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Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis.

ABSTRACT: Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell markers, including B-cell maturation antigen (BCMA), FcRH5, and G protein-coupled receptor GPRC5D. These bispecific antibodies so effectively deplete plasma cells (and to some extent T-cells) that patients are at increased risk of developing infections. A systematic review and meta-analysis of infections in published studies of patients with myeloma treated with bispecific antibodies was conducted to better characterize the infection risks. A literature search used MEDLINE, EMBASE, and Cochrane to identify relevant studies between inception and February 10, 2023, including major conference presentations. Phase 1b-3 clinical trials and observational studies were included. Sixteen clinical trials comprising 1666 patients were included. Median follow-up was 7.6 months and 38% of the cohort had penta-drug refractory disease. Pooled prevalence of all-grade infections was 56%, whereas the prevalence of grade ≥3 infections was 24%. Patients who were treated with BCMA-targeted bispecifics had significantly higher rates of grade ≥3 infections than non-BCMA bispecifics (25% vs 20%). Similarly, patients treated with bispecifics in combination with other agents had significantly higher rate of all-grade infection than those receiving monotherapy (71% vs 52%). In observational studies (n = 293), excluded from the primary analysis to ensure no overlap with patients in clinical trials, several infections classically associated with T-cell depletion were identified. This systematic review identifies BCMA-targeted bispecifics and bispecific combination therapy as having higher infection risk, requiring vigilant infection screening and prophylaxis strategies.

SUBMITTER: Reynolds G

PROVIDER: S-EPMC10558589 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis.

Reynolds Gemma G Cliff Edward R Scheffer ERS Mohyuddin Ghulam Rehman GR Popat Rakesh R Midha Shonali S Liet Hing Melissa Ng MN Harrison Simon J SJ Kesselheim Aaron S AS Teh Benjamin W BW

Blood advances 20231001 19

Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell markers, including B-cell maturation antigen (BCMA), FcRH5, and G protein-coupled receptor GPRC5D. These bispecific antibodies so effectively deplete plasma cells (and to some extent T-cells) that patients are at increased risk of developing infections. A systematic review and meta-analysis of infections in published studies of p ...[more]

PMID: 37467036

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Project description:BackgroundIn recent years, several bispecific antibodies (BsAbs) have been introduced that revolutionized the treatment approach for patients with multiple myeloma (MM). In the present study, we sought for conducting a systematic review and meta-analysis with the aim of evaluating the safety and efficacy of BsAbs in MM patients.MethodsPubMed, Scopus, Web of Science, and Embase databases were systematically searched on June 10, 2022. Two steps of title/abstract and full-text screening were performed for selecting the relevant articles. The primary endpoint was considered to evaluate the safety of BsAbs by examining the rate of hematologic and non-hematologic adverse effects (AEs). The secondary outcome was set at the efficacy of BsAbs through pooling objective response rate (ORR), (stringent) complete response (sCR/CR), very good partial response (VGPR), and partial response (PR).ResultsEleven publications with a total of nine evaluable BsAbs were included for qualitative and quantitative data synthesis. Hematologic AEs were more common among patients than non-hematologic events, with the most frequent events being anemia (41.4%), neutropenia (36.4%), and thrombocytopenia (26.3%). The most common non-hematological AE was infection, which occurred in 39.9% of patients, followed by dysgeusia (28.3%), fatigue (26.5%), and diarrhea (25.8%). Besides, 8.1% of patients experienced immune effector cell-associated neurotoxicity syndrome and neurotoxicity occurred in 5.1% of them. Moreover, 59.8% of patients experienced cytokine release syndrome. The pooled rate of deaths attributable to BsAbs was estimated at 0.1%. In terms of efficacy measures, the ORR was achieved in 62.6% of MM patients, and the pooled rates of sCR/CR, VGPR, and PR were 22.7%, 23.0%, and 12.1%, respectively.ConclusionsIn an era with several emerging promising treatments for MM, BsAbs have achieved a high ORR and tolerable AEs in heavily pretreated patients. However, there is still room for developing BsAbs with a lower rate of AEs and capable of bypassing tumor evasion mechanisms.

Project description:ObjectiveBispecific antibody (BsAbs) therapy represents a promising immunotherapeutic approach with manageable toxicity and noteworthy preliminary efficacy in treating patients with relapsed or refractory multiple myeloma (RRMM). The objective of this systematic review and meta-analysis was to compare the efficacy and safety of B-cell maturation antigen (BCMA)-targeted BsAbs and non-BCMA-targeted BsAbs in the treatment of RRMM patients.MethodsPubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library and meeting libraries were searched from inception to August 16th, 2023. The efficacy evaluation included the complete objective response rate (ORR), complete response (CR) rate, stringent CR (sCR) rate, partial response (PR) rate, and very good PR (VGPR) rate. The efficacy evaluation included any grade adverse events (AEs) and grade ≥ 3 AEs.ResultsFourteen studies with a total of 1473 RRMM patients were included. The pooled ORR of the entire cohort was 61%. The non-BCMA-targeted BsAbs group displayed a higher ORR than the BCMA-targeted BsAbs group (74% vs. 54%, P < 0.01). In terms of hematological AEs, BCMA-targeted BsAbs therapy exhibited higher risks of neutropenia (any grade: 48% vs. 18%, P < 0.01; grade ≥ 3: 43% vs. 15%, P < 0.01) and lymphopenia (any grade: 37% vs. 8%, P < 0.01; grade ≥ 3: 31% vs. 8%, P = 0.07). Regarding non-hematological AEs, there were no significant differences in the risks of cytokine release syndrome (CRS, any grade: 64% vs. 66%, P = 0.84; grade ≥ 3: 1% vs. 1%, P = 0.36) and infections (any grade: 47% vs. 49%, P = 0.86; grade ≥ 3: 24% vs. 20%, P = 0.06) between the two groups. However, non-BCMA-targeted BsAbs therapy was associated with a higher risk of immune effector cell-associated neurotoxicity syndrome (ICANS, any grade: 11% vs. 2%, P < 0.01) and lower risks of fatigue (any grade: 14% vs. 30%, P < 0.01) and pyrexia (any grade: 14% vs. 29%, P < 0.01).ConclusionThis analysis suggest that non-BCMA-targeted BsAbs therapy may offer a more favorable treatment response and tolerability, while BCMA-targeted BsAbs therapy may be associated with diminished neurotoxic effects.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42018090768.

Project description:AimThis study aimed to quantitatively summarise risk factors associated with surgical site infection (SSI) following surgically managed tibial fractures.MethodWe searched the Embase/Medline, Cochrane Library, and Scopus databases for relevant studies in October 2023. We included original studies investigating risk factors for SSI following surgically managed traumatic tibial fractures that included ≥10 adult patients with SSIs. Meta-analysis was performed when >5 studies investigated the same risk factor. The risk of bias was assessed using the critical appraisal checklist from Joanna Briggs Institute for cohort studies.ResultsThis study included 42 studies comprising 24,610 patients with surgically managed tibial fractures and 2,418 SSI cases. The following were identified as significant risk factors for SSI (p < 0.05): compartment syndrome (odds ratio [OR] = 3.8, 95% confidence interval [CI]: 2.4-6.0), blood transfusion (OR = 3.8, 95% CI: 2.1-6.6), open fracture (OR = 3.6, 95% CI: 2.5-5.1), Gustilo-Anderson classification >2 (OR = 3.1, 95% CI: 2.1-4.6), external fixation (OR = 2.9, 95% CI: 2.3-3.8), American Society of Anesthesiologists classification >2 (OR = 2.5, 95% CI: 1.5-4.1), polytrauma (OR = 2.4, 95% CI: 1.5-4.0), dual incision approach (OR = 2.1, 95% CI: 1.5-3.0), smoking (OR = 1.8, 95% CI: 1.5-2.1), male sex (OR = 1.6, 95% CI: 1.3-1.8), high energy trauma (OR = 1.5, 95% CI: 1.1-2.1), and prolonged surgery time (OR = 0.62, 0.43-0.82). Other factors, including diabetes, hypertension, and time to surgery, were not identified as risk factors for SSI. However, the included studies were generally of poor quality and at risk of bias.ConclusionsThe review provides a basis for preoperatively assessing a patient's risk of developing an SSI, which could be used to initiate adjusted antibiotic regimes and more frequent postoperative controls. Furthermore, it indicates the risk factors future research should include when adjusting for confounding factors.

Dataset Information

Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis.

Publications

Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis.

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