Ciltacabtagene autoleucel 3.2million-100million cells 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

B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapies have drastically improved outcomes for patients with relapsed or refractory multiple myeloma. While CAR-T associated cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS) are well characterized, non-ICANS neurologic toxicities (NINTs) remain poorly defined, with limited data regarding incidence and risk factors. We performed a systematic review and meta-analysis of prospective clinical trials and real-world studies reporting neurologic toxicities following BCMA-directed CAR T therapy, following PRISMA guidelines. Random-effects meta-analysis was used to calculate a pooled point estimate of NINTs. Meta-regression was conducted to evaluate treatment-related predictors of risk. Reported NINTs were categorized by clinical phenotype when sufficient detail was available. Fifty-five cohorts comprising 4,630 treated patients were included. The pooled point estimate for NINTs was 0.81% (95% CI, 0.37-1.77%). Incidence differed significantly by product, with a significantly higher frequency of NINTs following ciltacabtagene autoleucel (cilta-cel) compared with idecabtagene vicleucel (ide-cel) (4.6% vs 0.5%; p=0.001) and experimental BCMA-directed constructs (4.6% vs 0.3%; p=0.02). Additionally, meta-regression identified cilta-cel as independently associated with increased NINTs risk compared with ide-cel. Cranial nerve palsies were the most frequently reported phenotype (32.3% 43 events), followed by movement and neurocognitive treatment-emergent adverse events (12%, 16 events), then peripheral neuropathies (7.5%, 10 events). This meta-analysis establishes that NINTs are a rare but important toxicity following BCMA-directed CAR-T therapy, particularly cilta-cel. Standardized definitions and improved reporting of NINTs are needed to better characterize risk and inform surveillance strategies.

Abstract licence: CC BY-NC-ND

Background/Objectives: Ciltacabtagene autoleucel (cilta-cel) for relapsed/refractory multiple myeloma is typically administered inpatient (IP) to monitor for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Because cilta-cel toxicities are typically delayed, outpatient (OP) administration (infusion and early monitoring) is being explored. We synthesized available evidence on OP and IP administration. Methods: MEDLINE, Embase, and Cochrane Library were searched from inception to 5 August 2025, supplemented by conference and gray literature searches. Eligible studies of adults with multiple myeloma receiving cilta-cel reported efficacy, safety, resource use, costs, and/or quality-of-life outcomes; findings were synthesized descriptively due to heterogeneity. Results: Seventy-four records (56 studies) were included; 90 patients received OP cilta-cel. OP clinical evidence (primarily three real-world studies) showed high response rates (ORR: 95%; median follow-up 4.6 months) and reported 1-year PFS and OS of 86% and 96%. In IP studies, median ORR was 91%, with median 1-year PFS 76% and median 1-year OS 85%. Any-grade CRS and ICANS occurred in 79–84% and 17–22% of OP patients (largely low grade); IP cohorts reported a median ICANS incidence of 17% (range 5–23%). Most OP patients were later hospitalized (86–93%), but stays were shorter (median 4–6.5 days) than in an IP cohort (median 19 days). Comparisons were unadjusted and may reflect selection differences. One modeling-based economic analysis estimated savings of ~$19,000 per OP-treated patient. Conclusions: OP cilta-cel appears feasible for selected patients and may reduce costs without compromising outcomes. Findings are descriptive and hypothesis-generating and prospective multicenter studies are needed to define long-term safety, durability, quality of life, and cost-effectiveness.

Abstract licence: CC BY 4.0

Abstract Background Therapeutic resistance remains one of the main causes of treatment failure, disease progression, and reduced survival in oncology. Although systemic antineoplastic therapies have expanded substantially in recent years, the magnitude and certainty of their benefits in resistant, refractory, relapsed, or previously treated adult malignancies remain variable across tumor types and therapeutic classes. Objective: To synthesize contemporary randomized evidence on the efficacy, safety, and certainty of evidence for systemic antineoplastic therapies used in adults with treatment-resistant, refractory, relapsed, recurrent, advanced, metastatic, or previously treated malignancies. Methods This systematic review, exploratory meta-analysis, and GRADE assessment was prospectively registered in PROSPERO under the number CRD420261386007 and conducted according to PRISMA 2020 recommendations. PubMed/MEDLINE, Cochrane CENTRAL, SciELO, and Google Scholar were searched for randomized clinical evidence published between 2021 and 2026. Eligible studies included adults with malignant tumors treated with systemic antineoplastic therapies, including chemotherapy, immunotherapy, molecular targeted therapy, antibody–drug conjugates, cellular therapy, endocrine-based regimens, antiangiogenic therapy, tumor treating fields, or combination strategies. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated using the GRADE approach. When clinically appropriate, exploratory random-effects meta-analyses were performed for time-to-event outcomes. The current manuscript reports PROSPERO registration, PRISMA 2020 conduct, RoB 2 assessment, GRADE evaluation, 18 included randomized clinical studies, and 19 high-certainty outcomes. Results A total of 219 records were identified, and 18 randomized clinical studies were included. The studies evaluated a broad range of resistant or previously treated malignancies, including breast cancer, urothelial carcinoma, differentiated thyroid cancer, lymphoma, multiple myeloma, ovarian cancer, colorectal cancer, gastrointestinal stromal tumor, lung cancer, and hematologic malignancies. The most robust evidence was observed for cabozantinib, ciltacabtagene autoleucel, axicabtagene ciloleucel, sacituzumab govitecan, palbociclib, and enfortumab vedotin. Exploratory pooled analysis suggested improved progression-free survival with systemic antineoplastic therapies, although heterogeneity was substantial. Overall survival was also improved in the pooled analysis, with moderate heterogeneity. The GRADE assessment identified 19 high-certainty outcomes, mainly involving progression-free survival, event-free survival, overall survival, objective response, complete response, hematologic toxicity, diarrhea, and grade 3 or higher adverse events. Conclusion Contemporary randomized evidence indicates that selected systemic antineoplastic therapies can provide clinically meaningful benefits in treatment-resistant, refractory, relapsed, or previously treated adult malignancies. However, high-certainty evidence is concentrated in specific therapeutic contexts rather than uniformly distributed across all interventions. Exploratory pooled estimates should be interpreted cautiously because of substantial clinical and statistical heterogeneity. Treatment decisions should integrate survival benefit, tumor response, adverse events, risk of bias, and certainty of evidence.

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