Lisocabtagene maraleucel 1.1million-70million cells/ml / 1.1million-70million cells/ml dispersion for infusion vials

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

This global phase 3 study compared lisocabtagene maraleucel (liso-cel) with a standard of care (SOC) as second-line therapy for primary refractory or early relapsed (≤12 months) large B-cell lymphoma (LBCL). Adults eligible for autologous stem cell transplantation (ASCT; N = 184) were randomly assigned in a 1:1 ratio to liso-cel (100 × 106 chimeric antigen receptor-positive T cells) or SOC (3 cycles of platinum-based immunochemotherapy followed by high-dose chemotherapy and ASCT in responders). The primary end point was event-free survival (EFS). In this primary analysis with a 17.5-month median follow-up, median EFS was not reached (NR) for liso-cel vs 2.4 months for SOC. Complete response (CR) rate was 74% for liso-cel vs 43% for SOC (P < .0001) and median progression-free survival (PFS) was NR for liso-cel vs 6.2 months for SOC (hazard ratio [HR] = 0.400; P < .0001). Median overall survival (OS) was NR for liso-cel vs 29.9 months for SOC (HR = 0.724; P = .0987). When adjusted for crossover from SOC to liso-cel, 18-month OS rates were 73% for liso-cel and 54% for SOC (HR = 0.415). Grade 3 cytokine release syndrome and neurological events occurred in 1% and 4% of patients in the liso-cel arm, respectively (no grade 4 or 5 events). These data show significant improvements in EFS, CR rate, and PFS for liso-cel compared with SOC and support liso-cel as a preferred second-line treatment compared with SOC in patients with primary refractory or early relapsed LBCL. This trial was registered at www.clinicaltrials.gov as #NCT03575351.

Abstract licence: CC BY-NC-ND

Background/Objectives: Lisocabtagene maraleucel (liso-cel) is a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy approved for relapsed or refractory large B-cell lymphoma (R/R LBCL). However, most published meta-analyses of CAR-T therapy in LBCL pool data across products, limiting product-specific interpretation. Methods: We conducted a systematic review and meta-analysis of clinical trials and retrospective real-world studies evaluating liso-cel monotherapy in R/R LBCL. The primary endpoint was the overall response rate (ORR). Secondary endpoints included complete response (CR), incidence of grade ≥ 3 adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), overall mortality rate (OMR), disease progression-related mortality, and adverse event-related mortality. Pooled proportions were estimated using random-effects models. Results: Eleven studies including 1206 patients were analyzed, comprising five clinical trials and six real-world retrospective cohorts. The pooled ORR was 78%, and the pooled CR rate was 60%. The pooled OMR was 38%, with a disease progression-related mortality of 28% and an adverse event-related mortality of 4%. Severe (grade ≥ 3) CRS and ICANS occurred in 2% and 8%, respectively. Severe (grade ≥ 3) hematologic toxicities were frequent, particularly neutropenia, thrombocytopenia, and anemia. Conclusions: Liso-cel monotherapy demonstrated high pooled response rates and low pooled incidences of severe CRS and ICANS across clinical trials and real-world settings in R/R LBCL. Severe ICANS, although uncommon, remains clinically meaningful, and severe hematologic toxicities were frequent and warrant careful monitoring and supportive care. These findings provide product-specific benchmarks for liso-cel in R/R LBCL.

Abstract licence: CC BY 4.0

BackgroundCurrently, three chimeric antigen receptor (CAR)-T cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have been approved by the U.S. Food and Drug Administration for the treatment of large B cell lymphoma, which provide a novel and promising choice for patients with relapsed or refractory to traditional anti-tumor treatments. Thus, it is pertinent to describe the efficacy and safety profile of the three products available by summarizing the current evidence.MethodsTwo reviewers independently searched the Embase, PubMed, Web of Science, and Cochrane Library, to identify studies related to the use of the three CAR-T cell products for treating hematologic malignancies published up to October 5, 2020. We pooled the overall response rate, complete response rate, cytokine release syndrome, and immune effector cell-associated neurotoxicity syndrome of three products, and then performed subgroup analysis based on the type of product and type of tumor.ResultsThirty-three studies involving 2,172 patients were included in the analysis. All three products showed promising results in patients with different pathological subtypes and clinical characteristics that included those who did not meet the eligibility criteria of licensing trials, with overall response rates of nearly 70% or above and complete response rates of more than 50%. However, high rates of severe immune effector cell-associated neurotoxicity syndrome in patients undergoing axicabtagene ciloleucel treatment and life-threatening cytokine release syndrome in patients with leukemia undergoing tisagenlecleucel treatment required special attention in practice (31%; 95% CI: 0.27–0.35 and 55%; 95% CI: 0.45–0.64, respectively). Moreover, lisocabtagene maraleucel that showed a favorable efficacy and safety in the licensing trial lacked corresponding real-world data.ConclusionBoth axicabtagene ciloleucel and tisagenlecleucel showed considerable efficacy in practice, but need special attention with respect to life-threatening toxicity that can occur in certain situations. Lisocabtagene maraleucel demonstrated excellent efficacy and safety profiles in the licensing trial, but lacked corresponding real-world data. Additional data on the three products are needed in rare histological subtypes to benefit a broader patient population.

Abstract licence: CC BY 4.0

BackgroundThe advent of novel therapies including chimeric antigen receptor (CAR) T cells, bispecific antibodies (BsAbs), and antibody-drug conjugates (ADCs), has markedly improved clinical outcomes for relapsed or refractory large B-cell lymphoma (R/R LBCL). However, direct comparisons of efficacy and safety among systemic treatments for R/R LBCL are lacking, complicating clinical decision-making.MethodsA systematic literature search was conducted across PubMed, Embase, and the Cochrane Library to identify eligible randomized controlled trials (RCTs). A Bayesian network meta-analysis (NMA) was performed to evaluate the systemic therapies across transplant-eligible and transplant-ineligible patients with R/R LBCL. The primary endpoint was progression-free survival (PFS), secondary endpoints included event-free survival (EFS), overall survival (OS), objective response rate (ORR) and grade ≥3 treatment-emergent adverse events (TEAEs).ResultsThe analysis included 14 RCTs comprising a total of 3,329 patients. Among the transplant-eligible cohort (7 evaluated regimens), CAR-T therapies maximized disease control; lisocabtagene maraleucel (liso-cel) ranked highest for PFS [hazard ratio (HR) =0.42; 95% credible intervals (CrI): 0.28-0.64] and EFS (HR =0.37, 95% CrI: 0.26-0.54), whereas axicabtagene ciloleucel (axi-cel) was associated with the highest incidence of grade ≥3 TEAEs [risk ratio (RR) =2.09; 95% CrI: 1.08-4.19]. In the transplant-ineligible cohort (9 evaluated regimens), glofitamab plus gemcitabine and oxaliplatin (Glofit-GemOx) ranked highest for PFS (HR =0.32; 95% CrI: 0.23-0.45), while polatuzumab vedotin plus bendamustine and rituximab (Pola-BR) yielded the maximum benefit for OS (HR =0.42; 95% CrI: 0.24-0.73) and ORR [odds ratio (OR) =5.21; 95% CrI: 2.01-14.3]. Both regimens were associated with higher toxicities, but remained overall manageable.ConclusionsThis NMA provides a comprehensive comparison of systemic treatment strategies for R/R LBCL regarding efficacy and safety profiles.

Abstract licence: CC BY-NC-ND

[This corrects the article DOI: 10.3389/fonc.2021.698607.].

Abstract licence: CC BY 4.0