Cost-effectiveness of axicabtagene ciloleucel for adult patients with relapsed or refractory follicular lymphoma in the United States.

OBJECTIVES: The results of a recent single-arm trial (ZUMA-5) of axicabtagene ciloleucel (axi-cel) for relapsed/refractory (r/r) FL demonstrated high rates of durable response and tolerable toxicity among treated patients. To quantify the value of axi-cel compared to standard of care (SOC) to manage r/r FL patients who have had at least two prior lines of systemic therapy (3L+), a cost-effectiveness model was developed from a US third-party payer perspective. METHODS: A three-state partitioned survival cost-effectiveness model was developed with a lifetime horizon. Patient-level analyses of the 36-month ZUMA-5 (axi-cel) and SCHOLAR-5 (SOC) studies were used to extrapolate progression-free and overall survivals. After 5 years of survival, an estimated 40% of the modeled population was assumed to experience long-term remission based on literature. Results include the incremental cost-effectiveness ratio (ICER) measured as incremental cost per quality-adjusted life year (QALY) gained. One-way sensitivity analysis (OWSA), probabilistic sensitivity analysis (PSA), and scenario analyses were performed. All outcomes were discounted 3% per year. RESULTS: Axi-cel led to an increase of 4.28 life-years, 3.64 QALYs and a total cost increase of $321,192 relative to SOC, resulting in an ICER of $88,300 per QALY. Across all parameters varied in the OWSA, the ICER varied between $133,030 and $67,277. In the PSA, axi-cel had a 99% probability of being cost-effective across 5,000 iterations using a $150,000 willingness-to-pay threshold. CONCLUSIONS: Given the robustness of the model results and sensitivity analyses, axi-cel is expected to be a cost-effective treatment in 3L+ r/r FL.

Cost-effectiveness of axicabtagene ciloleucel versus tisagenlecleucel for the treatment of 3L + relapsed/refractory large B-cell lymphoma in the United States: incorporating longer survival results.

AIMS: To provide an update on the cost-effectiveness of the chimeric antigen receptor (CAR) T-cell therapies axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) for the treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL) among patients who have previously received ≥2 lines of systemic therapy using more mature clinical trial data cuts (60 months for axi-cel overall survival [OS] and 45 months for tisa-cel OS and progression-free survival [PFS]). METHODS: A partitioned survival model consisting of three health states (pre-progression, post-progression and death) was used to estimate quality-adjusted life years (QALYs) and costs associated with axi-cel and tisa-cel over a lifetime horizon. PFS and OS inputs for axi-cel and tisa-cel were based on a previously published matching-adjusted indirect treatment comparison (MAIC). Long-term OS and PFS were extrapolated using parametric survival mixture cure models (PS-MCMs). Costs of CAR-T cell therapy drug acquisition and administration, conditioning chemotherapy, apheresis, CAR T-specific monitoring, stem cell transplant, hospitalization, adverse events, routine care, and terminal care were sourced from US cost databases. Health state utilities were derived from previous publications. Model inputs were varied using a range of sensitivity and scenario analyses. RESULTS: Compared with tisa-cel, axi-cel resulted in 2.51 additional QALYs and $50,185 additional costs (an incremental cost-effectiveness ratio [ICER] of $19,994 per QALY gained). In probabilistic sensitivity analysis (PSA), the ICER for axi-cel versus tisa-cel was ≤$50,000/QALY in 99.4% of simulations and ≤$33,500 in 99% of simulations. Axi-cel remained cost-effective versus tisa-cel (assuming a willingness-to-pay threshold of $150,000 per QALY) across a range of scenarios. CONCLUSIONS: With longer-term survival data, axi-cel continues to represent a cost-effective option versus tisa-cel for treatment of r/r LBCL among patients who have previously received ≥2 lines of systemic therapy, from a US payer perspective.

An updated cost-effectiveness analysis of axicabtagene ciloleucel in second-line large B-cell lymphoma patients in the United States.

AIMS: This economic evaluation of axicabtagene ciloleucel (axi-cel) versus previous standard of care (SOC; salvage chemotherapy followed by high-dose therapy with autologous stem cell rescue) in the second line (2L) large B-cell lymphoma population is an update of previous economic models that contained immature survival data. METHODS: This analysis is based on primary overall survival (OS) ZUMA-7 clinical trial data (median follow-up of 47.2 months), from a United States (US) payer perspective, with a model time horizon of 50 years. Mixture cure models were used to extrapolate updated survival data; subsequent treatment data and costs were updated. Patients who remained in the event-free survival state by 5 years were assumed to have achieved long-term remission and not require subsequent treatment. RESULTS: Substantial survival and quality of life benefits were observed despite 57% of patients in the SOC arm receiving subsequent cellular therapy: median model-projected (ZUMA-7 trial Kaplan-Meier estimated) OS was 78 months (median not reached) for axi-cel versus 25 months (31 months) for SOC, resulting in incremental quality-adjusted life year (QALY) difference of 1.63 in favor of axi-cel. Incrementally higher subsequent treatment costs were observed in the SOC arm due to substantial crossover to cellular therapies, thus, when considering the generally accepted willingness to pay threshold of $150,000 per QALY in the US, axi-cel was cost-effective with an incremental cost-effectiveness ratio of $98,040 per QALY. CONCLUSIONS: Results remained consistent across a wide range of sensitivity and scenario analysis, including a crossover adjusted analysis, suggesting that the mature OS data has significantly reduced the uncertainty of axi-cel's cost-effectiveness in the 2L setting in the US. Deferring treatment with CAR T therapies after attempting a path to transplant may result in excess mortality, lower quality of life and would be an inefficient use of resources relative to 2L axi-cel.

The Cost-Effectiveness of Axicabtagene Ciloleucel as Second-Line Therapy in Patients with Large B-Cell Lymphoma in the United States: An Economic Evaluation of the ZUMA-7 Trial.

Axicabtagene ciloleucel (axi-cel) was found to have superior clinical outcomes compared to standard of care (SOC; salvage chemoimmunotherapy, followed by high-dose therapy with autologous stem cell rescue for responders) for second-line large B-cell lymphoma (2L LBCL) in the pivotal ZUMA-7 trial. The aim of this analysis was to evaluate the cost effectiveness of using axi-cel compared to the current standard 2L LBCL therapy. A 3-state partitioned-survival model estimated the cost effectiveness and budget impact from a payer perspective in the United States. Clinical outcomes were extrapolated based on the pivotal trial. The model calculated expected quality-adjusted life years (QALYs), total costs (in United States dollars [USD], and the incremental cost-effectiveness ratio (ICER), along with the budget impact. Sensitivity and scenario analyses were performed. The proportion alive at 10 years was estimated as 48% for axi-cel and 38% for SOC; median overall survival was estimated at 59 and 24 months for axi-cel and SOC, respectively. Over a lifetime horizon, the model estimated a total of 5.56 and 7.08 QALYs for SOC and axi-cel, respectively, of which 41% and 74% were in the event-free state, respectively. Incremental QALYs and costs were 1.51 and $100,366 USD, resulting in an ICER of $66,381 USD per QALY for axi-cel versus SOC. Despite crossover to subsequent CAR T in the SOC arm, second-line CAR T use was found to improve the quality and length of life compared to SOC. Cost offsets due to subsequent CAR T use led to a limited incremental cost difference. Treatment with axi-cel is a cost-effective option that addresses an important unmet clinical need for patients with LBCL who relapse or are refractory to front-line therapy.

Burden of illness and outcomes in second-line large B-cell lymphoma treatment: real-world analysis of Medicare beneficiaries.

Aims: To characterize elderly large B-cell lymphoma patients who progress to second-line treatment to identify potential unmet treatment needs. Patients & methods: Retrospective USA cohort study, patients receiving second-line autologous stem cell transplant (SCT) preparative regimen ('ASCT-intended') versus those who did not; stratified further into those who received a stem cell transplant and those who did not. Primary outcomes were: healthcare resource utilization, costs and adverse events. Results: 1045 patients (22.0%) were included in the ASCT-intended group, 23.3% of whom received SCT (5.1% of entire second-line population). Non-SCT patients were older and had more comorbidities and generally higher rates of healthcare resource utilization and costs. Conclusion: Elderly second-line large B-cell lymphoma patients incurred substantial costs and a minority received potentially curative SCT, suggesting significant unmet need.

Lay abstract Large B-cell lymphoma (LBCL) is an aggressive form of cancer. Although chemotherapy is often initially successful, LBCL recurs in about 50% of patients. For many years, the standard of care for recurrent LBCL has been a course of strong chemotherapy followed by stem cell transplant (SCT). However, many older patients cannot tolerate or do not respond well to chemotherapy and therefore cannot proceed to SCT. In this real-world study of Medicare patients, we found that only 5.1% of patients with recurrent LBCL ever received potentially curative SCT. They also had higher healthcare costs than similar patients who did receive SCT. This shows a significant unmet need in elderly LBCL patients that may potentially be addressed with recent treatment innovations.

Economic and Clinical Burden Associated With Intensification of Glaucoma Topical Therapy: A US Claims-based Analysis.

PRECIS: Incremental addition of intraocular pressure-lowering topical drops is associated with shorter-lasting benefit and higher health-related costs with each additional agent, suggesting a need for new treatment options to improve disease control and reduce treatment burden. PURPOSE: The purpose of this study was to evaluate treatment intensification as a driver of clinical and economic burden in patients receiving topical glaucoma medications for open-angle glaucoma/ocular hypertension. METHODS: This retrospective analysis of administrative claims data (January 2011 to July 2017) from the IQVIA PharMetrics Plus database included diagnosed patients who initiated or intensified treatment with 1 to 4 topical glaucoma medications of a different drug class between January 2012 and July 2015 (index date being the first such event during this period). Patients with prior open-angle glaucoma surgery or an equal or greater number of topical glaucoma medication classes during the preindex period were excluded. Treatment intensification rates and eye-related outpatient costs were assessed over 24 months postindex. RESULTS: Of 48,402 patients (mean age: 61.4 y), 22,874 (47.3%), 16,214 (33.5%), 7137 (14.7%), and 2177 (4.5%) received a first, second, third, or fourth medication class, respectively, as their first observed initial or intensified regimen. Among cohorts receiving 1, 2, 3, or 4 medication classes, 7.8%, 12.2%, 17.2%, and 22.6% of patients and 12.6%, 18.5%, 25.9%, and 33.7% of patients had subsequent treatment augmentation (class addition or glaucoma procedure, laser or surgical) within 12 and 24 months postindex, respectively. Eye-related outpatient costs over 24 months increased with each additional topical glaucoma medication class at index [mean (SD): $1610 ($3460), $2418 ($4863), $2872 ($5110), and $3751 ($6608) in the 1, 2, 3, or 4 class cohorts, respectively]. CONCLUSION: Multiple-drop therapies yielded shorter-lasting benefits with each additional agent and were associated with the increased clinical and economic burden.

Burden of non-adherence to latent tuberculosis infection drug therapy and the potential cost-effectiveness of adherence interventions in Canada: a simulation study.

OBJECTIVE: Pharmaceutical treatment of latent tuberculosis infection (LTBI) reduces the risk of progression to active tuberculosis (TB); however, poor adherence tempers the protective effect. We aimed to estimate the health burden of non-adherence, the maximum allowable cost of hypothetical new adherence interventions to be cost-effective and the potential value of existing adherence interventions for patients with low-risk LTBI in Canada. DESIGN: A microsimulation model of LTBI progression over 25 years. SETTING: General practice in Canada. PARTICIPANTS: Individuals with LTBI who are initiating drug therapy. INTERVENTIONS: A hypothetical intervention with a range of effectiveness was evaluated. Existing drug adherence interventions including peer support, two-way text messaging support, enhanced adherence counselling and adherence incentives were also evaluated. PRIMARY AND SECONDARY OUTCOME MEASURES: Simulation outcomes included healthcare costs, TB incidence, TB deaths and quality-adjusted life years (QALYs). Base case results were interpreted against a willingness-to-pay threshold of $C50 000/QALY. RESULTS: Compared with current adherence levels, full adherence to LTBI drug therapy could reduce new TB cases from 90.3 cases per 100 000 person-years to 35.9 cases per 100 000 person-years and reduce TB-related deaths from 7.9 deaths per 100 000 person-years to 3.1 deaths per 100 000 person-years. An intervention that increases relative adherence by 40% would bring the population near full adherence to drug therapy and could have a maximum allowable annual cost of approximately $C450 per person to be cost-effective. Based on estimates of effect sizes and costs of existing adherence interventions, we found that they yielded between 900 and 2400 additional QALYs per million people, reduced TB deaths by 5%-25% and were likely to be cost-effective over 25 years. CONCLUSION: Full adherence could reduce the number of future TB cases by nearly 60%, offsetting TB-related costs and health burden. Several existing interventions are could be cost-effective to help achieve this goal.

Betting on the fastest horse: Using computer simulation to design a combination HIV intervention for future projects in Maharashtra, India.

OBJECTIVE: To inform the design of a combination intervention strategy targeting HIV-infected unhealthy alcohol users in Maharashtra, India, that could be tested in future randomized control trials. METHODS: Using probabilistic compartmental simulation modeling we compared intervention strategies targeting HIV-infected unhealthy alcohol users on antiretroviral therapy (ART) in Maharashtra, India. We tested interventions targeting four behaviors (unhealthy alcohol consumption, risky sexual behavior, depression and antiretroviral adherence), in three formats (individual, group based, community) and two durations (shorter versus longer). A total of 5,386 possible intervention combinations were tested across the population for a 20-year time horizon and intervention bundles were narrowed down based on incremental cost-effectiveness analysis using a two-step probabilistic uncertainty analysis approach. RESULTS: Taking into account uncertainty in transmission variables and intervention cost and effectiveness values, we were able to reduce the number of possible intervention combinations to be used in a randomized control trial from over 5,000 to less than 5. The most robust intervention bundle identified was a combination of three interventions: long individual alcohol counseling; weekly Short Message Service (SMS) adherence counseling; and brief sex risk group counseling. CONCLUSIONS: In addition to guiding policy design, simulation modeling of HIV transmission can be used as a preparatory step to trial design, offering a method for intervention pre-selection at a reduced cost.

Economic evaluation of mobile phone text message interventions to improve adherence to HIV therapy in Kenya.

BACKGROUND: A surge in mobile phone availability has fueled low cost short messaging service (SMS) adherence interventions. Multiple systematic reviews have concluded that some SMS-based interventions are effective at improving antiretroviral therapy (ART) adherence, and they are hypothesized to improve retention in care. The objective of this study was to evaluate the cost-effectiveness of SMS-based adherence interventions and explore the added value of retention benefits. METHODS: We evaluated the cost-effectiveness of weekly SMS interventions compared to standard care among HIV+ individuals initiating ART for the first time in Kenya. We used an individual level micro-simulation model populated with data from two SMS-intervention trials, an East-African HIV+ cohort and published literature. We estimated average quality adjusted life years (QALY) and lifetime HIV-related costs from a healthcare perspective. We explored a wide range of scenarios and assumptions in one-way and multivariate sensitivity analyses. RESULTS: We found that SMS-based adherence interventions were cost-effective by WHO standards, with an incremental cost-effectiveness ratio (ICER) of $1,037/QALY. In the secondary analysis, potential retention benefits improved the cost-effectiveness of SMS intervention (ICER = $864/QALY). In multivariate sensitivity analyses, the interventions remained cost-effective in most analyses, but the ICER was highly sensitive to intervention costs, effectiveness and average cohort CD4 count at ART initiation. SMS interventions remained cost-effective in a test and treat scenario where individuals were assumed to initiate ART upon HIV detection. CONCLUSIONS: Effective SMS interventions would likely increase the efficiency of ART programs by improving HIV treatment outcomes at relatively low costs, and they could facilitate achievement of the UNAIDS goal of 90% viral suppression among those on ART by 2020.