Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study.

BACKGROUND: Brentuximab vedotin was approved for adult patients with CD30-expressing cutaneous T-cell lymphoma treated with prior systemic therapy based on improved response rates and progression-free survival with brentuximab vedotin (1.8 mg/kg once every 3 weeks; ≤16 cycles) versus physician's choice (methotrexate/bexarotene; ≤48 weeks) in the phase III ALCANZA study. Quality of life (QoL) in ALCANZA patients was also examined. METHODS: QoL measures in ALCANZA were based on the Skindex-29, Functional Assessment of Cancer Therapy-General (FACT-G) and European QoL 5-dimension (EQ-5D) questionnaires. RESULTS: Mean maximum reduction from the baseline Skindex-29 symptom domain score (key secondary end-point) was greater with brentuximab vedotin than physician's choice (-27.96 versus -8.62); the difference, -18.9 (95% confidence interval -26.6, -11.2; adjusted p < 0.001), exceeded the study-defined minimally important difference (9.0-12.3). Mean changes from baseline to end-of-treatment visit total FACT-G scores were similar with brentuximab vedotin and physician's choice (0.15 versus -2.29). EQ-5D changes were also comparable between arms. Among brentuximab vedotin-treated patients with peripheral neuropathy (PN), mean maximum reduction in Skindex-29 symptom domain was -35.54 versus -11.11 in patients without PN. PN had no meaningful effect on FACT-G and EQ-5D QoL scores. CONCLUSIONS: In summary, brentuximab vedotin produced superior reductions in symptom burden compared with physician's choice, without adversely impacting QoL. QoL was unaffected by the presence of PN in brentuximab vedotin-treated patients. CLINICAL TRIAL REGISTRATION: NCT01578499.

Cost-effectiveness of brentuximab vedotin plus chemotherapy as frontline treatment of stage III or IV classical Hodgkin lymphoma.

OBJECTIVE: The ECHELON-1 trial demonstrated efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline therapy for stage III/IV classical Hodgkin lymphoma. This analysis evaluated the cost-effectiveness of A + AVD from a US healthcare payer perspective. METHODS: The incremental cost-effectiveness ratio (ICER), defined as the incremental costs per quality-adjusted life year (QALY) gained, was estimated using a non-homogenous semi-Markov cohort model with health states defined on progression following frontline treatment, and for those with progression, receipt of autologous stem-cell transplant (ASCT), and progression after ASCT. Patients undergoing ASCT were classified as refractory or relapsed based on timing of progression. Probabilities of progression/death with frontline therapy were based on parametric survival distributions fit to data on modified progression-free survival (mPFS) from ECHELON-1. Duration of frontline treatment and incidence of adverse events were from ECHELON-1. Utility values for patients in the frontline mPFS state were based on EQ-5D data from ECHELON-1. Other inputs were from published sources. A lifetime time horizon was used. Costs and QALYs were discounted at 3%. Analyses were conducted alternately using data on mPFS for the overall and North American populations of ECHELON-1. RESULTS: The ICER for A + AVD vs ABVD was $172,074/QALY gained in the analysis using data on mPFS for the overall population and $69,442/QALY gained in the analysis using data on mPFS for the North American population of ECHELON-1. The ICER is sensitive to estimated costs of ASCT and frontline failure. CONCLUSION: The ICER for A + AVD vs ABVD based on ECHELON-1 is within the range of threshold values for cost-effectiveness in the US. A + AVD is, therefore, likely to be a cost-effective frontline therapy for patients with stage III/IV classical Hodgkin lymphoma from a US healthcare payer perspective.

Patient-reported distress in Hodgkin lymphoma across the survivorship continuum.

PURPOSE: Hodgkin lymphoma (HL) survivors face long-term, elevated risk of treatment-related sequelae, including psychosocial distress associated with poor health outcomes. The magnitude and sources of distress are not well described in the routine care of HL outside of clinical trials. METHODS: We conducted a retrospective cohort study of patients visiting a tertiary-care center for treatment or long-term follow-up of HL. Patient-reported distress was documented using the National Comprehensive Cancer Network Distress Thermometer (DT) and Problem List. Three survivor groups were compared using descriptive methods: on treatment, surviving < 5 years, and surviving ≥ 5 years since diagnosis. RESULTS: A total of 1524 DT were abstracted for 304 patients (106 on treatment, 77 surviving < 5 years, and 121 surviving ≥ 5 years). Distress was low overall (median DT = 1, inter-quartile range 0-4) and was similar across survivor groups. However, actionable distress (score ≥ 4) was reported at 29.5% of clinical encounters. Patients on treatment more frequently reported actionable distress (32.5% of visits) compared with patients surviving < 5 years (20.4%) and ≥ 5 years (28.7%) (P = 0.065). Distress was associated primarily with physical and emotional problems, especially fatigue, worry, and sleep. We did not observe any associations between distress and clinical prognostic factors. CONCLUSIONS: Distress burden is low in HL, but survivorship is marked by periods of actionable distress, largely related to physical symptoms and emotional issues. This burden may be higher when on treatment and is unrelated to disease-related prognostic factors. Survivorship research typically focuses on the post-therapy period, but our results support testing the efficacy of interventions to address distress in HL during active treatment as well.

Real-world analysis of cost, health care resource utilization, and supportive care in Hodgkin lymphoma patients with frontline failure.

PURPOSE: The purpose of this study was to evaluate the economic burden of frontline failure (FLF) among classical Hodgkin lymphoma (HL) patients during and after treatment. PATIENTS AND METHODS: The population consisted of adult HL patients identified from January 2010 through September 2015 without any other primary cancer prior to HL diagnosis, who also had a frontline (FL) regimen indicative of curative intent. Patients were characterized as FLF (those who restart, switch to any chemotherapy; had a hematopoietic stem cell transplant; or newly initiated radiation therapy [RT] after discontinuing FL) or non-FLF (those not considered as FLF). Direct health care utilization and expenditures were measured over both fixed and variable length follow-up periods and during FL therapy. RESULTS: There were 77 FLF and 602 non-FLF patients who met the final inclusion criteria. FLF and non-FLF patients were demographically similar with mean age 38.5 years and 47.5% females. Average per patient per month (PPPM) costs were significantly higher for FLF patients during all follow-up (US$20,266 vs US$7,772, P<0.05). Annual total expenditures were significantly higher among FLF patients (US$198,388) vs non-FLF patients (US$37,549). FLF (vs non-FLF) patients had a significantly shorter duration of FL therapy (116 vs 131 days, P=0.024) and higher total PPPM expenditures during FL (US$29,040 vs US$16,369, P<0.05). Annual cost varied by failure type with those who failed due to restart incurring the highest cost (US$269,189) and those who switched incurring the lowest cost (US$46,951). FLF patients had a significantly greater utilization in every health care resource category during follow-up. CONCLUSION: FLF (vs non-FLF) patients utilized substantially more health care resources and incurred a substantially higher economic burden. Over 5 years, FLF patients with at least two lines of treatment were projected to incur US$535,846 of health care costs. Further research is needed to determine optimal treatment that could reduce the risk of progression, need for treatment after FL, and enhance long-term clinical and economic outcomes.

Brentuximab vedotin consolidation post-autologous stem cell transplant in Hodgkin lymphoma patients at risk of residual disease: number needed to treat.

The number needed to treat (NNT) with brentuximab vedotin consolidation therapy post-autologous stem cell transplant (ASCT) versus placebo in the phase 3 AETHERA trial to avoid one additional event of disease progression/death was evaluated. AETHERA included 329 Hodgkin lymphoma patients at increased risk of progression post-ASCT who received brentuximab vedotin 1.8 mg/kg (n = 165) or placebo (n = 164) on day 1 of each 21-d cycle (up to 16 cycles). Over 60 months, the NNT with brentuximab vedotin ranged from 4.08 to 7.79 for the intent-to-treat population, 3.18-6.07 for patients with ≥2 risk factors, and 2.98-5.65 for patients with ≥3 risk factors. At various time points, and dependent on the risk group, 3-8 patients would need to be treated with brentuximab vedotin consolidation therapy to prevent a disease progression/death, compared with placebo. Patients with increased risk of relapse may benefit most from brentuximab vedotin.

Real-world economic burden of hematopoietic cell transplantation among a large US commercially insured population with hematologic malignancies.

AIMS: Approximately 20,000 hematopoietic cell transplantation (HCT) procedures are performed in the US annually. This study aims to study the healthcare resource utilization and costs among commercially-insured patients with hematologic malignancies who received autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT) in the US. MATERIALS AND METHODS: Adult patients with hematologic malignancies undergoing auto- or allo-HCT between January 1, 2011 and June 30, 2014 were identified in the Truven Health MarketScan Research Databases. Patients with 12 months of continuous pharmacy and medical enrollment pre- and post-HCT were included. Patients with prior HCT were excluded. Controls were selected from patients without any claims for HCT and matched with HCT recipients in a 3:1 ratio based on age, gender, insurance type, and Deyo-Charlson Comorbidity Index categories. Total healthcare resource uses and costs were compared between auto- or allo-HCT recipients and controls. RESULTS: In total, 10,527 patients (HCT, n = 2,672 vs control, n = 7,855) were included, with the majority of HCT recipients (63.6%) undergoing auto-HCT. During the 6-month pre-index and 12-month post-index period, auto-HCT recipients incurred $313,562 (p < .01) higher all-cause costs than controls, attributable to inpatient admission (54.1%), outpatient services (33.4%), and prescriptions (12.5%). The all-cause costs for allo-HCT recipients were $621,895 (p < .01) higher vs controls during the 18-month observation period, attributable to inpatient admissions (75.5%), outpatient services (22.1%), and prescriptions (2.4%). CONCLUSIONS: The use of HCT among patients with hematologic malignancies is associated with considerable economic burden in direct healthcare costs in a commercially insured population. Incremental costs for HCT recipients were mainly driven by costs related to hospitalization and other medical services.

Real-World Economic Burden Associated with Transplantation-Related Complications.

Approximately 20,000 hematopoietic cell transplantation (HCT) procedures are performed annually in the United States. Real-world data on the costs associated with post-transplantation complications are limited. Patients with hematologic malignancies aged ≥18 years undergoing autologous HCT (auto-HCT) or allogeneic HCT (allo-HCT) between January 1, 2011, and June 30, 2014, were identified in the Truven Health MarketScan Research Databases. Patients were required to have 12 months of continuous medical and pharmacy enrollment before and after HCT; patients who experience inpatient death within 12 months post-HCT were also included. Patients with previous HCT were excluded. Potential HCT-related complications were identified if they had a medical claim with a diagnosis code for relapse; infection; cardiovascular, renal, neurologic, pulmonary, hepatic, or gastrointestinal disease; secondary malignancy; thrombotic microangiopathy; or posterior reversible encephalopathy syndrome within 1 year post-HCT. Healthcare costs attributable to these complications were evaluated by comparing total costs in HCT recipients with complications and those without complications. The MarketScan Research Databases were further linked to the Social Security Administration's Master Death File to obtain patient death events in a subset of patients. A total of 2672 HCT recipients were included in the analysis. The mean ± SD age of recipients was 54.5 ± 11.6 years, and the majority of recipients (63.6%) underwent auto-HCT. Complications were identified in 81% of auto-HCT recipients and in 95.5% of allo-HCT recipients. Most complications occurred within 180 days post-HCT. Compared with Auto-HCT recipients without complications, those with complications incurred $51,475 higher adjusted total costs (P < .01). Compared with allo-HCT recipients without complications, those with complications incurred $181,473 higher adjusted total costs (P < .01). Among the patients with mortality data, auto-HCT recipients with complications had a higher mortality rate (13.4% vs 5.7%, P < .01) and a lower probability of survival (P < .01) compared with those without complications. In allo-HCT recipients, however, the mortality rate and probability of survival were not significantly different between those with complications and those without complications. HCT recipients with complications were associated with considerable economic burden in terms of direct healthcare costs in a commercially insured population, and in the case of auto-HCT, a higher mortality rate was observed in those with complications.

Quality of life results from a phase 3 study of brentuximab vedotin consolidation following autologous haematopoietic stem cell transplant for persons with Hodgkin lymphoma.

Brentuximab vedotin (BV) significantly improved progression-free survival in a phase 3 study in patients with relapsed or refractory Hodgkin lymphoma (RR-HL) post-autologous-haematopoietic stem cell transplant (auto-HSCT); we report the impact of BV on quality of life (QOL) from this trial. The European Quality of Life five dimensions questionnaire was administered at the beginning of each cycle, end of treatment, and every 3 months during follow-up; index value scores were calculated using the time trade-off (TTO) method for UK-weighted value sets. Questionnaire adherence during the trial was 87·5% (N = 329). In an intent-to-treat analysis, compared with placebo, TTO scores in the BV arm did not exceed the minimally important difference (MID) of 0·08 except at month 15 (-0·084; 95% confidence interval, -0·143 to -0·025). On-treatment index scores were similar between arms and did not reach the MID at any time point; mixed-effect modelling showed that BV treatment effect was not significant (P = 0·2127). BV-associated peripheral neuropathy did not meaningfully impact QOL. Utility scores for patients who progressed declined compared with those who did not; TTO scores between these patients exceeded the MID beginning at month 15. In conclusion, QOL decreased modestly with BV consolidation treatment in patients with RR-HL at high risk of relapse after auto-HSCT.

Systematic Review of Low-Density Lipoprotein Cholesterol Apheresis for the Treatment of Familial Hypercholesterolemia.

BACKGROUND: Apheresis is an important treatment for reducing low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia (FH). We systematically reviewed the current literature surrounding LDL-C apheresis for FH. METHODS AND RESULTS: Electronic databases were searched for publications of LDL-C apheresis in patients with FH. Inclusion criteria include articles in English published in 2000-2013 that provide descriptions of practice patterns, efficacy/effectiveness, and costs related to LDL-C apheresis in patients with FH. Data were stratified by country and FH genotype where possible. Thirty-eight studies met the inclusion criteria: 8 open-label clinical trials, 11 observational studies, 17 reviews/guidelines, and 2 health technology assessments. The prevalence of FH was not well characterized by country, and underdiagnosis was a barrier to FH treatment. Treatment guidelines varied by country, with some guidelines recommending LDL-C apheresis as first-line treatment in patients with homozygous FH and after drug therapy failure in patients with heterozygous FH. Additionally, guidelines typically recommended weekly or biweekly LDL-C apheresis treatments conducted at apheresis centers that may last 2 to >3 hours per session. Studies reported a range for mean LDL-C reduction after apheresis: 57-75% for patients with homozygous FH and 58-63% for patients with heterozygous FH. Calculated annual costs (in US$2015) may reach US$66 374 to US$228 956 per patient for weekly treatment. CONCLUSIONS: LDL-C apheresis treatment may be necessary for patients with FH when drug therapy is inadequate in reducing LDL-C to target levels. While apheresis reduces LDL-C, high per-session costs and the frequency of guideline-recommended treatment result in substantial annual costs, which are barriers to the optimal treatment of FH.

Medical costs associated with cardiovascular events among high-risk patients with hyperlipidemia.

OBJECTIVES: This study descriptively examined acute and longer term direct medical costs associated with a major cardiovascular (CV) event among high-risk coronary heart disease risk-equivalent (CHD-RE) patients. It also gives a firsthand look at fatal versus nonfatal CV events. METHODS: The MarketScan(®) Commercial Claims and Encounters Database was used to identify adults with a CV event in 2006-2012 with hyperlipidemia or lipid-lowering therapy use in the 18 months prior to one of the following inpatient CV events: myocardial infarction, ischemic stroke, unstable angina, transient ischemic attack, percutaneous coronary intervention, or coronary artery bypass graft (CABG). Patients were required to have a preindex diagnosis of at least one of the following: peripheral arterial disease, abdominal aortic aneurysm, carotid artery disease, or diabetes. A subset analysis was conducted with patients with data linkable to the Social Security Administration Master Death File. Direct medical costs were reported for each quarter following a CV event, for up to 36 months after the first CV event. RESULTS: In total, 38,609 CHD-RE patients were included, mean age 57 years, 31% female. CABG, myocardial infarction, and percutaneous coronary intervention were the most frequent and most expensive first CV events, accounting for >75% of all first CV events with mean first quarter costs ranging from $17,454 (nonfatal transient ischemic attack) to $125,690 (fatal CABG). Overall, 15% of those with a first CV event went on to have a second event during the 36-month study period with mean first quarter nonfatal and fatal costs similar to first event levels. Third CV events were rare, happening in less than 3% of patients. CONCLUSION: CV events among CHD-RE patients were costly regardless of sequence, averaging $47,433 in the first 90 days following an event and remaining high, never returning to preevent levels. When fatal, first CV event costs were 1.2 to 2.9 times higher than when nonfatal.

Use of intravenous bisphosphonates in patients with breast, lung, or prostate cancer and metastases to bone: a 15-year study in two large US health systems.

PURPOSE: The purpose of this paper is to document the use of intravenous (IV) bisphosphonates for prevention of skeletal-related events (SREs) in patients with bone metastases (BM) due to breast cancer (BC), lung cancer (LC), or prostate cancer (PC). METHODS: Using data from two large US health systems, we identified all patients aged ≥ 18 years with primary BC, LC, or PC and newly diagnosed BM between 1/1/1995 and 12/31/2009. Starting with the diagnosis of BM, we reviewed medical and administrative records for evidence of receipt of IV bisphosphonates (zoledronic acid or pamidronate) and occurrence of SREs. Initiation of IV bisphosphonates prior to occurrence of an SRE was designated "primary prophylaxis"; use following an SRE was designated "secondary prophylaxis". RESULTS: We identified a total of 1,193 patients with newly diagnosed BM, including 400 with BC, 332 with LC, and 461 with PC. Use of IV bisphosphonates was substantially higher in BC (55.8 % of all patients) than in LC (14.8 %) or PC (20.2 %). Use of IV bisphosphonates was fairly evenly split between primary and secondary prophylaxis in BC (26.3 vs. 29.5 %, respectively) and PC (10.6 vs 9.5 %); in LC, however, primary prophylaxis was much less common than secondary prophylaxis (4.8 vs 9.9 %). CONCLUSIONS: Almost one half of all patients with BM due to BC, and substantially more with LC and PC, do not receive IV bisphosphonates. Among patients receiving such therapy, treatment often is not initiated until after the occurrence of an SRE. Our study suggests that IV bisphosphonates may be substantially underutilized in patients with BM due to these common cancers.

Natural history of skeletal-related events in patients with breast, lung, or prostate cancer and metastases to bone: a 15-year study in two large US health systems.

PURPOSE: To document the risk of skeletal complications in patients with bone metastases from breast cancer (BC), lung cancer (LC), or prostate cancer (PC) in routine clinical practice. METHODS: We used data from two large US health systems to identify patients aged ≥18 years with primary BC, LC, or PC and newly diagnosed bone metastases between January 1, 1995 and December 31, 2009. Beginning with the date of diagnosis of bone metastasis, we estimated the cumulative incidence of skeletal-related events (SREs) (spinal cord compression, pathologic fracture, radiation to bone, bone surgery), based on review of medical records, accounting for death as a competing risk. RESULTS: We identified a total of 621 BC, 477 LC, and 721 PC patients with newly diagnosed bone metastases. SREs were present at diagnosis of bone metastasis in 22.4, 22.4, and 10.0 % of BC, LC, and PC patients, respectively. Relatively few LC or PC patients received intravenous bisphosphonates (14.8 and 20.2 %, respectively); use was higher in patients with BC, however (55.8 %). In BC, cumulative incidence of SREs during follow-up was 38.7 % at 6 months, 45.4 % at 12 months, and 54.2 % at 24 months; in LC, it was 41.0, 45.4, and 47.7 %; and in PC, it was 21.5, 30.4, and 41.9 %. More than one half of patients with bone metastases had evidence of SREs (BC: 62.6 %; LC: 58.7 %; PC: 51.7 %), either at diagnosis of bone metastases or subsequently. CONCLUSIONS: SREs are a frequent complication in patients with solid tumors and bone metastases, and are much more common than previously recognized in women with BC.

Treatment patterns in patients with prostate cancer and bone metastasis among US community-based urology group practices.

OBJECTIVE: To evaluate a cohort of United States-based urology practices for patterns related to screening, diagnosis, and treatment of bone metastases in men with castration-resistant prostate cancer. METHODS: Chart audits at 15 community-based urology group practices were conducted in the United States. Patient charts were eligible for study inclusion and review if they had documented bone metastasis secondary to castration-resistant prostate cancer. Data abstracted include site and patient demographics, diagnosis patterns, and bone metastases treatment between July 2006 and July 2009. A sample of approximately 10 charts per practice was used, starting with the most recent patient who met eligibility requirements. RESULTS: Eligible patients (n = 147) from 15 practices had a mean (SD) age of 67.8 (9.3) years at prostate cancer diagnosis and 72.5 (8.6) years at diagnosis of bone metastasis. Bone metastasis occurred 31.3 months (median) after cancer diagnosis. Seventy-three percent (n = 108) of patients had multiple bone metastases, and 82% (n = 120) had bone metastases in weight-bearing bones at last follow-up. Intravenous bisphosphonates were administered to 49% (72/147) of patients, with 97% (70/72) receiving zoledronic acid. CONCLUSION: Among patients with castration-resistant prostate cancer and documented bone metastases, approximately one half received intravenous zoledronic acid. This suggests that the other half of patients with bone metastases from prostate cancer remained undertreated for the prevention of skeletal complications based on National Comprehensive Cancer Network guidelines during the study time period.

Time associated with intravenous zoledronic acid administration in patients with breast or prostate cancer and bone metastasis.

PURPOSE: Intravenous (IV) zoledronic acid (ZA) is commonly used to delay skeletal complications secondary to bone metastases. However, the time associated with ZA administration may represent a significant burden to healthcare providers and patients. This study assessed the time associated with IV ZA infusion in patients with bone metastases secondary to breast or prostate cancer (BC or PC) in the clinic setting. METHODS: Eligible BC or PC patients with bone metastases scheduled to receive IV ZA were observed at seven US-based oncology clinics. Trained observers recorded the time for preinfusion tasks, ZA drug preparation, intravenous infusion, and follow-up activities. RESULTS: Data are reported for 39 patients (BC: 24; PC: 15). Mean administration time was 69 (standard deviation [SD] 42) minutes for all patients combined, 72 (SD 47) minutes for BC, and 65 (SD 33) minutes for PC. Activity times were comparable between tumor types. Mean time for preinfusion tasks (eg, assessment of vital signs, blood draw) and ZA preparation were 12 (SD 20) minutes and 2 (SD 1) minutes, respectively. Mean time required for intravenous infusion (ZA infusion and hydration, when provided) and follow-up activities were 54 (SD 31) minutes and 2 (SD 1) minutes, respectively. CONCLUSION: Infusion time was the greatest time commitment associated with IV ZA administration, representing 78% of the total time on average. Time for preinfusion activities varied substantially. Overall, the mean time for ZA administration represents a notable time burden for healthcare providers and patients.