Budget Impact of Introducing Fixed-Duration Mosunetuzumab for the Treatment of Relapsed or Refractory Follicular Lymphoma After Two or More Lines of Systemic Therapy in the USA.

OBJECTIVE: This study aimed to assess the budget impact of introducing fixed-duration mosunetuzumab as a treatment option for adult patients with relapsed or refractory follicular lymphoma after at least two prior systemic therapies and to estimate the total cumulative costs per patient in the USA. METHODS: A 3-year budget impact model was developed for a hypothetical 1-million-member cohort enrolled in a mixed commercial/Medicare health plan. Comparators were: axicabtagene ciloleucel, tisagenlecleucel, tazemetostat, rituximab plus lenalidomide, copanlisib, and older therapies (rituximab or obinutuzumab ± chemotherapy). Costs per patient comprised treatment-associated costs including the drug, its administration, adverse events, and routine care. Dosing and safety data were ascertained from respective package inserts and clinical trial data. Drug costs (March 2023) were estimated based on the average wholesale acquisition cost reported in AnalySource®, and all other costs were based on published sources and inflated to 2022 US dollars. Market shares were obtained from Genentech internal projections and expert opinion. Budget impact outcomes were presented on a per-member per-month basis. RESULTS: Compared with a scenario without mosunetuzumab, its introduction over 3 years resulted in a budget increase of $69,812 (1% increase) and an average per-member per-month budget impact of $0.0019. Among the newer therapies, mosunetuzumab had the second-lowest cumulative per patient cost (mosunetuzumab = $202,039; axicabtagene ciloleucel = $505,845; tisagenlecleucel = $476,293; rituximab plus lenalidomide = $263,520; tazemetostat = $250,665; copanlisib = $127,293) and drug costs, and its introduction only increased total drug costs by 0.1%. By year 3, the cumulative difference in the per patient cost with mosunetuzumab was -$303,805 versus axicabtagene ciloleucel, -$274,254 versus tisagenlecleucel, -$61,481 versus rituximab plus lenalidomide, -$48,625 versus tazemetostat, and $74,747 versus copanlisib. Older therapies were less costly with 3-year cumulative costs that ranged from $36,512 to $147,885. CONCLUSIONS: Over 3 years, the estimated cumulative per patient cost of mosunetuzumab is lower than most available newer therapies, resulting in a small increase in the budget after its formulary adoption for the treatment of relapsed or refractory follicular lymphoma.

Cost-effectiveness of obinutuzumab plus bendamustine in Chinese patients with relapse and refractory follicular lymphoma.

A decision analytic model was constructed to assess the cost-effectiveness of obinutuzumab plus bendamustine followed by obinutuzumab maintenance therapy (O-B-O) in Chinese patients with relapsed and refractory follicular lymphoma (rrFL). O-B-O was associated with a dominant or more favorable cost-effectiveness than the conventional therapies. Survival outcomes, quality of life of progression-free survival, and subsequent treatment costs for progressive disease were the main drivers of the cost-effectiveness of O-B-O. The cost-effectiveness proportions of O-B-O relative to conventional therapies under the recommended cost-effectiveness threshold ranged from 61.0% to 99.9%. Thus, O-B-O was highly cost-effective for treating patients with rrFL in China compared with conventional therapies.

Incidence, characteristics, management and outcome of patients with follicular lymphoma with tumor epidural compression, a study on 22 cases.

PURPOSE: Follicular lymphoma (FL) is one of the most common lymphoma. Occasionally, FL is associated with tumoral epidural compression and management of these patients remain poorly codified. This study aims to report incidence, clinical characteristics, management and outcomes of patients with FL and tumoral epidural compression. MATERIAL AND METHODS: Observational, retrospective cohort study of adult patients with FL and epidural tumor compression, treated in a French Institute over the last 20 years (2000-2021). RESULTS: Between 2000 and 2021, 1382 patients with FL were followed by the haematological department. Of them, 22 (1.6%) patients (16 men and 6 women) had follicular lymphoma with epidural tumor compression. At epidural tumor compression occurrence, 8/22 (36%) patients had a neurological clinical deficit (motor, sensory or sphincter function) and 14/22 (64%) had tumor pain. All patients were treated with immuno-chemotherapy; the main regimen being used was R-CHOP plus high dose IV methotrexate in 16/22 (73%) patients. Radiotherapy for tumor epidural compression was performed in 19/22 (86%) patients. With a median follow-up of 60 months (range=[1-216]), 5 year local tumor relapse free survival was achieved in 65% (95% CI 47-90%) of patients. The median PFS was of 36 months (95% CI 24-NA) and 5 years OS estimate was 79% (95% CI 62-100%). Two patients developed a relapse at a second epidural site. CONCLUSION: FL with tumoral epidural compression reached 1.6% of all FL patients. Management based on immuno-chemotherapy with radiotherapy appeared to produce comparable outcomes with the general FL population.

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.

A novel comorbidity score for older adults with non-Hodgkin lymphoma: the 3-factor risk estimate scale.

For patients with non-Hodgkin lymphoma (NHL), formal comorbidity assessment is recommended but is rarely conducted in routine practice. A simple, validated measure of comorbidities that standardizes their assessment could improve adherence to guidelines. We previously constructed the 3-factor risk estimate scale (TRES) among patients with chronic lymphocytic leukemia (CLL). Here, we investigated TRES in multiple NHL subtypes. In the surveillance, epidemiology, and end results-Medicare database, patients with NHL diagnosed from 2008 to 2017 were included. Upper gastrointestinal, endocrine, and vascular comorbidities were identified using ICD-9/ICD-10 codes to assign TRES scores. Patient characteristic distributions were compared using χ2 or t test. Association of mortality and TRES score was assessed using Kaplan-Meier and multivariable Cox regression model for competing risk. A total of 40 486 patients were included in the study. Median age was 77 years (interquartile range [IQR], 71-83 years). The most frequent NHL subtypes were CLL (28.2%), diffuse large B-cell (27.6%), and follicular lymphoma (12.6%). Median follow-up was 33 months (IQR, 13-60 months). TRES was low, intermediate, and high in 40.8%, 37.0%, and 22.2% of patients, corresponding to median overall survival (OS) of 8.2, 5.3, and 2.9 years (P < .001), respectively. TRES was associated with OS in all NHL subtypes. In multivariable models, TRES was associated with inferior OS and NHL-specific survival. TRES is clinically translatable and associated with OS and lymphoma-specific survival in older adults with NHL.

Yttrium-90 Ibritumomab Tiuxetan is Cost-Effective Compared to Bendamustine + Rituximab in Low-grade Lymphomas.

BACKGROUND: Yttrium-90 ibritumomab tiuxetan [(90)Y-IT] is a CD20-targeted radio-immunotherapeutic agent. It has shown an excellent therapeutic activity with high tolerability against previously untreated follicular lymphoma (FL) and marginal zone B cell lymphoma (MZL). It is an attractive therapeutic option as the treatment schedule is short and convenient. The aim of our study is to determine the cost-effectiveness of (90)Y-IT in comparison to the standard-of-care bendamustine + rituximab (BR) in the first-line treatment of low-grade FL (LG-FL) and MZL in the real world. PATIENTS AND METHODS: We included all patients who were treated with standard-dose (90)Y-IT for previously untreated LG-FL and MZL at the Mayo Clinic Cancer Center (N = 51). A comparator arm with a historical cohort of previously untreated LG-FL and MZL patients who received BR was used (N = 92). RESULTS: Inverse propensity weighting was utilized to balance the 2 study arms. There were no differences in terms of overall response rate (100% vs. 98%, P = .18), complete response rate (94% vs. 95%, P = .91), or 5 years progression-free survival (76% vs. 75%, P = .63) between patients who received (90)Y-IT and BR, respectively. Within the first year, patients who received (90)Y-IT required an average of 4.5 fewer oncology clinic visits (P < .001), an average of 10 fewer days of therapeutic use (P < .001), and 40% less use of growth factors (P < .001) as compared to the BR group. The direct therapeutic cost of (90)Y-IT treatment was 54% less than that of 6 cycles of BR. CONCLUSION: The findings suggest that (90) Y-IT is more cost-effective than BR and is a viable alternative in up-front management of LG-FL and MZL.

Relevance of Bone Marrow Biopsies for Response Assessment in US National Cancer Institute National Clinical Trials Network Follicular Lymphoma Clinical Trials.

PURPOSE: Bone marrow biopsies (BMB) are performed before/after therapy to confirm complete response (CR) in patients with lymphoma on clinical trials. We sought to establish whether BMB add value in assessing response or predict progression-free survival (PFS) or overall survival (OS) outcomes in follicular lymphoma (FL) subjects in a large, multicenter, multitrial cohort. METHODS: Data were pooled from seven trials of 580 subjects with previously untreated FL through Alliance for Clinical Trials in Oncology (Alliance) and SWOG Cancer Research Network (SWOG) completing enrollment from 2008 to 2016. RESULTS: Only 5/580 (0.9%) had positive baseline BMB, CR on imaging, and subsequent positive BMB (P < .0001). Therefore, BMB were irrelevant to response in 99% of subjects. A sensitivity analysis of 385 FL subjects treated on an Eastern Cooperative Oncology Group study was included. In the Eastern Cooperative Oncology Group cohort, 5/385 (1.3%) had BMB that affected response assessment. Since some subjects do not undergo confirmatory BMB, we performed a landmark survival analysis from first radiologic CR with data from 580 subjects from Alliance and SWOG. Of subjects with CR on imaging (n = 187), PFS and OS were not significantly different among those with negative BMB to confirm CR (n = 47) versus those without repeat BMB (n = 140; PFS: adjusted hazard ratio, 1.10, 95% CI, 0.62 to 1.94, log-rank P = .686; OS: hazard ratio, 0.59, 95% CI, 0.23 to 1.53, log-rank P = .276). CONCLUSION: We conclude that BMB add little value to response assessment in subjects with FL treated on clinical trials and we recommend eliminating BMB from clinical trial requirements. BMB should also be removed from diagnostic guidelines for FL except in scenarios in which it may change management including confirmation of limited stage and assessment of cytopenias. This would reduce cost, patient discomfort, resource utilization, and potentially remove a barrier to trial enrollment.

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.

Cost-effectiveness of chimeric antigen receptor T-cell therapy in adults with relapsed or refractory follicular lymphoma.

Follicular lymphoma (FL) is traditionally considered treatable but incurable. In March 2021, the US Food and Drug Administration approved the use of chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory (R/R) FL after ≥2 lines of therapy. Priced at $373 000, CAR T-cell therapy is potentially curative, and its cost-effectiveness compared with other modern R/R FL treatment strategies is unknown. We developed a Markov model to assess the cost-effectiveness of third-line CAR T-cell vs standard of care (SOC) therapies in adults with R/R FL. We estimated progression rates for patients receiving CAR T-cell and SOC therapies from the ZUMA-5 trial and the LEO CReWE study, respectively. We calculated costs, discounted life years, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) of CAR T-cell vs SOC therapies with a willingness-to-pay threshold of $150 000 per QALY. Our analysis was conducted from a US payer's perspective over a lifetime horizon. In our base-case model, the cost of the CAR T-cell strategy was $731 682 compared with $458 490 for SOC therapies. However, CAR T-cell therapy was associated with incremental clinical benefit of 1.50 QALYs, resulting in an ICER of $182 127 per QALY. Our model was most sensitive to the utilities associated with CAR T-cell therapy remission and third-line SOC therapies and to the total upfront CAR T-cell therapy cost. Under current pricing, CAR T-cell therapy is unlikely to be cost-effective in unselected patients with FL in the third-line setting. Both randomized clinical trials and longer term clinical follow-up can help clarify the benefits of CAR T-cell therapy and optimal sequencing in patients with FL.

Accuracy and prognostic impact of FDG PET/CT and biopsy in bone marrow assessment of follicular lymphoma at diagnosis: A Nation-Wide cohort study.

BACKGOUND: In the workup of follicular lymphoma (FL), bone marrow biopsy (BMB) assessment is a key component of FLIPI and FLIPI2, the most widely used outcome scores. During the previous decade, several studies explored the role of FDG-PET/CT for detecting nodal and extranodal disease, with only one large study comparing both techniques. METHODS: The aim of our study was to evaluate the diagnostic accuracy and the prognostic impact of both procedures in a retrospective cohort of 299 FL patients with both tests performed at diagnosis. In order to avoid a collinearity bias, FLIPI2 was deconstructed in its founding parameters, and the bone marrow involvement (BMI) parameter separately included as: a positive BMB, a positive PET/CT, the combined "PET/CT and BMB positive" or "PET/CT or BMB positive". These variables were also confronted independently with the POD24 in 233 patients treated with intensive regimens. RESULTS: In the total cohort, bone marrow was involved in 124 and 60 patients by BMB and PET/CT, respectively. In terms of overall survival, age > 60 y.o. and the combined "PET/CT or BMB positive" achieved statistical independence as a prognostic factor. In patients treated with an intensive regimen, only the combined "PET/CT or BMB positive" added prognostic value for a shorter overall survival, when confronted with the POD24. CONCLUSION: Our results show that in FL both BMB and PET/CT should be considered at diagnosis, as their combined assessment provides independent prognostic value in the context of the most widely use clinical scores.

The Impact of Sequence of Therapy for Older Patients With Follicular Lymphoma: SEER-Medicare Analysis.

BACKGROUND: One key clinical challenge remains in how to sequence treatments in follicular lymphoma (FL). The chemoimmunotherapy rituximab cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone (R-CHOP) has been a standard treatment option for two decades. However, there are limited data to suggest in which line R-CHOP should be used for older patients. PATIENTS AND METHODS: We leveraged population-based surveillance, epidemiology, and end results-medicare data and identified 675 patients aged ≥65 years newly diagnosed with FL from 2000 to 2009 who received R-CHOP in either the first or second line. We estimated restricted mean survival time using Kaplan-Meier curves, propensity scores (PS), and regression models comparing patients who received R-CHOP as a first versus second line. RESULTS: We found that patients who received R-CHOP as first line had significantly longer 9-year RMST than those who received R-CHOP in the second line using Kaplan-Meier curves (P = .01), PS stratification (P = .002), PS matching (P = .005), and the inverse of PS as the treatment weight (P < .0001). The subgroup analyses using linear regression models showed that the 9-year restricted mean survival time of patients who received R-CHOP as the first line was longer in patients aged ≥80 years (P = .002) and with histological grade 1 or 2 (P = .02), compared to those who received R-CHOP as second line. CONCLUSION: R-CHOP given in the first line was associated with longer overall survival compared to R-CHOP given as second line for older patients with FL.

'Fast but not so Furious': Short observation time after subcutaneous Daratumumab administration is both a safe and cost-effective strategy.

BACKGROUND: Daratumumab, an anti-CD38 monoclonal antibody, is a key component in the treatment paradigms of multiple myeloma and AL amyloidosis in both the newly diagnosed and relapsed and/or refractory setting. Intravenous (IV) daratumumab administration requires extended infusion times and is associated with higher rates of infusion related reactions (IRRs) when compared to the subcutaneous (SC) formulation. We report real world safety outcomes and infusion chair time savings associated with SC administration in daratumumab naïve patients. METHODS: We retrospectively analyzed medical records at our institution for the incidence and severity of IRRs following differing observation periods post SC daratumumab administration. Infusion chair time was calculated to quantify chair time savings with SC administration. RESULTS: Sixty-six daratumumab naïve patients were included. Nine percent of patients developed IRRs with SC daratumumab with all reactions occurring within six hours of the first dose. All reactions were grade ≤ 2 in severity and were reversible with supportive care. Over the 18 month study period, a total of 904 SC doses were administered, amounting to a potential 1785 hours of infusion chair time savings when compared to IV administration. CONCLUSION: SC daratumumab may be given safely with a short initial observation period and without observation for subsequent doses, resulting in reduced infusion chair time as well as administration related cost and resources.

Assessing the transition from intravenous to subcutaneous delivery of rituximab: Benefits for payers, health care professionals, and patients with lymphoma.

Subcutaneous (SC) administration of rituximab provides an opportunity for reduced patient treatment burden and increased healthcare efficiencies as an alternative to intravenous (IV) rituximab. There is minimal evidence comparing costs associated with SC and IV rituximab in a US setting. This research assessed the impact of transitioning patients from IV to SC rituximab for treatment of non-Hodgkin's lymphoma (NHL) from the US payer, provider, and patient perspective. We developed a model to estimate cost differences for transitioning 20% of a patient cohort from IV to SC rituximab. We included patients with incident diffuse large B-cell lymphoma, incident and recurrent follicular lymphoma, and incident and recurrent chronic lymphocytic leukemia. In the model, each patient received the same number of doses and that there was no difference in discontinuation between cohorts due to non-inferior efficacy and a similar safety profile. Model inputs were collected from published literature and publicly available data. Scenario analyses tested the impact of availability of low-cost biosimilars. In the base case (1,000,000 covered lives), we estimated a total of 157 patients, with 769 total drug administrations. A transition of 20% of patients from IV to SC was projected to generate $153,000 in payer savings, increase provider capacity by 270 hours, and free 470 hours of patient time. Scenario analyses suggest SC administration will be cost saving for payers even with a market where biosimilars approach 50% market share. A 20% transition to SC rituximab in a single cohort of patients has the potential to generate significant US health system value in the form of payer savings, increased practice capacity, and patient time.

PET-Based Staging Is Cost-Effective in Early-Stage Follicular Lymphoma.

The objective was to assess the cost-effectiveness of staging PET/CT in early-stage follicular lymphoma (FL) from the Canadian health-care system perspective. Methods: The study population was FL patients staged as early-stage using conventional CT imaging and planned for curative-intent radiation therapy (RT). A decision analytic model simulated the management after adding staging PET/CT versus using staging CT alone. In the no-PET/CT strategy, all patients proceeded to curative-intent RT as planned. In the PET/CT strategy, PET/CT information could result in an increased RT volume, switching to a noncurative approach, or no change in RT treatment as planned. The subsequent disease course was described using a state-transition cohort model over a 30-y time horizon. Diagnostic characteristics, probabilities, utilities, and costs were derived from the literature. Baseline analysis was performed using quality-adjusted life years (QALYs), costs (2019 Canadian dollars), and the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were conducted, evaluating net monetary benefit at a willingness-to-pay threshold of $100,000/QALY. Probabilistic sensitivity analysis using 10,000 simulations was performed. Costs and QALYs were discounted at a rate of 1.5%. Results: In the reference case scenario, staging PET/CT was the dominant strategy, resulting in an average lifetime cost saving of $3,165 and a gain of 0.32 QALYs. In deterministic sensitivity analyses, the PET/CT strategy remained the preferred strategy for all scenarios supported by available data. In probabilistic sensitivity analysis, the PET/CT strategy was strongly dominant in 77% of simulations (i.e., reduced cost and increased QALYs) and was cost-effective in 89% of simulations (i.e., either saved costs or had an incremental cost-effectiveness ratio below $100,000/QALY). Conclusion: Our analysis showed that the use of PET/CT to stage early-stage FL patients reduces cost and improves QALYs. Patients with early-stage FL should undergo PET/CT before curative-intent RT.

Recurrence Score Testing Does not Appear to Benefit Patients With Grade 1, Progesterone Receptor-Positive Breast Cancers: An Opportunity to Eliminate Overtreatment and Decrease Testing Costs.

BACKGROUND: We previously described a risk prediction model (Anne Arundel Medical Center [AAMC] model) based on pathology which may eliminate the need for recurrence score (RS) testing in select early-stage breast cancers. There is a concern that patients in discordant risk prediction groups (AAMC vs. RS) may be overtreated or undertreated if RS testing were omitted. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database for all breast cancer patients between 2004 and 2015. AAMC low-risk was defined as Grade 1 and progesterone receptor-positive (PR + ) tumors, while AAMC high-risk was defined as Grade 3 or estrogen-negative tumors. RS low-risk group was defined as RS < 16 and age ≤ 50 years, or RS ≤ 25 and age > 50 years. RS high-risk group was defined as RS > 25. RESULTS: A total of 71,212 cases were analyzed. Of these, 590 were AAMC low-risk/RS high-risk discordant, while 5,596 were AAMC high-risk/RS low-risk discordant. For AAMC low-risk/RS high-risk discordant, 10-year breast cancer-specific survival (BCSS) did not differ for patients who received adjuvant chemotherapy versus those who did not (93% chemotherapy vs. 99% unknown/no chemotherapy, p = .12). Overall survival (OS) was also comparable (92% chemotherapy vs. 91% unknown/no chemotherapy, p = .42). In the AAMC high-risk/RS low-risk discordant group, 10-year BCSS (92% chemotherapy vs. 96% unknown/no chemotherapy, p = .06) and OS (87% chemotherapy vs. 90% unknown/no chemotherapy, p = .52) did not differ between adjuvant chemotherapy and unknown/no chemotherapy groups. CONCLUSIONS: Adjuvant chemotherapy in the AAMC low-risk/RS high-risk and AAMC high-risk/RS low-risk discordant groups did not improve survival. This supports consideration of omission of RS testing in Grade 1, PR + tumors. Patients with Grade 3 tumors do benefit from RS testing.

Investigating the inequalities in route to diagnosis amongst patients with diffuse large B-cell or follicular lymphoma in England.

INTRODUCTION: Diagnostic delay is associated with lower chances of cancer survival. Underlying comorbidities are known to affect the timely diagnosis of cancer. Diffuse large B-cell (DLBCL) and follicular lymphomas (FL) are primarily diagnosed amongst older patients, who are more likely to have comorbidities. Characteristics of clinical commissioning groups (CCG) are also known to impact diagnostic delay. We assess the association between comorbidities and diagnostic delay amongst patients with DLBCL or FL in England during 2005-2013. METHODS: Multivariable generalised linear mixed-effect models were used to assess the main association. Empirical Bayes estimates of the random effects were used to explore between-cluster variation. The latent normal joint modelling multiple imputation approach was used to account for partially observed variables. RESULTS: We included 30,078 and 15,551 patients diagnosed with DLBCL or FL, respectively. Amongst patients from the same CCG, having multimorbidity was strongly associated with the emergency route to diagnosis (DLBCL: odds ratio 1.56, CI 1.40-1.73; FL: odds ratio 1.80, CI 1.45-2.23). Amongst DLBCL patients, the diagnostic delay was possibly correlated with CCGs that had higher population densities. CONCLUSIONS: Underlying comorbidity is associated with diagnostic delay amongst patients with DLBCL or FL. Results suggest a possible correlation between CCGs with higher population densities and diagnostic delay of aggressive lymphomas.

Cost-effectiveness of lenalidomide plus rituximab versus rituximab monotherapy in patients with previously treated follicular lymphoma: a societal view.

INTRODUCTION: Efficacy of lenalidomide plus rituximab (R-LEN) compared to rituximab monotherapy (R-mono) for patients with previously treated follicular lymphoma (FL) was investigated in AUGMENT (NCT01938001). Our aim was to evaluate the cost-effectiveness of R-LEN versus R-mono in this setting from a Dutch perspective. AREAS COVERED: Cost-effectiveness was assessed through a partitioned survival model from three perspectives (i.e. societal, healthcare, and societal, including future non-medical costs). Patient-level data from AUGMENT informed effectiveness parameters (i.e. long-term survival) and health state utilities. Resource use and prices were based on AUGMENT and the literature. Clinical experts validated efficacy input parameters and results. Uncertainty was explored through sensitivity and scenario analyses. EXPERT OPINION: R-LEN resulted in 1.7 incremental discounted quality-adjusted life years (QALYs). Total incremental discounted costs were 67,161 EUR from a societal perspective. In conclusion, R-LEN was cost-effective at a willingness-to-pay (WTP) threshold of 50,000 EUR/QALY in the base-case analyses(incremental cost-effectiveness ratio = 40,493 EUR/QALY). Scenario and sensitivity analyses indicated some level of uncertainty regarding this conclusion, depending on the chosen WTP-threshold and perspective.

Lifetime Costs for Treated Follicular Lymphoma Patients in the US.

BACKGROUND AND OBJECTIVE: The objective of this study was to estimate the lifetime costs of patients receiving treatment for follicular lymphoma (FL) in the United States. METHODS: A Markov model was programmed in heRo3 with a 6-month cycle length, 35-year time horizon (lifetime projection), and health states for line of treatment, response, receipt of maintenance therapy among responders, transformation to diffuse large B-cell lymphoma (DLBCL), development of second primary malignancy (SPM), and death. The model was used to estimate the expected lifetime costs of FL (in 2019 USD), including costs of drug acquisition and administration, transplant procedures, radiotherapy, adverse events, follow-up, DLBCL, SPM, end-of-life care, and indirect costs. Model inputs were based on published sources. RESULTS: In the US, patients with FL receiving treatment have a life expectancy of approximately 14.5 years from initiation of treatment and expected lifetime direct and indirect costs of US$515,884. Costs of drugs for induction therapy represent the largest expenditure (US$233,174), followed by maintenance therapy costs (US$88,971) and terminal care costs (US$57,065). Despite the relatively advanced age of these patients, indirect costs (due to patient morbidity and mortality and caregiver lost work time) represent a substantial share of total costs (US$40,280). Treated FL patients spend approximately 6.9 years in the health states associated with first-line therapy. Approximately 66 and 46% continue to second- and third-line therapies, respectively. The mean (95% credible interval) of expected lifetime costs based on the probabilistic sensitivity analyses was US$559,202 (421,997-762,553). CONCLUSIONS: In the US, the expected lifetime costs of care for FL patients who receive treatment is high. The results highlight the potential economic benefits that might be achieved by treatments for FL that prevent or delay disease progression.