Living Evidence Synthesis Updated Report. Servicio Navarro de Salud-Sección de innovación y organización. LE-IHD.
Creators: name: Rojas- Reyes, María
name: Erviti, Juan
name: Fernández, Luis
name: Leache, Leire
name: Valencia, Marta
Publisher: name: Open Science Framework
Year: 2022
Subjects: subject: Medicine and Health Sciences
subject: CAR-T therapy
subject: chemotherapy cytokine-release syndrome
subject: Continuos update
subject: Epistemonikos L.OVE Platform
subject: Evidence-based medicine
subject: Evidence Synthesis
subject: hematologic stem cell transplantation
subject: Inform Health Decisions
subject: Living Evidence

description: Tittle: Efficacy and safety of Chimeric Antigen Receptor T-Cell (CAR-T) therapy in hematologic malignancies: A living systematic review. Authors: Luis Carlos Saiz ORCID: [0000-0002-9143-5709] Afilliation: Unit of Innovation and Organization, Navarre Health Service, Pamplona, Spain Leire Leache ORCID: [0000-0003-2272-7086] Afilliation: Unit of Innovation and Organization, Navarre Health Service, Pamplona, Spain Marta Gutiérrez Valencia ORCID: [0000-0002-3229-6614] Afilliation: Unit of Innovation and Organization, Navarre Health Service, Pamplona, Spain Juan Erviti ORCID: [0000-0003-3396-2102] Afilliation: Unit of Innovation and Organization, Navarre Health Service, Pamplona, Spain María Ximena Rojas Reyes ORCID: [0000-0001-5752-7653] Afilliation: Institut d’Recerca-Servei d’Epidemiologia Clínica I Salut Pública. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain Corresponding author: Luis Carlos Saiz Email address: lsaizfer@navarra.es Postal address: Tudela 20, Pamplona, Spain, 31003 Funding sources/sponsors: This work is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No MSCA-IF-EF-ST #894990 (to María Ximena Rojas). This work is also supported by the Unit of Innovation and Organization, Navarre Health Service. The funders and institutions did not take any part in the development of this study. Conflicts of interest: Authors have declared no conflict of interest. ABSTRACT: Objective This living systematic review aims to provide a timely, rigorous and continuously updated summary of the evidence available on the role of Chimeric Antigen Receptor T-Cell (CAR-T) therapy for the treatment of patients with hematologic malignancies. Design Living systematic review. Database The Epistemonikos-L.OVE platform was used for evidence identification, screening, and selection. This platform has been validated as a repository for COVID-19, and proved to be a highly comprehensive source of evidence. The main search source for the L.OVE platform is the Epistemonikos database (https://www.epistemonikos.org), a comprehensive database that collates information from multiple sources to identify systematic reviews and their included primary studies, including Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, DARE, HTA Database, Campbell database, JBI Database of Systematic Reviews and Implementation Reports, EPPI-Centre Evidence Library. The team maintaining the Epistemonikos-L·OVE platform devised the literature search, using the following approach: i) Identification of terms relevant to the population and intervention components of the search strategy, using Word2vec technology to the corpus of documents available in Epistemonikos Database; ii) Discussion of search terms with methods experts to identify relevant, irrelevant and missing terms, iii) Creation of a sensitive boolean strategy encompassing all the relevant terms. The results of the literature searches were automatically incorporated into the L·OVE platform (automated retrieval) and organized in the corresponding L.OVE of "Chimeric antigen receptor T cell therapy for hematological malignancies". Methods Randomized controlled trials (RCTs) and comparative non-randomized studies of interventions (NRSI) evaluating the effect of CAR-T therapy versus other active treatments, hematopoietic stem cell transplantation, standard of care (SoC) or any other intervention in patients with hematologic malignancies were considered for inclusion. The primary outcome is overall survival (OS). Certainty of the evidence was determined using the GRADE approach. Results This is the first report (baseline report) of this LSR. We included the evidence published up to 1 July 2022. We considered 139 RCTs and 1725 NRSI as potentially eligible. Two RCTs (N = 681) comparing CAR-T therapy with SoC in patients with recurrent/relapsed (R/R) B-cell lymphoma were included. RCTs did not show statistical differences in OS, serious adverse events (SAEs) or total adverse events (TAEs) with grade ≥3. Higher complete response (CR) with substantial heterogeneity [RR=1.59; 95%CI (1.30 to 1.93); I 2 =89%; 2 studies; 681 participants; very low certainty evidence] and higher progression-free survival (PFS) [HR for progression or death = 0.49; 95%CI (0.37 to 0.65); 1 study; 359 participants; moderate certainty evidence] were reported with CAR-T therapies. Nine NRSI (N=540) in patients with T or B-cell acute lymphoblastic leukemia or R/R B-cell lymphoma were also included, providing secondary data. In general, the GRADE certainty of the evidence for main outcomes was mostly low or very low due to inconsistency. The evidence monitoring will continue for the next six months in order to identify emerging evidence. Conclusions Two RCTs on the use of CAR-T versus standard care in the management of patients with R/R B-cell lymphoma have been identified so far. Low to very low certainty evidence shows that probably there would be no differences in the effect of these interventions on OS (primary outcome), SAEs, or TAE grade ≥ 3. However, CAR-T therapy may provide better results in terms of PFS and CR (moderate to very low certainty evidence). Evidence from NRSI could not be used as complementary evidence because of its low certainty, downgraded due to the important risk of bias and inconclusive results in estimates. Larger trials specifically designed to minimize bias are needed in order to determine the efficacy and safety of the use of CAR-T in patients with hematological malignancies. © 2022 Servicio Navarro de Salud-Sección de innovación y organización, Spain/ EU H2020, Living Evidence to Inform Health Decisions Project. All rights reserved