Estimating the Burden of Illness of Relapsed Follicular Lymphoma and Marginal Zone Lymphoma in Ontario, Canada.

BACKGROUND: Many patients with advanced follicular lymphoma (FL) and marginal zone lymphoma (MZL) relapse after first-line chemotherapy. OBJECTIVE: To examine healthcare resource utilization (HCRU) and cost, treatment patterns, progression, and survival of patients with FL and MZL who relapse after first-line treatment, in Ontario, Canada. METHODS: A retrospective, administrative data study identified patients with relapsed FL and MZL (1 January 2005-31 December 2018). Patients were followed for up to three years post relapse to assess HCRU, healthcare costs, time to next treatment (TTNT), and overall survival (OS), stratified by first- and second-line treatment. RESULTS: The study identified 285 FL and 68 MZL cases who relapsed after first-line treatment. Average duration of first-line treatment was 12.4 and 13.4 months for FL and MZL patients, respectively. Drug (35.9%) and cancer clinic costs (28.1%) were major contributors to higher costs in year 1. Three-year OS was 83.9% after FL and 74.2% after MZL relapse. No statistically significant differences were observed in TTNT and OS between patients with FL who received R-CHOP/R-CVP/BR in the first line only versus both the first- and second- line. A total of 31% of FL and 34% of MZL patients progressed to third-line treatment within three years of initial relapse. CONCLUSION: Relapsing and remitting nature of FL and MZL in a subset of patients results in substantial burden to patients and the healthcare system.

Follicular lymphoma treatment patterns between 2000 and 2014: a SEER-Medicare analysis of elderly patients.

Aim: Characterize follicular lymphoma (FL) treatment patterns among elderly patients using a dataset with longer follow-up time. Materials & methods: Using the linked Surveillance, Epidemiology and End Results-Medicare data, we identified patients diagnosed with FL between 2000 and 2013 with claims data until 2014. We investigated the treatments received and assigned them to lines of treatment. Results: We identified 10,238 elderly patients. Over a 4.7-year median follow-up, 78% of the patients received at least first-line treatment. Fewer individuals received second-line (47%) and third-line (30%) treatments. RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), RCVP (rituximab, cyclophosphamide, vincristine and prednisolone) and rituximab monotherapy were the most common treatment regimens. Conclusion: One in five elderly patients did not receive FL-directed therapy. The most common treatment regimens were limited to RCHOP, RCVP and rituximab monotherapy.

Costs associated with follicular lymphoma among individuals diagnosed with non-Hodgkin lymphoma: a longitudinal analysis using SEER-Medicare data.

There is limited information on the cost burden associated with follicular lymphoma (FL) and how it compares to other non-Hodgkin lymphoma (NHL) subtypes. We examined the direct medical costs associated with FL and estimated the incremental 3-year cost of FL compared to other NHL subtypes. Using the linked Surveillance, Epidemiology and End Results-Medicare dataset, we identified 16,691 NHL patients aged 66 years or older who were diagnosed with NHL between 2007 and 2013. The mean 3-year cost among the full NHL sample was $120,120 (standard error (SE) 839). The mean 3-year cost per patient was $114,443 (SE 1738) for FL and $121,402 (SE 950) for non-FL subtypes. The incremental 3-year cost of FL compared to non-FL was US$-5458 (95% confidence interval: US$-9325 to US$-1590). Longitudinally, FL was less costly than other NHL subtypes in the first year only, and became more expensive in the second and third years.

Quantifying time-varying cause-specific hazard and subdistribution hazard ratios with competing risks data.

Various non-proportional hazard models have been developed in the literature for competing risks data. The regression coefficients under these models, however, typically cannot be compared directly. We propose new methods to quantify the average of the time-varying cause-specific hazard ratios and subdistribution hazard ratios through two general classes of transformations and weight functions that are chosen to reflect the relative importance of the hazard ratios in different time periods. We further propose an L∞ -norm type of test statistic that incorporates the test statistics for all possible pairs of the transformation function and weight function under consideration. Extensive simulations are conducted under various settings of the hazards and demonstrate that the proposed test performs well under all settings. An application to a clinical trial in follicular lymphoma is examined in detail.

Congestive heart failure in older adults diagnosed with follicular lymphoma: A population-based study.

BACKGROUND: To the authors' knowledge, there is limited information regarding the long-term risk of congestive heart failure (CHF) among patients with follicular lymphoma, a prevalent non-Hodgkin lymphoma diagnosis among those aged >65 years, especially within the context of therapeutic exposures and preexisting comorbidities. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data from 1999 through 2013, the authors identified 6109 patients with follicular lymphoma who were diagnosed at age ≥66 years between January 1, 2000 and December 31, 2011, and a frequency-matched Medicare noncancer sample. Subdistribution hazards models assessed risks associated with new-onset CHF through December 31, 2013. Propensity score-matched models examined CHF risk in patients receiving anthracyclines when compared with matched noncancer controls. RESULTS: When compared with matched controls, patients with follicular lymphoma receiving anthracyclines at ages 66 to 75 years had a 1.7-fold (95% confidence interval, 1.4-fold to 2.1-fold) higher risk of new-onset CHF; patients diagnosed at age >75 years did not differ from noncancer controls with regard to CHF risk. Preexisting hypertension was associated with a 1.7-fold and 1.35-fold, respectively, increased hazard of CHF for each age group, independent of anthracycline exposure. Preexisting diabetes was associated with 1.5-fold increased hazard of CHF only in those patients aged 66 to 75 years. Patients with new-onset CHF had a 18% lower 10-year survival compared with those without CHF. CONCLUSIONS: Patients with follicular lymphoma who were exposed to anthracyclines between the ages of 66 years and 75 years were found to be at an increased risk of new-onset CHF; preexisting hypertension and diabetes appeared to increase this risk. The findings of the current study support and inform the risk-based follow-up of vulnerable populations.

SMABcare study: subcutaneous monoclonal antibody in cancer care: cost-consequence analysis of subcutaneous rituximab in patients with follicular lymphoma.

Rituximab is used as a standard of care for follicular lymphoma and is usually administered intravenously. A novel subcutaneous formulation recently showed non-inferior efficacy with similar pharmacokinetic and safety profiles compared to intravenous rituximab in patients with follicular lymphoma. This new approach is promising in terms of comfort for patients and time-saving for hospital staff. To evaluate the real-life economic impact of subcutaneous rituximab as maintenance therapy in patients with follicular lymphoma in real life, we conducted a cost-consequence analysis from the hospital's point of view in three French teaching hospitals. Health-related quality of life (EQ-5D-3L) was investigated as well as patients' and nurses' perception. Compared to intravenous rituximab, subcutaneous administration showed an estimated cost-saving of €109.20 per patient per cycle (p < 0.001), 78.6% of which could be attributed to the rituximab cost. Health-related quality of life showed no significant difference between the two groups despite tendencies for greater pain in the subcutaneous group and greater anxiety in the intravenous group. Thus, subcutaneous rituximab had a favorable pharmacoeconomic profile, with clinical efficacy similar to that of intravenous rituximab. The subcutaneous form was preferred by almost all patients, but further consideration should be given to improve the patients' experience: a dedicated day unit with trained medical, nursing, and pharmaceutical staff could be helpful.

Rituximab for the first-line treatment of stage III-IV follicular lymphoma (review of Technology Appraisal No. 110): a systematic review and economic evaluation.

BACKGROUND: Follicular lymphoma (FL) is a non-Hodgkin's lymphoma which typically presents when the disease is at an advanced stage. The majority of patients receive first-line therapy of rituximab in combination with chemotherapy, with two-thirds receiving cyclophosphamide, vincristine and prednisolone. The clinical and cost-effectiveness of other chemotherapies in combination with rituximab in first-line therapy is not known. OBJECTIVE: To systematically evaluate and appraise the clinical effectiveness and cost-effectiveness of rituximab (MabThera(®), Roche Products) in combination with chemotherapy, compared with chemotherapy alone, for the first-line treatment of symptomatic stage III-IV FL. DATA SOURCES: A systematic review of literature and an economic evaluation were carried out. Key databases [including MEDLINE In-Process & Other Non-Indexed Citations; Cumulative Index to Nursing and Allied Health Literature (CINAHL); EMBASE; The Cochrane Library, including the Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED) and Health Technology Assessment (HTA) databases; Science Citation Index (SCI); and BIOSIS], plus research registers and conference proceedings, were searched for relevant studies from inception up to October 2010. REVIEW METHODS: One reviewer assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers and screened them against inclusion criteria. Data from included studies were extracted by one reviewer using a standardised data extraction form and checked by a second reviewer. The quality of included studies was assessed by one reviewer and checked by a second. A patient-level simulation model was developed to estimate the costs and quality-adjusted life-year (QALY) gains from the perspective of the UK NHS and Personal Social Services, with costs and benefits discounted at 3.5% annually. RESULTS: Four randomised controlled trials comparing rituximab plus chemotherapy (R-chemotherapy) with chemotherapy alone in untreated, symptomatic patients with stage III-IV FL were identified. R-chemotherapy compared with chemotherapy alone increased the likelihood of a response to treatment in all four trials, with no additional toxicity of clinical relevance. Overall response rates were significantly improved in all four trials, with a difference between the R-chemotherapy and chemotherapy arms of between 5% and 24%, respectively. Complete response rates were also improved, with a difference between the R-chemotherapy and chemotherapy arms of between 2% and 25%, respectively. Exploratory meta-analyses were conducted; the level of statistical heterogeneity was very high and thus we believe the response rates from the individual trials to be a more robust estimator of the efficacy of the specific R-chemotherapy regimens. Over a follow-up period of 4-5 years, R-chemotherapy significantly increased the overall survival rate compared with chemotherapy alone in three trials, although data for two trials were compromised owing to the use of additional treatments. The incremental cost-effectiveness ratio (ICER) for the addition of rituximab to CVP (cyclophosphamide, vincristine and prednisolone), CHOP (cyclophosphamide, doxorubicin/adriamycin, vincristine and prednisolone) and MCP [mitoxantrone, chlorambucil (Leukeran(®), Aspen) and prednisolone] was £7720, £10,834 and £9316 per QALY gained, respectively, when it was assumed that first-line rituximab maintenance was not used. A scenario analysis is also presented, assuming that responders to R-chemotherapy in first-line induction receive maintenance with rituximab, increasing the ICER to £14,959, £21,687 and £20,493 per QALY gained, respectively. LIMITATIONS: These relate to the sources of data used for the effectiveness in first and second line and the assumed utility values; there is uncertainty about the effect of salvage treatment on patients who had been previously treated with an anthracycline regimen. There is uncertainty whether or not rituximab is as effective in second-line treatment when patients have been previously treated with rituximab. CONCLUSIONS: The results from four randomised trials comparing R-chemotherapy with chemotherapy alone showed an improvement in clinical effectiveness outcomes, with minimal clinically relevant additional adverse events or toxicity. The cost per QALY gained is estimated to be < £25,000 for all three comparisons under our base-case assumption and is considerably lower if first-line rituximab maintenance is not assumed. More data on patients pre-treated with rituximab and on the effect of first-line maintenance with rituximab is required for future work. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Economic burden of follicular non-Hodgkin's lymphoma.

Follicular non-Hodgkin's lymphoma (FNHL), a slow-growing cancer of the immune system, constitutes about 15-30% of all incident non-Hodgkin's lymphoma in developed countries. Its incidence is rising worldwide. Patients can live many years, but FNHL is considered incurable. We systematically reviewed the English-language MEDLINE-indexed and non-indexed economic literature published in the past 10 years on FNHL, identifying 23 primary economic studies. The economic burden of FNHL is significant, but available data are generally limited to retrospective considerations of hospital-based direct treatment costs, with little information available regarding societal cost of illness. Most direct cost information originates from the US, with one estimate of $US36 000 for the per-patient incremental cost of FNHL care during the first year following diagnosis. The most studied treatment is rituximab, which may offer similar overall costs to fludarabine considering higher resource use with fludarabine complications. Nearly all cost-effectiveness models identified by this review evaluated rituximab for relapsed/refractory FNHL responding to chemotherapy induction. Rituximab is supported as a cost-effective addition to standard chemotherapy by two models in the UK and one in the US, as maintenance therapy instead of stem-cell transplant by one UK model, and as maintenance therapy instead of observation alone by one model each in France, Spain and Canada. The UK National Institute for Health and Clinical Excellence updated guidance on rituximab in February 2008, concluding that it is cost effective when added to induction chemotherapy, and when used as maintenance therapy. No studies of per-patient or national indirect costs of illness were identified, with the only study of indirect costs a Canadian survey documenting lost work productivity. Across all study types identified by our review, the most common focus was on the direct costs of rituximab. As new treatments for FNHL come to market, more real-life cost data are imperative to calculate their relative cost effectiveness.

Sensitivity analysis of cost factors for various therapy options in the treatment of follicular lymphoma.

BACKGROUND: In Germany, patients with relapsed follicular non-Hodgkin's lymphoma do not all receive the same treatment. In this study, 3 therapy regimens were analyzed which were considered to be similar. With the goal of determining the treatment option with the lowest direct costs whilst maintaining the same degree of effectiveness, a cost analysis model was established and applied by way of example to the existing illness constellation. METHODS: The German doctors' fee scale (Einheitlicher Bewertungsmassstab, EBM) valid until 2005 served as the basis for the calculation of medical services within the scope of the present statutory health insurance guidelines. A virtual standard patient was constructed for the cost model and treated with the different therapy regimens. The incidences of individual adverse events described in literature served as the basis for the characterization of the average toxicity of the respective treatment methods. RESULT: The overall costs result from the sum of the treatment costs and the toxicity-related costs. The effect of additional interventions on the overall cost was also examined. CONCLUSION: Whereas the accompanying documentation of costs in clinical studies is organizationally complex and very tedious, the model applied here offers a reliable method of quantifying the costs of the different therapy regimens. It permits the comparison of different treatment alternatives, and it enables, by means of a cost variance analysis, the identification of cost drivers and less expensive measures within a therapy method.

Costs of chemotherapy for indolent follicular non-Hodgkin's lymphoma in the UK: an observational study.

Non-Hodgkin's lymphoma (NHL) is the sixth most common cancer in the United Kingdom (UK). This analysis assessed the health service costs of patients receiving chemotherapy for indolent follicular NHL based on a retrospective analysis of patient records in the UK. Each patient was followed up for a period of 3 years or until death. The analysis included 181 patients, who received a total of 187 treatment periods. Costs were estimated from the perspective of the UK National Health Service. The study found the cost of providing treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) or fludarabine to patients with indolent follicular NHL to be lower than previously reported.

Cost analysis of common treatment options for indolent follicular non-Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: We assessed direct health care costs associated with the most commonly prescribed treatments for indolent follicular non-Hodgkin's lymphoma (FL). DESIGN AND METHODS: New and previously diagnosed FL patients (>or=18 years) known during 1997-1998 to 15 Dutch hospitals were selected for inclusion. Each patient was followed for 3 years, and resource use associated with each of the treatments, including watchful waiting, was recorded. The hospital perspective was adopted. Unit costs were based on 2003 price levels. RESULTS: Two hundred patients were included of whom 75% underwent one or more treatments during the 3-year data collection period [25% were not treated because of a watchful waiting strategy (10%) or complete remission (15%)]. Allogeneic and autologous stem cell transplantations were the most expensive treatments, with a mean (median) per patient cost of 45,326 euro(44,237; n=7) and 18,866 euro (16,532; n=9), respectively (up to discharge only). Intravenous fludarabine cost 10,651 euro (9,995; n=33), rituximab (10,628 euro; 10,124; n=7), and CHOP 7,547 euro (5,833; n=42). Classical FL treatments were found to be the least expensive treatments used with an estimated cost for cylophosphamide, vincristine and prednisone of 5,268 euro (2,644; n=58), for radiotherapy of 4,218 euro (4,313; n=52), and for chlorambucil of 2,476 euro (1,098; n=53). INTERPRETATION AND CONCLUSIONS: This study presents information on resource use and costs associated with the most commonly prescribed FL treatments. In addition to differences in effectiveness, commonly used treatments vary considerably in terms of resource use and overall cost. This information is of value for resource planning, given the high costs of new treatment modalities.