Real-World Persistence and Time to Next Treatment With Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Including Patients at High Risk for Atrial Fibrillation or Stroke.

BACKGROUND: Atrial fibrillation (AF) is a recognized adverse consequence associated with all Bruton's tyrosine kinase inhibitors used to treat chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); however, real-world time to discontinuation (TTD) and time to next treatment (TTNT) of CLL/SLL patients with a high baseline AF/stroke risk remain unknown. MATERIALS AND METHODS: Patients with CLL/SLL from a nationwide electronic health record-derived database (February 12, 2013-January 31, 2021) initiating first-line (1L) or second or later-line (2L+) treatment with ibrutinib or other regimens on or after February 12, 2014 (index date) were analyzed. Kaplan-Meier survival analysis was used to assess TTD and TTNT among all patients, patients with high AF risk (CHARGE-AF risk score ≥10.0%), and patients at high risk of stroke (CHA2DS2-VASc risk score ≥3 [females] or ≥2 [males]). RESULTS: In 1L/2L+, 2190/1851 patients received ibrutinib and 4388/4135, were treated with other regimens. Median TTD for ibrutinib was similar regardless of AF/stroke-related risk (1L: all patients, 15.7 months; high AF risk, 11.7 months; high stroke risk, 13.7 months; similar results in 2L+). Median TTNT was significantly longer for ibrutinib vs. other regimens (1L: not reached vs. 45.9 months; 2L+: not reached vs. 23.6 months; both P < .05), including among those with high AF/stroke risk. TTNT was similar between all patients and high-risk cohorts in 1L and 2L+ (all P > .05). CONCLUSION: This study highlights that elevated baseline AF/stroke-related risk does not adversely impact TTD and TTNT outcomes associated with ibrutinib use. Additionally, TTNT was significantly longer for patients treated with ibrutinib vs. other regimens.

Real-world evidence for carfilzomib dosing intensity on overall survival and treatment progression in multiple myeloma patients.

INTRODUCTION: Carfilzomib dosing as a single agent or in combination with dexamethasone (Kd) has evolved from the initial 27 mg/m2 twice-weekly (legacy dose), to more recently approved doses of 56 mg/m2 twice-weekly and 70 mg/m2 once-weekly (optimized doses). The objective of this study was to evaluate the overall survival (OS), and time to next treatment (TTNT) among multiple myeloma patients treated with Kd optimized vs legacy doses. METHODS: A retrospective analysis of patients receiving Kd between 01/01/2013-07/31/2017 was conducted using IQVIA's oncology electronic medical records database. Kd dose was estimated based on body surface area. OS was measured from the Kd-initiation date until death. TTNT was defined as the time from Kd-initiation until the start of subsequent treatment. Kaplan-Meier analysis and Cox models were used to evaluate OS and TTNT. RESULTS: Of the 1,469 patients evaluated, 129 (8.8%) received optimized dose and 1,340 (91.2%) received legacy dose. Risk of mortality was 64% lower for patients receiving the optimized doses (HR: 0.36, 95% CI: 0.178-0.745). Patients receiving the optimized doses had significantly longer TTNT compared to patients receiving the legacy dose (median TTNT: 17.5 months [95% CI: 14.8-NE] and 13.2 months, [95% CI: 12.4-14.4], respectively; p = 0.023), and 33% lower risk of progressing to the subsequent treatment (HR: 0.67, 95% CI: 0.48-0.93). CONCLUSIONS: Patient outcomes could be improved if eligible MM patients are treated with the optimized, recently approved Kd doses (56 mg/m2 twice-weekly and 70 mg/m2 once-weekly).

Health-Related and Economic Burden Among Family Caregivers of Patients with Acute Myeloid Leukemia or Hematological Malignancies.

INTRODUCTION: Acute myeloid leukemia (AML) is associated with lower survival and greater unmet need compared with some other hematologic malignancies (HMs). Despite differences in acuteness between AML and other HMs, the burden of family caregivers (FCs) of patients with these malignancies offer similar patient experiences. A targeted literature review was conducted to explore FC burden of patients with AML and HM with and without hematopoietic stem cell transplant (HSCT). Instruments to measure and interventions to address FC burden were identified. METHODS: Studies on economic burden and compromised health-related quality of life (HRQoL) associated with FC burden, family affairs, and childcare from 1 January 2010 to 30  June 2019 were identified through database and hand searches. Published English articles on randomized controlled trials or standardized qualitative or quantitative observational studies were included. FCs were those in close familial proximity to the patient (i.e., spouse, parents, children, relatives, other family members, significant others). RESULTS: Seventy-one publications were identified (AML, n = 3; HM, n = 29; HSCT, n = 39). Predominant burden categories included humanistic (n = 33), economic (n = 17), and interventions (n = 22); one study was classified as humanistic and economic. FCs lack sufficient resources to manage stressors and experience negative psychological, behavioral, and physiological effects. FCs of patients with HMs reported post-traumatic stress disorder, significant sleep problems, moderate-to-poor HRQoL, and negative impacts on family relationships. Instruments designed to measure caregiver burden were generic and symptom-specific. Educational, expressional, and self-adjustment interventions were used to improve FC burden. CONCLUSION: Findings indicate a need for additional research, public health approaches to support FCs, and effective interventions to address FC burden. Minimizing FC burden and improving quality of life may reduce the overall healthcare service use and allow FCs to more effectively fulfill caregiver tasks. Support systems to alleviate caregiver burden may create reinforced integrators, thus positively affecting quality of life and possibly the outcomes of patients.

The value of survival gains from therapeutic innovations for US patients with relapsed/refractory multiple myeloma.

AIMS: This study quantifies the value of survival gains attributable to novel treatments approved since 2003 for United States (US) patients with relapsed/refractory multiple myeloma (RRMM). METHODS: We estimated the increase in survival attributable to lenalidomide and bortezomib for multiple myeloma (MM) patients in the 1983-2013 Surveillance, Epidemiology, and End Results (SEER) registry. To estimate the survival benefit of treatments approved since 2015 (carfilzomib, elotuzomab, daratumumab, used in combination with lenalidomide and dexamethasone) we used clinical trial data to calibrate survival estimated using the SEER data. We then conducted an economic valuation of the estimated shift in survival curves for all therapies. Finally, we estimated the share of the value accruing to patients and manufacturers using treatment costs estimated from MarketScan data. RESULTS: The introduction of bortezomib in combination with dexamethasone (Vd) and lenalidomide in combination with dexamethasone (Rd) resulted in substantial survival gains and societal value for multiple myeloma patients, generating 1.7 additional life-years per RRMM patient. More recently, approved novel treatments have improved survival over effective treatments (i.e. Rd/Vd) by an additional 2.5 life-years - the monetary value of this incremental survival benefit far exceeds the incremental cost of treatment. At the patient level, the incremental benefit of Rd/Vd is $335,500 and with novel treatments is $565,000. Applying this benefit to all future cohorts of US RRMM patients translates into a value of at least $75 billion and $130 billion with Rd/Vd and the novel treatments, respectively. CONCLUSIONS: SEER registry data were only available through 2013. Therefore, survival gains for recently approved treatments were estimated based on clinical trials, rather than observed survival. Our valuation analysis does not capture sources of value aside from survival gains, for example, better quality of life, increased productivity, or the value of surviving until subsequent novel therapies become available. Substantial extensions in life expectancy in RRMM since 2003 translate into real economic value gained by society.

Economic burden of disease progression among multiple myeloma patients who have received transplant and at least one line of therapy in the US.

Effects of disease progression on healthcare resource utilization (HRU) and costs among multiple myeloma (MM) patients with ≥1 line of therapy (LOT) who received their first stem cell transplant (SCT) within 1 year of initial MM diagnosis were estimated using a large US claims database. Disease progression was defined as advancement to the next LOT, bone metastasis, hypercalcemia, soft tissue plasmacytoma, skeletal related events, acute kidney disease, or death within 12 months of LOT initiation. Annual HRU and costs in the first three LOTs (L1-L3) were compared for patients with versus without disease progression using inverse probability of treatment weighting to adjust for differences between groups in baseline characteristics. In all LOTs, mean annual hospitalizations and healthcare costs were greater for patients with versus without progression. Total incremental annual costs among patients with versus without progression in L1-L3 were $18,359, $87,055, and $71,917, respectively, among LOTs initiated between 2006 and 2018. In LOTs initiated between 2013 and 2018, the figures were $46,024, $100,329, and $101,942 in L1-L3, respectively. The economic burden of disease progression is substantial in this population of MM patients who underwent SCT and received systemic anti-myeloma therapy.

Adaptation and Evaluation of a Symptom-Monitoring Digital Health Intervention for Patients With Relapsed and Refractory Multiple Myeloma: Pilot Mixed-Methods Implementation Study.

BACKGROUND: Relapsed and refractory multiple myeloma (RRMM) is a bone marrow cancer that requires systemic treatment, which often results in severe symptom burden. Recent studies have found that electronic patient-reported outcome (ePRO) interventions implemented in the clinic setting have had positive outcomes for other oncology populations. Evidence of the efficacy of a similar approach is lacking for patients with RRMM. OBJECTIVE: Recent recommendations for digital health interventions call for the publication of descriptions of iterative development processes in order to improve reproducibility and comparability. This study is an implementation pilot aiming to evaluate the acceptability and appropriateness of an ePRO intervention for patients with RRMM and to explore its impact on clinic workflow. METHODS: A total of 11 patients with RRMM were recruited from the John Theurer Cancer Center in Hackensack, New Jersey. Patients used a mobile app to report on 17 symptoms at 4 sessions, each a week apart. Patients could also report symptoms ad hoc. When reports met predefined thresholds, the clinic was alerted and patients received automated guidance. Study end points were assessed using qualitative and quantitative methods. RESULTS: A total of 9 patients (mean age 69.7 years) completed the study. Overall, 83% (30/36) of weekly sessions were completed. Patients found the frequency and time required to complete reporting acceptable. All patients agreed that the app was easy to use and understand. Providers felt the alerts they received required refinement. Patients and providers agreed it would be beneficial for patients to report for longer than 4 weeks. Patients felt that the training they received was adequate but contained too much information for a single session. All patients found the symptoms tracked to be appropriate; providers suggested shortening the list. All patients understood how to use the app for weekly reporting but had confusion about using it ad hoc. Providers felt the ad hoc feature could be removed. Neither patients nor providers viewed the in-app data reports but agreed on their potential value. Patients reported benefitting from symptom reporting through increased awareness of their symptoms. Clinic staff reported that app alerts were too numerous and redundant. They had difficulty responding to alerts within their existing workflow, partially because the data were not integrated into the electronic medical record system. CONCLUSIONS: Overall, the intervention was found to be acceptable and appropriate for patients with RRMM. Points of friction integrating the intervention into the clinic workflow were identified. Clinic staff provided recommendations for addressing these issues. Once such modifications are implemented, ePRO data from patients with RRMM could be used to inform and improve clinical research and care. This study underlines the importance of an iterative approach to implementation that includes all stakeholders in order to ensure successful adoption.

Cost-effectiveness of once weekly carfilzomib 70 mg/m2 plus dexamethasone in patients with relapsed and refractory multiple myeloma in the United States.

BACKGROUND: In the US, carfilzomib 70 mg/m2 once-weekly plus dexamethasone (Kd70 QW) was recently indicated for relapsed and/or refractory multiple myeloma. In current US clinical practice, most patients treated with Kd receive carfilzomib at a previously approved dose of 27 mg/m2 twice-weekly (Kd27 BIW). This analysis assessed the cost-effectiveness (CE) of Kd70 QW vs Kd27 BIW regimens which were compared in the randomized phase 3 ARROW trial. METHODS: Based on clinical outcomes (overall survival and utilities) from ARROW, a partitioned survival model was developed to estimate life years (LYs) and quality-adjusted life years (QALYs). Long-term survival was extrapolated using SEER registry data matched to ARROW patients. Costs were estimated using a US healthcare payer perspective. RESULTS: The analysis estimated that treatment with Kd70 QW vs Kd27 BIW resulted in an increase of 1.10 LYs, 0.91 QALYs, and additional lifetime costs of $74,858, yielding an incremental CE ratio (ratio of incremental costs to QALYs) of $82,257 per QALY gained. Results were robust to sensitivity and subgroup analyses. CONCLUSIONS: When compared with Kd27 BIW, Kd70 QW is the optimal dose that represents a cost-effective utilization of health care budget with incremental CE ratios well below the accepted willingness-to-pay thresholds in the US.

Burden of disease progression in patients with multiple myeloma in the US.

Effects of disease progression on healthcare resource utilization (HRU) and costs among multiple myeloma (MM) patients with ≥1 line of therapy (LOT) and without receipt of stem cell transplant were estimated using large US claims database. Disease progression was defined as advancement to the next LOT, bone metastasis, hypercalcemia, soft tissue plasmacytoma, skeletal related events, acute kidney failure, or death within 12 months of LOT initiation. Annual HRU and costs in the first four LOTs were compared for patients with versus without progression using inverse probability of treatment weighting to adjust for differences between groups in baseline characteristics. In all LOTs, mean annual hospitalizations and healthcare costs were greater for patients with versus without progression. Total incremental annual costs among patients with versus without progression in 1LOT to 4LOT were $25,920, $30,632, $47,320, and $19,769, respectively. For MM patients receiving drug therapy, the economic burden of disease progression is substantial.

Healthcare resource utilization and costs in patients with multiple myeloma with and without skeletal-related events.

AIM: To compare healthcare resource use and costs between newly diagnosed multiple myeloma (NDMM) patients with and without skeletal-related events (SREs). METHODS: Adults newly diagnosed with MM (1 January 2006 and 30 June 2017) with at least 12 months continuous health coverage prior to diagnosis were identified using the IBM MarketScan administrative claims. To control for baseline differences, NDMM patients with SREs were propensity score matched to NDMM patients without SREs. Outcomes included annual HRU and costs during follow-up along with number and type of SREs (SRE cohort only). Patients with SREs were stratified by number of SREs, and annual SRE-related costs were reported. Student's t test and Chi-squared test were used to compare outcomes. RESULTS: Before matching, the 6648 patients in the SRE cohort had more comorbidities, were more likely to have MM treatment, and had higher pre-index healthcare costs than the 7458 patients in the non-SRE cohort. After matching, cohorts of 3432 patients were well balanced on baseline characteristics. Patients with SREs (vs. without SREs) had significantly higher inpatient, outpatient, and pharmacy HRU. Patients with SREs had significantly higher mean annual all-cause healthcare costs ($213,361 vs. $94,896, p < 0.001) with hospitalization being the leading driver of increased costs (38.7% of total). Among 6648 patients with SREs, the mean annual SRE-related healthcare costs were $39,603, $45,463, and $50,111 for patients with one, two, and three or more events, respectively. CONCLUSIONS: NDMM patients with SREs have more than twice the all-cause healthcare costs than matched patients without SREs. Costs increase with the number of SRE events.

Estimation of minimally important differences and responder definitions for EORTC QLQ-MY20 scores in multiple myeloma patients.

OBJECTIVES: Thresholds for the minimally important difference (MID) or responder definition (RD) in health-related quality-of-life (HRQoL) scores are required to interpret the impact of an intervention or change in the trajectory of the condition which is meaningful to patients. This study aimed to establish MID and RD for the European Organisation for Research and Treatment of Cancer Quality of Life Multiple Myeloma questionnaire (EORTC QLQ-MY20). METHODS: A novel mixed-methods approach was applied by utilizing both existing clinical trial data and prospective patient interviews. Anchor-based, distribution-based, and qualitative-based estimates of meaningful change were triangulated to form recommended RDs for each scale of the EORTC QLQ-MY20. Anchor-based MIDs were summarized using weighted correlation. RESULTS: Recommended MIDs were as follows: Disease Symptoms (DS 10 points), Side Effects of Treatment (SE 10 points), Body Image (BI 13 points), and Future Perspective (FP 9 points). Recommended RDs were as follows: DS (16 improvement; 11 worsening), SE (6 improvement; 9 worsening), BI (33 improvement; 33 worsening), and FP (11 improvement; 11 worsening). CONCLUSIONS: The study generated estimates of the MID and RD for each scale of the EORTC QLQ-MY20. Published estimates will enable investigators and clinicians to adopt these as standard for interpretation and for hypothesis testing. Consequently, analyses from trials of different interventions can be more comparable.

Healthcare utilization and costs among relapsed or refractory multiple myeloma patients on carfilzomib or pomalidomide as monotherapy or in combination with dexamethasone.

Aim: To compare monthly healthcare resource utilization (HRU) and costs among adult patients with multiple myeloma (MM) receiving second or subsequent line of treatment (LOT) with carfilzomib or pomalidomide as monotherapy or in combination with dexamethasone. Methods and materials: Adult MM patients who received carfilzomib or pomalidomide as second/subsequent LOT between 2006 and 2014 were selected from the MarketScan databases. LOT was determined using Medical/pharmacy claims using a published algorithm. For each patient, first LOT with carfilzomib or pomalidomide was defined as index LOT. Patients with first LOT as index LOT, who received other chemotherapy in combination with carfilzomib or pomalidomide, or who underwent stem cell transplant (STC) during index LOT were excluded. Monthly HRU and costs during index LOT were compared using inverse probability of treatment weights (IPTW) based on propensity scores for receipt of carfilzomib estimated by logistic regression with LOT, patient demographics, Charlson index, comorbidities, pre-index healthcare cost, and receipt of prior SCT as covariates. Results: After weighting, baseline characteristics were well balanced among 114 carfilzomib and 144 pomalidomide patients. Mean (95% CI) numbers of outpatient visits per month were 7.1 (5.2-8.0) with carfilzomib and 4.7 (3.9-6.1) with pomalidomide (p = 0.006). Otherwise, there were no statistically significant differences between the groups in mean monthly HRU and costs or median time to therapy discontinuation. Mean (95% CI) monthly total healthcare costs were $19,776 (15,322-27,748) with pomalidomide and $17,321 (12,412-21,874) with carfilzomib (p = 0.522). Limitations: Comparison of carfilzomib vs pomalidomide may be biased if there are unobserved factors not balanced by IPTW. The relatively small sample size limits the power of analyses to detect potential differences between treatment groups. Conclusions: Monthly HRU and costs are similar among patients with relapse or refractory MM patients receiving carfilzomib or pomalidomide as monotherapy or in combination with dexamethasone.

Convenience, satisfaction, health-related quality of life of once-weekly 70 mg/m2 vs. twice-weekly 27 mg/m2 carfilzomib (randomized A.R.R.O.W. study).

We compared patient-reported outcomes (PROs) with once-weekly carfilzomib 70 mg/m2 (Kd70 mg/m2) vs. twice-weekly carfilzomib 27 mg/m2 (Kd27 mg/m2) plus dexamethasone in relapsed or refractory multiple myeloma (RRMM). Patient-reported convenience/satisfaction collected at Cycle 2, Day 1 was compared between groups using logistic regression. European Organization for Research and Treatment of Cancer QOL Questionnaire (QLQ-C30), MM-module (QLQ-MY20), and EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) questionnaires were administered at baseline, then every other cycle. PROs were compared between groups using mixed models for repeated measures. Times from randomization to first deterioration (TTD) in scores were analyzed using Cox regression. PRO analyses included 469 patients. Once-weekly Kd70 mg/m2 patients reported greater convenience (odds ratio [OR], 4.98; p < 0.001) and satisfaction (OR, 2.41; p = 0.059) vs. twice-weekly Kd27 mg/m2. The mixed models for repeated measures demonstrated no clinically meaningful differences in scores between treatment arms. Clinically meaningful deterioration in QLQ-C30 Global Health Status/QOL rates were 34.2% (once-weekly Kd70 mg/m2) vs. 40.3% (twice-weekly Kd27 mg/m2). TTD was longer for once-weekly Kd70 mg/m2 vs. twice-weekly Kd27 mg/m2 for QLQ-C30 fatigue (HR, 0.79; p = 0.035), QLQ-MY20 disease symptoms (HR, 0.67; p = 0.008), EQ-5D-5L index score (HR, 0.58; p = 0.002), and EQ-5D-5L Visual Analog Scale (HR, 0.75, p = 0.031). Once-weekly Kd70 mg/m2 improved convenience/satisfaction, and reduced HRQOL deterioration vs. twice-weekly Kd27 mg/m2, supporting convenient, once-weekly Kd70 mg/m2 dosing in RRMM.

Cost of peripheral neuropathy in patients receiving treatment for multiple myeloma: a US administrative claims analysis.

BACKGROUND: Peripheral neuropathy (PN) is a common consequence of multiple myeloma (MM) among those commonly treated with older-generation proteasome inhibitors (PIs). In this study, we evaluated the economic burden attributable to PN among MM patients in real-world practice settings in the US. METHODS: Adults diagnosed with MM and first treated (index event) between 1 July 2006 and 28 February 2017 were identified from MarketScan® Commercial and Medicare claim databases. Continuous enrollment for at least 12 months without treatment and PN diagnoses were required pre-index. Patients were followed for at least 3 months until inpatient death or end of data. The International Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM) and ICD-10-CM diagnosis codes were used to identify PN. Propensity-score matching was applied to match every patient with PN to two MM patients without a PN diagnosis (controls). Healthcare utilization and expenditures per patient per month (PPPM) in the postindex period were estimated. RESULTS: Of 11,851 patients meeting the study criteria, 15.5% had PN. After matching 1387 patients with PN and 2594 controls were identified. Baseline characteristics were well balanced between cohorts; mean follow up was 23-26 months. PPPM total costs were significantly higher by $1509 for patients with PN than controls, driven by higher hospitalization (PN 77.4%, controls 67.2%; p < 0.001) and emergency department rates (PN 67.8%, controls 58.4%; p < 0.001) and more outpatient hospital-based visits PPPM (PN 13.5 ± 14.7, controls 11.5 ± 18.0; p < 0.001). CONCLUSIONS: PN is a prevalent MM treatment complication associated with a significant economic burden adding to the complexity and cost of MM treatment. Highly effective novel treatments such as carfilzomib may reduce the overall disease burden.

A real-world comparative analysis of carfilzomib and other systemic multiple myeloma chemotherapies in a US community oncology setting.

BACKGROUND: Most multiple myeloma (MM) patients ultimately progress, with remission duration decreasing after first relapse. Recently, novel agents have been approved for the treatment of relapsed MM. There is a paucity of real-world data on these treatments. We sought to compare time to next treatment (TTNT) in MM patients in their second line of therapy (LOT2), treated with common proteasome inhibitor (PI)-based triplets. METHODS: Adult MM patients who received carfilzomib (K) between 1 November 2013 and 29 February 2016 at US Oncology Network (USON) clinics utilizing iKnowMed™ electronic health records (EHRs) were identified. Patients were included if they were ⩾18 years of age, not enrolled in clinical trials, had ⩾2 visits at a USON clinic and received LOT2 regimens consisting of: K+lenalidomide with steroid (KRd), bortezomib+lenalidomide with steroid (VRd), or bortezomib+cyclophosphamide with steroid (VCyd). TTNT was estimated from LOT2 initiation to LOT3 initiation using the Kaplan-Meier method, and hazard ratios (HRs) were estimated using Cox modeling. RESULTS: A total of 718 patients received a K-containing regimen sometime during their MM treatment (LOT1 to LOT5). Of these, 156 patients received: KRd (n = 112; 71.8%), VRd (n =27; 17.3%), or VCyd (n = 17; 10.9%). Baseline characteristics were similar between groups (mean age: 64.8 years; 58% male). Median TTNT was longest for KRd [25.3 months; 95% confidence interval (CI): 19.71-NR], versus VRd or VCyd (VRd median TTNT: 10.2 months, 95% CI: 4.24-12.71; VCyd: 6.5 months, 95% CI: 3.02-12.78; log-rank p < 0.0001). The adjusted HR for KRd was 0.19 (95% CI: 0.11-0.37), compared with VRd. CONCLUSIONS: Considering the real-world nature of these data, the median TTNT observed with KRd was relatively consistent, with progression-free survival (PFS) for KRd observed in the phase III ASPIRE trial (median PFS: ITT population = 26.3 months; LOT2 = 29.6 months). Patients who received KRd at first relapse had significantly longer TTNT, compared with those on VRd or VCyd, confirming the value of KRd as an important treatment option for relapsed MM.

Reframing the Value of Treatments for Relapsed/Refractory Multiple Myeloma.

DISCLOSURES: Ailawadhi reports research support from Pharmacyclics and consulting relationships with Takeda, Amgen, and Celgene. Jakubowiak reports consulting and advisory board relationships with AbbVie, Amgen, BMS, Celgene, Karyopharm, SkylineDX, and Takeda. Panjabi, Campioni, and Majer are employees of and stockholders in Amgen.

Cost-effectiveness of carfilzomib plus dexamethasone compared with bortezomib plus dexamethasone for patients with relapsed or refractory multiple myeloma in the United States.

BACKGROUND: We assessed the economic value of carfilzomib 56 mg/m2 and dexamethasone (Kd56) vs. bortezomib and dexamethasone (Vd) for relapsed/refractory multiple myeloma (R/RMM) using ENDEAVOR trial results. METHODS: Cost-effectiveness of Kd56 vs. Vd was assessed using a partitioned survival model by estimating progression-free survival, overall survival, and direct costs over a lifetime horizon. Surveillance Epidemiology and End Results (SEER) survival data were extrapolated after matching registry and ENDEAVOR patients. Utilities were sourced from the literature and mapped from patient-reported quality of life in ENDEAVOR to estimate quality-adjusted life-years (QALYs) from life-years (LYs). RESULTS: The model predicted an average gain of 1.66 LYs and 1.50 QALYs with Kd56 vs. Vd, and lifetime additional costs of $182,699, resulting in an incremental cost-effectiveness ratio (ICER) of $121,828/QALY gained. The ICER was $114,793/QALY in patients with 1 prior treatment; $99,263/QALY in those not transplanted, and <$150,000/QALY up to an 85% discount in bortezomib price. CONCLUSIONS: Kd56 is cost-effective for patients with R/RMM at a willingness-to-pay threshold of $150,000/QALY. Trial data in the model may limit generalizability; however, SEER registry data mitigates this challenge. Kd56 provides additional value in key subgroups, and remains cost-effective after steep comparator discounts.

Cost-effectiveness of adding carfilzomib to lenalidomide and dexamethasone in relapsed multiple myeloma from a US perspective.

OBJECTIVE: To assess the economic value of carfilzomib (Kyprolis), this study developed the Kyprolis Global Economic Model (K-GEM), which examined from a United States (US) payer perspective the cost-effectiveness of carfilzomib-lenalidomide-dexamethasone (KRd) versus lenalidomide-dexamethasone (Rd) in relapsed multiple myeloma (RMM; 1-3 prior therapies) based on results from the phase III ASPIRE trial that directly compared these regimens. METHODS: A partitioned survival model that included three health states of progression-free (on or off treatment), post-progression, and death was developed. Using ASPIRE data, the effect of treatment regimens as administered in the trial was assessed for progression-free survival and overall survival (OS). Treatment effects were estimated with parametric regression models adjusting for baseline patient characteristics and applied over a lifetime horizon. US Surveillance, Epidemiology and End Results (1984-2014) registry data were matched to ASPIRE patients to extrapolate OS beyond the trial. Estimated survival was adjusted to account for utilities across health states. The K-GEM considered the total direct costs (pharmacy/medical) of care for patients treated with KRd and Rd. RESULTS: KRd was estimated to be more effective compared to Rd, providing 1.99 life year and 1.67 quality-adjusted life year (QALY) gains over the modeled horizon. KRd-treated patients incurred $179,393 in total additional costs. The incremental cost-effectiveness ratio (ICER) was $107,520 per QALY. LIMITATIONS: Extrapolated survival functions present the greatest uncertainty in the modeled results. Utilities were derived from a combination of sources and assumed to reflect how US patients value their health state. CONCLUSIONS: The K-GEM showed KRd is cost-effective, with an ICER of $107,520 per QALY gained against Rd for the treatment of patients with RMM (1-3 prior therapies) at a willingness-to-pay threshold of $150,000. Reimbursement of KRd for patients with RMM may represent an efficient allocation of the healthcare budget.

Clinical and economic outcomes associated with amlodipine/renin-angiotensin system blocker combinations.

OBJECTIVES: Since treatment regimen type can influence adherence and other outcomes, this study examined adherence, cardiovascular events, and economic outcomes in patients with hypertension treated with fixed-dose combination (FDC) amlodipine/olmesartan (AML/OM), FDC AML/benazepril (AML/BEN), and loose-dose combination AML plus angiotensin II receptor blockers (LDC AML/ARBs). METHODS: Commercial health plan enrollees aged at least 18 years with index claim(s) for AML/OM, AML/BEN, or LDC AML/ARB were identified. Absence of study drug 6 months pre index, and continuous enrollment for at least 12 months post index were required. Descriptive analyses were executed to make comparisons between treatments, as well as multivariate models adjusting for baseline demographic and clinical characteristics, including propensity for assignment to study drug. RESULTS: Descriptive results suggested mean follow-up adherence was higher in the AML/OM cohort [proportion of days covered (PDC) = 0.63] compared with the AML/BEN (PDC = 0.55; p < 0.001) and LDC AML/ARB cohorts (PDC = 0.34; p < 0.001). The proportion of individuals with an incident follow-up cardiovascular event composite was lower in the AML/OM cohort versus the AML/BEN and LDC AML/ARB cohorts (5.94% versus 7.85% and 16.89% respectively). Adjusted Cox models suggested that patients initiated on LDC AML/ARB (hazard ratio 1.35; p < 0.001), but not on AML/BEN, were at greater risk of a follow-up cardiovascular event (composite) compared with AML/OM. Adjusted generalized linear models suggested that mean follow-up per-member-per-month overall costs were higher in the AML/BEN (cost ratio = 1.169; p < 0.001; unadjusted mean cost US$780) and LDC AML/ARB cohorts (cost ratio = 1.286; p < 0.001; unadjusted mean cost US $1394) compared with the AML/OM cohort (unadjusted mean cost US $740). CONCLUSION: The results suggested that treatment with FDC AML/OM was associated with greater likelihood of adherence and lower overall costs than with FDC AML/BEN and LDC AML/ARB, and lower risk of cardiovascular event composite versus LDC AML/ARB.

Comparative effectiveness analysis of amlodipine/renin-angiotensin system blocker combinations.

A comparative effectiveness analysis of antihypertensive therapy amlodipine (AML) and angiotensin receptor blocker (ARB) fixed- and loose-dose combinations (FDCs and LDCs) in achieving blood pressure (BP) reduction and Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) goal attainment was made using retrospective electronic medical record (EMR) data. Treatment goal rates ranged from 35.0% for LDC AML/losartan to 45.7% for FDC AML/olmesartan (OM). FDC AML/OM achieved significantly greater reductions in systolic BP than FDC AML/benazepril (BEN), FDC AML/valsartan (VAL), and LDC AML/ARBs, respectively, and significantly greater reductions in diastolic BP than FDC AML/VAL and LDC therapy, respectively. Compared with patients treated with AML/OM, patients prescribed AML/VAL and LDC AML/ARB were significantly less likely to attain JNC 7 BP goal. Among subpopulations, AML/OM yielded higher rates of goal attainment among both African Americans and obese/overweight patients relative to AML/VAL and combined LDCs. Switchers from monotherapy with AML, OM, or VAL to AML/OM were significantly more likely to attain JNC 7 goals than those switching to AML/VAL or AML/BEN.