Gamifant (emapalumab-lzsg) / SOBI - LARVOL DELTA

EMERALD: Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still's or SLE (clinicaltrials.gov) - P3 | N=33 | Completed | Sponsor: Swedish Orphan Biovitrum | Active, not recruiting ➔ Completed

Trial completion • Hemophagocytic lymphohistiocytosis • Immunology • Inflammatory Arthritis • Lupus • Rare Diseases • Systemic Lupus Erythematosus

A Post-authorization Study to Describe the Safety and Efficacy of Emapalumab for the Treatment of pHLH in Treatment Experienced Chinese Patients (clinicaltrials.gov) - P4 | N=13 | Active, not recruiting | Sponsor: Swedish Orphan Biovitrum | Trial primary completion date: Jul 2025 ➔ Feb 2025

Trial primary completion date • Hemophagocytic lymphohistiocytosis • Immunology • Rare Diseases • IL2 • IL2RA • ISG20

Exposure–safety analysis from two clinical trials of emapalumab in patients with macrophage activation syndrome in Still's disease (EULAR 2025) - P2, P3 | "In a pooled analysis of data from two prospective clinical studies of patients with MAS in Still’s disease, increasing emapalumab exposure was not associated with an increased risk of moderate or severe events, serious, nor infection TEAEs. This observation is consistent with a previous safety–exposure analysis in patients with pHLH administered emapalumab [3] and suggests that greater exposure to emapalumab to control hyperinflammation in this patient population may reduce the incidence of moderate and severe TEAEs, as well as infections. Accordingly, this pharmacological exposure–safety analysis confirms that repeated administration and/or increasing doses of emapalumab are well tolerated by patients with MAS in Still’s disease."

Clinical • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Rare Diseases • IFNG

Efficacy and Safety of Emapalumab in Patients with Macrophage Activation Syndrome in Still's disease: Results from a Pooled Analysis of Two Prospective Trials (EULAR 2025) - P2, P3 | "31 (79.5%) patients had been administered anakinra for MAS. Emapalumab rapidly controlled MAS in >80% of patients and enabled a reduction in GC dose in 72% of patients with MAS in Still’s disease. All patients had an initial inadequate response to high-dose GCs, and many patients also had an inadequate response to other targeted biologics prior to emapalumab initiation. Demographics, baseline characteristics and treatment outcomes in patients with MAS in Still’s disease administered emapalumab."

Retrospective data • Idiopathic Arthritis • Immunology • Infectious Disease • Inflammation • Rheumatology • CXCL9 • IFNG • IL2RA

Management of Refractory Malignancy-Associated Hemophagocytic Lymphohistiocytosis in Adolescent Patients: A Case Series of Novel Therapeutics and Treatment Challenges. (PubMed, Hematol Rep) - "Our findings emphasize the need for individualized treatment approaches in adolescent m-HLH and importance of further research to establish evidence-based therapeutic guidelines for refractory cases."

Journal • Hemophagocytic lymphohistiocytosis • Immunology • Oncology • Rare Diseases • IFNG

Synergistic Immunotherapy in Refractory EBV-Positive T-Cell Lymphoproliferative Disorder: A Case Report (ASPHO 2025) - "Despite initial treatments with dexamethasone, etoposide, rituximab, and ruxolitinib, hyperinflammation and EBV replication persisted. Combination therapy with emapalumab and nivolumab led to a sustained clinical and molecular remission in a patient with refractory EBV-positive T-cell LPD with HLH. This targeted approach may reduce the need for cytotoxic chemotherapy or stem cell transplantation, warranting further investigation as an upfront treatment option."

Case report • Clinical • IO biomarker • Bone Marrow Transplantation • Dyslipidemia • Epstein-Barr Virus Infections • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hypertriglyceridemia • Immunology • Lymphoma • Oncology • Pneumonia • Rare Diseases • T Cell Non-Hodgkin Lymphoma • IFNG

Emapalumab With Post-Transplant Cyclophosphamide, Tacrolimus and Mycophenolate Mofetil for the Prevention of Graft-versus-Host Disease After Donor Reduced-Intensity Hematopoietic Cell Transplant (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P1 trial • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

A Unique Presentation of T-Cell/Histiocyte-Rich Large B-Cell Lymphoma With HLH in a 10-Year-Old (ASPHO 2025) - "Although etoposide was initially deferred due to concern for infection, HLH treatment was initiated with emapalumab-lzsg and dexamethasone...He subsequently received two pre-phase cycles of cyclophosphamide, rituximab, and dexamethasone, as well as HLH-directed therapy with etoposide... THRLBCL is exceedingly rare in pediatric populations, and our patient is the youngest to be reported with THRLBCL and concomitant HLH. Our case highlights challenges in pursuing definitive diagnosis and clinical management of rare lymphomas compounded by infrequent yet serious complications."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Fatigue • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hepatology • Immunology • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pain • Pediatrics • Rare Diseases • Respiratory Diseases • T Cell Histiocyte Rich Large B Cell Lymphoma • ALK • BCL2 • CD20 • IL2 • PAX5 • TNFRSF8

EMAPALUMAB IN PEDIATRIC PATIENTS WITH HIGH-GRADE CYTOKINE RELEASE SYNDROME (CRS) FOLLOWING CHIMERIC ANTIGEN RECEPTOR T-CELL (CAR-T) THERAPY (EHA 2025) - "This is a retrospective analysis of pediatric patients with relapsed or refractory (r/r) leukemia or other malignancies who developed high-grade CRS after CAR-T therapy and did not respond adequately to glucocorticoids (GCs) and tocilizumab...The characteristics of enrolled patients.CharacteristicsTotal (N=38)Age, median (range)9 (2, 16)Gender, female/male15/23Weight, median (range)27.25 (13.50, 80.55)ECOG score, median (range)1 (1, 2)Underlying disease, N (%) B-ALL32 (84.21%) Burkitt's lymphoma3 (7.89%) T-ALL1 (2.63%) AML1 (2.63%) Neuroblastoma1 (2.63%)Prior therapy lines, median (range)1 (1, 5)HSCT history, N (%)8 (21.05%)CAR-T cell targets, N (%) CD19/CD22/CD7228 (73.68%) CD19/CD224 (10.53%) CD19/CD22/CD202 (5.26%) CD22/CD721 (2.63%) CD7/CD991 (2.63%) CD33/CLL11 (2.63%) GD21 (2.63%)% of MRD in the bone marrow before CAR-T cell infusion, median (range)21.78 (0.00, 92.27)CAR-T cell infusion dose, ×106 cells/kg, median (range)6.00 (2.19, 8.62)Lymphodepleting..."

CAR T-Cell Therapy • Clinical • Cytokine release syndrome • Bone Marrow Transplantation • Burkitt Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Leukemia • Lymphoma • Neuroblastoma • Oncology • Pediatrics • Septic Shock • Solid Tumor • CD22 • CD33 • CD7 • CD99 • IFNG • IL10 • IL2 • MELTF • TNFA

THE JANUS KINASE INHIBITOR RUXOLITINIB RESOLVED RECURRENT CNS DISEASE POST- HEMATOPOIETIC STEM CELL TRANSPLANT IN HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (EHA 2025) - "Also, in the treatment of CNS-HLH, the consensus recommends intrathecal administration of methotrexate and steroids, however, intrathecal injection may not always be feasible in post-HSCT. The use of high-dose systemic dexamethasone after HSCT poses a higher risk of complications such as opportunistic infections and gastrointestinal hemorrhage...He was treated with ruxolitinib, emapalumab and anti-PD-1 antibody and achieved remission... This is the first report documenting CNS disease in secondary HLH patients post-HSCT. Cases analysis suggested that post-HSCT CNS relapse of sHLH is related to the primary cause (EBV). Also, the successful using of JAK-STAT inhibitor indicates that ruxolitinib in higher doses can effectively pass through the BBB, control the excessive inflammatory state in the CNS."

Bone Marrow Transplantation • CNS Disorders • Epilepsy • Epstein-Barr Virus Infections • Gastrointestinal Disorder • Hematological Disorders • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Inflammation • Rare Diseases • Transplantation

EMAPALUMAB IN PATIENTS WITH PRIMARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS: EFFICACY AND SAFETY OUTCOMES FROM A MULTINATIONAL, OPEN-LABEL, SINGLE-ARM STUDY (EHA 2025) - "When initiating emapalumab in pts with pHLH at 3 mg/kg 80% of pts responded with a median time of 4 days. Pts who responded to treatment achieved the clinical stability necessary to undergo HSCT while maintaining a favorable safety profile. These outcomes were consistent with those of pts with pHLH treated with emapalumab in a previous clinical trial and in real-world clinical practice."

Clinical • Acute Respiratory Distress Syndrome • Bone Marrow Transplantation • Hemophagocytic lymphohistiocytosis • Immunology • Inflammation • Pediatrics • Rare Diseases • CXCL10 • CXCL9 • IFNG

T Cell Tropic Epstein Barr Virus in a Patient with Hemophagocytic Lymphohistiocytosis (CIS 2025) - "HLH-specific therapy was initiated with partial response to dexamethasone and emapalumab and minimal improvement in EBV viremia. EBVPCR wasrepeatedonsortedlymphocytes which demonstrated T cell tropism, so nivolumab was added with gradual resolution of EBV viremia...Identification of the underlying trigger is necessary to prevent recurrence by controlling the underlying disease. This case demonstrates the importance of considering other risk factors, such as our patient's T cell tropism and potentially her Native American ethnicity, when no other etiology can be identified."

Clinical • CNS Disorders • Cough • Epilepsy • Epstein-Barr Virus Infections • Hematological Disorders • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Oncology • Rare Diseases • Respiratory Diseases • Rheumatology

Transplant Related Outcomes in Patients With HLH Treated With Emapalumab as a Bridge to HSCT (ASPHO 2025) - "Median (IQR) duration of conditioning was 10 (7,12) days with melphalan/reduced intensity-based regimens (17/35; 48.6%) being the most common conditioning regimen. This study reported transplant-related outcomes in the real-world among patients with HLH who received their first transplant following emapalumab treatment. Overall, 80% of patients with evaluable data achieved engraftment and 74.3% survived."

Clinical • Bone Marrow Transplantation • Graft versus Host Disease • Hemophagocytic lymphohistiocytosis • Immunology • Rare Diseases • Transplantation • IFNG

Radiosynthesis of [89Zr]Zr-DFO-Emapalumab for IFN-γ PET Imaging (SNMMI 2025) - "Emapalumab, buffer-exchanged into saline, was conjugated with 5 equivalents of p-SCN-Bn-Deferoxamine via 1 hour incubation at 37 oC and pH ~ 9. Radiosyntheses of [89Zr]Zr-DFO-emapalumab were validated with great radiochemical yields and excellent radiochemical purities. Quality standards with respect to antibody integrity, antigen binding, endotoxin levels and sterility all met the requirement for initiating a first-in-human immunoPET imaging study using [89Zr]Zr-DFO-emapalumab."

Hemophagocytic lymphohistiocytosis • Immunology • Oncology • Rare Diseases • IFNG

Impact of Emapalumab on Patients with Hemophagocytic Lymphohistiocytosis (CIS 2025) - "Since emapalumab was introduced, 41,750 patients have been diagnosed with primary or secondary HLH. Treatment with emapalumab steadily increased from 0.73% in 2019 to 1.9% in 2024. Death rate of HLH in 2018 prior to introduction of emapalumab was 4%."

Clinical • Hemophagocytic lymphohistiocytosis • Immunology • Inflammation • Rare Diseases • IFNG

The Difference in Presentation of Cases of X-Linked Lymphoproliferative Disease Type 1 in a Family of Three Boys (CIS 2025) - "He passed away despite treatment with gamifant and anakinra. Our case highlights the clinical variability of XLP-1 presentation in a family with the same pathogenic variant in SH2D1A. We conclude that the SH2D1A VUS is pathogenic and that SAP levels can correlate with severity of disease."

Clinical • B Cell Lymphoma • Epstein-Barr Virus Infections • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Otorhinolaryngology • Pediatrics • Pneumonia • Rare Diseases • Respiratory Diseases • Tetanus • CD4 • CD8

Acute Liver Failure Unmasking XIAP Deficiency in Very Early-Onset Inflammatory Bowel Disease (CIS 2025) - "He was initiated on infliximab with good clinical response...Flow cytometry showed XIAP deficiency, and anakinra was added with gradual resolution of liver dysfunction...Emapalumab was replaced with ruxolitinib as the patient was preparing for hematopoietic stem cell transplant...Laboratory trends and therapeutics. Day 0 represents initial hospitalization for acute liver failure."

Bone Marrow Transplantation • Cholestasis • CNS Disorders • Epstein-Barr Virus Infections • Gastroenterology • Gastrointestinal Disorder • Hemophagocytic lymphohistiocytosis • Hepatology • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Liver Failure • Ocular Inflammation • Ophthalmology • Pain • Rare Diseases • Uveitis • CXCL9 • IFNG • IL18 • XIAP

Specific drugs for rare diseases in a province of eastern China under catalog management: from 2021 to 2023. (PubMed, Front Pharmacol) - "Spesolimab, Sodium Phenylbutyrate, Nitisinone and Emapalumab are currently in short supply, and the delivery rate of 16 drugs such as Selumetinib, Sirolimus (tablet), Octreotide, Dimethyl Fumarate and Lanreotide is below 80%...This indicates a generally high level of accessibility to drugs for rare diseases in China. However, attention should be given to improving the supply capacity for drugs that are in short supply and have a low delivery rate."

Journal • Rare Diseases

Dose-modified Emapalumab and Ruxolitinib (E-Ru) Regimens for Hemophagocytic Lymphohistiocytosis (clinicaltrials.gov) - P2/3 | N=30 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Soochow University

New P2/3 trial • Hemophagocytic lymphohistiocytosis • Immunology • Rare Diseases

Case Report: Successful use of emapalumab in adult B-cell acute lymphoblastic leukemia experiencing severe neurotoxicity and hemophagocytic lymphohistiocytosis-like features after CAR-T cell therapy. (PubMed, Front Immunol) - "We report an adult B-cell acute lymphoblastic leukemia (B-ALL) patient treated with brexucabtagene autoleucel (brexu-cel)...Treatment included tocilizumab, high-dose corticosteroids, anakinra, siltuximab, and ruxolitinib...The patient recovered from IEC-HS and underwent allogeneic stem cell transplantation. This case highlights the role of emapalumab in managing refractory IEC-HS and persistent neurotoxicity in adults, underscoring the need for targeted interventions in severe CAR-T complications."

IO biomarker • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Leukemia • Oncology • Rare Diseases • Transplantation • IFNG

Emapalumab for severe cytokine release syndrome in solid tumor CAR-T: a case report. (PubMed, Front Oncol) - "This case demonstrates the clinical use of emapalumab to treat refractory cytokine release syndrome in a solid tumor CAR-T while potentially preserving therapeutic efficacy of CAR-T therapy. Further studies with larger patient populations are needed to evaluate the use of emapalumab as a treatment for CRS."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hematological Malignancies • Inflammation • Leukemia • Lymphoma • Melanoma • Multiple Myeloma • Oncology • Prostate Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • CXCL10 • IFNG

CXCL9 and IL-18: potential biomarkers for efficacy evaluation in refractory hemophagocytic lymphohistiocytosis treated with RED (ruxolitinib, emapalumab and dexamethasone). (PubMed, Ann Hematol) - "No grade 3 or higher adverse effects were linked to the RED regimen. This comprehensive investigation of the RED approach in HLH, although small in sample size, supports the possibility that RED can serve as an effective and relatively safe salvage therapy for refractory HLH."

Biomarker • Journal • Bone Marrow Transplantation • Epstein-Barr Virus Infections • Hemophagocytic lymphohistiocytosis • Immunology • Inflammation • Rare Diseases • Transplantation • CXCL9 • IL18

THE JANUS KINASE INHIBITOR RUXOLITINIB RESOLVED RECURRENT CNS DISEASE POST-HEMATOPOIETIC STEM CELL TRANSPLANT IN HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (EBMT 2025) - "Also, in the treatment of CNS-HLH, the consensus recommends intrathecal administration of methotrexate and steroids, however, intrathecal injection may not always be feasible in post-HSCT. The use of high-dose systemic dexamethasone after HSCT poses a higher risk of complications such as opportunistic infections and gastrointestinal hemorrhage...He was treated with ruxolitinib, emapalumab and anti-PD-1 antibody and achieved remission... This is the first report documenting CNS disease in secondary HLH patients post-HSCT. Cases analysis suggested that post-HSCT CNS relapse of secondary HLH is related to the primary cause (EBV infection in this report). Also, the successful using of JAK-STAT inhibitor indicates that ruxolitinib in higher doses can effectively pass through the BBB, control the excessive inflammatory state in the CNS."

Bone Marrow Transplantation • CNS Disorders • Epilepsy • Epstein-Barr Virus Infections • Gastrointestinal Disorder • Hematological Disorders • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Rare Diseases • Transplantation

THE JANUS KINASE INHIBITOR RUXOLITINIB RESOLVED RECURRENT CNS DISEASE POST-HEMATOPOIETIC STEM CELL TRANSPLANT IN HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (EBMT 2025) - "Also, in the treatment of CNS-HLH, the consensus recommends intrathecal administration of methotrexate and steroids, however, intrathecal injection may not always be feasible in post-HSCT. The use of high-dose systemic dexamethasone after HSCT poses a higher risk of complications such as opportunistic infections and gastrointestinal hemorrhage...He was treated with ruxolitinib, emapalumab and anti-PD-1 antibody and achieved remission... This is the first report documenting CNS disease in secondary HLH patients post-HSCT. Cases analysis suggested that post-HSCT CNS relapse of secondary HLH is related to the primary cause (EBV infection in this report). Also, the successful using of JAK-STAT inhibitor indicates that ruxolitinib in higher doses can effectively pass through the BBB, control the excessive inflammatory state in the CNS."

Bone Marrow Transplantation • CNS Disorders • Epilepsy • Epstein-Barr Virus Infections • Gastrointestinal Disorder • Hematological Disorders • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Rare Diseases • Transplantation

EXPERIENCE WITH T-CELL DEPLETED ALLOGENEIC HSCT FOR REFRACTORY SJIA ASSOCIATED WITH LUNG DISEASE (EBMT 2025) - " We report our single center retrospective analysis of 4 pediatric patients with sJIA-LD who underwent allogeneic HSCT with reduced intensity conditioning (RIC) with alemtuzumab (days 14-12), fludarabine (150 mg/2 over days -8 to -4), melphalan (140 mg/m2 on day -3) and thiotepa (200 mg/m2 on day-2) and received either a CD34+ selected (n=3) or TCR-αβ depleted (n=1) peripheral blood stem cell product. Emapalumab was given to prevent macrophage activation syndrome (MAS) flare and to facilitate engraftment...One patient (patient #1) experienced secondary graft failure on day+43 requiring a second HSCT with a haploidentical parental donor and post-transplant cyclophosphamide (Table 1)... Our experience suggests that allo-HSCT with a T-cell depleted approach for patients with sJIA-LD offers durable engraftment with low risk of GVHD, pulmonary complications and TRM. While survival is excellent, benefits of this approach need to be weighed against risk of graft rejection."

Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Idiopathic Arthritis • Immunology • Inflammation • Pediatrics • Pneumonia • Pulmonary Disease • Respiratory Diseases • Rheumatology • Transplant Rejection • CD34 • IL18