Enjaymo (sutimlimab-jome) / Sanofi - LARVOL DELTA

Treatment of Cold Agglutinin Syndrome Secondary to Chronic Lymphocytic Leukemia With Sutimlimab and Obinutuzumab-Venetoclax. (PubMed, Case Rep Hematol) - "Sutimlimab provided rapid cessation of hemolysis, acting as a bridge while the obinutuzumab-venetoclax addressed the underlying CLL that was presumably responsible for the autoantibody production. This case demonstrates that combining sutimlimab with obinutuzumab-venetoclax is an effective and safe treatment for patients with CAS in the setting of CLL, supporting the use of short-term sutimlimab for CAS as a bridge to more durable treatment for underlying LPD such as CLL."

Journal • Autoimmune Hemolytic Anemia • Chronic Lymphocytic Leukemia • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • Rare Diseases

Complement targeting in autoimmune diseases. (PubMed, Curr Opin Hematol) - "Recognizing complement's role in the pathophysiology of hematological and autoimmune diseases has driven effective new therapies. Comprehensive profiling complement biomarkers, now feasible through complementomics in fluids and tissues, may reveal responsive endotypes and optimal cascade steps to target in diseases where complement is implicated but trials have not yet matched the right drug to the right patients."

Journal • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Systemic Lupus Erythematosus

Cold agglutinin disease: pathophysiology, diagnosis, and the evolving therapeutic landscape. (PubMed, Blood Res) - "Contemporary management combines B-cell-directed therapy with complement inhibition, the latter being transformed by the anti-C1s antibody, sutimlimab. This review summarizes the pathophysiology, diagnostic approaches, and rapidly evolving treatment landscapes for CAD, including emerging complement- and clone-directed agents."

Journal • Review • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Oncology

Safety and Efficacy of Classical Complement Pathway Inhibition with Sutimlimab in Chronic Immune Thrombocytopenia. (PubMed, Blood Adv) - P1 | "These results demonstrate that in some ITP patients autoantibodies activate the classical complement pathway, accelerating platelet destruction or impairing platelet production, contributing to treatment failure. C1s inhibition may be a safe and beneficial therapeutic approach for patients with chronic/refractory ITP."

Journal • CNS Disorders • Hematological Disorders • Migraine • Thrombocytopenia • Thrombocytopenic Purpura

Sutimlimab in patients with cold agglutinin disease: Results of the randomized placebo-controlled phase 3 CADENZA trial. (PubMed, Blood) - P3 | "These data demonstrate that sutimlimab has potential to be an important advancement in the treatment of CAD. (ClinicalTrials.gov: NCT03347422)."

Journal • P3 data • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Hypertension • Inflammation • Pain • Rheumatology

Combination therapy of sutimlimab and rituximab can lead to stable remission in autoimmune hemolytic anemia: a case series. (PubMed, Ann Hematol) - "The other patient is also in remission but with ongoing therapy. This highly informative case series reports on an innovative therapeutic concept and may form the basis for further clinical studies in AIHA."

Journal • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology

Complement-Dominant Relapse of Mixed Autoimmune Hemolytic Anemia After Rituximab Response. (PubMed, EJHaem) - "Hemoglobin increased without transfusion after sutimlimab, with C4 recovery and total hemolytic complement activity (CH50) suppression despite persistent cold agglutinin activity. Serial reassessment may identify complement-mediated relapse in mixed AIHA. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission."

Journal • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • CD20

Use of sutimlimab to manage anemia in a patient with high-grade B-cell lymphoma and complement binding anti-AnWj autoantibody. (PubMed, Transfusion) - "Management strategies for clinically significant anti-AnWJ are not well defined. To our knowledge, this is the first case using sutimlimab to manage complement-mediated hemolysis due to an auto-anti-AnWj antibody. While initial response to sutimlimab was favorable, the patient's comorbid lymphoma, multiple therapies, and short treatment period limit definitive conclusions regarding efficacy. Anti-complement therapy warrants further study for refractory antibody-mediated hemolysis with evidence of complement activation in the absence of compatible transfusions."

Journal • Anemia • B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Temperature Safeguards and Peri-Procedural Strategies for Stem Cell Collection in Cold Agglutinin Disease: A Case Report and Literature Review. (PubMed, J Clin Apher) - "He was treated with RBC transfusions, steroids, and Rituximab...The patient received cyclophosphamide for cytoreduction, granulocyte colony-stimulating factor for mobilization, and sutimlimab for complement inhibition...Conditioning with high-dose melphalan and autologous infusion was completed without complication, with successful engraftment. This case highlights the feasibility of pragmatic, multidisciplinary temperature management strategies during stem cell collection and processing in patients with cold agglutinin disease."

Journal • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Multiple Myeloma • Novel Coronavirus Disease • Oncology • Transplantation • CD34

Immune thrombocytopenia: Evolving mechanistic understanding and clinical development of new therapies. (PubMed, Tzu Chi Med J) - "Although corticosteroids, intravenous immunoglobulin, anti-D immunoglobulin, rituximab, splenectomy, and thrombopoietin receptor agonists have constituted the therapeutic foundation for decades, these approaches remain limited by transient responses, toxicity, and insufficient disease modification...Bruton tyrosine kinase (BTK) inhibitors (rilzabrutinib and orelabrutinib) modulate B-cell activation and macrophage effector pathways; spleen tyrosine kinase inhibitors (fostamatinib) block Fcγ receptor-mediated phagocytosis, neonatal Fc receptor inhibitors (efgartigimod and rozanolixizumab) accelerate IgG catabolism and rapidly reduce pathogenic autoantibody burden; and complement inhibition (sutimlimab) provides a rational strategy for patients in whom classical pathway activation contributes to refractory disease. Collectively, these agents represent the most significant expansion of the ITP treatment landscape in decades, offering steroid-sparing options and enabling more..."

Journal • Review • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura

Sutimlimab for cold agglutinin disease: an updated perspective from approval to real-world clinical treatment. (PubMed, Expert Rev Hematol) - "Opportunities remain to increase our understanding of the role of complement inhibition combined with immunosuppressive therapy in CAD. The impact of complement inhibition on both morbidity and mortality in CAD remains to be determined."

First-in-human • Journal • Real-world evidence • Review • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders

Felzartamab, an Anti-CD38 Antibody, in Late AMR: Efficacy Independent of Prior Rejection History or Therapy (ATC 2026) - P1, P2 | "In total, 11 patients underwent immunoadsorption-based desensitization (n=8) and/or anti-humoral therapy (n=6), the latter including plasmapheresis (n=2), rituximab (n=2), IVIG (n=1), tocilizumab (n=1), clazakizumab (n=2), and/or the C1s monoclonal antibody BIVV009. Five patients had previously participated in AMR trials evaluating clazakizumab (NCT03444103; n=2), imlifidase (NCT03897205; n=1; control), bortezomib (NCT01873157; n=2; placebo), or BIVV009 (NCT02502903; n=1). Felzartamab is able to reverse AMR, even in patients with a long-standing rejection history and different forms of previous rejection treatment."

Clinical • Antibody-mediated Rejection • Inflammation

SUTIMLIMAB IN PATIENTS WITH COLD AGGLUTININ DISEASE AND PRIOR RITUXIMAB EXPOSURE: A POST-HOC ANALYSIS OF THE PHASE 3 CADENZA STUDY (EHA 2026) - P3 | "Summary/Conclusion In this exploratory post-hoc subgroup analysis, the clinical efficacy of SUT vs PBO in patients with prior RTX exposure was consistent with the overall CADENZA population across key endpoints. The findings suggest that prior RTX treatment does not negatively impact response to SUT in patients with CAD without recent transfusion history, warranting further prospective validation in a larger study."

Clinical • P3 data • Retrospective data • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • HP

HEALTH-RELATED QUALITY OF LIFE OUTCOMES AND HEALTHCARE RESOURCE UTILISATION IN PATIENTS WITH COLD AGGLUTININ DISEASE (CAD) FROM THE SECOND INTERIM ANALYSIS OF THE CADENCE REGISTRY (EHA 2026) - "Further planned analyses will inform the understanding of the long-term HRQoL and HCRU benefits of sutimlimab outside of the controlled clinical trial setting and its value in CAD patient management. Figure: Model-based incidence rates and incidence rate ratios (IRR) for hospitalisation, outpatient visits, and emergency room (ER) visits by treatment group"

Clinical • HEOR • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Orthopedics

The Therapeutic Potential of Complement Inhibitors in Xenoreactive Human Complement-Dependent Cytotoxicity in Vitro. (PubMed, Xenotransplantation) - "Although these results might reflect experiments conducted at concentrations lower than clinical doses, our data suggest that, of the limited number of agents tested, pegcetacoplan may be the most effective in inhibiting xenoreactive human complement activation in this experimental setting (i.e., CDC of human complement in the pooled-serum against WT pig PBMCs). However, the results we obtained are puzzling because the C5 inhibitor, eculizumab, has been proven to be highly effective in inhibiting human complement activation in the in vitro CDC model. Furthermore, tesidolumab was reported to be effective in an in vivo NHP model. To obtain the additional information required for clinical application, further investigation would be needed. We would need to (i) ensure that the tesidolumab we were using had not deteriorated in any way and lost its efficacy, and (ii) compared pegcetacoplan with other C5 inhibitors (e.g., ravulizumab, eculizumab)."

Journal • Preclinical • Transplant Rejection • Transplantation

A diagnostic pitfall in cold agglutinin disease: KMT2D-mutated CAD-associated lymphoproliferative disorder with a CLL-like immunophenotype. (PubMed, Oxf Med Case Reports) - "Despite the absence of peripheral lymphocytosis or established treatment indications for chronic lymphocytic leukemia (CLL), B-cell-directed therapy, including ibrutinib and venetoclax plus rituximab, was administered over the course of approximately one year based on the initial diagnostic impression, but failed to control hemolysis. Subsequent treatment with the C1s inhibitor sutimlimab resulted in sustained resolution of hemolysis. This case highlights diagnostic pitfalls in CAD and underscores the value of molecular profiling in guiding appropriate therapy."

Journal • Autoimmune Hemolytic Anemia • Chronic Lymphocytic Leukemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • KMT2D

French protocol for the diagnosis and management of autoimmune hemolytic anemia in adults. (PubMed, Rev Med Interne) - "The management of AIHAs which has has long been empirical is mostly based on corticosteroids±rituximab for wAIHAs and on rituximab±bendamustine for CAD requiring to be treated, complement inhibition with sutimlimab being a new therapeutic option for CAD. This article reporting the French guidelines focused on diagnosis and treatment of adult AIHAs is adapted from the last update of the Protocole National de Diagnostic et de Soins (French protocol for diagnosis and management). These guidelines have been set up and led by the French national center for adult' immune cytopenias (CeReCAI)."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology

CADENCE: Cold Agglutinin Disease Real World Evidence Registry (clinicaltrials.gov) - P=N/A | N=429 | Active, not recruiting | Sponsor: RECORDATI GROUP | Recruiting ➔ Active, not recruiting

Enrollment closed • HEOR • Real-world evidence • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders

Safety and Effectiveness of Sutimlimab in Cold Agglutinin Disease: A Real-World International Experience. (PubMed, Am J Hematol) - "At baseline, patients had severe to moderate anemia (median Hb 8.9 g/dL) and active hemolysis, with a substantial transfusion burden despite a median of 2 prior therapies, including corticosteroids and rituximab. Thrombotic complications were rare. Overall, sutimlimab demonstrated rapid, durable effectiveness and a favorable safety profile in heavily pretreated real-world CAD patients."

Journal • Real-world evidence • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease

Case Report: Refractory cold agglutinin disease with hypersplenism: efficacy of splenectomy in a patient treated with sutimlimab. (PubMed, Front Immunol) - "We report the case of a woman with refractory CAD who received multiple lines of therapy, including rituximab, bendamustine, sutimlimab, and pegcetacoplan, with suboptimal or transient responses. Given the rarity of CAD complicated by hypersplenism, large prospective trials may be difficult to conduct. Collaborative multicenter registries and prospective observational studies may represent more feasible approaches to define clinical and molecular predictors of response and to guide personalized therapeutic strategies in challenging subsets."

Journal • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Thrombocytopenia

Sutimlimab vs B-Cell-Targeted Therapy in Cold Agglutinin Disease: Which Is the Optimal Approach? (PubMed, Blood) - "The combination of rituximab with fludarabine or bendamustine significantly increased and prolonged response rates, though with a substantial infectious risk. Therefore, several unmet needs remain, including identifying patients who can discontinue sutimlimab while maintaining remission, developing combination strategies effective against cold-induced symptoms, and improving infection prevention and control of hemolytic flares. This perspective article briefly recapitulates the pathophysiology of CAD, outlines the evolution of its treatment landscape, and focuses on the role of sutimlimab-its clinical positioning, therapeutic benefits, and management considerations-offering insights into optimizing care for patients with this challenging condition."

Journal • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease

Sutimlimab as a bridge to recovery in a life-threatening case of secondary cold agglutinin syndrome​​​​ (OeGHO-AHOP 2026) - "Despite azithromycin therapy, hemolysis worsened, and the patient developed renal failure (creatinine 8.7 mg/dL) and respiratory compromise. Supportive therapy and treatment of the underlying cause are standard for secondary CAS. However, the rapid and sustained improvement following Sutimlimab strongly suggests that complement inhibition effectively halted intravascular hemolysis, prevented organ dysfunction, and promoted full recovery, indicating potential benefit of Sutimlimab in infection-associated CAS."

Clinical • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Pneumonia • Renal Disease • HP

Autoimmune hemolytic anemia: New frontiers in diagnosis and therapy. (PubMed, Blood Rev) - "Therapy is different in wAIHA and CAD: in the former, steroids represent the first-line, followed by rituximab, splenectomy and immunosuppressors, while in the latter rituximab is recommended frontline, followed by rituximab plus chemotherapy or the complement inhibitor sutimlimab. Plasmacell-directed therapies (bortezomib and daratumumab) may be administered in refractory patients. Several new therapies are under investigation, including inhibitors of Bruton's and spleen tyrosine kinases, neonatal Fc receptor, and cytokines, and bi-specific monoclonal antibodies."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • BTK • SYK

Cold Agglutinin Disease (ICKSH 2026) - "The diagnosis of CAD is established by evidence of hemolysis (anemia, elevated LDH and bilirubin, decreased haptoglobin) together with a direct antiglobulin test (DAT) showing C3d positivity (±IgG) , supportive cold agglutinin testing (commonly a titer ≥1:64), and assessment of thermal amplitude...Second, complement -directed therapy has emerged as an important option; the C1s inhib itor sutimlimab demonstrated improvements in hemoglobin and hemolysis markers and meaningful reduction in fatigue in clinical trials. More recently, complement C3 inhibition (e.g., pegcetacoplan) has shown potential activity in both CAD and warm AIHA, expa nding the therapeutic landscape...Berentsen S, Randen U, Oksman M, Birgens H, Tvedt THA, Dalgaard J, Galteland E, Haukas E, Brudevold R, Sorbo JH, Naess IA, Malecka A, Tjonnfjord GE (2017) Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial...Blood 145:397 -408...."

Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • HP

Selective Complement Inhibition in Anti-p200 Pemphigoid: Immune Infiltrate Profiles and Therapeutic Implications Compared to Bullous Pemphigoid. (PubMed, Biomolecules) - "Pharmacological inhibition of C1s (sutimlimab), C3 (compstatin), C5 (tesidolumab), or C5aR1 (avacopan) significantly blocked C3c or C5 deposition in vitro. These findings indicate that selective blockade of the classical, alternative, or terminal complement pathways effectively prevents BMZ complement deposition, highlighting pathway-specific complement inhibition as a potential therapeutic strategy for anti-p200 pemphigoid."

Journal • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology • C5AR1