[The clinical features, survival analysis, and geriatric assessment of 85 patients with follicular lymphoma: a single-center study].

Objective: To retrospectively analyze the clinical characteristics and prognosis of 85 newly diagnosed patients with follicular lymphoma (FL), as well as the prognostic value of comprehensive geriatric assessment (CGA) in patients with FL aged ≥ 60 years old. Methods: The clinical data and prognosis of 85 newly diagnosed FL patients admitted from August 2011 to June 2022 were collected. The clinical features, laboratory indicators, therapeutic efficacy, survival and prognostic factors of patients were statistically analyzed, and the prognosis of patients was stratified using various geriatric assessment tools. Results: ① The patients with FL were mostly middle-aged and older, with a median age of 59 (20-87) years, including 41 patients (48.2%) aged ≥60 years. The ratio of male to female was 1∶1.36. Overall, 77.6% of the patients were diagnosed with Ann Arbor stage Ⅲ-Ⅳ, and 17 cases (20.0%) were accompanied by B symptoms. Bone marrow involvement was the most common (34.1%). ②Overall, 71 patients received immunochemotherapy. The overall response rate was 86.6%, and the complete recovery rate was 47.1% of 68 evaluated patients. Disease progression or relapse in the first 2 years was observed in 23.9% of the patient. Overall, 14.1% of the patients died during follow-up. ③Of the 56 patients receiving R-CHOP-like therapies, the 3-year and 5-year progression-free survival (PFS) rates were 85.2% and 72.8%, respectively, and the 3-year and 5-year overall survival (OS) rates were 95.9% and 88.8%, respectively. The univariate analysis showed that age ≥60 years old (HR=3.430, 95% CI 1.256-9.371, P=0.016), B symptoms (HR=5.030, 95% CI 1.903-13.294, P=0.016), Prognostic Nutritional Index (PNI) <45.25 (HR=3.478, 95% CI 1.299-9.310, P=0.013), Follicular Lymphoma International Prognostic Index (FLIPI) high-risk (HR=2.918, 95% CI 1.074-7.928, P=0.036), and PRIMA-prognostic index (PRIMA-PI) high-risk (HR=2.745, 95% CI 1.057-7.129, P=0.038) significantly predicted PFS. Moreover, age ≥60 years old and B symptoms were independent risk factors for PFS. Progression of disease within 24 months (POD24) significantly predicted OS in the univariate analysis. Conclusions: FL is more common among middle-aged and older women. Age, B symptoms, PNI score, FLIPI high-risk, PRIMA-PI high-risk, and POD24 influenced PFS and OS. The CGA can be used for treatment selection and risk prognostication in older patients with FL.

Assessment of Healthcare Resource Utilization and Hospitalization Costs in Patients With Relapsed or Refractory Follicular Lymphoma Undergoing CAR-T Cell Therapy With Tisagenlecleucel: Results From the ELARA Study.

Follicular lymphoma (FL) is generally considered an indolent disease, although patients with relapsing FL experience progressively shorter durations of response to second or later lines of therapy. The ongoing ELARA trial in adult patients with relapsed/refractory (r/r) FL treated with tisagenlecleucel demonstrated an overall response rate of 86.2% and a complete response rate of 69.1%, with no treatment-related deaths. Tisagenlecleucel was administered in the outpatient setting in 18% of patients in ELARA; however, there is limited knowledge concerning the impact of inpatient versus outpatient tisagenlecleucel administration on healthcare resource utilization (HCRU) among patients with r/r FL. Here, we present the first HCRU analysis among patients with r/r FL who received tisagenlecleucel in the Phase II, single-arm, multicenter ELARA trial. HCRU was characterized using hospitalization data from day 1 to month 2 after tisagenlecleucel infusion. Information on length of stay, facility use, and discharge was assessed in patients who received tisagenlecleucel in the outpatient or inpatient setting. All costs were inflated to 2020 US dollars. As of August 3, 2021 (20-month median follow-up), 17/97 (18%) r/r FL patients were infused in an outpatient setting. Patients infused in the outpatient setting generally had favorable Eastern Cooperative Oncology Group performance status and Follicular Lymphoma International Prognostic Index scores, and less bulky disease at baseline. However, the outpatients had higher proportions of patients with grade 3A FL, primary refractory disease, and >5 lines of prior therapy compared with inpatients. Forty-one percent of patients treated in the outpatient setting did not require hospitalization within 30 days after infusion, and outpatients who did require hospitalization had a shorter average length of stay compared with inpatients (5 versus 13 days). No outpatients required intensive care unit (ICU) admission, whereas 9% of inpatients were admitted to the ICU. The mean postinfusion hospitalization costs were $7477 and $40,054 in the outpatient and inpatient settings, respectively. Efficacy between both groups was similar. Tisagenlecleucel can be safely administered to some patients in the outpatient setting, which may reduce HCRU for patients with r/r FL.

A cost-effectiveness analysis of front-line treatment strategies in early-stage follicular lymphoma.

Recent data suggest the use of radiotherapy alone (RT) in Early-Stage Follicular Lymphoma is declining. Cost-effectiveness analysis of treatments has not been performed. We constructed a partitioning model (15-year horizon) to compare RT, combined-modality therapy (CMT) and immunochemotherapy with rituximab maintenance (ICT + RM) from a PET-staged cohort from the Australian Lymphoma Alliance. Lifetime direct health care costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. AUD $75,000 was defined as the willingness-to-pay threshold (WTP). The direct healthcare costs were: RT $12,791, CMT $29,391 and ICT + RM $42,644. Compared with RT, CMT demonstrated minimal improvement in QALYs (+0.01) and an ICER well above the WTP threshold ($1,535,488). Compared with RT, ICT + RM demonstrated an improvement in QALYs (+0.41) with an ICER of $73,319. Modeling a 25% cost reduction with a rituximab biosimilar led to further ICER reductions with ICT + RM ($52,476). ICT + RM is cost-effective in early-stage FL from the Australian taxpayer perspective.

Cost-effectiveness analysis of allogeneic versus autologous stem cell transplant versus chemo-immunotherapy for early relapse of follicular lymphoma within 2 years of initial therapy.

This study compared the quality-adjusted effectiveness and costs of three treatment options for transplant-eligible patients with early progression (POD24) of follicular lymphoma. A Markov decision-analytic model using a 20-year time horizon was used to compare allogeneic stem cell transplant (alloSCT), autologous stem cell transplant (ASCT), and chemo-immunotherapy (O-CHOP). For second relapse/refractory disease, novel therapy use was modeled, including lenalidomide and rituximab/obinutuzumab, and PI3K inhibitors (PI3Ki). Costs were considered from a Canadian public health payer's perspective. Probabilistic analyses (10,000 simulations) demonstrated that at a willingness-to-pay threshold of $50,000, ASCT was most cost effective 60% of the time. ASCT resulted in more life years (10.2 vs. alloSCT 9.9 vs. O-CHOP 10.0) and quality-adjusted life years (7.5 vs. alloSCT 6.6 vs. O-CHOP 7.4), with the lowest direct costs ($190,128 CAD). In sensitivity analyses, the model was robust to key variables, including differing probabilities of progression, non-relapse mortality, graft-versus-host-disease (GVHD), costs of treating GVHD, costs of PI3Ki, and probability of secondary malignancy from ASCT. However, if patients were older than 65 years or their life expectancy was less than 10 years, chemo-immunotherapy was the preferred strategy. When considering cost, effectiveness, and toxicities, the preferred treatment strategy for most patients with POD24 follicular lymphoma is ASCT.

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.

Patient-level Factors Associated With the Initial Management of Older Adults Diagnosed With Follicular Lymphoma: A Surveillance, Epidemiology, and End Results-Medicare Analysis.

INTRODUCTION: We evaluated patient-level factors associated with the initial management of older adults diagnosed with follicular lymphoma (FL). MATERIALS AND METHODS: Using linked Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) data; we identified 11,500 beneficiaries aged ≥ 66 years, diagnosed with FL between 2000 and 2013. A logistic regression model was used to estimate adjusted odds ratios (AORs) for factors associated with the receipt of active treatment versus watchful waiting (WW) as an initial management strategy. A multinomial logistic regression model was used to predict factors associated with receipt of specific active treatments, namely chemoimmunotherapy, rituximab monotherapy, chemotherapy, or radiation as compared with WW. RESULTS: Overall, the initial management strategies adopted were WW (49%), chemoimmunotherapy (25%), radiation (10%), rituximab monotherapy (9%), and chemotherapy (7%). In reference to WW, grade III FL (AOR, 2.21; 95% confidence interval [CI], 1.99-2.46), increasing disease stage (Stage IV AOR, 1.80; 95% CI, 1.62-2.00), and use of preventive services (AOR, 1.18; 95% CI, 1.07-1.30) were associated with increased odds of active treatment receipt. Age > 80 years (AOR, 0.79; 95% CI, 0.71-0.87), Non-Hispanic African-American race (AOR, 0.64; 95% CI, 0.50-0.80), and state buy-in coverage (AOR, 0.81; 95% CI, 0.70-0.94) were associated with decreased odds of active treatment receipt. In reference to WW, the multinomial logistic regression model displayed differences in the receipt of rituximab-based therapies by age and comorbidity burden. Non-Hispanic African-American race and state buy-in coverage were associated with decreased odds of receiving rituximab-based therapies. CONCLUSION: The present analysis identifies disparities in the initial management of older adults with FL owing to race and socioeconomic status. Future research should examine implications for subsequent treatment and health outcomes.

Where does transplant fit in the age of targeted therapies?

The role of hematopoietic cell transplantation (HCT) for indolent lymphoma has evolved over the last 5 years with the availability of novel low-toxicity therapies and a better understanding of the prognosis of these entities. However, despite numerous treatment options for patients with follicular lymphoma, none are thought to be curative, and many require ongoing therapy with chronic toxicity. Historical trials indicate that autologous HCT as initial consolidation leads to improved progression-free survival, but not overall survival (OS) and, thus, is not typically recommended. However, autologous HCT for chemosensitive relapse can be carried out with ∼1% early mortality risk, affording disease control lasting a median of 3 to 5 years and the potential to improve OS. These results may compare favorably in efficacy, toxicity, and cost vs multiple sequential novel therapies with shorter durations of benefit. Recent data indicate that autologous HCT in follicular lymphoma patients with early initial progression will result in more than one third being alive and without relapse at 5 years, leading to improved OS when used within a year of the first recurrence. Unlike other available therapies, allogeneic HCT has the potential to cure up to one half of those transplanted with indolent B-cell non-Hodgkin lymphoma, although the risks need to be recognized and appropriate patient and donor selection is critical to ensure the best outcomes. HCT continues to remain a viable option in the current era of multiple targeted agents.

Economic burden and treatment patterns for patients with diffuse large B-cell lymphoma and follicular lymphoma in the USA.

AIM: Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are common types of non-Hodgkin's lymphoma, and real-world evidence continues to be lacking for healthcare costs and utilization among DLBCL and FL patients. Our study aims to describe medical and pharmacy costs and health resource utilization and to characterize longitudinal treatment patterns among these patients. METHODS: A retrospective observational study was performed among adult patients with DLBCL or FL using the US MarketScan (Truven) administrative claims data from 1 January 2007 to 31 December 2015. Diagnoses of DLBCL and FL were based upon ICD-9 codes. Identifications of treatment lines involved 30 lymphoma-specific anticancer systemic agents. Direct healthcare costs and utilizations were computed in the 1-year postdiagnosis period. Generalized linear models with a gamma link were used to compare healthcare costs between therapies with and without rituximab. RESULTS: A total of 2767 DLBCL and 5989 FL patients received frontline therapy. The majority received treatment within 3 months after initial diagnosis (DLBCL 79.9% and FL 62.4%) and were treated with rituximab or bendamustine either alone or in combination (DLBCL 67.4% and FL 84.7%). The total healthcare costs were US $15,555 and $10,192 per patient per month within 1 year following their initial diagnosis for DLBCL and FL, respectively. The medical costs were nearly twice as much as the drug costs for DLBCL patients. Both DLBCL and FL patients receiving rituximab had higher pharmacy costs but lower medical costs (p < 0.001). During the first year following initial diagnosis, the resource utilization (per patient per month) of DLBCL patients included 0.21 inpatient admissions, 0.26 radiation therapy, 2.63 outpatient or office visits, 0.18 emergency room visits, 0.06 intensive care unit admissions and 0.10 stem cell transplantation. FL patients occupied less health resources than DLBCL patients. CONCLUSION: The healthcare costs and health resources utilized were considerable in non-Hodgkin's lymphoma, especially DLBCL patients.

Cost associated with hematopoietic stem cell transplantation: a retrospective claims data analysis in Germany.

AIM: Quantify hematopoietic stem cell transplantation (HSCT) costs in German patients with acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). METHODS: The primary outcome was direct and indirect costs in patients with ALL/DLBCL/FL who received HSCT between 2010 and 2014. Costs were evaluated two to four quarters before to eight quarters after HSCT. RESULTS: Among 258 patients with HSCT, direct costs were €290,125/patient (pediatric ALL), €246,266/patient (adult ALL), €230,399/patient (DLBCL/FL allogeneic) and €107,457/patient (DLBCL/FL autologous). Indirect costs with HSCT were €52,939/patient (adult ALL), €20,285/patient (DLBCL/FL allogeneic) and €29,881/patient (DLBCL/FL autologous). CONCLUSION: Direct and indirect costs associated with HSCT are substantial for patients with ALL, DLBCL and FL. Novel therapies that reduce HSCT use could reduce medical costs.

A Generic Model for Follicular Lymphoma: Predicting Cost, Life Expectancy, and Quality-Adjusted-Life-Year Using UK Population-Based Observational Data.

OBJECTIVES: To use real-world data to develop a flexible generic decision model to predict cost, life expectancy, and quality-adjusted life-years (QALYs) for follicular lymphoma (FL) in the general patient population. METHODS: All patients newly diagnosed with FL in the UK's population-based Haematological Malignancy Research Network (www.hmrn.org) between 2004 and 2011 were followed until 2015 (N = 740). Treatment pathways, QALYs, and costs were incorporated into a discrete event simulation to reflect patient heterogeneity, including age and disease management. Two scenario analyses, based on the latest National Institute for Health and Clinical Excellence (NICE) guidelines (rituximab induction therapy for newly diagnosed asymptomatic patients and rituximab maintenance therapy for patients between treatments), were conducted and their economic impacts were compared to current practice. RESULTS: Incidence-based analysis revealed expected average lifetime costs ranging from £6,165 [US$7,709] to £63,864 [US$79,862] per patient, and average life expectancy from 75 days to 17.56 years. Prevalence-based analysis estimated average annual treatment costs of £60-65 million [US$75-80 million], accounting for approximately 10% of the United Kingdom's annual National Health Service budget for hematological cancers as a whole. Assuming that treatment effects reported in trials are applicable to all patient groups, scenario analyses for two recent NICE guidelines demonstrated potential annual cost savings for the United Kingdom that ranged with uptake frequency from £0.6 million to £11 million [US$0.75-2.75 million]. CONCLUSIONS: Costs, survival, and QALYs associated with FL vary markedly with patient characteristics and disease management. Allowing the production of more realistic outcomes across the patient population as a whole, our model addresses this heterogeneity and is a useful tool with which to evaluate new technologies/treatments to support healthcare decision makers.

Disparities in survival by insurance status in follicular lymphoma.

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma and most common indolent non-Hodgkin lymphoma. Lower socioeconomic status is associated with poor outcomes in FL, suggesting that access to care is an important prognostic factor; however, the association between insurance status and FL survival has not been sufficiently examined. The National Cancer Database, a nationwide cancer registry, was used to evaluate 43 648 patients with FL diagnosed between 2004 and 2014. All analyses were performed on 2 cohorts segmented at age 65 years to account for changes in insurance status with Medicare eligibility. Cox proportional hazard models calculated hazard ratios (HRs) with confidence intervals (CIs) for the association between insurance status and overall survival (OS) controlling for the available sociodemographic and prognostic factors. Kaplan-Meier curves display outcomes by insurance status for patients covered by private insurance, no insurance, Medicaid, or Medicare. When compared with patients younger than age 65 years with private insurance, patients younger than age 65 years with no insurance (HR, 1.96; 95% CI, 1.69-2.28), with Medicaid (HR, 1.82; 95% CI, 1.57-2.12), and with Medicare (HR, 1.96; 95% CI, 1.71-2.24) had significantly worse OS after adjusting for sociodemographic and prognostic factors. Compared with patients age 65 years or older with private insurance, those with Medicare only (HR, 1.28; 95% CI, 1.17-1.4) had significantly worse OS. For adults with FL, expanding access to care through insurance has the potential to improve outcomes.

Economic burden of patients with diffuse large B-cell and follicular lymphoma treated in the USA.

AIM: Evaluate healthcare costs and utilization of treated diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) patients. MATERIALS & METHODS: Adults with newly diagnosed DLBCL and FL between 1 January 2008 and 31 October 2015 were identified in the Optum™ claims database. Healthcare costs and utilization were assessed from diagnosis date until end of follow-up. RESULTS: A total of 1267 DLBCL- and 1595 FL-treated patients were identified. Mean per-patient, per-month cost during follow-up was US$11,890 for DLBCL and US$10,460 for FL. Healthcare costs and utilization decreased from year 1 to 2 following diagnosis, due to a decrease in chemotherapy services, inpatient admissions and other outpatient services. CONCLUSION: The economic burden of treated DLBCL and FL is considerable, especially in the first year following diagnosis.

Management of untreated advanced stage follicular lymphoma: Role of patient discernment.

Follicular lymphoma is the most common indolent non-Hodgkin lymphoma. Advanced stage disease is common at diagnosis. The timing of treatment for follicular lymphoma is best approached by considering the combination of presence or absence of symptoms along with estimation of tumor burden. Upfront treatment strategies should take into initial presentation variables, pace of disease progression and goals of care after discussion with the patient. Treatment approaches remain diverse and patient discernment is paramount.

The cost-effectiveness of immediate treatment or watch and wait with deferred chemotherapy for advanced asymptomatic follicular lymphoma.

Recent evidence has shown that immediate treatment with rituximab induction, with and without maintenance, substantially reduces the need for further treatment in patients with advanced asymptomatic follicular lymphoma. This analysis estimates the cost-effectiveness of immediate treatment approaches in comparison to a watch and wait approach from the perspective of the UK National Health Service. A Markov decision model was developed to estimate the cost-effectiveness of treatment strategies in patients with asymptomatic follicular lymphoma. The model was populated using effectiveness data from a systematic literature review with the key clinical data sourced from a randomised trial, in which the treatment strategies were compared. Costs were estimated using UK national sources. In comparison to watchful waiting, both rituximab strategies were found to be more effective and cost saving. In comparison to rituximab induction, the addition of rituximab maintenance marginally increased effectiveness but substantially increased costs, resulting in an incremental cost-effectiveness ratio (ICER) of £69 406 per quality-adjusted life year (QALY). In probabilistic sensitivity analysis, rituximab induction was found to have a 68% probability of being cost-effective at a threshold of £20 000 per QALY. In conclusion, active treatment with rituximab induction is a cost-effective strategy to adopt in patients with asymptomatic follicular lymphoma.

Bone marrow biopsies do not impact response assessment for follicular lymphoma patients treated on clinical trials.

Clinical trials enrolling follicular lymphoma (FL) patients typically require bone marrow biopsies (BMBs) at baseline and at a subsequent point if complete response is achieved. These procedures are painful, take time and add cost. We hypothesized that BMBs do not provide information significant for response assessment in most follicular lymphoma patients on clinical trials. We identified 99 patients treated on clinical trials for follicular lymphoma between 2000 and 2016. BMBs resulted in a possible response assessment change in 1·0% of patients (95% confidence interval: 0·0-5·5%). We conclude that mandatory BMBs at baseline and for response assessment are unnecessary in clinical trials for follicular lymphoma.

Unmet needs in the first-line treatment of follicular lymphoma.

For the majority of patients with newly diagnosed follicular lymphoma (FL), current treatments, while not curative, allow for long remission durations. However, several important needs remain unaddressed. Studies have consistently shown that ∼20% of patients with FL experience disease progression within 2 years of first-line treatment, and consequently have a 50% risk of death in 5 years. Better characterization of this group of patients at diagnosis may provide insight into those in need of alternate or intensive therapies, facilitate a precision approach to inform clinical trials, and allow for improved patient counseling. Prognostic methods to date have employed clinical parameters, genomic methods, and a wide assortment of biological and biochemical markers, but none so far has been able to adequately identify this high-risk population. Advances in the first-line treatment of FL with chemoimmunotherapy have led to a median progression-free survival (PFS) of approximately 7 years; creating a challenge in the development of clinical trials where PFS is a primary end point. A surrogate end point that accurately predicts PFS would allow for new treatments to reach patients with FL sooner, or lessen toxicity, time, and expense to those patients requiring little to no therapy. Quality of response to treatment may predict PFS and overall survival in FL; as such complete response rates, either alone or in conjunction with PET imaging or minimal residual disease negativity, are being studied as surrogates, with complete response at 30 months after induction providing the strongest surrogacy evidence to date. A better understanding of how to optimize quality of life in the context of this chronic illness is another important focus deserving of further study. Ongoing efforts to address these important unmet needs are herein discussed.

Guía de Práctica Clínica para la detección, tratamiento y seguimiento de Linfomas Hodgkin y No Hodgkin en población mayor de 18 años / Clinical practice guideline for the detection, treatment and follow-up of Hodgkin and Non-Hodgkin lymphomas in a population over 18 years of age

Esta guía esta dirigida al personal de la salud involucrado directamente en la atención de pacientes adultos mayores de 18 años con sospecha o diagnóstico de linfoma no Hodgkin B difuso de célula grande (Linfoma B difuso de células grandes), linfoma folicular (LF), linfoma de células del manto (LCM) y linfoma Hodgkin (LH), y a las instancias administrativas, empresas aseguradoras y entes gubernamentales involucrados en la generación de políticas en salud. Esta GPC basada en la evidencia incluye los temas de diagnóstico y tratamiento del Linfoma B difuso de células grandes, LF, LM y LH, bajo la perspectiva del Sistema General de Seguridad Social en Salud colombiano. Objetivos: Determinar los métodos diagnósticos más apropiados en pacientes con LBDCG para garantizar un diagnóstico preciso que permita una adecuada selección del tratamiento; Establecer las líneas de tratamiento en pacientes con LF para disminuir la heterogeneidad en la atención y mejorar los resultados del tratamiento; Determinar los esquemas de tratamiento de primera línea para pacientes con LCM en diferentes grupos de edad para disminuir la heterogeneidad y mejorar los resultados del mismo; y Mejorar la supervivencia libre de enfermedad y la supervivencia global de los pacientes adultos con LH.

Frontline rituximab monotherapy induction versus a watch and wait approach for asymptomatic advanced-stage follicular lymphoma: A cost-effectiveness analysis.

BACKGROUND: A watch and wait (WW) strategy is the standard of care for patients with asymptomatic advanced-stage follicular lymphoma. Recent data have demonstrated an improvement in the time to progression with rituximab induction (RI) with or without rituximab maintenance (RM) in comparison with a WW strategy wait in such patients. It remains unclear whether this is a cost-effective strategy. METHODS: A Markov decision analysis model was developed to compare the clinical outcomes, costs, and cost-effectiveness of RI (4 weekly doses) plus RM (12 doses every 2 months), RI (4 weekly doses), and a WW strategy for patients newly diagnosed with low-burden, asymptomatic advanced-stage follicular lymphoma over a lifetime horizon. Baseline probabilities and utilities were derived from a systematic review of published studies, and they were evaluated on a 6-month cycle. A Canadian public health payer's perspective was adopted, and costs were presented in 2012 Canadian dollars. RESULTS: RI was the cheapest strategy. It was less costly at $59,953 versus $67,489 for the RM arm and $75,895 for the WW arm. It was also associated with a slightly lower quality-adjusted life expectancy at 6.16 quality-adjusted life years (QALYs) versus 6.28 QALYs for the RM strategy but was superior to WW (5.71 QALYs). In sensitivity analyses of key variables, this effectiveness was sensitive to the probability of first and second progression in the RI arm, and this indicated relatively neutral effectiveness between the 2 rituximab arms. CONCLUSIONS: RI without maintenance for asymptomatic advanced-stage follicular lymphoma is the preferred strategy: it minimizes costs per patient over a lifetime horizon.

Joint modeling approach for semicompeting risks data with missing nonterminal event status.

Semicompeting risks data, where a subject may experience sequential non-terminal and terminal events, and the terminal event may censor the non-terminal event but not vice versa, are widely available in many biomedical studies. We consider the situation when a proportion of subjects' non-terminal events is missing, such that the observed data become a mixture of "true" semicompeting risks data and partially observed terminal event only data. An illness-death multistate model with proportional hazards assumptions is proposed to study the relationship between non-terminal and terminal events, and provide covariate-specific global and local association measures. Maximum likelihood estimation based on semiparametric regression analysis is used for statistical inference, and asymptotic properties of proposed estimators are studied using empirical process and martingale arguments. We illustrate the proposed method with simulation studies and data analysis of a follicular cell lymphoma study.

End-therapy positron emission tomography for treatment response assessment in follicular lymphoma: a systematic review and meta-analysis.

PURPOSE: Use of 2[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in postchemotherapy response assessment in follicular lymphoma is still a controversial issue. Here, we conducted the first systematic review and meta-analysis to determine the predictive value of FDG-PET in predicting outcome after chemotherapy of follicular lymphoma. EXPERIMENTAL DESIGN: Comprehensive literature search in Ovid-MEDLINE and EMBASE databases was performed to identify studies which evaluate predictive value of end-therapy PET and/or computed tomography (CT) in patients with follicular lymphoma. To quantitatively compare the predictive value of PET and CT, pooled hazard ratios (HRs) comparing progression-free survival (PFS) between patients with positive and negative results were adopted as the primary indicators for meta-analysis. To explore the efficiency in determining complete remission (CR), pooled CR rates of PET- and CT-based response criteria were calculated. Pooling of these parameters was based on the random-effects model. RESULTS: Review of 285 candidate articles identified eight eligible articles with a total of 577 patients for qualitative review and meta-analysis. The pooled HRs of end-therapy PET and CT were 5.1 [95% confidence interval (CI), 3.7-7.2] and 2.6 (95% CI, 1.2-5.8), respectively, which implies that PET is more predictive of PFS after chemotherapy than CT. The pooled CR rates of PET- and CT-based response criteria were 75% (95% CI, 70-79%) and 63% (95% CI, 53-73%), respectively, which implies that PET is more efficient in distinguishing CR (without residual disease) from other states with residual disease. In addition, qualitative systematic review indicates the same findings. CONCLUSIONS: Consistent evidence favoring PET-based treatment assessment should be considered in the management of patients with follicular lymphoma.