Search Results (504)

Background/Objectives: T-cell-redirecting immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs), have transformed the treatment of relapsed/refractory multiple myeloma (RRMM). However, pivotal registration trials routinely excluded patients with significant renal impairment (RI), creating a critical evidence gap in a population where kidney disease affects 20–50% of patients at diagnosis. Direct comparisons of outcomes across the estimated glomerular filtration rate (eGFR) spectrum for both modalities are lacking. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, a federated electronic health record research platform. Adult patients with RRMM treated with CAR-T therapy (idecabtagene vicleucel or ciltacabtagene autoleucel) or BsAbs (teclistamab, elranatamab, or talquetamab) were stratified by baseline renal function: severe RI (eGFR <30 mL/min/1.73 m²), moderate RI (eGFR 30–60 mL/min/1.73 m²), and preserved renal function (eGFR >60 mL/min/1.73 m²). Propensity score matching (PSM) (1:1), adjusted for key clinical and demographic covariates, was performed for each comparison within each therapy type. Long-term outcomes (all-cause mortality and time to next treatment [TTNT]) were assessed at 1, 2, and 3 years. Overall survival (OS) was additionally evaluated using Kaplan–Meier analysis. Short-term safety outcomes were assessed at 1, 3, and 6 months. Results: A total of 2716 CAR-T and 3376 BsAb recipients were identified. After matching, 281 pairs (severe RI vs. preserved) and 878 pairs (moderate RI vs. preserved) were analyzed in the CAR-T cohort; 645 and 1158 pairs, respectively, were analyzed in the BsAb cohort. Neither severe nor moderate RI was significantly associated with increased mortality or shorter TTNT after either CAR-T or BsAb therapy. However, patients with RI experienced significantly higher rates of anemia, thrombocytopenia, and acute kidney injury (AKI) across both modalities. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and neutropenia rates were comparable across renal strata. In the BsAb cohort, infections were transiently elevated at 1 month in the severe RI group (RR 1.29; 95% CI 1.06–1.58; p = 0.011) but equilibrated by 3 months. Conclusions: In this retrospective analysis, renal impairment was not associated with inferior survival outcomes following CAR-T therapy or BsAb treatment in RRMM, suggesting that RI alone should not preclude the use of these agents. However, RI conferred increased hematologic toxicity and AKI risk, warranting enhanced supportive care and monitoring. These findings support broadening access to T-cell-redirecting immunotherapies for patients with RI with appropriate surveillance, though prospective validation is needed. Full article

Background/Objectives: Population aging has increased the incidence of non-Hodgkin lymphoma in older adults, who often receive suboptimal treatment. Geriatric assessment is a key tool to evaluate frailty and guide therapeutic decisions. CAR T-cell therapy is effective but associated with significant toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which may be more severe in older patients. This study evaluated the role of geriatric assessments in patients aged 70 years and older referred for CAR T-cell therapy, focusing on patient profiles, treatment-related toxicities and clinical outcomes. Methods: This retrospective descriptive study included all patients aged 70 years and older for whom CAR T-cell therapy was considered at our institution between 15 December 2022 and 31 January 2026. Data were collected through medical record review. Descriptive and exploratory statistical analyses were performed. Results: A total of 43 patients aged 70 years or older with a diagnosis of refractory non-Hodgkin lymphoma underwent geriatric assessment prior to CAR T-cell therapy (median age: 73 years; 58% male). Most patients lived at home (98%), often with a cohabiting partner (65%). Polypharmacy (72%), mobility impairment (19%) and cognitive impairment (49%) were prevalent among our study population. Among the evaluated patients, CAR T-cell therapy was recommended in 35 cases, of whom 27 subsequently received treatment. In total, 85% developed CRS and 59% developed ICANS. ICANS occurred slightly more frequently in patients with pre-existing neurocognitive impairment (7 out of 11, 64%), compared with 9 out of 16 (56%) among those without cognitive impairment. The median length of hospitalization was 16 days. Mean overall survival post CAR T-cell therapy reached 324 days as of 31 January 2026 (median 277 days). Patients who were not recommended for CAR T-cell therapy exhibited a markedly higher burden of frailty compared with those who were and most of these vulnerabilities had not been identified before the geriatric evaluation. Conclusions: This study highlights the importance of oncogeriatric assessment in the context of CAR T-cell therapy to personalize treatment strategies according to patients’ frailty profiles. It may help optimize the care plan, potentially identifying patients most likely to benefit from therapy, while minimizing treatment-related toxicities. It also helps estimate the risk of treatment-related toxicities and facilitates the identification of previously unrecognized vulnerabilities. Full article

Background: The objective of this study was to evaluate the efficacy and safety of CAR-T immunotherapy in inducing remission in patients with Acute Lymphoblastic Leukemia (ALL). Methods: The search strategy was conducted in the BVS, Embase, PubMed, and ScienceDirect databases, where 4138 studies were initially identified. Results: The final analysis resulted in the inclusion of 35 studies, all of which were incorporated into the meta-analysis, covering a cohort of 1313 patients. Statistical analysis was performed using R software (version 4.5.2), revealing a Complete Remission rate of 70.68% and a Minimal Residual Disease negativity rate of 76.68%. Tactical superiority was observed in the second-generation cells and in the dual CD19/CD22 target (82.20% CR). The risk of bias assessment using the ROBINS-I tool indicated high quality for most of the studies. The certainty of evidence according to the GRADE system was classified as moderate. Adverse events such as cytokine release syndrome (46.81%) and neurotoxicity (23.52%) were frequent but reversible. Conclusions: We thus observe that CAR-T therapy is an effective strategic bridge to bone marrow transplantation, with advances in cell persistence being fundamental for sustained cure. Full article

Immunotherapies, including chimeric antigen receptor (CAR) T cells, bispecific T-cell engagers (BiTEs), and antibody–drug conjugates (ADCs), have revolutionized the treatment landscape for multiple myeloma (MM). Despite robust initial response rates, achieving durable remissions remains challenging due to frequent relapses driven by complex therapeutic resistance mechanisms. In this review, we comprehensively examine intrinsic tumor resistance, such as innate and acquired antigen escape mediated by genomic alterations, structural variations, and epigenetic silencing. Furthermore, we highlight the critical role of the highly permissive bone marrow microenvironment in blunting the efficacy of modern therapies. Cellular compartments, including mesenchymal stromal cells, osteoclasts, and expanded immunosuppressive immune populations, actively foster tumor survival, promote metabolic competition, and T-cell exhaustion. We also review the unique clinical toxicities associated with T-cell-redirecting modalities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Ultimately, deciphering the complex interplay between malignant plasma cells and their surrounding microenvironment is essential for optimizing treatment sequencing, preventing effector cell exhaustion, and designing next-generation therapeutic strategies to secure long-term, durable responses for patients. Full article

Background: Chimeric antigen receptor (CAR) T-cell therapy has transformed haematological-malignancy care, but its dermatologic safety profile remains incompletely characterised across products and indications. Methods: We analysed 8,431,841 deduplicated FDA Adverse Event Reporting System reports from 2016 Q3 to 2026 Q1. Seven approved CAR T-cell products were identified. The primary outcome was any dermatologic adverse event, defined using the MedDRA Skin and subcutaneous tissue disorders system organ class. Secondary outcomes included broad severe cutaneous adverse reactions, narrow Stevens-Johnson syndrome/toxic epidermal necrolysis, and 14 phenotype-specific categories. Multivariable models adjusted for demographics, polypharmacy, cancer, immune checkpoint inhibitor exposure, lymphodepleting chemotherapy and cytokine release syndrome. Additional sensitivity analyses evaluated HSCT/GVHD co-reporting proxies, infection and cytopenia/bleeding proxies, severe-event clinical characteristics, comparator robustness and multiplicity correction. Results: Dermatologic adverse events were identified in 996,654 reports, including 425 CAR-T-associated cases. CAR T-cell exposure was associated with reduced adjusted reporting odds for the primary outcome (adjusted odds ratio 0.13, 95% confidence interval 0.09–0.20) and broad severe cutaneous adverse reactions (0.35, 0.23–0.52). The primary SKIN_ANY reduced-reporting pattern was consistent across all-FAERS, haematological-malignancy and active haematology-oncology comparators. HSCT/GVHD proxy co-reporting was uncommon and did not materially alter estimates. Severe dermatologic reports frequently co-mentioned CRS and serious outcomes. The tisagenlecleucel vascular cutaneous signal was nominally significant but attenuated after excluding infection-attributable and cytopenia/bleeding-proxy reports. Conclusions: Within spontaneous reporting systems, CAR T-cell therapy showed reduced relative reporting of dermatologic adverse events across broad, phenotype-specific and product-level analyses. These results should be interpreted as differences in reporting behaviour, not as evidence of reduced true clinical incidence or lower patient-level risk. Early severe cutaneous reports frequently overlapped with cytokine release syndrome, while infection, cytopenia/bleeding proxies and supportive-care drugs were important alternative explanations for selected cutaneous signals. Full article

Background: Chimeric antigen receptor T-cell (CAR-T) therapies have transformed the treatment of haematologic malignancies, yet their adverse event (AE) profiles across all approved agents have not been consolidated using a pharmacovigilance methodology in a single comparative analysis. Methods: Using the FDA Adverse Events Reporting System (FAERS) and OpenVigil 2.1, disproportionality analyses for all six FDA-approved CAR-T therapies were performed, stratified by target antigen: anti-CD19 agents (axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, brexucabtagene autoleucel) and anti-BCMA agents (idecabtagene vicleucel, ciltacabtagene autoleucel). For each of the 25 most frequently reported AEs per agent, the report event counts, reporting odds ratio (ROR) with 95% confidence interval, proportional reporting ratio (PRR), and chi-squared statistic were calculated. Results: A total of 36,567 AEs were identified across all six agents. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were the most frequent and most disproportionate AEs across all six therapies, with RORs exceeding 240 in every agent. Idecabtagene vicleucel had the highest ROR for cytokine release syndrome among all agents (ROR 1934.6), while brexucabtagene autoleucel had the highest ROR for immune effector cell-associated neurotoxicity syndrome (ROR 2089.6). Ciltacabtagene autoleucel exhibited a unique neurological toxicity profile, cranial nerve paralysis (ROR 3167.6, PRR 3055.0, chi² 199,190), parkinsonism (ROR 145.5, PRR 136.6, chi² 24,840), Bell’s palsy (ROR 380.4, PRR 370.3), and facial paralysis (ROR 72.7), consistent with the late neurotoxicity syndrome previously characterized, and absent from other agents’ top 25 AE lists. Brexucabtagene autoleucel demonstrated secondary malignancy signals including squamous cell carcinoma of skin (ROR 308.2) and myelodysplastic syndrome (ROR 97.9). Tisagenlecleucel showed the highest hypogammaglobulinemia signal among all agents (ROR 614.1, PRR 536.5, chi² 144,832) alongside a broad pancytopenia profile. Hemophagocytic lymphohistiocytosis was a significant finding with ciltacabtagene autoleucel (ROR 71.0) and brexucabtagene autoleucel (ROR 57.8). Conclusions: CAR-T therapies share class-wide toxicities in cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, but exhibit clinically important drug-specific and target-class-specific AE profiles. This consolidated FAERS-based analysis corroborates and extends prior pharmacovigilance work by providing direct cross-agent comparisons, and supports the use of agent-tailored monitoring strategies, particularly for the distinctive late neurological toxicity associated with ciltacabtagene autoleucel. Full article

B-cell maturation antigen (BCMA), G protein-coupled receptor class C group 5 member D (GPRC5D)-directed immunotherapies, chimeric antigen receptor T-cell (CAR-T) products, bispecific T-cell engagers (BsAbs), and antibody–drug conjugates (ADCs), have transformed the management of MM. Their adoption is now extending beyond tertiary centers following FDA modifications for CAR-T safety and the rapid uptake of off-the-shelf bispecifics suitable for community delivery. Clinicians outside specialist hubs must therefore be conversant with the full toxicity spectrum, including rare but high-consequence events, both for informed consent and for the work-up of post-therapy complications. In this narrative review, we report on the published literature around toxicities of approved and investigational BCMA- and GPRC5D-directed therapies, drawing on pivotal trial data, real-world cohorts, pharmacovigilance studies, and consensus management recommendations, with emphasis on practical recognition and risk mitigation. This review presents toxicities by a temporal pattern including acute (CRS, ICANS, infection, ocular, mucocutaneous), subacute (cranial nerve palsies, parkinsonism, myelitis, peripheral neuropathies IEC-associated enterocolitis and cardiovascular events), and long-term (prolonged cytopenias, second primary malignancies). We discuss validated risk stratification tools, such as the CAR-HEMATOTOX score, EASIX index, and multidisciplinary geriatric assessment, which predicts severe ICANS, infection, and resource utilization, supporting individualized pre-treatment planning. Safe delivery of immune therapies in community settings requires infrastructure for acute critical care, neurology, ophthalmology, infectious disease and long-term surveillance, but is achievable when paired with validated risk stratification and clear referral pathways. Full article

Background: BCMA-targeted Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of Relapsed/Refractory Multiple Myeloma (RRMM). However, the disease is not curable and progression after CAR T-cell treatment remains a challenge. Clonal hematopoiesis, specifically mutations in the DNA damage response gene PPM1D, has been linked to therapy resistance and inferior survival in lymphoma patients undergoing cellular therapy. The impact of PPM1D mutations on MM patient outcome after CAR T-cell therapy remains undefined. Methods: We conducted a retrospective single-center study of 83 patients with RRMM patients treated with idecabtagene vicleucel or ciltacabtagene autoleucel between 2022 and 2025. Next-generation sequencing was performed on peripheral blood mononuclear cells collected prior to CAR T-cell infusion to identify PPM1D exon 6 mutations (variant allele frequency > 0.01). We analyzed associations between mutational status, clinical characteristics, toxicity, and survival. Results: PPM1D mutations were detected in 14.5% (12/83) of patients. PPM1D-mutated patients had fewer prior autologous stem cell transplantation compared to wild-type patients (50% vs. 82%, p = 0.02) and presented more advanced disease burden and adverse prognostic features (R-ISS stage III 58% vs. 20%, p = 0.05). Notably, PPM1D status did not impact initial efficacy; complete remission rates were comparable between groups (67% vs. 69%). However, PPM1D mutations were significantly associated with inferior progression-free survival (PFS) (median PFS: 6 months vs. 16 months, p = 0.04). Regarding toxicity, the mutated subgroup exhibited significantly higher rates of grade ≥2 cytokine release syndrome and a trend toward increased neurotoxicity (25% vs. 7%). Conclusions: PPM1D clonal hematopoiesis is frequent in RRMM and despite deep initial responses, patients harboring PPM1D mutations face a significantly higher risk of early relapse. PPM1D mutations may serve as a biomarker for poor durability of response and should be further evaluated in larger, prospective trials. Full article

Background/Objectives: Lisocabtagene maraleucel (liso-cel) is a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy approved for relapsed or refractory large B-cell lymphoma (R/R LBCL). However, most published meta-analyses of CAR-T therapy in LBCL pool data across products, limiting product-specific interpretation. Methods: We conducted a systematic review and meta-analysis of clinical trials and retrospective real-world studies evaluating liso-cel monotherapy in R/R LBCL. The primary endpoint was the overall response rate (ORR). Secondary endpoints included complete response (CR), incidence of grade ≥ 3 adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), overall mortality rate (OMR), disease progression-related mortality, and adverse event-related mortality. Pooled proportions were estimated using random-effects models. Results: Eleven studies including 1206 patients were analyzed, comprising five clinical trials and six real-world retrospective cohorts. The pooled ORR was 78%, and the pooled CR rate was 60%. The pooled OMR was 38%, with a disease progression-related mortality of 28% and an adverse event-related mortality of 4%. Severe (grade ≥ 3) CRS and ICANS occurred in 2% and 8%, respectively. Severe (grade ≥ 3) hematologic toxicities were frequent, particularly neutropenia, thrombocytopenia, and anemia. Conclusions: Liso-cel monotherapy demonstrated high pooled response rates and low pooled incidences of severe CRS and ICANS across clinical trials and real-world settings in R/R LBCL. Severe ICANS, although uncommon, remains clinically meaningful, and severe hematologic toxicities were frequent and warrant careful monitoring and supportive care. These findings provide product-specific benchmarks for liso-cel in R/R LBCL. Full article

Medulloblastoma is one of the most prevalent pediatric brain tumors. Currently, existing therapies for this devastating type of cancer can only prolong survival time with severe side-effects and relapse. These therapies are not curative for almost a third of treated patients, while most survivors are condemned to a poor quality of life. The addition of immune checkpoint inhibitors (ICIs) to immune therapy has given some hope to those suffering from this type of cancer. Although ICIs provide a valuable contribution to immunotherapy, the exploitation of immune checkpoint inhibition within existing therapeutic strategies to cure Medulloblastoma remains understudied. However, the identification of the main molecular subgroups of medulloblastoma is considered one of the success stories of oncology. This advancement in molecular profiling of MB paved the way to subgroup-directed clinical trials, which may lead to efficacious immune-targeted therapy. However, this relatively new development is still hampered by a substantial biological heterogeneity of the disease and the absence of a full understanding of the various mechanisms behind its resistance to existing therapeutic modalities. The inclusion of chimeric antigen receptor (CAR) T and CAR NK cell therapy within various therapeutic strategies and ongoing clinical trials has given fresh hope those suffering from this fatal disease. However, ongoing clinical trials suggest that this highly promising therapy can be impaired by a number of serious limitations, including cytokine release syndrome, Graft-versus-host disease, the scarcity of target antigens, and severe adverse events. Some of the ongoing clinical trials also suggest that CAR NK is less prone to some of these limitations. This review also highlights the contribution of mass spectrometry-based proteomics, and the increasing role of liquid biopsy rather than tissue biopsy. Full article

Chimeric antigen receptor (CAR) T-cell therapy is a new standard of care for patients with diffuse large B-cell lymphoma (DLBCL); however, studies including healthcare resource utilization (HRU) during routine care are lacking. Accordingly, a population-based study was conducted using linked administrative databases from Ontario, Canada. Patients with DLBCL that failed ≥2 lines of systemic therapy were included. Cox proportional hazard models estimated associations between covariates and overall survival (OS). Logistic, binomial and Poisson regression explored associations between covariates with toxicity and HRU. We identified 308 patients enrolled to receive CAR T-cell therapy of which 255 patients received CAR T-cells (mean age 59 years; 39% female). From the date of CAR T-cell infusion, the median OS was 25.0 months (95% CI, 21.6–28.1 months). Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome data were available for 155 patients and were reported in 135 (87.1%) and 42 (27.1%) patients, respectively. Of those that received CAR-T cells, 172 patients (67%) were hospitalized with a median length of stay of 5 days (IQR, 0–20) and 243 (95%) had an emergency department visit without hospitalization. Our prospective population-based study demonstrates comparable efficacy and safety of CAR T-cell therapy in the real-world to the pivotal trials and highlights this as an efficacious and relatively safe treatment option for patients with DLBCL in routine clinical care. Full article

Polycystic ovary syndrome (PCOS) is frequently accompanied by visceral obesity, insulin resistance, low-grade chronic inflammation, and metabolic syndrome (MetS). These alterations promote significant dysfunction in adipose tissue and liver metabolism through cytokine production. Growing evidence indicates that the interaction between hepatokines and adipokines plays a central role in the development of metabolic and hepatic abnormalities in women with PCOS. This narrative review was conducted to analyze the relationship between adipose tissue dysfunction and liver metabolic impairment in women with PCOS, emphasizing the involvement of hepatokines and adipokines in insulin resistance, inflammation, hepatic steatosis, hepatic fibrosis and MetS. From this perspective, contemporary clinical, biochemical, and molecular studies were reviewed to evaluate how adipocyte-derived factors and hepatocyte-derived cytokines influence metabolic homeostasis in the liver and adipose tissue in women with PCOS. Increased visceral adiposity in PCOS enhances the release of free fatty acids (FFAs) to the liver, resulting in hepatotoxicity, oxidative stress, and hepatic inflammation. Several hepatokines, including fetuin-A, angiopoietin-like protein 3 (ANGPTL3), selenoprotein P(Sep-P), and hepassocin (HPS), show abnormal circulating levels in PCOS and are strongly associated with insulin resistance, dyslipidemia, and progression to hepatic steatosis. In contrast, fibroblast growth factor 21 (FGF-21), follistatin, and interleukin (IL-6) may exert dual effects. Adipokines, such as resistin, visfatin, apelin, and retinol-binding protein 4 (RBP-4), contribute to chronic inflammation, impaired glucose metabolism, androgen excess, and hepatic steatosis and fibrosis. Some of these adipokines, such as leptin and vaspin, may exert both beneficial and detrimental effects, while others, including chemerin and omentin, appear to play predominantly beneficial roles in metabolism. Reduced adiponectin-to-leptin levels further aggravate metabolic dysfunction. These changes indicate that adipose tissue–liver crosstalk is a key mechanism linking PCOS and MetS. Overall, metabolic disturbances in PCOS are strongly mediated by dysregulated communication between adipose tissue and the liver. Altered hepatokine and adipokine profiles contribute to insulin resistance, liver dysfunction, hypertension and the development of MetS in women with PCOS. Understanding these intricate interactions may support the early identification of high-risk patients and the development of targeted therapeutic strategies. Full article

(1) Background: Cognitive dysfunction represents an emerging concern in chimeric antigen receptor T-cell (CAR-T) therapy recipients, yet longitudinal data using simple, clinically applicable tools are lacking. (2) Methods: We conducted a single-center prospective cohort study of consecutive adults with hematologic malignancies treated with commercially available CAR-T cell products between May 2023 and November 2025 at our center. Cognitive function was evaluated with the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) at baseline (before the administration of lymphodepleting chemotherapy) (T1), 6 h after infusion (T2), at 3 months (T3), and at 6 months (T4). MoCA scores ≤ 25 and/or MMSE scores ≤ 23 were considered indicative of impaired cognitive function. (3) Results: Thirty-six patients were enrolled in the present study, while cytokine release syndrome occurred in 33/36 patients (91.7%), and immune effector cell-associated neurotoxicity syndrome of any grade occurred in 23/36 (63.9%). At baseline (T1), cognitive impairment was identified in 12/36 patients (33.3%) by MoCA. Following infusion (T2), 11/35 (31.4%) exhibited cognitive impairment, while baseline cognitive impairment and older age were associated with early post-infusion cognitive dysfunction. Across follow-up (T3 and T4), no significant overall changes were observed in MoCA- or MMSE-defined cognitive status or in total test scores. However, abstraction in MoCA and attention/calculation in MMSE showed time-dependent variation. (4) Conclusions: These findings support the use of simple longitudinal cognitive assessment in CAR-T recipients. Full article

Background and Objectives: Relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHL) remain associated with poor outcomes despite advances in chemoimmunotherapy and chimeric antigen receptor (CAR) T-cell therapy. Many patients are ineligible for or relapse after cellular therapies, highlighting the need for effective off-the-shelf immunotherapeutic approaches. CD20 × CD3 bispecific antibodies (BsAbs) redirect endogenous T cells against malignant B cells and have emerged as a promising therapeutic class in B-NHL. To summarize current clinical evidence regarding mosunetuzumab, glofitamab, epcoritamab, and odronextamab in B-NHL, focusing on efficacy, safety, and emerging therapeutic applications. Materials and Methods: A structured review of published phase I–III clinical trials evaluating the four currently approved CD20 × CD3 BsAbs in B-NHL was conducted. Efficacy outcomes, durability of response, and safety data were assessed across indolent and aggressive lymphoma subtypes. Results: CD20 × CD3 BsAbs demonstrated substantial and durable clinical activity in heavily pretreated B-NHL, including patients with prior CAR T-cell exposure. Mosunetuzumab showed high response rates and durable remissions in follicular lymphoma (FL), while glofitamab demonstrated significant efficacy in aggressive lymphomas, particularly diffuse large B-cell lymphoma (DLBCL). Epcoritamab exhibited consistent activity across lymphoma subtypes with favorable tolerability supported by subcutaneous administration and step-up dosing. Odronextamab also demonstrated clinically meaningful responses in both FL and DLBCL, including high-risk populations. Across studies, cytokine release syndrome (CRS) was the most common adverse event, predominantly low grade and manageable with established mitigation strategies. Immune effector cell-associated neurotoxicity syndrome (ICANS) was uncommon. Infections and hematologic toxicities, particularly neutropenia, represented clinically relevant adverse events across all treatment programs, highlighting the need for special supportive care. Conclusions: CD20 × CD3 BsAbs represent a major therapeutic advancement in R/R B-NHL, combining high clinical activity, manageable toxicity, and off-the-shelf availability. Their expanding integration into earlier treatment settings and combination strategies is expected to further reshape the therapeutic landscape of B-NHL. Full article

This translational synthesis highlights the potential role of obesity-induced low-grade chronic inflammation in modulating clinical outcomes among patients with spondyloarthritis (SpA). Obesity transforms adipose tissue into a pro-inflammatory endocrine organ, where hypertrophic adipocytes release adipokines such as leptin alongside cytokines including TNF-α and IL-6, potentially contributing to macrophage polarization toward an M1 phenotype and activating NF-κB signaling pathways. This systemic immunometabolic priming may lower activation thresholds at the enthesis—the primary pathological site in SpA—potentially amplifying IL-23/IL-17 axis activity via Th17 bias, innate-like lymphocyte responses, and stromal–immune crosstalk under mechanical stress. Clinically, patients with SpA and obesity have been reported to demonstrate heightened disease activity (BASDAI, ASDAS), impaired function (BASFI), accelerated radiographic progression (syndesmophytes, enthesophytes), and diminished biologic response rates, potentially attributable to pharmacokinetic alterations (e.g., subtherapeutic TNF inhibitor levels) and pharmacodynamic resistance. Multisystem comorbidities, including non-alcoholic fatty liver disease, cardiovascular events, metabolic syndrome, sleep disturbances, and depression, further exacerbate morbidity and diminish quality of life. Therapeutic implications emphasize obesity as a modifiable disease modifier. Weight loss interventions, including hypocaloric diets, anti-inflammatory regimens (e.g., Mediterranean diet), multicomponent exercise, GLP-1 receptor agonists, and bariatric surgery, have been associated with reductions in inflammatory biomarkers, improved remission rates (MDA, DAPSA), and prolonged drug survival by restoring adipokine balance and disrupting mechano-inflammatory loops. Future randomized controlled trials should prioritize long-term evaluations of integrated multidisciplinary strategies that combine metabolic optimization with immunomodulatory therapies, addressing adherence challenges through psychological support and patient-tailored protocols, while elucidating dose–response relationships for GLP-1RAs and exercise in diverse SpA subtypes to establish precision management paradigms that mitigate cardiometabolic burden and improve holistic outcomes. Full article