MB-CART 19.1 / Miltenyi Biotec, Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology - LARVOL DELTA

Decentralized Point-of-Care Manufacturing of CD19 Chimeric Antigen Receptor T Cells in Mexico. (PubMed, JCO Glob Oncol) - "Our study demonstrates an effective methodology with satisfactory and comparable performance to international reports. Point-of-care manufacturing is a feasible alternative to increase access to CAR-T cells in academic centers."

Journal

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

Safety and Preliminary Efficacy of CD19 CAR-T Cell Treatment in Rheumatic Disease – Data from the First Part of the Phase I/II CASTLE Basket Study (ACR Convergence 2024) - "Standard cyclophosphamide/fludarabine conditioning therapy was followed by a single infusion of an advanced therapy medicinal product (MB-CART19.1) containing 1×106 CD19-CAR-T cells/kg body weight. These data underline the safety of CD19-CAR-T therapy in the treatment of autoimmune disease. No higher-grade CRS or ICANS and no myelotoxicity was observed. Also, the preliminary efficacy data met the expectations in SLE, IIM and SSc."

CAR T-Cell Therapy • Clinical • P1/2 data • Pan tumor • Hematological Disorders • Immunology • Inflammation • Inflammatory Arthritis • Leukopenia • Lupus • Myositis • Neutropenia • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Safety of CD19-targeted CAR T-cell therapy in refractory systemic lupus erythematosus versus B-cell lymphoma – experiences of a center (DGHO 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 2 nd 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... Taken together, we observed less toxicities and severe adverse events in SLE patients than in lymphoma patients despite similar CAR T-cell expansion and dynamics."

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

Interim analysis of the phase I safety run in the cohort of the monocentric study "CD19-CAR-T cells in systemic B-cell-mediated autoimmune disease" (CASTLE) (DGHO 2024) - "Following lymphodepletion a single dose of 1 mio MB-CART19.1 CD19 CAR T cells/kg BW was infused... Our data emphasize the safety of CD19 CAR-T therapy in autoimmune diseases without a higher degree of CRS, ICANS or bone marrow toxicity."

CAR T-Cell Therapy • Clinical • P1 data • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Leukopenia • Lupus • Myositis • Neutropenia • Pneumonia • Respiratory Diseases • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

MB-CART19.1 in Refractory SLE (clinicaltrials.gov) - P1/2 | N=29 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2027 ➔ Aug 2027 | Initiation date: Mar 2024 ➔ Aug 2024 | Trial primary completion date: Mar 2025 ➔ Aug 2025

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

CAR T cell therapy for CD19-positive cancer - phase I clinical trial (ANZCTR) - P1 | N=25 | Recruiting | Sponsor: Metro North Hospital and Health Service | N=15 ➔ 25

CAR T-Cell Therapy • Enrollment change • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • CD19

LONGSAFE: Long-Term Follow-up of Patients Treated With Miltenyi Cell and Gene Therapies (clinicaltrials.gov) - P=N/A | N=40 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH

Gene therapy • New trial • Chronic Lymphocytic Leukemia • Gene Therapies • Hematological Malignancies • Leukemia • Lymphoma • Melanoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Solid Tumor

Expanding Data Pool for CAR T-Cell Treatment Demonstrates Consistent Efficacy Across Refractory Rheumatic Diseases (Medscape) - "Of the reports, an update from a 15-patient case series with at least 1 year of follow-up provides "the first long-term evidence of safety and efficacy in multiple rheumatic diseases...The three rheumatic diseases represented in this series of patients, all of whom had failed multiple previous immune suppressive treatments, were systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis...The proprietary investigational product, called MB-CART19.1 (Miltenyi Biotec), was administered in a single dose of one million cells per kg bodyweight...The response rates have been, and continue to be, impressive. For the eight patients with SLE, all achieved the definition of remission in SLE criteria after one dose of treatment. Complete resolution of all major symptom types was achieved after 6 months of follow-up. So far, no patient has relapsed."

Clinical data • Inflammation • Myositis • Systemic Lupus Erythematosus • Systemic Sclerosis

MB-CART19.1 r/r CD19+ B-cell Malignancies (BCM) (clinicaltrials.gov) - P1/2 | N=48 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Trial primary completion date: Dec 2023 ➔ Dec 2024

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

LONG-TERM SAFETY AND EFFICACY OF CAR-T CELL TREATMENT IN SEVERE AND TREATMENT REFRACTORY AUTOIMMUNE DISEASE (EULAR 2024) - " CD19 CAR-T cells were prepared from leukapheresis specimen after enrichment of T cells and transfection with MB-CART19.1 lentiviral vector (Miltenyi). Cells were expanded for 12 days and 1 million CAR T cells/kg body weight were administered as a single intravenous infusion after standard conditioning therapy with 1g/m2 cyclophosphamide and 3x 25 mg fludarabine, as described previously [1,2]... This case series provides first evidence for the long-term safety and efficacy of CD19 CAR-T cell treatment in three different autoimmune diseases, providing the rationale for further controlled clinical trials."

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

SAFETY AND PRELIMINARY EFFICACY OF CD19 CAR-T CELL TREATMENT IN RHEUMATIC DISEASE- DATA FROM THE FIRST PART OF THE PHASE I/II CASTLE BASKET STUDY (EULAR 2024) - "All patients receive standard cyclophosphamide/fludarabine conditioning therapy followed a single infusion of an advanced therapy medicinal product (MB-CART19.1) containing 1x106 CD19-CAR-T cells/kg body weight that were transfected with a lentiviral vector encoding for a 4-1BB based second generation CAR. These data underline the safety of CD19-CAR-T therapy in autoimmune disease. No higher grade CRS or ICANS or no myelotoxicity is observed. Attention has to be given to late-stage neutropenia, exacerbation of the underlying diseases and infections."

CAR T-Cell Therapy • Clinical • P1/2 data • Pan tumor • Hematological Disorders • Infectious Disease • Inflammatory Arthritis • Leukopenia • Lupus • Myositis • Neutropenia • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

MB-CART19.1 in Refractory SLE (clinicaltrials.gov) - P1/2 | N=29 | Not yet recruiting | Sponsor: Miltenyi Biomedicine GmbH

New P1/2 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

MB-CART19.1 r/r CD19+ B-cell Malignancies (BCM) (clinicaltrials.gov) - P1/2 | N=48 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH

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

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 • Fibrosis • Immunology • Inflammatory Arthritis • Lupus • Myositis • Oncology • Otorhinolaryngology • Renal Disease • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • Vertigo • CD27

CAR T Cell Therapy Leads to Long-term Abrogation of Autoimmunity in SLE Patients While Vaccination Responses Are Maintained (ACR Convergence 2023) - "CAR T cells were manufactured from autologous T cells and transfected with the lentiviral vector MB-CART19.1 (Miltenyi) encoding the CD19 CAR...Standard conditioning treatment (1g/m2 cyclophosphamide, 75 mg fludarabine) was done before CAR T cell infusion... CD19 CAR T cells therapy lead to a sustained disappearance of autoantibodies in SLE patients, while vaccination responses remained stable. This observation suggests that the main cellular source of autoantibodies in SLE are CD19+ plasmablasts, which are depleted by CD19 CAR T cells, while antibodies related to vaccination responses appear to predominantly stem from CD19-negative plasma cells. The selective and sustained abrogation of disease specific autoimmunity without affecting vaccination responses provides a favorable combination for the safety and efficacy of CD19 CAR T cell therapy in SLE."

CAR T-Cell Therapy • Clinical • Epstein-Barr Virus Infections • Herpes Zoster • Infectious Disease • Inflammatory Arthritis • Measles • Mumps • Pneumococcal Infections • Rubella • Tetanus • Varicella Zoster

Tolerability of CAR T Cell Therapy in Autoimmune Disease (ACR Convergence 2023) - " Patients with active and treatment-refractory SLE, IIM and SSc received a single infusion of 1 million CD19 CAR T cells manufactured from autologous T cells and transfected with the lentiviral vector MB-CART19.1 (Miltenyi) encoding the CD19 CAR...Standard conditioning treatment (1g/m2 cyclophosphamide, 75 mg fludarabine) was administered before CAR T cell infusion...The cases of CRS grade 2, ICANS grade 1 and repeated tocilizumab treatment occurred in different patients... Overall safety of CD19 CAR T cells therapy in autoimmune disease appears to be high. Low-grade CRS is frequent but can be managed well. Higher grade CRS was not found and seems to be infrequent."

CAR T-Cell Therapy • CNS Disorders • Epilepsy • Fatigue • Fibrosis • Hematological Disorders • Hematological Malignancies • Hypotension • Immunology • Inflammatory Arthritis • Interstitial Lung Disease • Myositis • Oncology • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

First evidence for efficacy of CAR-T CELL TREATMENT in REFRACTORY ANTISYNTHETASE SYNDROME (EULAR 2023) - "Methods Autologous CD19 CAR-T cells were prepared from leukapheresis specimen after enrichment of T cells and transfection with MB-CART19.1 lentiviral vector (Miltenyi) encoding for a 4-1BB based CAR targeting CD19. Cells were expanded for 12 days and 1 million CAR-T cells/kg body weight were administered as a single intravenous infusion after standard conditioning therapy with cyclophosphamide/fludarabine, as described previously [1,2]...Patient 1 did not respond to 5 different immunosuppressive treatments including cyclophosphamide and rituximab, patient 2 did not respond to 10 treatments including cyclophosphamide, rituximab and ocrelizumab...Also, the highly positive anti-Jo1 antibodies (331 U/l) disappeared after CAR-T cell treatment (5 U/l; cut-off 25U/l, Orgentec ELISA, Mainz, Germany) in patient 1, while patient 2 awaits follow up measurement. Conclusion Taken together, these data suggest that CD19 CAR T-cell therapy provides a possibility to intercept with..."

CAR T-Cell Therapy • Clinical • Ataxia • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Movement Disorders • Myositis • Pneumonia • Rare Diseases • Systemic Lupus Erythematosus

LONG TERM SAFETY AND EFFICACY OF CAR-T CELL TREATMENT IN REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS - DATA FROM THE FIRST SEVEN PATIENTS (EULAR 2023) - "Patients received autologous 1x10 6 CD19-CAR-T cells/kg body weight by single infusion after standard conditioning therapy (cyclophosphamide/fludarabine). The investigational medicinal product MB-CART19.1 was produced as described before [1,2]...After CD19 CAR T-cell therapy SLE patients remain in drug free-remission of SLE even if B cells recur. This remission can be long-lasting as the longest disease -free observation period is now 22 months."

CAR T-Cell Therapy • Clinical • Immunology • Inflammatory Arthritis • Lupus • Nephrology • Renal Disease • Systemic Lupus Erythematosus

CD19 T-CAR for Treatment of Children and Young Adults With r/r B-ALL (clinicaltrials.gov) - P1/2 | N=18 | Active, not recruiting | Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology | Trial completion date: Oct 2022 ➔ Oct 2025

CAR T-Cell Therapy • Trial completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CD19

A Phase I Open Label Dose Escalation Study of MB-CART19.1 in Relapsed and Refractory CD19+ B Cell Malignancies, Interim Preliminary Results in Pediatric ALL, Adult ALL Including CLL Cohorts (ASH 2021) - P1/2 | "Subjects undergo lymphodepletion with fludarabine (25 mg/m 2 daily for 3 days) and cyclophosphamide (1000 mg/m 2 on day -3)...1 patient experienced grade III CRS and was treated with tocilizumab...Longer follow-up will establish whether treatment results in durable responses. The hybrid manufacturing model provides flexibility and a timely delivery of the fresh drug product to the patients"

Clinical • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Lymphocytic Leukemia • CNS Disorders • Diffuse Large B Cell Lymphoma • Epilepsy • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • CD19 • CD4 • CD8

MB-CART19.1 r/r CD19+ B-cell Malignancies (BCM) (clinicaltrials.gov) - P1/2; N=48; Recruiting; Sponsor: Miltenyi Biomedicine GmbH; Trial completion date: Jul 2022 ➔ Dec 2022; Trial primary completion date: Jul 2021 ➔ Aug 2022

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

CD19 T-CAR for Treatment of Children and Young Adults With r/r B-ALL (clinicaltrials.gov) - P1/2; N=18; Not yet recruiting; Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Clinical • New P1/2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CD19 • PCR

CD19 T-CAR for Treatment of Children and Young Adults With r/r B-ALL (clinicaltrials.gov) - P1/2; N=18; Active, not recruiting; Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology; Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CD19 • PCR