHIFT study is a cross-sectional web-based survey of patients with CML to collect their perspectives on the humanistic burden of AEs. Eligible participants include adults (≥ 18 years old) receiving a TKI for ≥ 3 months as first or second treatment for CP-CML at the time of the survey. AEs are self-reported using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Health-related QoL is measured using the Patient-Reported Outcomes Measurement Information System - Global Health (PROMIS-GH10; T-scores, lower scores are worse) and the Work Productivity and Activity Impairment Specific Health Problem (WPAI:SHP; impairment percentages, higher scores are worse) questionnaires. In addition to current state, responses on patients' “low point” are collected, defined as the time(s) when AEs had the biggest impact on QoL since start of the current TKI. Data collection began June 19, 2024 and is ongoing.

RESULTS:

As of July 8, 2024, 63 patients participated in the survey, with a median age of 52 years (86% female, 95% White, non-Hispanic). Most were commercially insured (62%; 27% Medicare, 8% Medicaid, 3% other/military) and half were employed (52%; 27% on disability, 15% retired, 6% not employed). Patients were evenly distributed between receiving a first (52%) or second TKI (48%), and half were treated in a community-based setting (51%; 37% in an academic center). The majority had been on their current TKI for ≥ 2 years (84%; 8% 1 to < 2 years, 8% < 1 year), with 25% treated with 1G and 70% with 2G TKIs.

In the last 7 days prior to the survey, patients experienced a median of 4.0 AEs (range: 0 - 14) with the most common being fatigue (75%), joint pain (51%), problems with memory (41%), diarrhea (32%), and muscle pain (32%). There were no reported hospitalizations in the last 7 days, suggesting these AEs were of low-grade. Persistent AEs were reported by almost all patients (91%). One quarter (24%) experienced a low point in the last 7 days, with 60% experiencing low point(s) before the last 7 days. Low point(s) were mostly experienced in the first 3 months of treatment (40%), with patients reporting multiple low points throughout their treatment with current TKI (23% > 3 to < 6 months, 36% 6 months to < 1 year, 23% 1 years to < 2 years, 32% ≥ 2 years).

The mean ± SD PROMIS-GH10 Global Physical Health (GPH) and Global Mental Health (GMH) T-scores were 43.1 ± 8.3 and 44.9 ± 8.3, respectively, reflecting poorer health than the general population (mean T-score 50). Over one-third reported a fair-to-poor rating for GPH (41.3%) and GMH (33.3%). GPH (mean ± SD 37.6 ± 6.6) and GMH (mean ± SD 38.8 ± 7.2) T-scores were worse in patients experiencing a low point in the last 7 days. Based on WPAI, mean percent activity impairment due to CML was 40.0%. Close to half (43%) reported modifying employment due to CML (i.e., changed from full time to part time or unemployed [21%], took early retirement [11%], stopped working temporarily [6%], increased working time to cover CML treatment costs [5%]). Among those employed, 75% reported some productivity loss due to CML, with a mean work productivity loss (percent overall work impairment) of 32.2%. Presenteeism (percent impairment while working) and absenteeism (percent work time missed) due to CML were reported at a mean of 29.1% and 6.6%, respectively.

CONCLUSIONS:

Findings of the ongoing SHIFT study demonstrate the humanistic burden of AEs associated with TKIs in patients with CML in the US. While survival of CML patients has improved with TKIs, nearly all participants reported persistent low-grade AEs that negatively impact their QoL, resulting in living with poorer global physical and mental health than the general population. Furthermore, nearly half had to modify their employment, and for those who continue to work, the majority reported impaired work productivity. Treatments with a better tolerability profile have the potential to reduce AEs, helping patients with CML to preserve a good QoL and maintain work productivity.

Schoenbeck:Novartis: Consultancy; Doximity: Current holder of stock options in a privately-held company. Clements:Novartis Pharmaceuticals: Consultancy, Honoraria; CML Buster Foundation: Current Employment, Membership on an entity's Board of Directors or advisory committees; iCMLf: Membership on an entity's Board of Directors or advisory committees; NCCN: Other: Volunteer, Patient Advocate reviewer, Clinical and Patient CML Guidelines; Confidential: Honoraria. Wei:Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Hazra:Analysis Group: Other: Nisha C Hazra is an employee of Analysis Group, Inc. (AG), an economic consulting firm. AG receives consulting fees from pharmaceutical companies and other ineligible companies, including Novartis. Constantinescu:Ipsos: Other: Cristina Constantinescu is an employee of Ipsos, a consulting company who received funding from Novartis for the design and execution of the study. Meng:Analysis Group: Other: Yan Meng is an employee of Analysis Group, Inc. (AG), an economic consulting firm. AG receives consulting fees from pharmaceutical companies and other ineligible companies, including Novartis. Latremouille-Viau:Analysis Group: Other: Dominick Latremouille-Viau is an employee of Analysis Group, Inc. (AG), an economic consulting firm. AG receives consulting fees from pharmaceutical companies and other ineligible companies, including Novartis. Jadhav:Novartis Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. McDermott:Novartis Ireland: Current Employment. Yang:Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company. Damon:Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company. Sadek:Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Guerin:Analysis Group: Other: Annie Guerin is an employee of Analysis Group, Inc. (AG), an economic consulting firm. AG receives consulting fees from pharmaceutical companies and other ineligible companies, including Novartis. Flynn:Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding; Inhibikase: Consultancy.