Sylvant (siltuximab) / BeOne Medicines, Jazz - LARVOL DELTA

Phase 1 evaluation of the safety and efficacy of rapcabtagene autoleucel (YTB323) in adult patients with Relapsed/Refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) (ASH 2025) - P1/2 | "Sixteen pts (46%) were previously treated with blinatumomaband 13 pts (37%) with inotuzumab...CRS management includedtocilizumab (70%), siltuximab (10%), corticosteroids (40%), tocilizumab plus corticosteroids (37%), andanakinra (7%)...Seven pts received supportive measures for ICANS,including dexamethasone (5 pts, 71%) and anakinra (3 pts, 43%)... Phase 1 results with long follow-up suggest rapcabtagene autoleucel is active with highcellular expansion, durable efficacy for DL2–DL4, and a manageable safety profile in adult pts with r/r B-ALL. DL3—at which 92% of pts achieved BOR of CR/CRi by 3 mo, with median DOR not reached after 22mo median follow-up—exhibited an acceptable balance of safety, efficacy, and cellular expansion."

Clinical • P1 data • Acute Lymphocytic Leukemia • Aplastic Anemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Leukemia • Neutropenia • Rare Diseases

Evolving idiopathic multicentric Castleman disease with thrombocytopenia, anasarca, fever/hyperinflammation, renal dysfunction and organomegaly presenting with severe hypoalbuminaemia, serositis and bicytopenia before lymphadenopathy. (PubMed, BMJ Case Rep) - "Treatment with corticosteroids and siltuximab was followed by clinical and biochemical improvement. This case illustrates how TAFRO syndrome may become recognisable before lymphadenopathy makes Castleman disease an obvious consideration."

Journal • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammation • Nephrology • Oncology • Rare Diseases • Renal Disease • Thrombocytopenia

A Proof-of-Principle of Split-Course Bridging Radiotherapy (SC-BRT) Prior to CAR T-Cell Therapies for Relapsed or Refractory B-Cell Lymphomas: A Phase 1a Pilot Cohort (ASH 2024) - P1 | "The feasibility outcome was achieved, as all pts successfully received SC-BRT and standard cyclophosphamide/fludarabine LD followed by commercial lisocabtagene maraleucel (n=4) or axicabtagene ciloleucel (n=2)...One patient was treated with steroids and tocilizumab for mild CRS and the patient with grade 5 CRS received steroids, tocilizumab and siltuximab but expired on day +6...This is the first reported delivery of any form of RT following administration of LD chemotherapy potentially opening the door for novel CART conditioning approaches. Given successful completion of Phase 1a, 14 additional patients are now being recruited to the Phase 1b expansion cohort (9 already accrued, data not presented) to confirm safety, assess preliminary outcomes and explore possible immune augmentation."

CAR T-Cell Therapy • P1 data • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • PTPRC

Interleukin-6 in hemolytic anemias: from inflammatory pathways to therapeutic targeting. (PubMed, Front Immunol) - "Current clinical evidence remains limited, but IL-6-directed therapy may be rational in selected refractory immune-mediated or macrophage-activation-associated hemolytic disorders. Future studies should prioritize mechanism-based biomarkers and prospective, biomarker-stratified trials."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hematological Disorders • Immunology • Inflammation • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Sickle Cell Disease • Thrombosis • IL6

Safety and Immunomodulatory Effects of Siltuximab Prophylaxis Prior to Standard of Care CD19 Directed Chimeric Antigen Receptor T-cell (CD19.CART) Therapy for B-cell Lymphomas: Final Phase I Trial Results (TCT-ASTCT-CIBMTR 2026) - "Siltux was safe as ppx prior to CD19.CART. No gr > 3 CRS occurred and only 1 pt developed gr > 3 ICANS which rapidly resolved. ORR and CR rate were excellent and responses were durable."

CAR T-Cell Therapy • Clinical • Immunomodulating • P1 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • CNS Disorders • Epilepsy • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • B3GAT1 • CCL3 • CD8 • CXCL10 • GZMB • IFNG • IL15 • IL2 • IL7 • TNFA

Corticosteroids With or Without Interleukin 6-Directed Therapy for the Management of Immune Effector Cell–Associated Neurotoxicity Syndrome: A Meta-Analysis (SOHO 2026) - " A systematic search of PubMed, ClinicalTrials.gov, and conference proceedings (2017–2025) was performed using the terms ICANS, CAR-T, IL-6, corticosteroid, tocilizumab, siltuximab, anakinra, axicabtagene, tisagenlecleucel, and lisocabtagene. The combination of corticosteroids with tocilizumab does not significantly improve ICANS rates or severity over either strategy. Costimulatory domains remain one of the strongest predictors of ICANS toxicity. Randomized, product-stratified trials are urgently needed to define optimal ICANS-prevention protocols."

Retrospective data • Oncology • IL6 • TNFA

Phase Ib study of siltuximab and spartalizumab in advanced pancreatic cancer (AACR 2024) - P1/2 | "The combination Sil/Sparta had an acceptable safety profile but did not elicit responses in advanced PDAC pts. Correlative studies using paired biopsies and blood are ongoing to determine how dual IL-6/PD-1 blockade impacts stromal and immune biomarkers in relationship to the clinical outcome measures."

IO biomarker • Metastases • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • IL6 • PD-L1

Risk of Diverticulitis in Rheumatoid Arthritis Patients Treated With IL-6 Inhibitors Versus JAK Inhibitors: A Real-World Propensity-Matched Study (ACG 2026) - "Two mutually exclusive cohorts were defined: IL-6 inhibitor users (tocilizumab, sarilumab, siltuximab) without JAK inhibitor exposure, and JAK inhibitor users (tofacitinib, baricitinib, upadacitinib, filgotinib) without IL-6 exposure...Outcomes were assessed at 5 years, 10 years, and all follow-up after 1:1 propensity score matching for age, sex, diabetes, obesity, tobacco use, prior diverticular disease, alcohol-related disorders, NSAID, glucocorticoid, and methotrexate use... After matching, 10,459 patients remained per cohort, well-balanced (all standardized differences < =0.04). At 5 years, diverticulitis occurred in 160 IL-6 patients (1.6%) versus 146 JAK patients (1.4%): RR 1.092 (95% CI 0.874-1.365), p=0.436; HR 1.196 (0.955-1.497). At 10 years, 192 (1.9%) versus 172 (1.7%): RR 1.113 (0.907-1.365), p=0.304; HR 1.182 (0.962-1.453)."

Clinical • Real-world • Real-world evidence • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Metabolic Disorders • Obesity • Rheumatoid Arthritis • Rheumatology

Diagnostic Delays and Comparable Response Rates to iMCD-Directed Therapies in Patients With and Without Expert-Confirmed Idiopathic Multicentric Castleman Disease Diagnoses (SOHO 2026) - "Response rates to siltuximab did not significantly differ between patients with expertconfirmed and low-likelihood diagnoses (68% vs 58%; P = 0.263).Other immunomodulator and rituximab-based therapies were associated with lower response rates in both expert-confirmed and lower-likelihood diagnoses. In this registry cohort of suspected iMCD cases, substantial delays in diagnosis were common, particularly among low-likelihood cases. Core needle biopsy was associated with a need for subsequent surgical excision, thus underscoring the importance of initial excisional biopsy. Among patients with suspected iMCD in the community, response rates to iMCD-directed therapies were comparable between patients with confirmed and low-likelihood diagnoses."

Clinical • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • IL6

New Paradigms in the Management of Castleman Disease. (PubMed, J Natl Compr Canc Netw) - "In addition, the recent paradigm of CD management emphasizes early identification of refractory disease and timely escalation beyond biologic therapy. This review provides an updated overview of CD management, drawing on recent advances to discuss practical considerations in treatment selection across disease subtypes, as well as ongoing challenges and future directions."

Journal • Review • Rare Diseases • IL6

Siltuximab with Anti-PD-1 Rechallenge After Severe Immune-Related Adverse Events in Advanced Cancers: Second Interim Analysis of the CIRES Trial (ESMO 2026) - No abstract available

Adverse events • Metastases • Oncology

Population Pharmacokinetic Model-Based Melphalan Dosing with Siltuximab Interleukin-6 Blockade in Older Multiple Myeloma Patients Undergoing AHCT: Phase II Run-In Results (IMS 2025) - P2 | "In this first prospective study of its kind, we demonstrate the safety and feasibility of using individualized pop PK model-based melphalan dosing to achieve a target AUC, along with IL-6 blockade to decrease symptom burden in older adults with MM undergoing AHCT. The upcoming randomized phase II portion of the study will evaluate efficacy and patient-reported outcomes compared to standard BSA-based dosing."

Clinical • Late-breaking abstract • P2 data • PK/PD data • Febrile Neutropenia • Hematological Malignancies • Mucositis • Multiple Myeloma • IL6

Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease (clinicaltrials.gov) - P2 | N=7 | Active, not recruiting | Sponsor: University of Pennsylvania | Trial completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Rare Diseases

Castleman disease: application of modern classification in a Canadian center. (PubMed, Expert Rev Clin Immunol) - "100% of iMCD-TAFRO, 100% of iMCD-IPL, and 86% of iMCD-NOS cases treated with Siltuximab or Tocilizumab had at least a partial response. This study demonstrates the heterogeneous presentation, natural history, and response to treatment of CD in a North American center, and highlights the importance of awareness of the different subtypes of CD. Key limitations are its retrospective design and small sample size."

Journal • Inflammation • Rare Diseases

Australian clinical practice guideline: diagnosis and treatment of idiopathic multicentric Castleman disease. (PubMed, Intern Med J) - "Targeting IL-6 activity forms the cornerstone of modern therapy for iMCD, with siltuximab recommended as first-line therapy. Rituximab-based regimens are recommended for second-line therapy...In the context of these substantial challenges, herein we provide a multidisciplinary Australasian clinical practice guideline to characterise clinical and pathological features, summarise treatment pathways and discuss clinical outcomes of the condition. The objective is to develop a multidisciplinary clinical practice guideline in the diagnosis and management of iMCD in Australia."

Clinical guideline • Journal • Rare Diseases • IL6

Diagnostic delay and histopathological subtyping challenges in idiopathic multicentric Castleman disease, not otherwise specified: a case report of a three-hospital odyssey. (PubMed, Front Med (Lausanne)) - "Following treatment with siltuximab plus prednisone, the patient's symptoms improved markedly, with resolution of fever and no recurrence of submandibular or cervical lymphadenopathy. (3) Systematic exclusion of HHV-8 infection, TAFRO/IPL features, and other mimickers is mandatory for proper iMCD-NOS subtyping. Enhanced awareness of this disease, as provided by this report, may facilitate early recognition and reduce diagnostic delays."

IO biomarker • Journal • Anesthesia • Eosinophilia • Fibrosis • Hematological Disorders • Immunology • Infectious Disease • Oncology • Rare Diseases • CD38 • CRP • IL6 • SDC1

Screening Trial for Pain Relief in Schwannomatosis (STARFISH) (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Nov 2027 ➔ Nov 2028 | Trial primary completion date: Nov 2026 ➔ Nov 2027

Trial completion date • Trial primary completion date • Brain Cancer • Pain • Solid Tumor

Treating Castleman disease: insights into the use and efficacy of monoclonal antibodies. (PubMed, Expert Opin Biol Ther) - "In this review, the authors discuss evidence for mAbs in CD, focusing on siltuximab, tocilizumab, and rituximab, as well as investigational biologics beyond anti-IL-6 and CD20. However, emerging data increasingly support subtype‑specific and severity‑adapted strategies. Future progress will depend on early identification of IL-6-refractory disease, biomarker-driven treatment selection, and rational combination strategies for aggressive phenotypes such as iMCD-TAFRO."

Journal • Review • Rare Diseases • CD20

Tocilizumab but not Siltuximab prevents systemic inflammation in a humanized mouse model. (PubMed, Front Immunol) - "These findings highlight the pivotal role of IL-6 signaling in the SSc related systemic inflammation within the humanized mouse model and underscore the therapeutic potential of IL-6 receptor blockade. Furthermore, the PBMCs-based humanized mouse model offers a valuable preclinical platform for evaluating human-specific therapeutic interventions in systemic inflammation."

Journal • Preclinical • Immunology • Inflammation • Scleroderma • Systemic Sclerosis • IL6

Sustained Complete Response in Refractory Idiopathic Multicentric Castleman Disease Following a Single CD19 CAR T-Cell Infusion: A Case Report With Mechanistic Insight. (PubMed, Hematol Oncol) - P=N/A | "Idiopathic multicentric Castleman disease (iMCD) is rare and life-threatening; although siltuximab is standard first-line therapy, a substantial proportion of patients are refractory or experience relapse...After fludarabine/cyclophosphamide lymphodepletion, she received 1 × 106 CAR + T cells/kg of autologous CD19 CAR T cells on day 0...Panhypogammaglobulinemia was managed with intravenous immunoglobulin replacement. At > 12 months post-infusion, she remains in complete, treatment-free remission. This observation supports a B-cell-centric model for refractory iMCD-IPL and motivates prospective evaluation of CD19 CAR T-cell therapy."

Journal • Hematological Disorders • Inflammation • Rare Diseases

CASTLEMAN DISEASE-RARE CAUSE OF COLD AGGLUTININ SYNDROME (EHA 2026) - "In addition to corticosteroid treatment, we started antiCD20 treatment (rituximab) due to severe hemolysis, and he received 6 cycles. Histological examination of the lung finally confirmed plasma cell CD, and therefore , anti-IL-6 and siltuximab treatment was started in February 2025...He has received 15 cycles so far, and a control chest CT confirmed regression. Summary/Conclusion The association between cold-type AIHA and CD is rare, and in our case we would like to highlight the diagnostic challenges of cold agglutinin syndrome."

Autoimmune Hemolytic Anemia • Chronic Cough • Cough • Eosinophilia • Immunology • Infectious Disease • Rare Diseases • Renal Disease • Respiratory Diseases

Successful treatment of idiopathic multicentric Castleman disease with TAFRO and kidney involvement: case report and literature review. (PubMed, Ren Fail) - "Although the exact etiology of iMCD-TAFRO is unknown, interleukin (IL)-6 has been identified as a critical pathological driver, and the IL-6 antagonist siltuximab is recommended as first-line treatment...We also present and discuss a case report of a patient with iMCD-TAFRO and acute kidney failure. Our aim is to draw attention to the spectrum of kidney involvement in iMCD-TAFRO, as well as raise awareness to the importance of early recognition and appropriate treatment of this rare condition."

Journal • Review • Acute Kidney Injury • Hematological Disorders • Myelofibrosis • Nephrology • Rare Diseases • Renal Disease • Respiratory Diseases • Rheumatology • Thrombocytopenia • IL6

MIF/MTOR PATHWAY DRIVES INFLAMMATION IN IMCD WITH ANA POSITIVITY PRONE TO SEVERE DISEASE AND WORSE PROGNOSIS (EHA 2026) - "Additionally, after the treatment of Siltuximab, MIF still existed to activate the PI3K-Akt-mTOR pathway, and mTOR showed higher expression, which underlined the approval of mTOR inhibitor, such as rapamycin for iMCD after Siltuximab treatment. (C) Expression level of cytokines in Plasma cell of iMCD patients with ANA positivity or not and AID. (D) mTOR expression of healthy donor (HD) and iMCD patients with ANA positivity before and after treatment."

Immunology • Inflammation • Rare Diseases • IL6 • MIF

IMMUNE EFFECTOR CELL–ASSOCIATED HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS FOLLOWING CAR T-CELL THERAPY: RESULTS OF A SINGLE-CENTER REAL-WORLD ANALYSIS (EHA 2026) - "CAR-T-cell products infused were ciltacabtagene autoleucel (cilta-cel) (4/14)), idecabtagene vicleucel (3/14), axicabtagene ciloleucel (axi-cel) (3/14), brexucabtagene autoleucel (2/14), tisagenlecleucel (1/14) and lisocabtagen maraleucel (1/14)...Treatment consisted primarily of corticosteroids (12/14) and anakinra (12/14). Refractory pts received intravenous immunoglobulin (5/14), tocilizumab (3/14), siltuximab (1/14), ruxolitinib (1/14), emapalumab (1/14), or etoposide (1/14)...Despite intensive immunosuppressive therapy, outcomes remain poor. Early biomarker-driven identification and multicenter studies are needed to improve diagnosis and management of IEC-HLH pts."

CAR T-Cell Therapy • Clinical • IO biomarker • Real-world • Real-world evidence • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hepatology • Immunology • Infectious Disease • Influenza • Liver Failure • Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma • Neutropenia • Rare Diseases • Respiratory Diseases • Septic Shock • Thrombocytopenia

SILTUXIMAB PROPHYLAXIS FOR CYTOKINE RELEASE SYNDROME (CRS) AND IMMUNE EFFECTOR CELL–ASSOCIATED NEUROTOXICITY SYNDROME (ICANS): REAL-WORLD EVIDENCE (RWE) (EHA 2026) - "Tocilizumab remains standard for CRS, corticosteroids for ICANS, and anakinra is increasingly incorporated for prophylaxis and treatment of ICANS (and CRS) (Park et al, 2023)...Methods We conducted a retrospective analysis of patients with B-cell non-Hodgkin lymphoma (B-NHL, n=23) and B-cell acute lymphoblastic leukemia (B-ALL, n=1) treated with anti-CD19 CAR T-cells (20 axi-cel, 2 brexu-cel, 1 tisa-cel, 1 zamto-cel) (October 2022 - November 2025)...These findings are consistent with results from the phase I siltuximab study (Denlinger et al, 2025). Our data warrants further exploration of siltuximab as a prophylactic agent for CRS and ICANS in CAR T- cell therapy."

Clinical • Cytokine release syndrome • HEOR • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Infectious Disease • Inflammation • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • IL6