Geriatric assessment-identified impairments and frailty in adults with cancer younger than 65: An opportunity to optimize oncology care.

INTRODUCTION: Frailty, a state of increased vulnerability to stressors due to aging or treatment-related accelerated aging, is associated with declines in physical, cognitive and/or social functioning, and quality of life for cancer survivors. For survivors aged <65 years, little is known about frailty status and associated impairments to inform intervention. We aimed to evaluate the prevalence of frailty and contributing geriatric assessment (GA)-identified impairments in adults aged <65 versus ≥65 years with cancer. MATERIALS AND METHODS: This study is a secondary analysis of clinical trial data (NCT04852575). Participants were starting a new line of systemic therapy at a community-based oncology private practice. Before starting treatment, participants completed an online patient-reported GA and the Physical Activity (PA) Vital Sign questionnaire. Frailty score and category were derived from GA using a validated deficit accumulation model: frail (>0.35), pre-frail (0.2-0.35), or robust (0-0.2). PA mins/week were calculated, and participants were coded as either meeting/not-meeting guidelines (≥90 min/week). We used Spearman (ρ) correlation to examine the association between age and frailty score and chi-squared/Fisher's-exact or ANOVA/Kruskal-Wallis statistic to compare frailty and PA outcomes between age groups. RESULTS: Participants (n = 96) were predominantly female (62%), Caucasian (68%), beginning first-line systemic therapy (69%), and 1.75 months post-diagnosis (median). Most had stage III to IV disease (66%). Common cancer types included breast (34%), gastrointestinal (23%), and hematologic (15%). Among participants <65, 46.8% were frail or pre-frail compared to 38.7% of those ≥65. There was no association between age and frailty score (ρ = 0.01, p = 0.91). Between age groups, there was no significant difference in frailty score (p = 0.95), the prevalence of frailty (p = 0.68), number of GA impairments (p = 0.33), or the proportion meeting PA guidelines (p = 0.72). However, older adults had more comorbid conditions (p = 0.03) and younger adults had non-significant but clinically relevant differences in functional ability, falls, and PA level. DISCUSSION: In our cohort, the prevalence of frailty was similar among adults with cancer <65 when compared to those older than 65, however, types of GA impairments differed. These results suggest GA and the associated frailty index could be useful to identify needs for intervention and inform clinical decisions during cancer treatment regardless of age. Additional research is needed to confirm our findings.

The association between food access and frailty among older adults with gastrointestinal malignancies-The CARE Registry.

BACKGROUND: Food access is associated with higher gastrointestinal (GI) cancer mortality; however, its association with frailty, which is a predictor of premature mortality among older adults with cancer, is less understood. METHODS: The authors included 880 adults aged 60 years and older who were recently diagnosed with GI cancers and were undergoing self-reported geriatric assessment at their first prechemotherapy visit to the University of Alabama at Birmingham oncology clinic. Food access was measured using the 2019 US Department of Agriculture Economic Research Service designation low-income, low-access (LILA), classifying census tracts based on income and/or access to food stores at various distances. The primary outcome was frailty on the CARE (Cancer and Aging Resilience Evaluation) Frailty Index, a composite of the proportion of impaired geriatric assessment measures. The authors examined the LILA-frailty association with modified Poisson regression accounting for census-tract clustering. RESULTS: The median patient age was 69 years, 58.1% were men, 22.5% were non-Hispanic Black, 29.2% had colorectal cancer, 28.0% had pancreatic cancer, 70.1% presented with stage III/IV disease, and 34.9% were frail. A higher proportion in LILA areas were non-Hispanic Black (44.1% vs. 10.8%; p < .001) and had less education (high school or less: 48.1% vs. 37.9%; p = .020). Adjusting for age, race and ethnicity, sex, cancer type and stage, and education, an LILA designation was associated with 58% greater odds of worsening frailty status (95% confidence interval, 1.18-2.12). An analysis of LILA subcategories revealed that associations were maintained across all LILA measures. CONCLUSIONS: Poor food access was associated with a greater risk of frailty among newly diagnosed older adults with GI cancers before they received systemic treatment. Intervening on local food access, particularly in LILA areas, may be a target for improving rates of frailty and promoting health equity in this population.

Management of Older Adults With Colorectal Cancer: The Role of Geriatric Assessment.

Older adults share a growing burden of cancer morbidity and mortality. This is present across the spectrum of oncologic diagnoses and is particularly true with colorectal cancer (CRC), where older adults continue to share the burden of diagnoses. However, optimal cancer treatment decision making in older adults remains a significant challenge, as the majority of previous clinical trials shaping the current treatment landscape have focused on younger patients, often with more robust performance status and fewer medical comorbid conditions. The heterogeneous aging process of older adults with CRC necessitates a personalized treatment approach, as approximately three-quarters of older adults with CRC also have a concominant geriatric syndrome and more than half of older adults with CRC are pre-frail or frail. Treatment decisions shoud be multifaceted, including consultation with the patient and their familes regarding their wishes, with consideration of the patient's quality of life, functional status, medical comorbid conditions, social support, and treatment toxicity risk. Geriatric assessment is a systematic and validated approach to assess an older adults's potential strengths and vulnerabilities, which can in turn be used to assist with comprehensive cancer care planning and support. In this review, we will summarize current treatment approaches for older adults with CRC, with a particular focus on the incorporation of the geriatric assessment.

Anxiety is Associated With Geriatric Assessment Impairments and Reduced Quality of Life Among Older Adults With Colorectal Cancer: Results From the CARE Registry.

BACKGROUND: Colorectal cancer (CRC) preferentially affects older adults. Modifiable factors, such as anxiety, can be measured as part of cancer-specific geriatric assessments (GA) completed prior to the start of treatment. We hypothesized that anxiety is prevalent among older adults with CRC and is associated with increased depression, increased frailty, and impaired health-related quality of life (HRQOL). PATIENTS AND METHODS: Patients ≥60 years old with newly diagnosed CRC completed a cancer-specific GA called the Cancer and Aging Resilience Evaluation (CARE). Between September 2017 and February 2023, we analyzed patients with CRC who had not yet received any systemic treatment. Anxiety was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety 4-item short form and reported as t-scores. We used modified Poisson models with robust variance estimation to assess for differences in the prevalence of depression, frailty, and impaired HRQOL. RESULTS: We analyzed 277 older adults with CRC. The median age of the study sample was 68 years. 57% were male, 72% were non-Hispanic White, and most had advanced CRC (35% stage III and 39% stage IV). Moderate/severe anxiety was present in 17% of older adults with newly diagnosed CRC. In adjusted models, as compared to patients without moderate/severe anxiety, patients with moderate/severe anxiety had significantly increased risk of depression (prevalence ratio [PR] 7.60, CI 4.90-11.78), frailty (PR 4.93, CI 3.01-8.07), impaired physical HRQOL (PR 3.57, CI 2.03-6.28), and impaired mental HRQOL (PR 3.82, CI 2.12-6.89). CONCLUSION: Among older adults with CRC, anxiety is associated with increased depression and frailty as well as reduced HRQOL.

Statin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia.

BACKGROUND: Polycythemia vera (PV) and essential thrombocythemia (ET) are linked to increased risk of cardiovascular morbidity and mortality. In addition to the reduction in of arterial thrombotic events, statins may prevent venous thrombosis including among patients with cancer. As previous registry- and claims-based studies revealed that the use of statins may improve the survival of patients with various malignancies we evaluated their impact on outcomes of older adults with PV and ET. METHODS: We identified 4010 older adults (aged 66-99 years at diagnosis) with PV (n = 1809) and ET (n = 2201) in a population-based cohort study using the Surveillance, Epidemiology, and End Results-Medicare database with median follow-up of 3.92 (interquartile range: 2.58-5.75) years. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) approaches were utilized to assess potential association between statins and overall survival. Multivariable competing risk models with death as a competing risk were used to evaluate possible relationship between statins and the incidence of thrombosis. RESULTS: 55.8% of the patients used statins within the first year after PV/ET diagnosis, and statin use was associated with a 22% reduction in all-cause mortality (PSM: hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.63-0.98, p = 0.03; IPTW: HR = 0.79, 95% CI: 0.64-0.97, p = 0.03). Statins also reduced the risk of thrombosis in this patient population (PSM: HR = 0.63, 95% CI: 0.51-0.78, p < 0.01; IPTW: HR = 0.57, 95% CI: 0.49-0.66, p < 0.01) as well as in PV and ET subgroups. CONCLUSIONS: These findings suggest that it may be important to incorporate statins into the therapeutic strategy for older adults with PV and ET.

Rural-urban disparities in mortality and geriatric assessment among older adults with cancer: The cancer & aging resilience evaluation (CARE) registry.

INTRODUCTION: Rural-urban disparities persist in cancer mortality, despite improvement in cancer screening and treatment. Although older adults represent the majority of cancer cases and are over-represented in rural areas, few studies have explored rural-urban disparities in mortality and age-related impairments among older adults with cancer. MATERIALS AND METHODS: We included 962 newly-diagnosed older adults (≥60 years) with cancer who underwent geriatric assessment (GA) at their first pre-chemotherapy visit to an academic medical center in the Southeastern United States. We used Rural-Urban Commuting Area (RUCA) codes to classify residence at time of diagnosis into urban and rural areas. We used one-year survival and pre-treatment frailty as outcomes. We used Cox proportional hazards regression to evaluate the association between residence and one-year mortality, and logistic regression to evaluate the association between residence and pre-treatment frailty. All tests were two-sided. RESULTS: Median age at GA was 68.0 (interquartile rage [IQR]: 64.0, 74.0) years; most had colorectal cancer (24.3%) with advanced stage (III/IV 73.2%) disease. Overall, 11.4% resided in rural and 88.6% in urban areas. Rural areas had a higher proportion of White and less educated participants. After adjustment for age, sex, race, education, employment status, and cancer type/stage, rural residence was associated with higher hazard of one-year mortality (hazard ratio [HR] = 1.78, 95% confidence interval [CI] = 1.23, 2.57) compared to urban residence. Frailty was an effect modifier of this association (HROverall = 1.83, 95% CI = 1.27, 2.57; HRFrail = 2.05, 95% CI = 1.23, 3.41; HRNot Frail = 1.55, 95% CI = 0.90, 2.68). DISCUSSION: Among older adults with newly diagnosed cancer, rural residence was associated with reduced one-year survival, particularly among frail older adults. The rural-urban disparities observed in the current study may be due to frailty in conjunction with disparities in social determinants of health across rural and urban areas. Future studies should focus on understanding and intervening on underlying causes of these disparities.

Camera-Based Short Physical Performance Battery and Timed Up and Go Assessment for Older Adults With Cancer.

This paper presents an automatic camera-based device to monitor and evaluate the gait speed, standing balance, and 5 times sit-stand (5TSS) tests of the Short Physical Performance Battery (SPPB) and the Timed Up and Go (TUG) test. The proposed design measures and calculates the parameters of the SPPB tests automatically. The SPPB data can be used for physical performance assessment of older patients under cancer treatment. This stand-alone device has a Raspberry Pi (RPi) computer, three cameras, and two DC motors. The left and right cameras are used for gait speed tests. The center camera is used for standing balance, 5TSS, and TUG tests and for angle positioning of the camera platform toward the subject using DC motors by turning the camera left/right and tilting it up/down. The key algorithm for operating the proposed system is developed using Channel and Spatial Reliability Tracking in the cv2 module in Python. Graphical User Interfaces (GUIs) in the RPi are developed to run tests and adjust cameras, controlled remotely via smartphone and its Wi-Fi hotspot. We have tested the implemented camera setup prototype and extracted all SPPB and TUG parameters by conducting several experiments on a human subject population of 8 volunteers (male and female, light and dark complexions) in 69 test runs. The measured data and calculated outputs of the system consist of tests of gait speed (0.041 to 1.92 m/s with average accuracy of >95%), and standing balance, 5TSS, TUG, all with average time accuracy of >97%.

Patient-reported geriatric assessment-based frailty index among older adults with gastrointestinal malignancies.

BACKGROUND: Older adults with cancer are at increased risk of treatment-related toxicities and excess mortality. We evaluated whether a patient-reported geriatric assessment (GA) based frailty index can identify those at risk of adverse outcomes. METHODS: Older adults (≥60 years) enrolled in a single-institutional prospective registry underwent patient-reported GA at initial evaluation in our medical oncology clinic. Using deficit accumulation method, we constructed a 44-item frailty index (CARE-FI), categorizing patients as robust, pre-frail, and frail. The primary outcome was overall survival (OS). Secondary outcomes included (a) functional decline at 3 months post-therapy (b) incident grade ≥3 treatment-related toxicities at six-month post-treatment. We used multivariate Cox and logistic regression models respectively to study the impact of frailty on primary and secondary outcomes. RESULTS: We identified 589 older adults with a median age of 69 years; 55% males and 73% Whites. Overall, 168 (29%) were pre-frail and 230 (39%) frail. Being frail (vs. robust) was associated with worse OS (Hazards Ratio, HR 1.83, 95% Confidence Interval, CI 1.34-2.49, p < 0.001) after adjusting for age, sex, race/ethnicity, cancer type, cancer stage, and line of therapy. Similarly, frailty was associated with increased risk of functional decline (OR 3.01; 95% CI 1.33-6.81; p = 0.008) and grade ≥3 non-hematologic toxicities (OR 3.65; 95% CI 1.54-8.69; p = 0.003) but not hematologic toxicities (OR 1.01; 95% CI 0.46-2.22; p = 0.97). CONCLUSIONS: Our frailty index using a patient-reported GA is a robust predictor of survival, functional decline, and treatment related toxicity among older adults with GI malignancies.

Geriatric Assessment Predictors of 1-Year Mortality in Older Adults With GI Malignancies: A Survival Tree Analysis.

PURPOSE: Identifying older patients with GI malignancies who are at increased risk of mortality remains challenging. The goal of our study was to examine geriatric assessment (GA) predictors of 1-year mortality and explore the use of a survival tree analysis in a prospective cohort of older adults (≥ 60 years) with newly diagnosed GI malignancies. METHODS: Survival tree analysis was performed to understand variable interactions and identify predictors of overall survival, computed from time of GA to death or last follow-up. Cox regression was used to estimate associations of 1-year mortality, first using a base model (age, race, cancer stage, cancer risk group, and planned chemotherapy), then using all significant predictors from the univariable analyses, and finally only those identified in survival tree analysis. RESULTS: A total of 478 participants met eligibility, with a mean age of 70 years. The survival tree analysis identified nutrition, cancer stage, physical and emotional health, age, and functional status as predictors of mortality. Older patients without malnutrition or depression had the best 1-year survival, whereas those with malnutrition, stage IV disease, and functional limitations had the worst 1-year survival. Our base model demonstrated good discrimination (area under curve [AUC] 0.76) but was improved with the addition of GA variables (AUC 0.82) or from survival tree analysis (AUC 0.82). CONCLUSION: Measures of function, nutrition, and mental health are important predictors of mortality in older adults with GI cancers. Using GA as part of clinical management can aid in the prediction of survival and help inform treatment decision making.

Impact of autologous hematopoietic cell transplantation on disease burden quantified by next-generation sequencing in multiple myeloma treated with quadruplet therapy.

The incremental impact of autologous hematopoietic cell transplantation (AHCT) on disease burden with quadruplet induction in newly diagnosed multiple myeloma (NDDM) can be reappraised with the serial assessment of minimal residual disease (MRD). We describe the impact of AHCT on MM burden assessed by next-generation sequencing (NGS) for patients enrolled in a clinical trial utilizing quadruplet induction, AHCT, followed by MRD-adapted consolidation. We describe quantitative changes in MRD burden with AHCT and explore patient and disease features influencing the magnitude of MRD reduction with AHCT. Among 123 included patients, 109 underwent AHCT and had MRD assessment pre and post AHCT. Forty percent achieved MRD < 10-5 post-induction, increasing to 70% after AHCT. Of the 65 patients (60%) who remained MRD positive post-induction, 54 (83%) had a reduction in MRD burden with AHCT. The median reduction in MRD with AHCT was 1.10 log10 (range, -1.26 to 3.41). Patients with high-risk cytogenetic abnormalities (HRCA) had greater reduction in MRD burden (p = .02) after AHCT. Median relative reduction was 0.91 log10 (range, -0.75 to 2.14), 1.26 log10 (range, -0.21 to 3.26) and 1.34 log10 (range, -1.28 to 3.41) for patients with 0, 1 and 2+ HRCA, respectively. The presence of HRCA was the only factor associated with greater than 1 log10 reduction in MRD burden with AHCT. Serial NGS MRD demonstrates the incremental effect of AHCT in MM marrow burden in the context of quadruplet induction, particularly in high-risk MM.

Racial disparities in frailty and geriatric assessment impairments in older adults with cancer in the Deep South: Results from the CARE Registry.

BACKGROUND: Despite recent advances in cancer, racial disparities in treatment outcomes persist, and their mechanisms are still not fully understood. The objective of this study was to examine racial differences in frailty and geriatric assessment impairments in an unselected cohort of older adults with newly diagnosed gastrointestinal (GI) malignancies. METHODS: This study used data from the Cancer and Aging Resilience Evaluation Registry, a prospective cohort study that enrolled older adults (≥60 years) with GI malignancies who were presenting for their initial consultation. Participants who had a geriatric assessment completed before chemotherapy initiation and self-reported as either White or Black were included. Frailty was defined with a frailty index based on the deficit accumulation method. The differences in the prevalence and adjusted odds ratios for frailty and geriatric assessment impairments between Black and White participants were examined. RESULTS: Of the 710 eligible patients who were seen, 553 consented with sufficient data for analyses. The mean age at enrollment was 70 ± 7.1 years, 58% were male, and 23% were Black. Primary cancer diagnoses included colorectal cancer (32%), pancreatic cancer (27%), and hepatobiliary cancer (18%). Black participants were more likely to be frail (50.0% vs 32.7%; P < .001) and report limitations in activities of daily living (27.3% vs 14.1%; P = .001), instrumental activities of daily living (64.8% vs 47.3%; P = .002), and walking 1 block (62.5% vs 48.2%; P = .004). These associations persisted even after adjustments for age, sex, education, cancer type, cancer stage, and comorbidity. CONCLUSIONS: Black participants were frailer and reported more limitations in function in comparison with White participants. These findings may partially explain disparities in cancer outcomes and warrant further examination.

Use of Single-Item Self-Rated Health Measure to Identify Frailty and Geriatric Assessment-Identified Impairments Among Older Adults with Cancer.

BACKGROUND: Poor self-rated health (SRH) is a known predictor of frailty and mortality in the general population; however, its role among older adults with cancer is unknown. We evaluated the role of SRH as a potential screening tool to identify frailty and geriatric assessment (GA)-identified impairments. MATERIALS AND METHODS: Adults ≥60 years diagnosed with cancer in the UAB Cancer & Aging Resilience Evaluation (CARE) registry underwent a GA at the time of initial consultation. We measured SRH using a single-item from the Patient-Reported Outcomes Measurement Information System global health scale and dichotomized responses as poor (poor, fair) and good (good, very good, and excellent). We evaluated the diagnostic performance of SRH in measuring frailty, and GA impairment (≥2 deficits among a set of seven GA domains). We examined the impact of SRH with survival using a Cox model adjusting for confounders, exploring the mediating role of frailty. RESULTS: Six hundred and three older adults with cancer were included, with a median age of 69 years. Overall, 45% (n = 274) reported poor SRH. Poor SRH demonstrated high sensitivity and specificity for identifying frailty (85% and 78%, respectively) and GA impairment (75% and 78%, respectively). In a Cox regression model, poor SRH was associated with inferior survival (HR = 2.26; 95% CI 1.60-3.18) after adjusting for confounders; frailty mediated 69% of this observed relationship. CONCLUSION: Self-rated health may be used as a screening tool to identify older adults with cancer with frailty and GA impairments. Poor SRH is associated with inferior survival, which is mediated by frailty.

The Evolution of Geriatric Oncology and Geriatric Assessment over the Past Decade.

Cancer is predominantly a disease of aging, and older adults represent the majority of cancer diagnoses and deaths. Older adults with cancer differ significantly from younger patients, leading to important distinctions in cancer treatment planning and decision-making. As a consequence, the field of geriatric oncology has blossomed and evolved over recent decades, as the need to bring personalized cancer care to older adults has been increasingly recognized and a focus of study. The geriatric assessment (GA) has become the cornerstone of geriatric oncology research, and the past year has yielded promising results regarding the implementation of GA into routine cancer treatment decisions and outcomes for older adults. In this article, we provide an overview of the field of geriatric oncology and highlight recent breakthroughs with the use of GA in cancer care. Further work is needed to continue to provide personalized, evidence-based care for each older adult with cancer.

Camera-Based Human Gait Speed Monitoring and Tracking for Performance Assessment of Elderly Patients with Cancer.

This paper presents a camera-based device for monitoring walking gait speed. The walking gait speed data will be used for performance assessment of elderly patients with cancer and calibrating wearable walking gait speed monitoring devices. This standalone device has a Raspberry Pi computer, three cameras (two cameras for finding the trajectory and gait speed of the subject and one camera for tracking the subject), and two stepper motors. The stepper motors turn the camera platform left and right and tilt it up and down by using video footage from the center camera. The left and right cameras are used to record videos of the person walking. The algorithm for operating the proposed system is developed in Python. The measured data and calculated outputs of the system consist of times for frames, distances from the center camera, horizontal angles, distances moved, instantaneous gait speed (frame-by-frame), total distance walked, and average speed. This system covers a large Lab area of 134.3 m2 and has achieved errors of less than 5% for gait speed calculation.Clinical Relevance- This project will help specialists to adjust the chemo dosage for elderly patients with cancer. The results will be used to analyze the human walking movements for estimating frailty and rehabilitation applications, too.

Cost-effectiveness of once-weekly selinexor, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma.

The BOSTON trial showed that use of once-weekly selinexor, bortezomib, and dexamethasone (SVd) prolonged progression-free survival compared to twice-weekly bortezomib and dexamethasone (Vd) in patients with relapsed or refractory (R/R) multiple myeloma (MM). In this study, we constructed a Markov model to assess the cost-effectiveness of SVd versus Vd in R/R MM. We calculated the incremental cost-effectiveness ratio (ICER) of each treatment strategy from a US payer perspective, using a lifetime horizon and a willingness-to-pay threshold of $150,000 per quality-adjusted life-year (QALY). Use of SVd was associated with an incremental cost of $170,002 compared to Vd alone ($1,015,120 vs. $845,118, respectively), an incremental effectiveness of 0.35 QALYs (3.43 vs. 3.08 QALYs, respectively), and an ICER of $487,361/QALY. These data suggest that use of once-weekly SVd for R/R M/M is unlikely to be cost-effective compared to twice-weekly Vd.

Association Between Chronologic Age and Geriatric Assessment-Identified Impairments: Findings From the CARE Registry.

BACKGROUND: The NCCN Guidelines for Older Adult Oncology recommend that, when possible, older adults with cancer undergo a geriatric assessment (GA) to provide a comprehensive health appraisal to guide interventions and appropriate treatment selection. However, the association of age with GA-identified impairments (GA impairments) remains understudied and the appropriate age cutoff for using the GA remains unknown. PATIENTS AND METHODS: We designed a cross-sectional study using the Cancer and Aging Resilience Evaluation (CARE) registry of older adults with cancer. We included adults aged ≥60 years diagnosed with gastrointestinal malignancy who underwent a patient-reported GA prior to their initial consultation at the gastrointestinal oncology clinic. We noted the presence of GA impairments and frailty using Rockwood's deficit accumulation approach. We studied the relation between chronologic age and GA impairments/frailty using Spearman rank correlation and chi-square tests of trend. RESULTS: We identified 455 eligible older adults aged ≥60 years with gastrointestinal malignancies; the median age was 68 years (range, 64-74 years) and colorectal (33%) and pancreatic (24%) cancers were the most common cancer type. The correlation between chronologic age and number of geriatric impairments was weak and did not reach statistical significance (Spearman ρ, 0.07; P=.16). Furthermore, the prevalence of domain-specific impairments or frailty was comparable across the 3 age groups (60-64 years, 65-74 years, ≥75 years) with the exception of comorbidity burden. Notably, 61% of patients aged 60 to 64 years had ≥2 GA impairments and 35% had evidence of frailty, which was comparable to patients aged 65 to 74 years (66% and 36%, respectively) and ≥75 years (70% and 40%, respectively). CONCLUSIONS: Using chronologic age alone to identify which patients may benefit from GA is problematic. Future studies should identify screening tools that may identify patients at high risk of frailty and GA impairments.

Cost-Effectiveness of First-Line Versus Second-Line Use of Daratumumab in Older, Transplant-Ineligible Patients With Multiple Myeloma.

PURPOSE: The MAIA trial found that addition of daratumumab to lenalidomide and dexamethasone (DRd) significantly prolonged progression-free survival in transplant-ineligible patients with newly diagnosed multiple myeloma, compared with lenalidomide and dexamethasone alone (Rd). However, daratumumab is a costly treatment and is administered indefinitely until disease progression. Therefore, it is unclear whether it is cost-effective to use daratumumab in the first-line setting compared with reserving its use until later lines of therapy. METHODS: We created a Markov model to compare healthcare costs and clinical outcomes of transplant-ineligible patients treated with daratumumab in the first-line setting compared with a strategy of reserving daratumumab until the second-line. We estimated transition probabilities from randomized trials using parametric survival modeling. Lifetime direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for first-line daratumumab versus second-line daratumumab from a US payer perspective. RESULTS: First-line daratumumab was associated with an improvement of 0.52 QALYs and 0.66 discounted life-years compared with second-line daratumumab. While both treatment strategies were associated with considerable lifetime expenditures ($1,434,937 v $1,112,101 in US dollars), an incremental cost of $322,836 for first-line daratumumab led to an ICER of $618,018 per QALY. The cost of daratumumab would need to be decreased by 67% for first-line daratumumab to be cost-effective at a willingness-to-pay threshold of $150,000 per QALY. CONCLUSION: Using daratumumab in the first-line setting for transplant-ineligible patients may not be cost-effective under current pricing. Delaying daratumumab until subsequent lines of therapy may be a reasonable strategy to limit healthcare costs without significantly compromising clinical outcomes. Mature overall survival data are necessary to more fully evaluate cost-effectiveness in this setting.

Second primary malignancy among older adults with multiple myeloma receiving first-line lenalidomide-based therapy: A population-based analysis.

OBJECTIVES: Clinical trials have suggested that patients with myeloma treated with lenalidomide may have an increased risk of second primary malignancies (SPM). Whether such risks are of significant relevance in the real-world clinical practice, particularly among older patients receiving first-line lenalidomide based therapy, remains unclear. METHODS: Using Surveillance Epidemiology and End Results-Medicare database, we identified adults ≥ 65 years with plasma cell myeloma diagnosed in 2007-2015 who received at least one oral anti-myeloma agent. We defined first-line lenalidomide-containing therapy as use within 90 days of diagnosis. SPM was defined as a malignancy reported to a cancer registry > 90 days after myeloma diagnosis. We computed cumulative incidence of SPM (with death being a competing event) and compared SPM rates between patients treated with or without first-line lenalidomide using a Fine-Gray's model, adjusting for age, sex, race, ethnicity, prior malignancy, and histologic subtype. RESULTS: Of 9850 Medicare beneficiaries, 4009 (41%) received first-line lenalidomide. During median follow up of 5.0 years, 423 patients (4.3%) developed SPM, including 361 solid tumors (85%) and 61 hematologic malignancies (14%). The cumulative incidence of any SPM at 5 years was similar among those who received first-line lenalidomide and those who did not (5.3% vs 4.4%; sub-hazard ratio, SHR 1.06, P = .53). Consistent results were seen in the risk of solid tumor (4.7% vs 3.6%; SHR 1.13, P = .24) or hematologic malignancy (4.7 vs 3.6%, SHR 0.73; P = .72). CONCLUSION: First-line lenalidomide therapy among older adults with myeloma was not associated with a significantly increased risk of any SPM.