Federico Spataro, Vanessa Desantis, Giuseppe Dicuonzo, Stefano Molica, Hermann Einsele, Angelo Vacca, Roberto Ria, Antonio Giovanni Solimando
{"title":"Real-world evidence on infection risk in multiple myeloma treated with BiTEs and CAR-T cells: a meta-analysis.","authors":"Federico Spataro, Vanessa Desantis, Giuseppe Dicuonzo, Stefano Molica, Hermann Einsele, Angelo Vacca, Roberto Ria, Antonio Giovanni Solimando","doi":"10.1186/s40164-026-00798-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>T-cell-redirecting therapies, including bispecific T-cell engagers (BiTEs) and chimeric antigen receptor T-cell (CAR-T) therapies, have substantially improved outcomes in relapsed or refractory multiple myeloma (RRMM). However, infectious complications remain a major safety concern, particularly in real-world settings, where patients are more heterogeneous than those enrolled in clinical trials.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis of real-world retrospective studies evaluating severe (grade 3-4) infections in adult patients with RRMM treated with approved BiTEs or CAR-T cell therapies. Pooled event rates were estimated using random-effects models. Heterogeneity was explored through subgroup analyses, meta-regression, and sensitivity analyses.</p><p><strong>Results: </strong>Sixteen studies encompassing 2,097 patients were included. Overall, 24.2% of patients developed grade 3-4 infections (pooled event rate 0.24; 95% CI, 0.21-0.28). Among BiTEs-treated patients (n = 1,602), the pooled severe infection rate was 0.26 (95% CI, 0.23-0.30), with higher rates observed for BCMA-directed BiTEs (0.27) compared with GPRC5D-directed BiTEs (0.25). CAR-T cell therapies (n = 495) were associated with a lower pooled infection rate (0.19; 95% CI, 0.12-0.27).</p><p><strong>Conclusions: </strong>In real-world practice, severe infections affect approximately one in four patients receiving T-cell-redirecting therapies for RRMM. Observed differences in infection rates across platforms and targets should be interpreted with caution, as they derive from indirect comparisons in non-randomized, heterogeneous cohorts. Nevertheless, these data support incorporating patient frailty and prior infection history into therapeutic decision-making. CAR-T therapy, or GPRC5D-directed BiTEs when CAR-T is not feasible, may represent reasonable options in patients at higher infectious risk, within an individualized and context-dependent treatment strategy.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5000,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282886/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Hematology & Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40164-026-00798-w","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: T-cell-redirecting therapies, including bispecific T-cell engagers (BiTEs) and chimeric antigen receptor T-cell (CAR-T) therapies, have substantially improved outcomes in relapsed or refractory multiple myeloma (RRMM). However, infectious complications remain a major safety concern, particularly in real-world settings, where patients are more heterogeneous than those enrolled in clinical trials.
Methods: We conducted a systematic review and meta-analysis of real-world retrospective studies evaluating severe (grade 3-4) infections in adult patients with RRMM treated with approved BiTEs or CAR-T cell therapies. Pooled event rates were estimated using random-effects models. Heterogeneity was explored through subgroup analyses, meta-regression, and sensitivity analyses.
Results: Sixteen studies encompassing 2,097 patients were included. Overall, 24.2% of patients developed grade 3-4 infections (pooled event rate 0.24; 95% CI, 0.21-0.28). Among BiTEs-treated patients (n = 1,602), the pooled severe infection rate was 0.26 (95% CI, 0.23-0.30), with higher rates observed for BCMA-directed BiTEs (0.27) compared with GPRC5D-directed BiTEs (0.25). CAR-T cell therapies (n = 495) were associated with a lower pooled infection rate (0.19; 95% CI, 0.12-0.27).
Conclusions: In real-world practice, severe infections affect approximately one in four patients receiving T-cell-redirecting therapies for RRMM. Observed differences in infection rates across platforms and targets should be interpreted with caution, as they derive from indirect comparisons in non-randomized, heterogeneous cohorts. Nevertheless, these data support incorporating patient frailty and prior infection history into therapeutic decision-making. CAR-T therapy, or GPRC5D-directed BiTEs when CAR-T is not feasible, may represent reasonable options in patients at higher infectious risk, within an individualized and context-dependent treatment strategy.
期刊介绍：
Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings.
Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
