zorpocabtagene autoleucel (MB-CART 19.1) / Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Miltenyi Biomedicine - LARVOL DELTA

Hormone levels of female patients with SLE after anti-CD19 CAR T-cell treatment do not suggest an impaired ovarian reserve (ACR Convergence 2026) - "Background/Purpose: Systemic lupus erythematosus (SLE) predominantly affects women of reproductive age and is associated with impaired fertility due to chronic inflammation and gonadotoxic immunosuppressive therapies, particularly cyclophosphamide (CYC)...We therefore investigated longitudinal changes in reproductive hormones before and after CAR T cell therapy in women with SLE. Thirteen female patients with severe, treatment‑refractory SLE treated with autologous anti‑CD19 CAR T‑cells (zorpocabtagene autoleucel) at two German university centers between 2021 and 2025 were analyzed. All patients received fludarabine‑ and CYC‑based lymphodepletion. Serum anti‑Müllerian hormone (AMH), estradiol (E2), follicle‑stimulating hormone (FSH), luteinizing hormone (LH), progesterone, and prolactin were measured at baseline and approximately 12 months post‑therapy using standardized commercial immunoassays... Anti‑CD19 CAR T‑cell therapy with standard lymphodepletion does not..."

CAR T-Cell Therapy • Clinical • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • Women's Health

MB-CART19.1 r/r CD19+ B-cell Malignancies (BCM) (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Miltenyi Biomedicine GmbH | Trial completion date: Jun 2026 ➔ Sep 2026 | Trial primary completion date: Jun 2026 ➔ Sep 2026

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • CD19

GOING FOR SECONDS: CLINICAL OUTCOMES AND RESPONSE PREDICTORS FOLLOWING SECOND CD19 CAR T-CELL INFUSION (EHA 2026) - "12 patients were included (DLBCL n=7, FL n=1, B-ALL n=4) treated with axi-cel (n=6), tisa-cel (n=2), liso- cel (n=1) or MB-CART19.1 (n=3). In addition, differences in LDH levels at CAR2 reinfusion are observed between responders vs non-responders while toxicity severity diminished between CAR1 and CAR2 within the same patient. Further analyses investigating biological mechanisms underlying these associations are ongoing and will be presented."

CAR T-Cell Therapy • Clinical • Clinical data • Diffuse Large B Cell Lymphoma • Hematological Malignancies

Management of relapses after autologous CD19 CAR T-cell therapy in SLE, SSc and IIM – a case series (EULAR 2026) - "Background CD19 chimeric antigen receptor (CD19 CAR) T-cell therapy with Zorpo-cel (MB-CART19.1, Miltenyi Biomedicine) has shown to induce sustained drug-free remission in patients with refractory B cell driven autoimmune disease (AID) (1)...Patient #1, a 46-year-old female with IIM (Jo1-positive anti-synthetase-syndrome) relapsed with myositis after 9 months and thereafter received BCMA-CAR T-cells (Idecabtagene vicleucel, BMS) achieving sustained drug-free remission (ACR Major Clinical Response) until the last follow up (18 months after BCMA- CAR T-cell therapy, (ref...Treatment with obinutuzumab and nintedanib improved skin manifestations, lung function and imaging signs of ILD until the last follow up (10 months after treatment initiation)...Tofacitinib was induced, leading to rapid but only temporary improvement of myositis and arthritis...Since some skin manifestation despite seroconversion of dsDNA antibodies was still present, skin biopsy was done showing..."

CAR T-Cell Therapy • Clinical • Cardiovascular • CNS Disorders • Dermatitis • Inflammatory Arthritis • Interstitial Lung Disease • Myositis • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Systemic Sclerosis • Urology

Baseline B-cell counts and inflammation markers predicting likelihood and severity of toxicity to CAR T-cell therapy in patients with autoimmune disease (EULAR 2026) - P=N/A, P1, P1/2 | "Most of the patients received lymphodepletion (LD) with cyclophosphamide and fludarabine prior CAR-treatment, one patient received bendamustine...78 (72%) patients received CD19-targeting (zorpocabtagene autoleucel (MB-CART19.1), mivocabtagene autoleucel (KYV-101), or BMS-986353) and 30 (28%) patients received CD19- and BMCA-targeting (co-infusion or dual-targeting CAR-T) therapy...Baseline B-cell counts and interleukin-6 may represent predictive biomarkers for CRS in AID patients treated with CAR T-cells. Strategies for B-cell depletion and better control of systemic inflammation prior to CAR T-cell therapy could improve the tolerability of CAR T-cell therapy."

CAR T-Cell Therapy • Clinical • IO biomarker • Hematological Malignancies • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Myositis • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • CRP • IL6

Extended follow up on safety and clinical efficacy from first eight SLE patients receiving autologous CD19-directed CAR-T cell therapy. (EULAR 2026) - "The temporary increase in antivirals was attributable to the COVID-19 pandemic (e.g., nirmatrelvir/ritonavir). Conclusions CD19-directed CAR-T cell therapy with Zorpocabtagene-autoleucel induces sustained drug-free remission and regression of organ damage in patients with severe refractory SLE over many years. Most strikingly, a sharp decline of infectious complications together with a decrease in the use of antibiotics/antivirals can be documented over several years after CD19-CAR T-cell therapy. This effect is likely based on the permanent absence of glucocorticoids and immunosuppressive-drugs providing a long-term safety advantage for SLE patients having undergone CAR T-cell therapy."

CAR T-Cell Therapy • Clinical • Cardiovascular • Infectious Disease • Inflammatory Arthritis • Lupus • Musculoskeletal Diseases • Nephrology • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Systemic Lupus Erythematosus

Immune Reset and Microbial Shifts: Gut Microbiota Dynamics After CD19 CAR T-Cell Therapy in Autoimmune Disease (EULAR 2026) - "Methods Patients with severe SLE, SSc, or IIM received a single infusion of 1x106/ kg body weight autologous CD19 CAR T-cells, manufactured by lentiviral-based transduction of T-cells with a vector encoding a second-generation CAR with a CD19 binder and a 4-1BB costimulatory domain (Zorpocabtagene-autoleucel (Zorpo-cel, MB- CART19.1); Miltenyi Biomedicine)...Notably, lower baseline fecal IgA predicted delayed B-cell reconstitution at 6 months, highlighting mucosal immune status as a potential regulator of post–CAR T-cell immune recovery. Image(s), graphic(s), or table(s)"

CAR T-Cell Therapy • Gut Microbiota • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Myositis • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

MB-CART19.1 r/r CD19+ B-cell Malignancies (BCM) (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Miltenyi Biomedicine GmbH | Trial completion date: Mar 2026 ➔ Jun 2026 | Trial primary completion date: Mar 2026 ➔ Jun 2026

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • CD19

CD19 CAR-T therapy induces remission in refractory autoimmune hemolytic anemia with ITP and antiphospholipid syndrome. (PubMed, Med) - "This case demonstrates that CD19-directed CAR-T cell therapy can induce rapid, durable remission of severe, refractory cold-agglutinin AIHA and simultaneously improve coexisting APLAS and ITP on a favorable toxicity profile. However, more data from controlled clinical trials are needed for final conclusions."

Clinical • IO biomarker • Journal • Anemia • Autoimmune Hemolytic Anemia • Genetic Disorders • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Inflammation • Thrombocytopenia • Thrombocytopenic Purpura

MB-CART19.1 in Relapsed/Refractory Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P=N/A | N=12 | Recruiting | Sponsor: King Hussein Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CD19

A Phase IIa Trial Evaluating the Efficacy of anti-CD19 Chimeric Antigen Receptor Engineered T-Cells in Patients With Systemic Sclerosis (SSc) Resistant to Immunosuppressive Drugs. SCLEROCAR (clinicaltrialsregister.eu) - P1/2 | N=6 | Not yet recruiting | Sponsor: Centre Hospitalier Universitaire De Montpellier

New P1/2 trial • Immunology • Scleroderma • Systemic Sclerosis

Anti-CD19 CAR T cells for pediatric patients with treatment-refractory autoimmune diseases. (PubMed, Nat Med) - "We present a case series of eight children with severe/refractory AD (four systemic lupus erythematosus, three dermatomyositis, one systemic sclerosis) treated at Ospedale Pediatrico Bambino Gesù, Rome, and University Hospital Erlangen with a single infusion of 1 × 106 kg-1 point-of-care manufactured autologous CD19 CAR T cells (zorpocabtagene autoleucel), in a hospital exemption (HE) program...This improvement enabled sustained discontinuation of immunomodulators, even after B cell reconstitution. The activation of formal clinical trials enrolling children and adolescents is urgently needed to confirm these preliminary results and to assess the long-term safety of this approach."

Journal • Dermatomyositis • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Myositis • Pediatrics • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

MB-CART19.1 in Relapsed/Refractory Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P=N/A | N=12 | Not yet recruiting | Sponsor: King Hussein Cancer Center

New trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CD19

CD19 CAR-T cells for treatment-refractory autoimmune diseases: the phase 1/2 CASTLE basket trial. (PubMed, Nat Med) - P1/2 | "A total of 24 patients were enrolled (10 with SLE, 9 with SSc and 5 with IIM), all receiving a single infusion of Zorpo-cel after stopping immunosuppressive treatments and receiving standard lymphodepletion with cyclophosphamide and fludarabine. CASTLE suggests the feasibility, safety and efficacy of Zorpo-cel in three different autoimmune diseases and paves the way for conducting a pivotal study. ClinicalTrials.gov identifier: NCT06347718 , EudraCT identifier: 2022-001366-35 ."

Journal • P1/2 data • Pan tumor • Immunology • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Lupus • Myositis • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Study of CART Cell (MB-CART19.1) in Patients With Relapsed or Refractory CD19 Positive NHL (clinicaltrials.gov) - P2 | N=26 | Recruiting | Sponsor: King Hussein Cancer Center

New P2 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Safety and preliminary efficacy of anti-CD19 CAR T cells zorpocabtagene-autoleucel in systemic autoimmune diseases: Final analysis of the castle trial (ASH 2025) - "The CASTLE study is the first phase I/II basket trial to demonstrate feasibility, favorablesafety, and high efficacy of zorpo-cel in three B-cell driven AIDs. These promising results provide strongrationale to further develop zorpo-cel in AID."

CAR T-Cell Therapy • Clinical • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Lupus • Myositis • Pneumonia • Pulmonary Disease • Renal Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Distinct inflammatory and immune recovery patterns after CD19-directed CAR T-cell therapy in SLE and B-cell lymphoma (ASH 2025) - "All patients received either commercial CAR T-cell products or theinvestigational medicinal product MB-CART19.1 (in-house manufactured 2nd generation anti-CD19 CAR T-cells with a 4.1BB co-stimulatory domain) in our center.To characterize inflammatory signatures, we performed serum proteomics using the Olink® Target 96Immuno-Oncology Panel across the CAR T-cell treatment course...Taken together, our data reveal a resolution of systemic inflammation specific to SLE patients followingCAR T-cell therapy, compared to patients with B-cell lymphoma. This resolution might be linked to theshorter persistence of CAR T-cells in SLE patients and thus benefit the reconstitution of the adaptiveimmune system."

CAR T-Cell Therapy • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Non-Hodgkin’s Lymphoma • Systemic Lupus Erythematosus • ANGPT1 • CXCL10 • CXCL12 • CXCL13 • CXCL5 • CXCL8 • IFNG • IL6 • IL7 • TGFB1

"On-site manufactured anti-CD19 CAR-T cell therapy normalized platelet count in a case of refractory immune thrombocytopenia (ITP)" (DGHO 2025) - "Here we report the case of a 68-year-old woman with refractory severe primary ITP treated with anti-CD19 CAR-T cells. Leukapheresis and processing were performed on-site using the CliniMACS Prodigy platform® and MB-CART19.1 lentiviral vector (Miltenyi Biotec). The patient underwent conditioning with fludarabine and cyclophosphamide, followed by fresh CAR-T cell infusion (vein-to-vein time: 13 days). The patient presented with a 16-month history of ITP and severe gastrointestinal bleeding, requiring repeated transfusions and critical care due to hemorrhagic shock and was refractory to standard treatments including steroids, IVIg, TPO receptor agonists, fostamatinib, rituximab, azathioprine, cyclosporine and splenectomy...The patient developed cytokine release syndrome (CRS) grade 1 on day 7, which escalated to grade 2 on day 8 but resolved following administration of tocilizumab... Anti-CD19 CAR-T cell therapy is an effective treatment for refractory ITP, with..."

CAR T-Cell Therapy • Clinical • Gastroenterology • Immune Thrombocytopenic Purpura • Immunology • Inflammation • Thrombocytopenia • Thrombocytopenic Purpura • CD4 • CD8

CD19-Targeted CAR-T Cells in Refractory Systemic Autoimmune Diseases: A Monocentric Experience from the First Fifteen Patients (ASH 2023) - "Autologous CD19 CAR T cells MB-CART19.1 were produced with the Miltenyi prodigy platform. After leukapheresis on day -13, manufacturing commenced in house and lymphodepletion was started with fludarabine 25 mg/m2/d intravenously (i.v.) on days -5 to -3 and cyclophosphamide 1000 mg/m2/d i.v. on day -3...6/15 patients received tocilizumab... CD19 CAR T cells induce persistent, drug-free remission in three distinct autoantibody dependent AID with very good tolerability. Though hypothetical cure appears possible, longer follow up is needed. This unprecedented drug-free remission is remarkable as B cells functionally reconstitute."

CAR T-Cell Therapy • Clinical • Immunology • Inflammatory Arthritis • Lupus • Myositis • Otorhinolaryngology • Renal Disease • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • Vertigo • CD27

MB-CART19.1 r/r CD19+ B-cell Malignancies (BCM) (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Miltenyi Biomedicine GmbH | Phase classification: P1/2 ➔ P1

Phase classification • Acute Lymphocytic Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • CD19

Distinct Safety and Toxicity Profile of CD19-Directed CAR T-Cell Therapy in Systemic Lupus Erythematosus Versus B-Cell Lymphoma – a Single-Center Experience (ASH 2024) - "All patients were treated in our center with either commercial CAR T-cell products or with the investigational medicinal product MB-CART19.1 (in-house manufactured 2nd generation anti-CD19 CAR T-cells with a 4.1BB co-stimulatory domain)...Consistent with reduced toxicity, SLE patients received less tocilizumab and glucocorticoid treatment...Despite comparable lymphodepletion with fludarabine/cyclophosphamide, SLE patients demonstrated on average a deeper nadir of neutrophils compared with lymphoma patients...Taken together, while both patient cohorts showed similar CAR T-cell expansion and dynamics, we observed less toxicity and less severe adverse events in SLE patients than in lymphoma patients. This is consistent with a lower base-line inflammation, a shorter CAR T-cell persistence, and a faster B-cell recovery in SLE patients, indicating an overall very good safety profile of CAR T-cell therapy in the treatment of SLE"

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Systemic Lupus Erythematosus

Update on Monocentric CD19-CAR T-Cell Therapy in 30 Patients with Autoimmune Disease (ASH 2024) - "Methods : Patients with treatment-refractory, progressive systemic SLE (18 patients), SSc (7) and IIM (5) were treated with 1x106 /kg autologous 2nd generation CD19 CAR-T cells MB-CART19.1 produced in-house in a closed system...Before CAR T-cell infusion, lymphodepletion was infused with fludarabine (25 mg/m², d-5 to d-3) and cyclophosphamide (1000 mg/m², d-3)...Tolerability has been high with no higher-grade acute toxicities and mild infectious complications in longer follow-up. Efficacy analysis showed long-standing drug-free remission (SLE and IIM) or no progression (SSc) with recurrence of disease in only one patient."

CAR T-Cell Therapy • Clinical • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Lupus • Myositis • Neutropenia • Pediatrics • Pneumonia • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

CD19 CAR T Cell Therapy in refractory autoimmune hemolytic anemia (AIHA) with concurrent immunethrombopenia (ITP) – a case report (DGHO 2025) - "We offered lymphodepletion with cyclophosphamide/fludarabine and by expanded access, a single dose of 1 million MB-CART19.1 cells/kg, which is a fresh CD19-directed, 4-1BB CAR T cell product.AIHA-response was defined by independence of blood transfusions, level of hemoglobin (Hb), and hemolysis parameters and response of ITP by platelet counts...A pulse of steroids combined with a single dose of rituximab was not effective and was therefore extended to IVIG and steroids... This single case shows early efficacy of MB-CART19.1 in severe and refractory AIHA with partial remission at day 7 and complete remission at day 25 with virtually absent toxicity. To confirm this favorable course, a longer follow-up and clinical trials expanding on more patients are needed."

CAR T-Cell Therapy • Case report • Clinical • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • Infectious Disease • Inflammation

Comparison of the safety profile of CD19-targeting CAR T-cell therapy in patients with refractory systemic lupus erythematosus and B-cell lymphoma (DGHO 2025) - "All patients were treated at the University Hospital of Erlangen with either commercial CAR T-cell products or with the investigational medicinal product MB-CART19.1 (in-house manufactured 2nd generation anti-CD19 CAR T-cells with a 4.1BB co-stimulatory domain). In contrast to similar peak and overall expansion of CAR T-cells, SLE patients showed lower incidence and severity of cytokine-release syndrome and immune-effector cell associated neurotoxicity syndrome than the B-NHL patients...Consistent with reduced toxicity, SLE patients received less tocilizumab and glucocorticoid treatment... Taken together, CAR T-cell treatment of SLE patients showed less toxicity and faster immune recovery than in the context of B-NHL, while CAR T-cell expansion and early kinetics were similar, indicating an overall excellent safety profile of CAR T-cell therapy in the treatment of SLE."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Non-Hodgkin’s Lymphoma • Systemic Lupus Erythematosus • CD4

Safety and efficacy of autologous CD19-CAR T-cell therapy in patients with autoimmune disease - data from the CASTLE Phase I/II basket study (ACR Convergence 2025) - "Their results will provide further insights in the therapeutic role of CAR T-cells in these diseases. CASTLE is a phase I/II basket study (Miltenyi Biomedicine, EudraCT-Nr.2022-001366-35) assessing the safety (primary endpoint) and efficacy (secondary endpoint) of 1x106 autologous CD19 CAR T-cells (MB-CART19.1) /kg BW after lymphodepleting chemotherapy with Fludarabin/Cyclophosphamide in patients with SLE, IIM and SSc. The CASTLE study met its primary safety and secondary efficacy endpoint. The data confirm favorable safety and high efficacy of MB-CART19.1 in the setting of a controlled phase I/II study in patients with autoimmune disease."

CAR T-Cell Therapy • Clinical • P1/2 data • Pan tumor • Cytomegalovirus Infection • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Lupus • Myositis • Neutropenia • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • Thrombocytopenia