Nulojix (belatacept) / BMS - LARVOL DELTA

Fgl2 regulates CD8+ T cell responses and promotes transplant acceptance in a cell-intrinsic manner (IMMUNOLOGY 2025) - "Of note, the addition of calcineurin inhibitor tacrolimus but not costimulation blocker belatacept significantly inhibited Fgl2 production by TIGIT+ CD8+ T cells (p<0.0001). We conclude that Fgl2 promotes contraction of CD8+ T cell effector responses during transplantation by inducing an exhaustion-like profile and inhibiting IL-2 production. Bolstering production of Fgl2 may be an effective immunotherapy to attenuate CD8+ T cell responses in transplantation.Keywords: Cells T Cells T Cells, Cytotoxic; Molecules FC Receptors; Processes Tolerance/Suppression/Anergy; Techniques/Approaches Transgenic/Knockout Mice"

IO biomarker • Immunology • Transplant Rejection • Transplantation • CD8 • IL2 • TIGIT

Belatacept as an Alternative Immunosuppressive Agent for Bone Marrow-Sparing in Idiopathic Pulmonary Fibrosis Lung Transplant Recipients with Short Telomeres. (PubMed, J Heart Lung Transplant) - "As we have previously shown, Idiopathic pulmonary fibrosis lung transplant recipients (IPF-LTRs) with short-telomere length (STL) are prone to develop significant cytopenias and poor tolerance to cell cycle inhibitors, specifically Mycophenolate mofetil (MMF), post-transplant...These patients were either challenged with MMF (majority) or immediately started on Belatacept post-transplant with the goal to bridge to Everolimus, an mTOR inhibitor that is commonly used post-transplant. We describe outcomes in the first-year post-transplant including the incidence of Acute Cellular Rejection (ACR), Epstein-Barr Virus (EBV) viremia, and one case of Post-Transplant Lymphoproliferative Disorder (PTLD) at 13 months. The use of Belatacept post-lung transplant may be an acceptable short-term alternative therapy to cell cycle inhibitors in ST-IPF-LTRs with cytopenias but may lead to higher risk of EBV viremia and PTLD when Belatacept is used long-term in these patients."

Journal • Epstein-Barr Virus Infections • Hematological Disorders • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Transplantation

Recurrent Pulmonary Alveolar Proteinosis With Negative Pathology After Bilateral Lung Transplant (ATS 2025) - "Prior to transplant, therapies including whole lung lavage and nebulized Sargramostim were trialed. Post transplant, belatacept, tacrolimus, mycophenolate, and prednisone were used for immunosuppression...Thus, clinicians should maintain a high suspicion for recurrent disease in patients with persistently positive GM-CSF autoantibodies. This case highlights the importance of early recognition and treatment for recurrent autoimmune PAP despite biopsy results after bilateral lung transplant."

Bronchiectasis • Cardiovascular • Diabetes • Fibrosis • Immunology • Infectious Disease • Metabolic Disorders • Obstructive Sleep Apnea • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Sleep Disorder • Transplantation • Type 2 Diabetes Mellitus • CSF2

Belatacept as an Alternative Immunosuppressant Agent for Bone Marrow Sparing in Pulmonary Fibrosis Lung Transplant Recipients With Short Telomeres (ATS 2025) - "Patients with STL are prone to develop significant cytopenias and poor tolerance to cell cycle inhibitors, specifically Mycophenolate mofetil (MMF), post-transplant...63% (5/8) were successfully transitioned to Everolimus with median time of Belatecept use being 8 months, while 38% continued Belatacept as part of there IS regimens, along with a calcineurin inhibitor and steroid... The use of Belatacept post-lung transplant may be a well-tolerated alternative to a cell cycle inhibitor in STLPF-LTRs who develop, or at risk to develop post-transplant cytopenias."

Clinical • Hematological Disorders • Hematological Malignancies • Immunology • Myelodysplastic Syndrome • Oncology • Pulmonary Disease • Respiratory Diseases • Transplantation • RTEL1 • TERT • TINF2

Safety of Continued Belatacept Treatment After Kidney Graft Rejection (ERA 2025) - No abstract available

Clinical • Transplant Rejection

Toxoplasma Gondii Replication During Belatacept Treatment in Kidney Transplantation: A Case Report and a Review of the Literature. (PubMed, Genes (Basel)) - "In conclusion, we highlight the importance of drug avoidance and/or increased surveillance in Toxo-g IgG-positive KTR. We also retain that further studies on the host defense pathways involved in the surveillance of opportunistic pathogens in KTR are strongly desirable."

IO biomarker • Journal • Review • Immune Modulation • Immunology • Infectious Disease • Transplant Rejection • Transplantation • CTLA4 • PRDM1

Real-world registry evidence beware: Old-world risk analysis may not be applicable to new-world belatacept utilization. (PubMed, Am J Transplant) - No abstract available

Journal • Real-world evidence

Exploring the Impact of Diabetes on Kidney Transplant: Patient Outcomes and Management Strategies. (PubMed, Cureus) - "Immunosuppression is a substantial challenge among diabetics as certain medications such as tacrolimus have shown to be considerably diabetogenic compared to cyclosporine and belatacept, and it is also postulated that corticosteroids can lead to hyperglycemia. Some studies proved that glucose-lowering medications, including insulin degludec, glucagon-like peptide-1 receptor agonists, thiazolidinediones, and sodium-glucose cotransporter 2 inhibitors, are safe and effective among KTRs. However, these studies are debatable and of low confidence. Hence, it is imperative to conduct large clinical trials and establish definitive guidelines to manage pre-existing diabetes and NODAT among KTRs with multidisciplinary care to help clinicians improve patient outcomes."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Genetic Disorders • Infectious Disease • Metabolic Disorders • Nephrology • Obesity • Renal Disease • Transplantation • Type 1 Diabetes Mellitus

Calcineurin Inhibitor Associated Nephrotoxicity in Kidney Transplantation-A Transplant Nephrologist's Perspective. (PubMed, Acta Physiol (Oxf)) - "CNIs have significantly improved kidney transplant outcomes, but their associated nephrotoxicity necessitates mitigation strategies. The decision to implement such regimens is always an individual choice balancing against the risk of immunologic injuries. Further long-term studies are needed to optimize immunosuppressive approaches and refine CNT management."

Journal • Review • Acute Kidney Injury • Nephrology • Transplantation

ASCEND: A Study of TCD601 in de Novo Renal Transplant Recipients (clinicaltrials.gov) - P2 | N=90 | Active, not recruiting | Sponsor: ITB-Med LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Nephrology • Transplantation

Long-Term Outcomes of Belatacept Versus Tacrolimus Following T-Cell Depleting Induction in Adult Kidney Transplantation. (PubMed, Clin Transplant) - "This is the largest longitudinal study to compare outcomes of belatacept versus tacrolimus-based therapy following T-cell depleting induction. Belatacept was associated with improved graft function despite an increased acute rejection rate. There was no difference in overall graft or patient survival compared to tacrolimus. This study suggests that belatacept-based therapy is not inferior to tacrolimus-based therapy following T-cell depletion."

Clinical • Journal • Retrospective data • Nephrology • Transplant Rejection • Transplantation

Similar Efficacy in Belatacept-Converted Kidney Transplant Recipients With Steroid-Avoiding Regimen. (PubMed, Kidney Int Rep) - "BelaS+ patients developed significantly more de novo DSA (14 [4.9%] vs. 2 [1.0%], P < 0.001). Avoiding steroids in KTRs who are late-converted to belatacept is associated with a similar efficacy along with lower mortality and reduced incidence of severe infections in selected low-sensitized patients."

Journal • Cytomegalovirus Infection • Diabetes • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Transplant Rejection • Transplantation

Compatibility of Post-Kidney Transplant Immunosuppression Therapy with Lactation. (PubMed, J Clin Med) - "In this review, we examine the current literature on the pharmacokinetics, safety profiles, and clinical outcomes associated with key immunosuppressive agents, including cyclosporine, tacrolimus, everolimus, azathioprine, corticosteroids, and belatacept. Therefore, we emphasize the need to design structured prospective studies to assess safety in the medium and long term. Our review aims to equip clinicians with the most up-to-date evidence on this topic, enabling them to make informed decisions regarding the compatibility of post-kidney transplant treatments with breastfeeding."

Journal • Review • Transplantation

COMPARATIVE EFFICACY AND SAFETY OF MTOR INHIBITORS, BELATACEPT, AND CALCINEURIN INHIBITORS IN HEART TRANSPLANT RECIPIENTS: BALANCING REJECTION, INFECTION, AND RENAL FUNCTION - Shahnawaz Notta (ACC 2025) - "New immunosuppressive agents such as mTOR inhibitors (e.g., everolimus, sirolimus) and biologics like belatacept, offer strategies to achieve this balance. mTOR inhibitors reduce rejection and preserve renal function without significantly increasing infection risk. Belatacept requires closer infection monitoring."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Infectious Disease • Oncology • Transplant Rejection • Transplantation

MERRLIN: Impact of the Microbiota on the Likelihood of Renal Graft Rejection (clinicaltrials.gov) - P=N/A | N=70 | Recruiting | Sponsor: Institut National de la Santé Et de la Recherche Médicale, France | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2024 ➔ Jan 2027 | Trial primary completion date: Sep 2023 ➔ Jan 2027

Enrollment open • Trial completion date • Trial primary completion date • Immunology • Transplant Rejection • Transplantation

Treatment of Antibody-Mediated Rejection (ABMR) With CarBel (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

New P2 trial • Antibody-mediated Rejection • Immunology • Transplant Rejection • Transplantation

A Study to Evaluate the Benefits and Risks of Conversion of Existing Adolescent Kidney Transplant Recipients Aged 12 to <18 Years to a Belatacept-based Immunosuppressive Regimen as Compared to Continuation of a Calcineurin Inhibitor-based Regimen, and Their Adherence to Immunosuppressive Medications (clinicaltrials.gov) - P3 | N=102 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial primary completion date: May 2026 ➔ Dec 2030

Trial primary completion date • Transplantation

Increasing Incidence of PTLD in the Modern Era of Immunosuppression: A Need for Increased Surveillance? (ISHLT 2025) - "Basiliximab was the most common induction agent (9 [81.8%]), and most LTRs (7 [63.6%]) were on standard 3-drug immunosuppression; 3 (27.2%) LTRs were on belatacept, all 3 were EBV IgG+...Of 10 LTRs with known pre-LT immune status, 4 were immunosuppressed (mycophenolate, n=3; tocilizumab, n=1) and developed PTLD earlier (median 122.5 days [IQR 57.5-168.7]) than those who were not immunosuppressed before LT (n=6; median 547 days [IQR 196.5-2115.5])...Rituximab was the most common treatment (6 [54.5%]), followed by R-CHOP (3 [27.3%])...The median time from PTLD diagnosis to death was 229 and 1136 days in the belatacept and non-belatacept groups, respectively.Conclusion The rising incidence of PTLD in LTRs, particularly in the past year, emphasizes the need for increased surveillance. Pre-LT immunosuppression and post-LT belatacept use may increase risk of PTLD, even without donor-recipient EBV mismatch."

Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Contemporary Approach to Desensitization: Targeted Therapies for HLA Sensitized Pediatric Heart Transplant Candidates - Study Design (ISHLT 2025) - "Recent adult studies show that a dual approach with Carfilzomib (CFZ), a proteasome inhibitor, and Belatacept (BELA), a costimulation blocker, reduces class I and II HLA antibodies (Abs). For protocol design, please refer to the figure.Results The study's unique design harmonizes the use of a novel protocol across sites using a central IRB and is the first prospective, registry-based investigation in pediatric HT using the Pediatric Heart Transplant Society (PHTS) registry. The HLA core will measure antibody response through MFIs, titers, and cPRA, while the mechanistic core will use advanced investigations to support the trial's clinical endpoints.Conclusion This multicenter study aims to establish a transformative, standardized approach to desensitization and antibody evaluation."

Clinical • Antibody-mediated Rejection • Hematological Disorders • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Oncology • Pediatrics • Transplantation

Contemporary Clinical Experience with Belatacept in Heart Transplant Recipients: A Case Series (ISHLT 2025) - "Adjuvant therapies for AMR included PLEX (83.3%), IVIG (92%), and/or rituximab or bortezomib (33.3%), which were followed by Belatacept 10mg/kg with maintenance dose of 5mg/kg monthly. Minor infections were reported in 16.7% of patients, including cellulitis and norovirus, with no cases of CMV or EBV viremia (Table 1).Conclusion Using Belatacept as adjuvant IS for AMR with DSA appears safe in carefully selected patients and may demonstrate efficacy in treating AMR with DSA. Additional research is needed to more precisely identify which patients with AMR will respond to adjuvant IS with costimulatory blockade and better to define the role of Belatacept in HT recipients."

Clinical • Antibody-mediated Rejection • Dermatology • Infectious Disease • Transplantation • CTLA4

Impact of Belatacept on Donor Specific Antibodies in Heart Transplant Recipients (ISHLT 2025) - "MMF and Prednisone doses were similar in BTC treated and controls. The distribution of DSAs prior to and after BTC initiation is illustrated in Fig.1. There was a significant decline in the number of low MFI class 1 DSAs (p=0.018), as well as moderate MFI class 2 DSAs (p=0.008) following BTC initiation.Conclusion Our findings suggest the potential benefit in using BTC to reduce DSA burden in HT recipients; however, further studies are required to elucidate this question."

Clinical • Transplantation

Rates of Viremia Before and After Initiation of Belatacept Therapy in Heart Transplant Recipients (ISHLT 2025) - "Most patients continued Tacrolimus therapy at a reduced dose, without significant changes in Prednisone and Mycophenolate doses. BTC was discontinued due to viral infection in 9% of patients.Conclusion We observed a higher rate of EBV and BK viremia post-BTC initiation. Heightened awareness of this elevated risk underscores the necessity for appropriate surveillance, facilitating timely discontinuation as needed."

Clinical • Cytomegalovirus Infection • Infectious Disease • Transplantation

Use of Belatacept in Heart Transplant Recipients - Rejection Rates and Mortality (ISHLT 2025) - "MMF and Prednisone doses were similar between BTC treated and controls. Furthermore, there was no difference in all-cause mortality between the groups (two deaths in each cohort).Conclusion In our cohort, there was no difference in rejection rates or mortality in patients treated with BTC compared to SOC. BTC may safely be used as an adjunct immunosuppressive agent in HT recipients with CNI nephrotoxicity or elevated immunological risk."

Clinical • Transplant Rejection • Transplantation

Impact of Belatacept on Renal Function in Heart Transplant Recipients (ISHLT 2025) - "Among patients who remained on BTC for at least 6 months (N=49), there was a significant improvement in eGFR from 38 [IQR 28-68] to 43 [IQR 34-64] ml/min/1.73m2 (p=0.04), Fig 1a. Among patients specifically started on BTC for its renal sparing effects, there was a 24% improvement in eGFR from 31.5 [IQR 26-42] to 39 [IQR 31-50] ml/min/1.73m2 (p=0.02), Fig.1b.Conclusion In our cohort, treatment with BTC was associated with an improvement in eGFR following initiation, particularly evident in patients given this medication for the purpose of preserving renal function."

Clinical • Chronic Kidney Disease • Nephrology • Renal Disease • Transplantation

Conversion to Belatacept-Based Immunosuppression as a Calcineurin Sparing Regimen in Lung Transplant: A Multi-Institutional Retrospective Study (ISHLT 2025) - "After controlling for age and CLAD, belatacept use was associated with an increased risk of mortality (OR:1.64 95%CI:1.04-2.58, p=0.03).Conclusion Belatacept CNI-sparing regimen was associated with stabilization in renal function without an increased risk of ACR, infection or malignancy. However, belatacept use was associated with increased mortality risk."

Retrospective data • Antibody-mediated Rejection • Infectious Disease • Nephrology • Oncology • Renal Disease • Transplantation