Elevated LIF and JAK-STAT activation drive severe COVID-19 in myeloma patients receiving the BCMA-CD3 bispecific antibody Elranatamab

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 26, 2025

Immunotherapy is a significant risk factor for severe COVID-19 in multiple myeloma (MM) patients. Understanding how immunotherapies lead to crucial improving patient outcomes. Human protein microarrays were used examine the expression of 440 molecules MM patients treated with bispecific T-cell engagers (BiTe) (n = 9), anti-CD38 monoclonal antibodies (mAbs) 10), and proteasome inhibitor (PI)-based regimens 10). Differentially expressed proteins (DEPs) identified analyzed using bioinformatics. BiTe therapy was associated higher incidence COVID-19. We 21 29 DEPs between mAbs group, PI-based respectively, along 25 PI groups. Principal component analysis clustering showed distinct profiles Gene Ontology (GO) revealed that groups related cytokine activity leukocyte migration. Kyoto Encyclopedia Genes Genomes (KEGG) these enriched cytokine-cytokine receptor interaction JAK-STAT signaling pathways. Leukemia inhibitory (LIF) most correlated other thus may play key role both pathways, level LIF highest group. linked due an inflammatory storm, pathway playing roles. Targeting help reduce BiTe.

Language: Английский

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Clinical characteristics and outcomes of BCMA-targeted CAR-T cell recipients with COVID-19 during the Omicron wave: a retrospective study

Bone Marrow Transplantation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Patients with relapsed or refractory multiple myeloma (R/R-MM) are more susceptible to develop severe coronavirus disease 2019 (COVID-19) for their immunocompromised states. Despite good responses B-cell maturation antigen (BCMA)-targeted chimeric receptor (CAR)-T cell therapy, deficiencies in humoral immunity following CAR-T infusions can still cause life-threatening complications these patients. We conducted a comparative study delineate the clinical characteristics and outcomes between recipients of BCMA-targeted therapy who contracted COVID-19 vs. unaffected counterparts. Advanced age (odds ratio [OR] = 1.367, 95% confidence interval [CI] 1.017–1.838, P 0.038) was risk factor developing COVID-19, while complete remission (CR) achieved by (OR 0.012, CI 0.000–0.674, 0.032) protective. Male sex (hazard [HR] 5.274, 1.584–17.562, 0.007) CR (HR 3.107, 1.025–9.418, 0.045) were protective factors associated duration. 0.064, 0.007–0.589, 0.015) also OS, progression at time diagnosis 14.206, 1.555–129.819, 0.019) regarded as factor. Thus, older patients R/R-MM those do not achieve after should be most protected from infection Omicron variant.

Language: Английский

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Outcomes of COVID‐19 in multiple myeloma patients treated with daratumumab

Cancer Science, Journal Year: 2023, Volume and Issue: 115(1), P. 237 - 246

Published: Oct. 26, 2023

Despite concerns about an increased risk of adverse outcomes following coronavirus disease (COVID-19) in multiple myeloma patients treated with anti-CD38 Abs, the impact COVID-19 on this group is unclear. We tried to evaluate clinical these patients. collected data from 1036 and enrolled 509 cases COVID-19. divided into daratumumab or nondaratumumab cohorts based whether they had received daratumumab-based treatment within 6 months infection. applied a propensity score matching method reduce bias baseline characteristics, then compared incidence between two cohorts. A total 117 were cohort, 392 cohort. After matching, 204 matched. The proportions who developed pneumonia (59.8% vs. 34.3%, p < 0.001), hospitalized (33.3% 11.8%, 0.001) severe (23.5% 6.9%, = higher matched By multivariate analysis, exposure was independent factor for disease. An ECOG performance status >2 history chronic kidney factors COVID-19-related mortality among therapy. This study suggested that exposed at

Language: Английский

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Endothelial injury and dysfunction with emerging immunotherapies in multiple myeloma, the impact of COVID-19, and endothelial protection with a focus on the evolving role of defibrotide

Blood Reviews, Journal Year: 2024, Volume and Issue: 66, P. 101218 - 101218

Published: June 3, 2024

Patients with multiple myeloma (MM) were among the groups impacted more severely by COVID-19 pandemic, higher rates of severe disease and COVID-19-related mortality. MM COVID-19, plus post-acute sequelae SARS-CoV-2 infection, are associated endothelial dysfunction injury, overlapping inflammatory pathways coagulopathies. Existing treatment options for MM, notably high-dose therapy autologous stem cell transplantation novel chimeric antigen receptor (CAR) T-cell therapies bispecific engaging antibodies, also injury mechanism-related toxicities. These pathologies include cytokine release syndrome (CRS) neurotoxicity that may be exacerbated underlying endotheliopathies. In context these risks, prophylaxis approaches mitigating pro-coagulant effects important considerations patient management, including antagonists, thromboprophylaxis low-molecular-weight heparin direct oral anticoagulants, protection defibrotide in appropriate clinical settings.

Language: Английский

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Risk of SARS-CoV-2 infection and severe COVID-19 in hematological patients who received or not pre-exposure prophylaxis with tixagevimab/cilgavimab: a target trial emulation

Leukemia & lymphoma/Leukemia and lymphoma, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 8

Published: June 4, 2024

We emulated a hypothetical target trial in which hematological subjects cared at the University Hospital of Pisa (Italy) received or not SARS-CoV-2 prophylaxis with tixagevimab/cilgavimab. Subjects who (cases) were compared to those did (controls). The main outcome was infection subsequent 6 months. Inverse probability weighting (IPW) used adjust for confounders. A multivariable analysis performed identify variables associated infection. recruited 462 patients: 228 prophylaxis, 234 controls. COVID-19 lower cases controls (16.7% vs 24.8%, p = 0.03, after IPW 14.3% 24.6%, 0.01). On analysis, B-cell depleting therapies (HR 2.09, 95%CI 1.05-4.18, 0.037) increased risk COVID-19, while tixagevimab/cilgavimab 0.45, 0.27-0.73, 0.001) and previous 0.27, 0.14-0.51, < protective. In conclusion, monoclonal antibodies may reduce patients.

Language: Английский

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Risk assessment and clinical implications of COVID-19 in multiple myeloma patients: A systematic review and meta-analysis

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(9), P. e0308463 - e0308463

Published: Sept. 6, 2024

Introduction Patients with multiple myeloma (MM) face heightened infection susceptibility, particularly severe risks from COVID-19. This study, the first systematic review in its domain, seeks to assess impacts of COVID-19 on MM patients. Method Adhering PRISMA guidelines and PROSPERO registration (ID: CRD42023407784), this study conducted an exhaustive literature search January 1, 2020, April 12, 2024, using specified terms major databases (PubMed, EMBASE, Web Science). Quality assessment utilized JBI Critical checklist, while publication bias was assessed Egger’s test funnel plot. The leave-one-out sensitivity analyses were performed robustness results by excluding one at a time identify studies high risk or those that significantly influenced overall effect size. Data synthesis involved fitting random-effects model estimating meta-regression coefficients. Results A total 14 studies, encompassing sample size 3214 yielded pooled estimates indicating hospitalization rate 53% (95% CI: 40.81, 65.93) considerable heterogeneity across (I2 = 99%). ICU admission 17% 11.74, 21.37), also significant 94%). mortality 22% 15.33, 28.93), showing 97%). survival stood 78% 71.07, 84.67), again exhibiting substantial S ubgroup analysis highlighted types, demographic factors, patient comorbidities contributed observed outcome heterogeneity, revealing distinct patterns. Mortality rates increased 15% for participants median age above 67 years. positively correlated obesity, 20% increase groups least 19% obesity. rose 33% group patients decreased same group. Conclusion Our meta-analysis sheds light diverse outcomes myeloma. Heterogeneity underscores complexities, demographics, co-morbidities influence results, emphasizing nuanced interplay factors.

Language: Английский

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The establishment of a multiple myeloma clinical registry in the Asia–Pacific region: The Asia–Pacific Myeloma and Related Diseases Registry (APAC MRDR)

BMC Medical Research Methodology, Journal Year: 2024, Volume and Issue: 24(1)

Published: May 2, 2024

Multiple myeloma (MM) is the second most common haematological cancer worldwide. Along with related diseases including monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukaemia (PCL) and plasmacytoma, MM incidence rising, yet it remains incurable represents a significant disease burden. Clinical registries can provide important information on management outcomes, are vital platforms for clinical trials other research. The Asia-Pacific Myeloma Related Diseases Registry (APAC MRDR) was developed to monitor explore variation in epidemiology, treatment regimens their impact outcomes across this region. Here we describe registry's design development, initial data, progress future plans.

Language: Английский

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