Brexucabtagene autoleucel 40million-200million cells/68ml dispersion for infusion bags

BackgroundChimeric antigen receptor (CAR) T-cell therapy is an area of rapid development, showing the promise of curing blood cancers. While substantial health gains may justify high costs, it is currently unclear the extent to which the overall cost effectiveness of these therapies is driven by i) context-specific factors, such willingness-to-pay thresholds and study perspective, or ii) important subgroups such as line of treatment and therapy product.ObjectiveThis paper aims to critically review published evidence on the cost effectiveness of CAR T-cell therapies and assess the key factors that drive their cost effectiveness.MethodsWe conducted a systematic review using PubMed, Scopus and Ovid (Embase) databases to identify full economic evaluations of CAR T-cell therapies published up to January 2024. One reviewer screened and extracted data from the studies and the second reviewer assessed a sample of the full-text studies against the inclusion/exclusion criteria. Studies were critically appraised using the CHEERS checklist. Cost data are presented in 2022 US dollars.ResultsThe review identified 45 full cost-effectiveness studies of CAR T-cell therapies. These studies considered a total of 92 treatment comparisons, which included tisagenlecleucel (n = 37), axicabtagene ciloleucel (n = 28), brexucabtagene autoleucel (n = 7), lisocabtagene maraleucel (n = 8), idecabtagene vicleucel (n = 6), ciltacabtagene autoleucel (n = 4) and relmacabtagene autoleucel (n = 2). Incremental cost ranged from - US$74,980 to US$714,178 and incremental quality-adjusted life year (QALY) gains ranged from - 0.02 to 10.77. The resulting cost-per-QALY-gained ratios ranged from - US$37,490,000 to US$7,972,845, and the range of willingness-to-pay (WTP) thresholds between US$36,184 to US$317,825. The price of CAR T-cell therapy represented 75% (mean US$391,060) of the total cost of CAR T-cell therapy but was not the sole factor influencing cost effectiveness. Hospitalisation made up 6% of the total cost (mean US$34,152), while adverse events accounted for 9% (mean US$47,350). Regression analysis indicated cost effectiveness did not change according to important clinical or contextual factors.ConclusionsThe findings demonstrate that the cost effectiveness of CAR T-cell therapies is determined by a combination of factors: the relative difference between the cost of the CAR T-cell therapy and comparator, the magnitude of the QALY gains and the WTP thresholds. Their cost- effectiveness does not differ according to therapy product, line of treatment, or country.

Abstract licence: CC BY-NC

PURPOSE CARTITUDE-1, a phase Ib/II study evaluating the safety and efficacy of ciltacabtagene autoleucel (cilta-cel) in heavily pretreated patients with relapsed/refractory multiple myeloma, yielded early, deep, and durable responses at 12 months. Here, we present updated results 2 years after last patient in (median follow-up [MFU] approximately 28 months), including analyses of high-risk patient subgroups. METHODS Eligible patients had relapsed/refractory multiple myeloma, had received ≥ 3 prior lines of therapy or were double refractory to a proteasome inhibitor and immunomodulatory drug and had received prior proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapy. Patients received a single cilta-cel infusion 5-7 days after lymphodepletion. Responses were assessed by an independent review committee. RESULTS At a MFU of 27.7 months (N = 97), the overall response rate was 97.9% (95% CI, 92.7 to 99.7); 82.5% (95% CI, 73.4 to 89.4) of patients achieved a stringent complete response. Median duration of response was not estimable. Median progression-free survival (PFS) and overall survival (OS) were not reached; 27-month PFS and OS rates were 54.9% (95% CI, 44.0 to 64.6) and 70.4% (95% CI, 60.1 to 78.6), respectively. Overall response rates were high across all subgroups (95.1%-100%). Duration of response, PFS, and/or OS were shorter in patients with high-risk cytogenetics, International Staging System stage III, high tumor burden, or plasmacytomas. The safety profile was manageable with no new cilta-cel–related cytokine release syndrome and one new case of parkinsonism (day 914 after cilta-cel) since the last report. CONCLUSION At approximately 28 months MFU, patients treated with cilta-cel maintained deep and durable responses, observed in both standard and high-risk subgroups. The risk/benefit profile of cilta-cel remained favorable with longer follow-up.

Abstract licence: CC BY-NC-ND

AbstractChimeric antigen receptor (CAR) T-cell therapies are highly effective for multiple myeloma (MM) but their impressive efficacy is associated with treatment-related neurotoxicities in some patients. In CARTITUDE-1, 5% of patients with MM reported movement and neurocognitive treatment-emergent adverse events (MNTs) with ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeted CAR T-cell therapy. We assessed the associated factors for MNTs in CARTITUDE-1. Based on common features, patients who experienced MNTs were characterized by the presence of a combination of at least two variables: high tumor burden, grade ≥2 cytokine release syndrome (CRS) or any grade immune effector cell-associated neurotoxicity syndrome (ICANS) after cilta-cel infusion, and high CAR T-cell expansion/persistence. Strategies were implemented across the cilta-cel development program to monitor and manage patients with MNTs, including enhanced bridging therapy to reduce baseline tumor burden, early aggressive treatment of CRS and ICANS, handwriting assessments for early symptom detection, and extended monitoring/reporting time for neurotoxicity beyond 100 days post-infusion. After successful implementation of these strategies, the incidence of MNTs was reduced from 5% to <1% across the cilta-cel program, supporting its favorable benefit–risk profile for treatment of MM.

Abstract licence: CC BY 4.0