At what <scp>COST</scp>?: A prospective longitudinal cohort assessment of financial toxicity, quality of life, and associated risk factors in patients with plasma cell disorders
Authors: Rahma M. Warsame, Walker M. Schmidt, Angela Dispenzieri, Amylou C. Dueck
Journal: American Journal of Hematology (2024)

Financial toxicity is prevalent and harmful to patients with plasma cell disorders. Among cancer patients, those with plasma cell disorders such as multiple myeloma (MM) and light chain amyloidosis (AL) may be at particular risk of experiencing financial hardship due to a relapsing and remitting disease course, prolonged maintenance therapy, the use of multidrug treatment regimens, and the rise of expensive novel therapeutics.1 Financial toxicity (FT) describes the adverse effects of financial stress among cancer patients and is associated with reduced quality of life (QoL) and worse survival.2 Despite this, conversations about FT are not occurring consistently or effectively.3 To support FT assessment, this study prospectively ascertained FT among patients with plasma cell disorders, evaluated changes in FT over time, identified risk factors and protective factors related to FT, and determined the impact of FT on patient QoL. Participants were recruited between December 2019 and May 2021 to a longitudinal prospective study assessing FT and QoL throughout MM or AL treatment at Mayo Clinic, Rochester. Follow-up was done at 3 and 6 months from the time of recruitment. Enrollment and follow-up were temporarily halted at the onset of the COVID-19 pandemic in the United States in early 2020. Patients were screened and identified for this study via a departmental database. This study was approved by the Mayo Clinic Institutional Review Board. Patient demographic data was obtained through self-reported responses to a baseline enrollment survey and abstraction from the electronic medical record (EMR). Data included participant age, gender, race, ethnicity, education level, marital status, yearly income, occupational status, source of primary insurance, use of supplemental insurance, and distance traveled for care. EMR clinical data abstraction included: the date of MM or AL diagnosis, Revised Multiple Myeloma International Staging System (R-ISS) score or Revised Mayo Clinic AL Amyloidosis Staging System score, presence of high-risk cytogenetics at diagnosis, number of lines of therapy received, autologous stem cell transplant (ASCT) status, presence of bone disease, presence of neuropathy, date of last clinical follow-up, performance status at last clinical follow-up, and, if AL, the number of organ systems involved. FT was assessed through the validated Comprehensive Score for financial Toxicity (COST) questionnaire, an 11-item survey with overall scores ranging from 0 to 44. Although the COST measure is not associated with specific norms or cutoffs, lower scores indicate greater financial toxicity,2 and scores ≤26 have been associated with adverse QoL outcomes.4 For this study, a more conservative score of ≤23 defined the presence of FT. Scores >23 were considered as low/no FT. QoL was assessed using the Patient-Reported Outcome Measurement Information System (PROMIS-29), a National Institute of Health (NIH) self-report survey that measures functioning and well-being across seven domains of physical, mental, and social health.5 T scores are computed for each domain and a score of 50 represents the mean of a healthy US population with a standard deviation (SD) of 10. An eighth domain—pain intensity—is measured through a 0–10 numeric rating scale. Electronic surveys were administered at the time of enrollment, 3, and 6 months follow-up. Mailed paper surveys were sent if electronic surveys were not completed within 1 week. Descriptive statistics included frequencies and relative frequencies for categorical variables, and means, medians, and SDs for continuous variables. Pairwise Pearson correlations were computed between baseline COST scores (as a continuous variable) and PROMIS-29 domain T scores and plotted using pairwise scatter plots. Pearson correlation ≥0.3 in absolute value was considered meaningful. Association between baseline COST scores (as a continuous variable) and categorical patient demographics and other patient, disease, or treatment characteristics were explored using Wilcoxon rank sum tests for binary characteristics, Jonckheere–Terpstra test for characteristics with more than two ordered categories, and Kruskal–Wallis test for characteristics with more than two unordered categories. p < .05 was considered statistically significant throughout and all statistical analysis was carried out using SAS software, version 9.4. A total of 116 patients participated in this study: 96 with MM (83%), and 20 with AL (17%). Patient demographics and clinical characteristics during the 6-month pre-index period are presented in Table 1. The cohort was characterized as follows. Fifty-seven participants (49%) were 65 years or older. Sixty-three participants (54%) were male. A total of 108 participants (93%) identified as White, five (4.3%) as Black, and one participant identified as Asian, of multiple races, or other/not reported, respectively. Four participants self-identified as Hispanic (3.5%). Fifty participants (43%) were newly diagnosed, while 66 (57%) had relapsed disease. Median time from diagnosis to baseline survey completion was 20.1 months (range 0–189.5). Most patients (N = 84, 72%) had received an autologous stem cell transplant. Eighty-two participants (71%) were currently married, 16 (14%) were divorced. Most individuals were insured primarily through Medicare (N = 60, 52%), or privately (N = 50, 43%), while five (4.3%) were insured through Medicaid. Approximately 44% of patients (N = 51) earned > USD $75 000 annually. Furthermore, most participants (N = 60, 52%) held a 4-year college degree or more. Among these individuals, 37 (32%) held a master's degree or doctorate degree. Most participants were either retired (N = 53, 46%) or currently employed (N = 42, 36%). Finally, patients traveled a median of 127.0 miles for treatment (range 1–1782, mean = 270.1, SD = 342.0). The mean baseline COST score was 25.9 (N = 116; SD = 10.2, median 26.5, range 2–44), with 46 participants (40%) reporting FT (score ≤23) at the time of enrollment. In addition to baseline surveys, 101 participants (87%) completed a 3- or 6-month follow-up COST survey. At 3 months follow-up, mean COST score was 26.1 (SD = 10.1, median 26.5, range 0–44). At 6 months follow-up, mean COST score was 27.3 (SD = 9.6, median 27, range 3–44). Among those with follow-up COST surveys, 38 participants reported FT at baseline and 63 reported low/no FT at baseline. Of the 63 participants with low/no baseline FT, 14 reported FT at 3 or 6 months. Of 38 participants with baseline FT, 11 had low/no FT at 3- or 6-month follow-up. Overall, this demonstrated that 25% of participants experienced a change in their FT status over time. The prevalence of FT was lower (p = <.05) among individuals earning >USD 75 K annually, retirees, those insured through Medicare, those with some college education or more, married individuals, males, and those who traveled more than 300 miles for care. Conversely, FT was associated with Medicaid as primary insurance (p = <.01). FT was more commonly present (p = <.01) among females and divorced individuals than their male and married counterparts, respectively. The prevalence of FT did not differ significantly by age, race, ethnicity, diagnosis (MM vs. AL), disease status (newly diagnosed vs. relapsed), or transplant status. The presence of FT was significantly associated with greater anxiety (Pearson r = −.35, p < .001), depression (Pearson r = −.38, p < .001), and pain interference (Pearson r = −.33, p < .001)—QoL domains on the PROMIS-29 survey. In this prospective study of FT in patients with plasma cell disorders, we show that FT is pervasive and dynamic over time. Furthermore, we identify patient characteristics associated with the presence or absence of FT. Finally, we demonstrate the negative impact of FT on specific domains of QoL. The baseline mean COST score of 25.9 (SD = 10.2) in this cohort is similar to findings in the COST validation study examining metastatic cancer patients, whose mean COST score was 22.2 (SD = 11.89).2 Nearly 40% of individuals in this cohort reported FT at baseline despite being a high-earning (44% >$75000) and well-educated (52% with 4-year degree or higher) group. We would expect the prevalence of FT to be even higher among less resourced populations. Roughly 25% of participants experienced a change in FT over time, necessitating intentional and frequent evaluation of a patient's reported financial strains throughout their cancer care continuum. Furthermore, identifying a patient's financial risk factors (divorced, Medicaid insurance, female sex) or protective factors (higher income, higher education, Medicare insurance) could aid in early referral to appropriate financial and social services. Patients who reported FT at baseline concurrently reported lower QoL in the domains of depression, anxiety, and pain interference. As a predictor of QoL, the presence of FT should prompt evaluation into other areas of the patient's physical and mental health. As this study demonstrated the dynamic nature of FT, it would be useful for further research to examine for changes in patient-reported QoL over time. The findings of this study should be interpreted in the context of its limitations and strengths. Our cohort consisted of predominantly non-Hispanic White individuals living in the upper Midwest which may diminish the generalizability of this study. Additionally, small numbers of participants among subgroups made direct comparison between groups challenging. Despite these limitations, this study was able to characterize the prevalence of FT both in cross section and over time. It did provide a unique lens of FT during the volatile early years of the COVID-19 pandemic, and would benefit from further research into how changes to healthcare delivery impacted patients with plasma cell disorders. This study demonstrates that FT is a pervasive clinical issue even among affluent patients with a tangible impact on patients' well-being. Clinicians should actively and regularly investigate patients' financial concerns to identify and mitigate FT through referral to appropriate financial and social services. At the health system level, the emphasis should be development of automated, systematic FT assessment and care processes to identify, support, and reassess patient financial distress. Such a system was tested by Blinder et al. and demonstrated that routine automatic assessment of FT can reduce the development or worsening of FT for cancer patients.6 When the delay, discontinuation, and even abandonment of treatment are some of the strategies that cancer patients use to manage the overwhelming financial burdens, addressing FT should be an expectation, as important as assessment of treatment toxicity. The authors have no funding or conflicts of interest to disclose.