Does Cost-Effectiveness Analysis Overvalue Potential Cures? Exploring Alternative Methods for Applying a "Shared Savings" Approach to Cost Offsets.

OBJECTIVES: To evaluate alternative methods to calculate and/or attribute economic surplus in the cost-effectiveness analysis of single or short-term therapies. METHODS: We performed a systematic literature review of articles describing alternative methods for cost-effectiveness analysis of potentially curative therapies whose assessment using traditional methods may suggest unaffordable valuations owing to the magnitude of estimated long-term quality-adjusted life-year (QALY) gains or cost offsets. Through internal deliberation and discussion with staff at the Health Technology Assessment bodies in England and Canada, we developed the following 3 alternative methods for further evaluation: (1) capping annual costs in the comparator arm at $150 000 per year; (2) "sharing" the economic surplus with the health sector by apportioning only 50% of cost offsets or 50% of cost offsets and QALY gains to the value of the therapy; and (3) crediting the therapy with only 12 years of the average annual cost offsets or cost offsets and QALY gains over the lifetime horizon. The impact of each alternative method was evaluated by applying it in an economic model of 3 hypothetical condition-treatment scenarios meant to reflect a diversity of chronicity and background healthcare costs. RESULTS: The alternative with greatest impact on threshold price for the fatal pediatric condition spinal muscular atrophy type 1 was the 12-year cutoff scenario. For a hypothetical one-time treatment for hemophilia A, capping cost offsets at $150 000 per year had the greatest impact. For chimeric antigen receptor T-cell treatment of non-Hodgkin's lymphoma, capping cost offsets or using 12-year threshold had little impact, whereas 50% sharing of surplus including QALY gains and cost offsets greatly reduced threshold pricing. CONCLUSIONS: Health Technology Assessment bodies and policy makers will wrestle with how to evaluate single or short-term potentially curative therapies and establish pricing and payment mechanisms to ensure sustainability. Scenario analyses using alternative methods for calculating and apportioning economic surplus can provide starkly different assessment results. These methods may stimulate important societal dialogue on fair pricing for these novel treatments.

Cost saving, patient centered algorithm for progenitor cell mobilization for autologous hematopoietic cell transplantation.

Administration of plerixafor with granulocyte-colony stimulating factor (G-CSF) mobilizes CD34+ cells much more effectively than G-CSF alone, but cost generally limits plerixafor use to patients at high risk of insufficient CD34+ cell collection based on low peripheral blood (PB) CD34+ counts following 4 days of G-CSF. We analyzed costs associated with administering plerixafor to patients with higher day 4 CD34+ cell counts to decrease apheresis days and explored the use of a fixed split dose of plerixafor instead of weight-based dosing. We analyzed 235 patients with plasma cell disorders or non-Hodgkin's lymphoma who underwent progenitor cell mobilization and autologous hematopoietic cell transplantation (AHCT) between March 2014 and December 2017. Two hundred ten (89%) received G-CSF plus Plerixafor and 25 (11%) received G-CSF alone. Overall, 180 patients (77%) collected in 1 day, 53 (22%) in 2 days and 2 (1%) in 3 days. Based on our data, we present a probabilistic algorithm to identify patients likely to require more than one day of collection using G-CSF alone. CD34+ cell yield, ANC and platelet recovery were not significantly different between fixed and standard dose plerixafor. Plerixafor enabled collection in 1 day and with estimated savings of $5000, compared to patients who did not receive plerixafor and required collection for three days. While collection and processing costs and patient populations vary among institutions, our results suggest re-evaluation of current algorithms.

The challenge of sustainability in healthcare systems: economic and organizational impact of subcutaneous formulations for rituximab and trastuzumab in onco-hematology.

Background: This study estimated the economic and organisational impact of using subcutaneous injection (SC) formulations of two monoclonal antibodies (rituximab and trastuzumab) in patients with non-Hodgkin's lymphoma (NHL) and HER2 + breast cancer (BC).Methods: The database of the Unit of Oncology and Haematology of the IRST of Meldola was used. The analysis was structured as follows: i) measurement of the volume of Day-Hospital activity; ii) identification of activities and time to complete the administration; iii) estimate the mean cost of an SC or IV (intravenous infusion); iv) estimate the impact of SC formulations on the volumes of activities provided; v) estimate the social impact of SC or IV formulations.Results: The use of an SC formulation was associated a significant reduction in the time that the patient takes to complete the administration (trastuzumab -1 hr 18 min; rituximab -2 hr 24 min) and in consumption of healthcare resources and related costs for trastuzumab (IV: € 1781; SC: € 1701) and rituximab (IV: € 2116; SC: € 1941).Conclusion: The adoption of the SC formulation for rituximab and trastuzumab can generate a greater value for both the national healthcare system and the patient compared to an IV formulation.

Burden of Hodgkin and non-Hodgkin lymphoma in Spain over a 10-year period: productivity losses due to premature mortality.

Background: Cancer is annually responsible for millions of deaths in Europe and billions of euros in productivity losses; the estimated mortality rate of lymphoma was of 7.07 per 100,000 individuals in Spain in 2018. This study aimed to evaluate the burden that lymphoma mortality represents for the Spanish society. Methods: The human capital approach was used to estimate the costs derived from premature mortality due to lymphoma between 2008 and 2017. Results: The number of deaths attributable to lymphoma increased steadily over the study period; the major number of deaths occurred among males aged 80 to 84 years. During the study period, 97,069 years of productive life were lost, a parameter that decreased noticeably over time due to the reduction in the number of deaths at working age. Productivity losses decreased accordingly. Lymphoma represented the 45.36% of losses due to hematological malignancies, generating €121 million in losses the year 2017. Hodgkin lymphoma was, among hematological malignancies, the malignancy accounting for the highest portion of losses per individual. Conclusions: Lymphoma represents a significant burden that can be reduced with the implementation of improved diagnosis and treatment methods, which must be taken into account in resource allocation and management policies.

Febrile neutropenia-related care and associated costs in elderly patients with breast cancer, lung cancer, or non-Hodgkin lymphoma.

PURPOSE: Limited information is available regarding elderly patients experiencing febrile neutropenia (FN). This study evaluated FN-related care among elderly cancer patients who received high/intermediate FN-risk chemotherapy and experienced ≥ 1 FN episodes. METHODS: We used Medicare data to identify patients aged ≥ 66 years who initiated high/intermediate FN-risk chemotherapy between 1 January 2008 and 31 August 2015 to treat breast cancer (BC), lung cancer (LC), or non-Hodgkin lymphoma (NHL) and had ≥ 1 FN episodes. We identified within-cycle FN episodes for each chemotherapy cycle on Part A inpatient claims or outpatient or Part B claims. We described the FN-related care setting (inpatient hospital, outpatient emergency department [ED], or outpatient non-ED) and reported mean total cost of FN-related care per episode overall and by care setting (adjusted to 2015 US$). RESULTS: We identified 2138, 3521, and 2862 patients with BC, LC, and NHL, respectively, with ≥ 1 FN episodes (total episodes: 2407, 3840, 3587, respectively). Most FN episodes required inpatient care (BC, 88.1%; LC, 93.0%; NHL, 93.2%) with mean hospital length of stay (LOS) 6.2, 6.5, and 6.8 days, respectively. Intensive care unit admission was required for 20.4% of BC, 29.0% of LC, and 25.7% of NHL hospitalizations (mean LOS: 4.7, 4.7, 5.5 days, respectively). The mean total cost of FN care per episode was $11,959 BC, $14,388 LC, and $15,006 NHL, with inpatient admission the costliest care component ($11,826; $14,294; and $14,873; respectively). CONCLUSIONS: Among elderly patients with BC, LC, or NHL who experienced FN, most FN episodes required costly hospital care, highlighting the FN burden on healthcare systems.

Impact of transitioning inpatient chemotherapy regimens to the outpatient setting.

BACKGROUND: Chemotherapy regimens historically have required admission of the patient to the hospital for extended infusions running over multiple days to complete each cycle of therapy. With the evolution of monitoring strategies readily available, a renaissance in patient care and healthcare cost utilization is necessary as transitioning the administration of these agents to the outpatient setting is seemingly achievable and is potentially more cost-effective. PURPOSE: This evaluation sought to primarily measure cost-savings for an institution by transitioning inpatient chemotherapy regimens to the outpatient setting. Secondary outcomes evaluated the effect of this transition on overall patient length of stay, prevalence of adverse effects, and overall chemotherapy schedule adherence as a result of implementing transitions in sites of care. Barriers to receiving care in the outpatient setting were assessed by evaluating the acuity of performance status as well as distance from the hospital. METHODS: This single-center retrospective, quantitative chart and expense analysis evaluated patients receiving rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (R-EPOCH) or rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) chemotherapy regimens based on treatment setting at a single institution. Included patients were treated at the University of Chicago Medical Center. Those receiving inpatient-only management as compared with patients who received therapy in outpatient settings were compared in a matched cohort analysis. The control group was matched from the period before transition of therapy was instituted between November 2014 and November 2015, with those patients transitioned to outpatient therapy (December 2015 to November 2016), using demographic, diagnostic, treatment, and clinical status data to assure group similarity. Mean cost of therapy was compared between inpatient and outpatient regimens. Descriptive and demographic categorical data were compared using the Fisher's exact test. Continuous data were evaluated using the Student's t test. A significance level of alpha <0.05 was used for all analysis. RESULTS: The cost of R-EPOCH therapy represented a significant difference across groups. R-ICE therapy similarly saw significant cost differences between inpatient and outpatient groups. If this was made standard of care for qualifying patients a retrospective annualized estimation of $466,507.85 with R-EPOCH therapy and $205,977.60 for R-ICE therapy could have been saved if this was utilized for patients who previously received their therapy as an inpatient. CONCLUSION: The population of patients cared for at the University of Chicago Medicine during this time-period qualified for outpatient treatment for those treated with R-EPOCH and R-ICE regimens with no significantly identifiable prohibitive barriers between groups. As no significant complications manifested, it is reasonable to continue transitioning patients receiving these regimens to the outpatient setting where appropriate. R-EPOCH and R-ICE therapies were shown to be reasonable outpatient therapy while providing significant cost-savings for the institution.

Reduced economic burden of AIDS-defining illnesses associated with adherence to antiretroviral therapy.

OBJECTIVES: We assessed the economic burden of AIDS-defining illnesses (ADIs), which was further stratified by adherence to antiretroviral therapy (ART). METHODS AND MATERIALS: A nationwide longitudinal cohort of 18,234 incident cases with HIV followed for 11years was utilized. Adherence to ART was measured by medication possession ratio (MPR). Generalized estimating equations modeling was used to estimate the cost impact of ADIs. RESULTS: Having opportunistic infections increased the annual cost by 9% (varicella-zoster virus infection) to 98% (cytomegalovirus disease), while the annual costs increased by 26% (Kaposi's sarcoma) to 95% (non-Hodgkin's lymphoma) in the year when AIDS-related cancer occurred. ADIs occurred more frequently in the years with low adherence for ART compared to the high-adherence years (e.g., 0.1≤MPR<0.8 vs. MPR≥0.8, event rate of cytomegalovirus disease 4.03% vs. 0.51%). The annual baseline costs in the years with MPR<0.1, 0.1≤MPR<0.8, and MPR≥0.8 were $250, $4,752, and $8,990 (in 2018 USD), respectively. The economic impact of ADIs in the years with low adherence (MPR<0.1) was larger than that in the high-adherence years (MPR≥0.8) (e.g., MPR<0.1 vs. MPR≥0.8, annual cost increased by 244% vs. 9% when candidiasis occurred). CONCLUSIONS: Adherence to ART may increase the baseline medical costs but mitigate the incidence and economic burden of ADIs.

Cost of Disease Progression in Patients with Chronic Lymphocytic Leukemia, Acute Myeloid Leukemia, and Non-Hodgkin's Lymphoma.

INTRODUCTION: To reduce health care costs and improve care, payers and physician groups are switching to quality-based and episodic or bundled-care models. Disease progression and associated costs may affect these models, particularly if such programs do not account for differences in disease severity and progression risk within the cohort. This study estimated the incremental cost of disease progression in patients diagnosed with chronic lymphoid leukemia (CLL), acute myeloid leukemia (AML), and non-Hodgkin's lymphoma (NHL) and compared costs among patients with and without progression. METHODS: This was a retrospective study using U.S. administrative claims data from commercial and Medicare Advantage health care enrollees with evidence of CLL, AML, and NHL and systemic antineoplastic agent use from July 1, 2006 to August 31, 2014. Outcome measures included disease progression, 12-month health care costs, and 3-year cumulative predictive health care costs. RESULTS: Of 1,056 patients with CLL, 514 patients with AML, and 7,601 patients with NHL, 31.1% of patients with CLL, 63.8% of those with AML, and 36.9% of those with NHL had evidence of disease progression. Among patients with CLL and NHL, adjusted and unadjusted health care costs were significantly higher among progressors versus nonprogressors. Per-patient-per-month costs, accounting for variable follow-up time, were almost twice as high among progressors versus nonprogressors in patients with CLL, AML, and NHL. In each of the three cancer types, the longer disease progression was delayed, the lower the health care costs. CONCLUSION: Progression of CLL, AML, and NHL was associated with higher health care costs over a 12-month period. Delaying cancer progression resulted in a substantial cost reduction in patients with all three cancer types. IMPLICATIONS FOR PRACTICE: Data on the rates and incremental health care costs of disease progression in patients with hematologic malignancies are lacking. This study estimated the incremental costs of disease progression in patients diagnosed with chronic lymphocytic leukemia, acute myeloid leukemia, and non-Hodgkin's lymphoma and compared health care costs in patients with and without evidence of disease progression in a real-world population. The data obtained in this study will assist future studies in quantifying the cost impact of decreased progression rates and will inform payers and physician groups about setting rates for episode and bundled payment programs.

Plerixafor in non-Hodgkin's lymphoma patients: a German analysis of time, effort and costs.

Mobilization and collection of peripheral blood stem cells is part of the standard treatment procedure for non-Hodgkin's lymphoma patients eligible for high-dose chemotherapy with autologous stem cell transplantation. Mobilization is usually achieved with chemotherapy and/or cytokines, but plerixafor might be added in case of poor mobilization. Due to the high cost several institutions have developed their own management pathway to optimize use of plerixafor. Such models are however rarely generalizable; in a multi-center, European, non-interventional study, evaluating the impact of plerixafor in poor mobilizers, country specific differences in patient treatment and cost structure were obvious. For German centers, there was a non-significant reduction in the number of apheresis sessions carried out and in apheresis costs. In contrast to other European countries the majority of German Plerixafor patients were very poor mobilizing patients with initial CD34+ cell count ≤ 10/µl (40/51). In this group the number of apheresis sessions decreased from 2.1 to 1.6 sessions per patient (p = 0.01) and costs decreased from €6246 to €4758 (p = 0.01). Our results show that preemptive plerixafor use has a strong effect in poor mobilizers with an initial CD34+ cell count ≤ 10 cells/µl.

The Rituximab Biosimilar CT-P10 in Rheumatology and Cancer: A Budget Impact Analysis in 28 European Countries.

INTRODUCTION: New biosimilars of monoclonal antibodies are anticipated to bring significant cost savings and increase access to treatment. The rituximab biosimilar CT-P10 has recently been approved in Europe in all indications held by reference rituximab (RTX), including rheumatoid arthritis, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia. We analyzed the budgetary impact of the introduction of CT-P10 into the European Union (EU) for use in patients with rheumatoid arthritis and cancer diagnoses, using a budget impact analysis model. METHODS: The model used a base case scenario in which the 1-year uptake of CT-P10 was estimated at 30%, and the cost of CT-P10 was assumed to be 70% of the cost of RTX. A second 1-year scenario was also modeled, in which the market share of CT-P10 was assumed to be 50% (scenario 2). Finally, 3-year time horizon outcomes were calculated, in which the market share of CT-P10 was assumed to be 30%, 40%, and 50% in the first, second, and third years, respectively. RESULTS: In the base case scenario, the introduction of CT-P10 was associated with projected savings of €90.04 million in the first year, which would allow 7531 additional patients to access rituximab treatment. This was equivalent to a 6.4% increase in the number of rituximab-treated patients. In scenario 2, budget savings were €150.10 million, with a total of 12,551 additional patients able to access rituximab, equivalent to a 10.7% increase. Over a 3-year time horizon, projected budget savings were approximately €570 million, equating to 47,695 additional patients able to access rituximab. CONCLUSIONS: The model predicted that the introduction of CT-P10 in the EU will be associated with significant budget savings, the reallocation of which will enable many more patients to access rituximab treatment. This is likely to have a significant impact on health gains at patient and societal levels. FUNDING: CELLTRION Healthcare Co., Ltd. sponsored the development and analysis of the budget impact analysis model.

Clinical and Cost Comparison Evaluation of Inpatient Versus Outpatient Administration of EPOCH-Containing Regimens in Non-Hodgkin Lymphoma.

BACKGROUND: Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-containing regimens are frequently utilized in non-Hodgkin's lymphoma, however, the incidence of febrile neutropenia (FN) in patients receiving inpatient versus outpatient EPOCH has not been described. Additionally, no comparisons have been made regarding financial implications of EPOCH administration in either setting. This study's primary objective was to compare hospital admissions for FN in patients receiving inpatient or outpatient EPOCH. METHODS: A single-center, institutional review board-approved review was conducted for adults receiving EPOCH beginning January 2010. Clinical and financial data were collected through chart review and the institution's financial department. Descriptive statistics were utilized for analysis. RESULTS: A total of 25 patients received 86 cycles of an EPOCH-containing regimen (61 [70.9%] inpatient). Five (8.2%) inpatient cycles resulted in an admission for FN compared to 4 (16%) outpatient cycles. Prophylactic antifungal and antiviral agents were prescribed more often after inpatient cycles (>80%) compared to outpatient cycles (<50%). Overall, 27 (31.4%) of 86 cycles did not receive granulocyte colony-stimulating factor support. Outpatient EPOCH administration was associated with a cost savings of approximately US$141 116 for both chemotherapy costs and hospital day avoidance. CONCLUSION: EPOCH-containing regimens can be safely administered in the outpatient setting, which may result in cost savings for healthcare institutions.

Paediatric non-Hodgkin lymphoma in low and middle income countries.

Great advances have been made in the treatment of paediatric non-Hodgkin lymphoma (NHL). In high-income countries (HIC), cure rates now exceed 85%. However, in low- and middle-income countries (LMIC), cure rates remain less than 50%. It is estimated that over 90% of paediatric NHL worldwide occur in LMIC; therefore, even modest improvements in outcome would have significant impact in reducing the burden of paediatric NHL globally. This article will discuss some of the issues required to improve the outcome of paediatric NHL in LMIC using data presented at the Fifth International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma held in Varese, Italy, 2015 to illustrate these issues. Additionally, potential bi-directional benefits for patients in both LMIC and HIC from future collaborations will be discussed.

The Cost-effectiveness of Pixantrone for Third/Fourth-line Treatment of Aggressive Non-Hodgkin's Lymphoma.

PURPOSE: Aggressive non-Hodgkin's lymphoma (aNHL) is associated with poor long-term survival after relapse, and treatment is limited by a lack of consensus regarding standard of care. Pixantrone was studied in a randomized trial in patients with relapsed or refractory aNHL who had failed ≥ 2 lines of therapy, demonstrating a significant improvement in complete or unconfirmed complete response and progression-free survival (PFS) compared with investigators' choice of single-agent therapy. The objective of this study was to assess the health economic implications of pixantrone versus current clinical practice (CCP) in the United Kingdom for patients with multiply relapsed or refractory aNHL receiving their third or fourth line of treatment. METHODS: A semi-Markov partition model based on overall survival and PFS was developed to evaluate the lifetime clinical and economic impact of treatment of multiply relapsed or refractory aNHL with pixantrone versus CCP. The empirical overall survival and PFS data from the PIX301 trial were extrapolated to a lifetime horizon. Resource use was elicited from clinical experts, and unit costs and utilities were obtained from published sources. The analysis was conducted from the perspective of the United Kingdom's National Health Service and personal social services. Outcomes evaluated were total costs, life-years, quality-adjusted life-years (QALYs), and cost per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty around the results. FINDINGS: Pixantrone was estimated to increase life expectancy by a mean of 10.8 months per patient compared with CCP and a mean gain of 0.56 discounted QALYs. The increased health gains were associated with an increase in discounted costs of approximately £18,494 per patient. The incremental cost-effectiveness ratio of pixantrone versus CCP was £33,272 per QALY gained. Sensitivity and scenario analyses suggest that the incremental cost-effectiveness ratio was sensitive to uncertainty in the PFS and overall survival estimates and the utility values associated with each health state. IMPLICATIONS: Pixantrone may be considered both clinically effective and cost-effective for patients with multiply relapsed or refractory aNHL who currently have a high level of unmet need.

Routine Primary Prophylaxis for Febrile Neutropenia with Biosimilar Granulocyte Colony-Stimulating Factor (Nivestim) or Pegfilgrastim Is Cost Effective in Non-Hodgkin Lymphoma Patients undergoing Curative-Intent R-CHOP Chemotherapy.

OBJECTIVE: This study aims to compare the cost-effectiveness of various strategies of myeloid growth factor prophylaxis for reducing the risk of febrile neutropenia (FN) in patients with non-Hodgkin lymphoma in Singapore who are undergoing R-CHOP chemotherapy with curative intent. METHODS: A Markov model was created to compare seven prophylaxis strategies: 1) primary prophylaxis (PP) with nivestim (biosimilar filgrastim) throughout all cycles of chemotherapy; 2) PP with nivestim during the first two cycles of chemotherapy; 3) secondary prophylaxis (SP) with nivestim; 4) PP with pegfilgrastim throughout all cycles of chemotherapy; 5) PP with pegfilgrastim during the first two cycles of chemotherapy; 6) SP with pegfilgrastim; and 7) no prophylaxis (NP). The perspective of a hospital was taken and cost-effectiveness was expressed as the cost per episode of FN avoided over six cycles of chemotherapy. A probabilistic sensitivity analysis was conducted. RESULTS: Strategies 3, 6, and 7 were dominated in the base case analysis by strategy 5. The costs associated with strategies 2, 5, 1, and 4 were US$3,813, US$4,056, US$4,545, and US$5,331, respectively. The incremental cost-effectiveness ratios for strategy 5 vs. strategy 2, strategy 1 vs. strategy 5, and strategy 4 vs. strategy 1 were US$13,532, US$22,565, and US$30,452, respectively, per episode of FN avoided. Strategy 2 has the highest probability to be cost-effective (ranged from 48% to 60%) when the willingness to pay (WTP) threshold is lower than US$10,000 per FN episode prevented. CONCLUSION: In Singapore, routine PP with granulocyte colony-stimulating factor (nivestim or pegfilgrastim) is cost-effective for reducing the risk of FN in patients receiving R-CHOP.

Subcutaneous vs intravenous rituximab in patients with non-Hodgkin lymphoma: a time and motion study in the United Kingdom.

OBJECTIVE: Rituximab is part of standard therapy for many non-Hodgkin lymphoma (NHL) patients, and is usually administered as an intravenous (IV) infusion. A formulation for subcutaneous (SC) injection will be available from June 2014. A time and motion study was conducted to investigate the staff time and costs associated with administration of SC and IV rituximab. RESEARCH DESIGN AND METHODS: The time and motion study was conducted in three UK centers alongside a phase III trial of SC rituximab in patients with NHL (ClinicalTrials.gov identifier NCT01461928). Active healthcare professional (HCP) time spent on the preparation and administration of IV and SC rituximab was recorded and used to calculate the associated costs. RESULTS: Total active HCP time associated with administration of IV rituximab was 223.3 min (95% CI = 218.0-228.7), vs 48.5 min (95% CI = 45.5-51.6) for SC rituximab, a saving of 174.8 min (95% CI = 172.5-177.1) per session. Patient time in the treatment room was 263.8 min (95% CI = 236.6-294.3) for IV rituximab and 70.0 min (95% CI = 57.1-87.2) for SC rituximab, per session. The SC formulation reduced total mean staff costs by £115.17 (95% CI = 98.95-136.93) per session. Differing monitoring scenarios during infusion consistently showed time and cost savings for SC rituximab. LIMITATIONS: Study limitations include the non-interventional design and lack of statistical power, and the investigational nature of SC rituximab. The data collected did not account for patient and center characteristics and variability on active HCP time. CONCLUSIONS: SC rituximab was associated with reduced active HCP time and costs vs IV rituximab, as well as reduced patient time in the treatment room. Switching from IV to SC rituximab could increase treatment room capacity and patient throughput, as well as improving the patient experience.

Limited utility of surveillance imaging for detecting disease relapse in patients with non-Hodgkin lymphoma in first complete remission.

INTRODUCTION: Surveillance imaging with computed tomography (CT) or positron emission tomography with CT (PET/CT) is commonly used in practice in patients with non-Hodgkin lymphoma (NHL) who are in remission after front-line therapies. We aimed to determine the utility of routine imaging for detecting first relapse in patients with NHL in complete remission (CR) after first-line therapies. PATIENTS AND METHODS: We retrospectively analyzed patients with NHL who achieved CR after first-line therapies and then subsequently had disease relapse. We evaluated whether the relapse was detected solely by surveillance CT or PET/CT or by patient-reported symptoms or physical examination findings, or both. Subgroup analysis was performed on baseline histologic type (indolent vs. aggressive NHL). Data were also collected to determine the cost of surveillance PET/CT and the number of additional diagnostic imaging procedures, invasive procedures, and iatrogenic complications directly resulting from an abnormality detected on a surveillance scan. RESULTS: One hundred sixty-three patients with first relapse of NHL between January 1, 2000 and December 31, 2010 were included. The majority of the relapses were detected by patient-reported symptoms or physical examination, or both, as opposed to surveillance imaging (77.9% [n = 127] vs. 22.1% [n = 36]; P < .0001). There was no overall survival difference between the 2 groups (P = .66). Patient-reported symptoms led to the detection of the majority of relapses in aggressive (85.7% [n = 72] vs. 14.3% [n = 12]; P < .0001) as well as indolent NHL (69.6% [n = 55] vs. 30.4% [n = 24]; P = .0007). Surveillance PET/CT contributed to more than 75% of follow-up health care costs in the first 2 years of monitoring for relapse. The surveillance imaging group had 1 reported case of iatrogenic pneumothorax. CONCLUSION: Our retrospective analysis suggests that there is a limited role for surveillance imaging by CT or PET/CT in detecting first relapse in NHL. There was no difference in survival outcomes between the 2 groups in our study.

Improvement of hospital care for patients with non-Hodgkin's lymphoma: protocol for a cluster randomized controlled trial (PEARL study).

BACKGROUND: Malignant lymphomas constitute a diverse group of cancers of lymphocytes. One well-known disease is Hodgkin's lymphoma; the others are classified as non-Hodgkin's lymphoma (NHL). NHLs are the most common hematologic neoplasms in adults worldwide, and in 2012 over 170,000 new cases were estimated in the United States and Europe.In previous studies, several practice gaps in hospital care for patients with NHL have been identified. To decrease this variation in care, the present study aims to perform a problem analysis in which barriers to and facilitators for optimal NHL care will be identified and, based on these findings, to develop (tailored) improvement strategies. Subsequently, we will assess the effectiveness, feasibility and costs of the improvement strategies. METHODS/DESIGN: Barriers and facilitators will be explored using the literature, using interviews and questionnaires among physicians involved in NHL care, and patients diagnosed with NHL. The results will be used to develop a tailored improvement strategy. A cluster randomized controlled trial involving 19 Dutch hospitals will be conducted. Hospitals will be randomized to receive either an improvement strategy tailored to the barriers and facilitators found or, a standard strategy of audit and feedback.The effects of both strategies will be evaluated using previously developed quality indicators. Adherence to the indicators will be measured before and after the intervention period based on medical records from newly diagnosed NHL patients. To study the feasibility of both strategies, a process evaluation will be additionally performed. Data about exposure to the different elements of the strategies will be collected using questionnaires. Economic evaluation from a healthcare perspective will compare the two implementation strategies, where the costs of the implementation strategy and changes in healthcare consumption will be assessed. DISCUSSION: The presence of variation in the use of diagnostic tests, treatment, and follow-up between different physicians in different hospitals in the Netherlands is important for patients. To reduce the existing variation in care, implementation of tailored interventions to improve NHL care is necessary. TRIAL REGISTRATION: This trial is registered at ClinicalTrial.gov as the PEARL study, registration number NCT01562509.

Cost-effectiveness analysis of a risk-adapted algorithm of plerixafor use for autologous peripheral blood stem cell mobilization.

Historically, up to 30% of patients were unable to collect adequate numbers of peripheral blood stem cells (PBSCs) for autologous stem cell transplantation (ASCT). Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) has shown superior results in mobilizing peripheral blood (PB) CD34+ cells in comparison to G-CSF alone, but its high cost limits general use. We developed and evaluated risk-adapted algorithms for optimal utilization of plerixafor. In plerixafor-1, PBSC mobilization was commenced with G-CSF alone, and if PB CD34 on day 4 or day 5 was <10/µL, plerixafor was administered in the evening, and apheresis commenced the next day. In addition, if on any day, the daily yield was <0.5 × 10(6) CD34/kg, plerixafor was added. Subsequently, the algorithm was revised (plerixafor-2) with lower thresholds. If day-4 PB CD34 <10/µL for single or <20/µL for multiple transplantations, or day-1 yield was <1.5 × 10(6) CD34/kg, or any subsequent daily yield was <0.5 × 10(6) CD34/kg, plerixafor was added. Three time periods were analyzed for results and associated costs: January to December 2008 (baseline cohort; 319 mobilization attempts in 278 patients); February to November 2009 (plerixafor-1; 221 mobilization attempts in 216 patients); and December 2009 to June 2010 (plerixafor-2; 100 mobilization attempts in 98 patients). Plerixafor-2 shows a significant improvement in PB CD34 collection, increased number of patients reaching minimum and optimal goals, fewer days of apheresis, and fewer days of mobilization/collection, albeit at increased costs. In conclusion, although the earlier identification of ineffective PBSC mobilization and initiation of plerixafor (plerixafor-2) increases the per-patient costs of PBSC mobilization, failure rates, days of apheresis, and total days of mobilization/collection are lower.

Effectiveness of etoposide chemomobilization in lymphoma patients undergoing auto-SCT.

The effectiveness of stem cell mobilization with G-CSF in lymphoma patients is suboptimal. We reviewed our institutional experience using chemomobilization with etoposide (VP-16; 375 mg/m(2) on days +1 and +2) and G-CSF (5 µg/kg twice daily from day +3 through the final day of collection) in 159 patients with lymphoma. This approach resulted in successful mobilization (>2 × 10(6) CD34+ cells collected) in 94% of patients (83% within 4 apheresis sessions). Fifty-seven percent of patients yielded at least 5 × 10(6) cells in 2 days and were defined as good mobilizers. The regimen was safe with a low rate of rehospitalization. Average costs were $14 923 for good mobilizers and $27 044 for poor mobilizers (P<0.05). Using our data, we performed a 'break-even' analysis that demonstrated that adding two doses of Plerixafor to predicted poor mobilizers at the time of first CD34+ cell count would achieve cost neutrality if the frequency of good mobilizers were to increase by 21%, while the frequency of good mobilizers would need to increase by 25% if three doses of Plerixafor were used. We conclude that chemomobilization with etoposide and G-CSF in patients with lymphoma is effective, with future opportunities for cost-neutral improvement using novel agents.