Gamifant (emapalumab-lzsg) / SOBI - LARVOL DELTA

IFN-γ driven hepatic injury exacerbates mortality in NK/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis (ASH 2025) - "Both patients achieved rapid liver function recovery following a targeted regimen combining chemotherapy and emapalumab, a human anti-IFN-γ monoclonal antibody approved for primary HLH. The GSD index emerges as a robust prognostic tool for NK/T-HLH patients with hepatic dysfunction, reflecting underlying IFN-γ-mediated immunopathology. Early intervention with anti-IFN-γ monoclonal antibody may improve clinical outcomes in this high-risk subgroup."

Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hepatology • Immunology • Liver Failure • Lymphoma • Natural Killer/T-cell Lymphoma • Rare Diseases • T Cell Non-Hodgkin Lymphoma • IFNG • IL10

Emapalumab induces rapid, durable responses and reliable bridging to curative HSCT in patients with primary HLH: Pooled analysis of prospective trials NI-0501-04, NI-0501-05 and NI-0501-09 (ASH 2025) - "This pooled post-hoc analysis from 3 different prospective clinical trials confirms thatemapalumab, through IFNγ activity neutralization, delivers rapid and durable responses, enablessubstantial GC tapering and secures HSCT or ≥3 months survival in >80% of patients with pHLH. Thesefindings reinforce and extend previously published evidence of emapalumab's efficacy and clinical utilityas a well-tolerated bridge to curative HSCT in this difficult-to-treat population of children with a highmortality rate (Locatelli 2020, 2025; Jordan et al. 2023)."

Retrospective data • Bone Marrow Transplantation • Hemophagocytic lymphohistiocytosis • Immunology • Inflammation • Rare Diseases • IFNG

Increased age-adjusted mortality rates from hemophagocytic lymphohistiocytosis (HLH), 2010-2023 (ASH 2025) - "Although treatment options haveexpanded to include etoposide, anakinra, emapalumab, ruxolitinib and intravenous immunoglobulintherapy, and sometimes cyclosporins in patients with an autoimmune trigger, known as macrophageactivation syndrome (MAS), secondary HLH itself remains underdiagnosed (Henter, 2025). There was a nearly linear increase in the AAMR per 1,000,000 from HLH between 2010 and2023. We compared this to the rest of the D76 cluster, which demonstrated a significant increase inAAMR over the same time period. GvHD did not demonstrate any consistent pattern over the years thatwere available."

Graft versus Host Disease • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Langerhans Cell Histiocytosis • Rare Diseases • PER1

CXCL9 is a predictive biomarker of survival with IFNγ-targeted therapy in adult HLH patients (ASH 2025) - "All pts received prior corticosteroids and39% received prior etoposide. Time from admission to initiation of IFNγ-targeted therapywas similar between pts with no CXCL9 testing (13 days), low CXCL9 (17 days), and high CXCL9 (10 days).CONCLUSIONAdult HLH patients with high CXCL9 levels—indicative of IFNγ-driven hyperinflammation—demonstratedimproved OS with emapalumab and/or ruxolitinib compared to those with low CXCL9 levels or withoutCXCL9 testing. These findings support CXCL9 as a clinically relevant biomarker in adult HLH whenconsidering IFNγ-targeted therapy."

Biomarker • Clinical • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Rare Diseases • Rheumatology • CXCL9 • IFNG • IL2RA

Use of emapalumab is associated with rapid and sustained benefits in primary HLH subgroups, including CNS involvement and previously untreated patients: Pooled analysis of prospective trials NI-0501-04, NI-0501-05 and NI-0501-09 (ASH 2025) - "Emapalumab provides substantial efficacy across pHLH subgroups. Despite slower CRkinetics, a high proportion of CNS-positive patients responded and reached HSCT or maintained durableresponse. Outcomes were equally robust in previously untreated and previously treated cohorts,supporting emapalumab's efficacy both as a first-line or second-line therapy."

Retrospective data • Bone Marrow Transplantation • CNS Disorders • Hemophagocytic lymphohistiocytosis • IFNG

Real-world outcomes of immune effector cell-associated hemophagocytic syndrome (IEC-HS) following ide-cel and cilta-cel therapy in relapsed/refractory multiple myeloma (ASH 2025) - "Some variables, such as splenomegaly andcoagulopathy, were not systematically collected.Nearly all pts received pharmacologic intervention: corticosteroids (94%, n=59), anakinra (76%, n=48),tocilizumab (71%, n=45), emapalumab (13%, n=8), ruxolitinib (16%, n=10), or etoposide (3%, n=2). IEC-HS is an uncommon but severe and early complication after CAR T-cell therapy for RRMM. Despitesimilar ORRs with or without IEC-HS, IEC-HS was associated with significantly worse PFS and OS for bothide-cel and cilta-cel. These findings support the need for vigilant monitoring and potential preemptivetreatment strategies to better manage this syndrome."

Clinical • Real-world • Real-world evidence • Dyslipidemia • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hepatology • Hypertriglyceridemia • Infectious Disease • Multiple Myeloma • Nephrology • Renal Disease • IL2RA

A novel spontaneous HLH mouse model by engrafting human HSCs into b-ndg MGMT3 mice (ASH 2025) - "First-line therapy (etoposide + dexamethasone) has significant toxicity, and refractory casesrequire costly biologics like emapalumab (anti-IFNγ). The B-NDG MGMT3 mice exhibits hallmark HLH features: cytopenias (erythrocytes/platelets),reticulocytosis, tissue-infiltrating T cells/macrophages, and hemophagocytosis with hemosiderindeposition. This mouse model faithfully recapitulates human HLH pathophysiology and is ideal forevaluating novel therapeutics. Its flexibility enables modeling of secondary HLH (e.g., via EBV infection) toinvestigate context-specific mechanisms and treatments."

Preclinical • Epstein-Barr Virus Infections • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Rare Diseases • CD68 • CSF2 • IFNG • PRF1 • PTPRC • UNC13D

Sobi to Showcase Scientific advances and Commitment to Haematology at ASH 2025 (PRNewswire) - "Sobi's innovative portfolio including data from efanesoctocog alfa, pegcetacoplan, avatrombopag, emapalumab, and pacritinib....Overview of treatment advances with complement Inhibitors in patients with Paroxysmal Nocturnal Haemoglobinuria; Optimising PNH treatment with the complement inhibitor Pegcetacoplan: A case report; User experience with Pegcetacoplan on-body Injector in patients with Paroxysmal Nocturnal Hemoglobinuria."

Clinical data • Aplastic Anemia • Chronic Myelomonocytic Leukemia • Hemophagocytic lymphohistiocytosis • Hemophilia A • Immune Thrombocytopenic Purpura • Myelofibrosis • Paroxysmal Nocturnal Hemoglobinuria

Emapalumab use in malignancy-associated hemophagocytic lymphohistiocytosis in the United States: The REAL-HLH study. (PubMed, Blood Adv) - "In conclusion, emapalumab-containing regimens improved or normalized most laboratory parameters in patients with mHLH. Future studies are warranted to establish appropriate emapalumab dosing and utility in this high-risk population."

Journal • Critical care • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Oncology • Rare Diseases • CXCL9 • IFNG

Managing Treatment-Emergent Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome Following CAR-T Cell Therapy: A Case-Based Review of the use of Emapalumab. (PubMed, Hematol Oncol) - "This paper presents a case of a 56-year-old woman with relapsed mantle cell lymphoma (MCL) treated with the CAR-T cell therapy, brexucabtagene autoleucel, who had subsequently developed CRS and later IEC-HS. Initial management included tocilizumab, corticosteroids, and anakinra, followed by the compassionate use of emapalumab, an interferon-γ blocker...Vigilant monitoring and tailored therapeutic approaches are required to effectively manage toxicities associated with CAR-T cell therapy, to maximize its benefits and minimize adverse effects. In more severe IEC-HS cases, emapalumab may be used as an effective targeted therapy."

Journal • Review • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Lymphoma • Mantle Cell Lymphoma • Oncology • Rare Diseases • IFNG

Pharmacological and non-pharmacological treatments for refractory paediatric Still's disease: a scoping review. (PubMed, Rheumatol Adv Pract) - "Various treatment strategies are reported in refractory Still's, including emapalumab, JAK inhibitors, rituximab and combination biologics, although the evidence base is currently limited. Consistent outcome reporting and innovative trial designs are required to provide further evidence in these challenging subgroups."

Journal • Review • Idiopathic Arthritis • Immunology • Interstitial Lung Disease • Pediatrics • Pulmonary Disease • Respiratory Diseases • Rheumatology • Transplantation • IFNG • IL6

Full recovery with left ventricular unloading via venoarterial extracorporeal membrane oxygenation and use of emapalumab in severe metapnomovirus myocarditis presenting with cardiogenic shock. (PubMed, Cardiol Young) - "Despite mechanical ventilation, inotropic support, and initial immunomodulatory therapy with intravenous immunoglobulin, high-dose methylprednisolone, and anakinra, the patient's clinical condition deteriorated rapidly, requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO) within the first 12 hours of admission. By day 12 of ECMO support, biventricular systolic function had normalized, and the patient was successfully weaned and discharged with full recovery. This case underscores the importance of early recognition, advanced immunomodulation, and effective ventricular unloading in managing fulminant hMPV myocarditis in children."

Journal • Cardiovascular • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Pediatrics • IFNG

Emapalumab Treatment For Anticipated Clinical Benefit In Sepsis Driven By The Interferon-Gamma Endotype (The EMBRACE Trial) (clinicaltrials.gov) - P2 | N=75 | Active, not recruiting | Sponsor: Hellenic Institute for the Study of Sepsis | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Septic Shock

Emapalumab as a Life-Saving Therapy for Macrophage Activation Syndrome in Refractory Systemic Juvenile Idiopathic Arthritis with Trisomy 21. (PubMed, Turk Arch Pediatr) - No abstract available

Journal • Idiopathic Arthritis • Immunology • Rheumatology

Hemophagocytic Lymphohistiocytosis (HLH) in a Post-COVID-19 Infection: A Case Report (ASH 2023) - "HLH diagnosis was established, and patient was started on HLH-94 protocol with etoposide and dexamethasone. Immunosuppressive therapies with steroids, and etoposide are the conventional first-line agents based on the HLH94 protocol; however, refractory cases have been shown to respond to other immunosuppressive agents and biologics including ruxolitinib, alemtuzumab, and emapalumab. Figure 1: A. Hemophagocytosis (Macrophage ingesting lymphocyte) B. Hemophagocytosis, more specifically-erythrophagocytosis (macrophage ingesting red blood cell)."

Case report • Clinical • Acute Kidney Injury • Anemia • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hepatology • Immunology • Infectious Disease • Inflammatory Arthritis • Liver Failure • Lymphoma • Nephrology • Oncology • Rare Diseases • Renal Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Thrombocytopenia • IL2

CXCL-9 and IL-18: Potential Biomarkers for Efficacy Evaluation in Refractory Hemophagocytic Lymphohistiocytosis Treated with RED (Ruxolitinib, Emapalumab and Dexamethasone) (ASH 2024) - "We didn't observe grade 3 or higher adverse effects related to the RED regimen. This is the first comprehensive research of RED in HLH, represents a viable and safe alternative treatment for salvaging R HLH."

Biomarker • Clinical • Bone Marrow Transplantation • Hemophagocytic lymphohistiocytosis • Immunology • Inflammation • Rare Diseases • CXCL9 • IL18

Hemophagocytic Syndrome Associated with CAR-T Cell Therapy (ASH 2024) - "on the use of drugs for cell therapy-related HLH at EBMT centers, common clinical combinations include corticosteroids + chemotherapy, corticosteroids + monoclonal antibodies + chemotherapy, corticosteroids + chemotherapy + cytokine blockade, corticosteroids + cytokine blockade, and corticosteroids alone. We introduce commonly used specific medications, including etoposide, emapalumab, the IL-six monoclonal antibody siltuximab, the anti-interleukin (IL)-six receptor monoclonal antibody tocilizumab, the interleukin-1 receptor antagonist anakinra, and JAK-one and JAK-two blockers such as ruxolitinib and the JAK-one inhibitor itacitinib, among others."

CAR T-Cell Therapy • IO biomarker • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hypertriglyceridemia • Immunology • Infectious Disease • Oncology • Rare Diseases • Rheumatology • Solid Tumor • Thrombocytopenia • IFNG

CD123-CAR T Cells Manufactured in the Presence of Dasatinib Induce High Grade CRS and/or IEC-HS without Improving Efficacy in Pediatric Patients with Recurrent/Refractory Leukemia (ASH 2024) - "We previously reported (Naik et al, Blood 2022, 140 (Supplement 1) : 4584-5) that infusion of CD123-CAR T cells after lymphodepleting chemotherapy with fludarabine and cyclophosphamide was well tolerated, with transient fevers representing grade 1 cytokine release syndrome (CRS) and without dose limiting toxicities...All DL4 patients required multiple doses of immune modulatory agents including tocilizumab, steroids and emapalumab. One patient also received ruxolitinib, anakinra and etanercept without benefit, and died of cardiorespiratory failure...Our findings are in contrast with CAR.dasa T-cell products that target other antigens. While additional mechanistic studies are in progress, our results highlight that dasatinib cannot be considered a universal agent to improve the effector function of CAR T cells for hematological malignancies."

CAR T-Cell Therapy • Clinical • IO biomarker • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Leukemia • Oncology • Pediatrics • Rare Diseases • CASP3 • CASP7 • CD123 • CSF2 • ENTPD1 • HAVCR2 • IFNG • IL10 • IL3RA • IL6 • PD-1 • TNFA

Enhancing Diagnostic and Prognostic Strategies in Secondary HLH: Insights from the Weill-Cornell Medicine Experience (ASH 2024) - "The most common treatments for sHLH included HLH-94-based therapies (n=13), malignancy-directed therapies (n=8), and chemotherapy (CTx) free combinations (with or without steroids), including anakinra, emapalumab or ruxolitinib (n=21).Median follow up time was 5.3 months ([IQR], 1.3-15.1). Our findings indicate that readily available laboratory values, correlate with sIL-2R levels, a marker that predicts long term OS. Clinical scores utilizing these variables will be presented at the time of meeting and we plan to expand our cohort to further assess its utility, which could ultimately facilitate timely initiation of appropriate tx."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hodgkin Lymphoma • Immunology • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • CRP • CXCL9 • IL18 • IL2

Randomized Stepped Wedge Study of Emapalumab in APECED Enteritis (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Not yet recruiting ➔ Recruiting

Enrollment open • Candidiasis • Gastrointestinal Disorder • Immunology

Advance and perspectives of emapalumab in hemophagocytic lymphohistiocytosis treatment (PubMed, Zhonghua Er Ke Za Zhi) - No abstract available

Journal • Hemophagocytic lymphohistiocytosis • Immunology • Rare Diseases

Compassionate Use of Emapalumab in Children with Life-Threatening Disorders: Real-World Data (ASH 2023) - "3 was able to reach remission and successfully bridge to SCT without complications after only 4 doses of VP-16 with continuation therapy using only dexamethasone and emapalumab. Emapalumab is a safe, effective, and well tolerated treatment for various HLH scenarios, and for similar hyper-inflammatory medical conditions. Administration of emapalumab early in the disease course is likely to be more effective as compared to administration of the drug when MOF has occurred or when the HSC graft has already been rejected. Since these diseases are life-threatening, eliminating delays in procurement of emapalumab is essential to expedite treatment before irreversible organ failure ensues."

Clinical • Real-world • Real-world evidence • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Inflammation • Pediatrics • Rare Diseases • Septic Shock • Transplant Rejection • IFNG

CD22 CAR T Cell-Related IEC-HS Is Associated with an IFN-γ Cytokine Signature (ASH 2023) - P1 | "Patients most commonly received high-dose glucocorticoids, tocilizumab and anakinra. Additional agents for grade 4 IEC-HS included anti-thymoglobulin, dasatanib and emapalumab...The observed IFN-γ cytokine signature is consistent with myeloid cell activation and Th1 T-cell skewing that likely contributes to IEC-HS pathogenesis. These cytokines may be amenable to therapeutic intervention and further study of approaches targeting JAK/STAT and IFN-γ are warranted."

CAR T-Cell Therapy • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Large B Cell Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Rare Diseases • CD22 • CXCL10 • CXCL9 • FASLG • IFNG • IL18 • IL1B • IL6 • TNFA

Real-World Treatment Patterns and Outcomes Among Patients with Secondary Hemophagocytic Lymphohistiocytosis Treated with Emapalumab in the United States: The Real-HLH Study (ASH 2023) - P3 | "This is the first study to report real-world treatment patterns with emapalumab across a diverse patient population with sHLH. A phase 3 clinical trial of emapalumab in patients with sHLH/macrophage activating syndrome (MAS) and underlying rheumatologic disease is ongoing (NCT05001737)."

Clinical • HEOR • Real-world • Real-world evidence • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Metabolic Disorders • Rare Diseases • Rheumatology • IFNG

Real-World Treatment Patterns and Outcomes Among Patients with Primary Hemophagocytic Lymphohistiocytosis with and without Infection at Diagnosis and Treated with Emapalumab: The Real-HLH Study (ASH 2023) - "This is the first study to report real-world treatment patterns with emapalumab across a diverse patient population with pHLH with or without infection at diagnosis. Over 54% of the patients with pHLH presented with infection at diagnosis. The infection status at diagnosis did not affect the overall survival rate and the proportion of patients proceeding to HSCT after emapalumab treatment."

Clinical • HEOR • Real-world • Real-world evidence • Bone Marrow Transplantation • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Rare Diseases • Transplantation • IFNG