A systematic review on the cost-effectiveness assessment of tisagenlecleucel for refractory or relapsing B-cell acute lymphoblastic leukemia (R/R B-ALL) treatment in children and young adults.

BACKGROUND AIMS: The advanced therapy product tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy that has brought hope for children and young adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We sought to evaluate the cost-effectiveness of tisagenlecleucel compared with conventional salvage therapies in pediatric and young adult patients with R/R B-ALL. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses parameters as registered in International Prospective Register of Systematic Reviews (CRD42021266998). Literature was searched using the MEDLINE databases via PubMed, EMBASE, Lilacs, the Cochrane Central Register of Controlled Trials and Web of Science in January 2022. Titles were screened independently by two reviewers. Articles deemed to meet the inclusion criteria were screened independently on abstract, and full texts were reviewed. RESULTS: In total, 5627 publications were identified, from which six eligible studies were selected. The conventional therapies identified were blinatumomab (Blina), clofarabine monotherapy (Clo-M), clofarabine combined with cyclophosphamide and etoposide (Clo-C) and the combination of fludarabine, cytarabine and idarubicin (FLA-IDA). The discounted incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained for tisagenlecleucel compared with Clo-C and Blina averages was $38 837 and $25 569, respectively. In relation to the cost of the drug, the average of tisagenlecleucel was approximately 4.3 times, 10.8 times or 4.7 times greater than the Clo-M, Clo-C and Blina, respectively. CONCLUSIONS: This systematic review highlighted that tisagenlecleucel is a much more expensive therapy than conventional alternatives. However, tisagenlecleucel performed well on the ICER, not exceeding $100 000/QALY. It was also found that the advanced therapy product was more effective than the conventional small molecule and biological drugs, in terms of life years and QALY gained.

Hallmarks of aging and immunosenescence: Connecting the dots.

Aging is a natural physiological process that features various and variable challenges, associated with loss of homeostasis within the organism, often leading to negative consequences for health. Cellular senescence occurs when cells exhaust the capacity to renew themselves and their tissue environment as the cell cycle comes to a halt. This process is influenced by genetics, metabolism and extrinsic factors. Immunosenescence, the aging of the immune system, is a result of the aging process, but can also in turn act as a secondary inducer of senescence within other tissues. This review aims to summarize the current state of knowledge regarding hallmarks of aging in relation to immunosenescence, with a focus on aging-related imbalances in the medullary environment, as well as the components of the innate and adaptive immune responses. Aging within the immune system alters its functionality, and has consequences for the person's ability to fight infections, as well as for susceptibility to chronic diseases such as cancer and cardiovascular disease. The senescence-associated secretory phenotype is described, as well as the involvement of this phenomenon in the paracrine induction of senescence in otherwise healthy cells. Inflammaging is discussed in detail, along with the comorbidities associated with this process. A knowledge of these processes is required in order to consider possible targets for the application of senotherapeutic agents - interventions with the potential to modulate the senescence process, thus prolonging the healthy lifespan of the immune system and minimizing the secondary effects of immunosenescence.