HD-CAR-1 / Heidelberg University Hospital - LARVOL DELTA

Antibiotic-induced loss of gut microbiome metabolic output correlates with clinical responses to CAR T-cell therapy. (PubMed, Blood) - "In this study, we observed that prior exposure to broad-spectrum ABX with extended anaerobic coverage like piperacillin-tazobactam and meropenem was associated with worsened anti-CD19 CAR-T therapy survival outcomes in large B-cell lymphoma patients (n=422), compared to other ABX classes...Together, these results suggest that broad-spectrum ABX deplete metabolically active commensals whose metabolites are essential for enhancing CAR-T efficacy, shedding light on the intricate relationship between ABX exposure, microbiome function and their impact on CAR-T cell efficacy. This highlights the potential for modulating the microbiome to augment CAR-T immunotherapy."

CAR T-Cell Therapy • Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Cardiovascular Adverse Event Reporting Patterns With CD19 CAR-T and CD20 × CD3 Bispecific Antibodies in Relapsed/Refractory Large B-Cell Lymphoma: A FAERS Disproportionality Analysis (SOHO 2026) - "Included therapies were axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, epcoritamab, glofitamab, and mosunetuzumab. In FAERS reports related to LBCL or DLBCL, both CAR-T and CD20 × CD3 bispecific antibodies showed CVAE signals. CAR-T therapies showed stronger relative reporting throughout the full post-approval period, but the platform difference was less pronounced during the shared modern treatment era. FDA: Food and Drug Administration, MedDRA: medical dictionary for regulatory activities."

Adverse events • Bispecific • CAR T-Cell Therapy • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Pre-CAR-T B-cell-directed immunotherapy exposure and outcomes after CD19 CAR-T for large B-cell lymphoma: An EBMT registry analysis. (PubMed, Bone Marrow Transplant) - No abstract available

Journal • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A distinct CAR-T cell phenotype mediates therapeutic response at limited doses. (PubMed, Nat Commun) - P1/2 | "To address this, we performed deep phenotyping of anti-CD19 CAR-T cell products and their corresponding leukapheresis starting materials from a phase I/II dose-escalation trial...Effective low-dose products were associated with high T-cell numbers and T-cell-supportive myeloid states in leukapheresis materials, whereas regulatory myeloid states promoted dysfunctional CAR-T cells and treatment failure. Our study provides insights into the phenotype, mechanisms, and biomarkers of CAR-T cells that drive therapeutic responses at low doses, with medical and socioeconomic implications."

IO biomarker • Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Human CART22.19 therapy in refractory pediatric B-ALL: insights from a named-patient cohort. (PubMed, J Immunother Cancer) - "CART22.19 therapy demonstrated a favorable safety profile and promising clinical activity in a high-risk pediatric population, with dual targeting enabling disease control in CD19-negative leukemia. Nonetheless, limited CAR T-cell persistence may represent an important obstacle to sustained remission. Our findings support further clinical development of CART22.19 and indicate that donor-derived CAR T-cells following RIC alloHSCT may represent a potential therapeutic strategy to enhance persistence and improve outcomes in heavily pretreated pediatric patients."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Transplantation • CD19 • CD22

Impaired hematopoiesis affects apheresis and CAR T-cell product composition and treatment response. (PubMed, Transfusion) - "These findings highlight the importance of early leukapheresis, ideally before intensive treatments, to optimize T-cell yield, product quality, and therapeutic efficacy."

Journal • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD8

OUTCOME OF SINGLE- AND DOUBLE-REFRACTORY HIGH-RISK CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): THE IMPACT OF CELLULAR THERAPY (EBMT 2026) - "AlloHCT was performed according to institutional standards (PMI 30630979) from matched related or unrelated donors, and CART with the 3G-CD19 CART Heidagenlecleucel within a clinical trial (PMI 39192036)...In the SRHR cohort, 70% were BTKi-refractory and 30% venetoclax-refractory, and the HR-defining abnormality was TP53 in 89%... These results demonstrate for the first time that the outlook of patients with SRHR CLL is dismal but still better than in patients with DR disease. In both settings, alloHCT and CART are feasible and may overcome clinical and biological disease refractoriness, with better results when used in SRHR status rather than DR status. However, the optimum timing and sequencing of CART and alloHCT, respectively, and the impact of CT on the natural course of SRHR/DR CLL remain to be determined."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • TP53

OUTCOME OF SINGLE- AND DOUBLE-REFRACTORY HIGH-RISK CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): THE IMPACT OF CELLULAR THERAPY (EBMT 2026) - "AlloHCT was performed according to institutional standards (PMI 30630979) from matched related or unrelated donors, and CART with the 3G-CD19 CART Heidagenlecleucel within a clinical trial (PMI 39192036)...In the SRHR cohort, 70% were BTKi-refractory and 30% venetoclax-refractory, and the HR-defining abnormality was TP53 in 89%... These results demonstrate for the first time that the outlook of patients with SRHR CLL is dismal but still better than in patients with DR disease. In both settings, alloHCT and CART are feasible and may overcome clinical and biological disease refractoriness, with better results when used in SRHR status rather than DR status. However, the optimum timing and sequencing of CART and alloHCT, respectively, and the impact of CT on the natural course of SRHR/DR CLL remain to be determined."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • TP53

HOSPITAL EXEMPTION FOR HEIDAGENLECLEUCEL (HEIDI-CEL), A THIRD GENERATION CD19.CAR T CELL PRODUCT IN GERMANY (EBMT 2026) - P1/2 | "Patients obtained the CAR-T-cells after standard conditioning with fludarabine and cyclophosphamide, and were followed-up clinically. This is a report on the definitively first time in Germany, that the PEI issued a hospital exemption for an ATMP, i.e. for our in-house manufactured CAR T cell product, designated heidagenlecleucel (Heidi-cel). This is remarkable for various reasons: simplification of logistics, increased flexibility, development and clinical testing of own approaches, achievement of autarky by strengthening of know-how in vector design and production of genetically modified cells and thus cost reduction in the German healthcare system."

CAR T-Cell Therapy • Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma

IMPACT OF PRIOR B-CELL-DIRECTED IMMUNOTHERAPY ON THE OUTCOME OF CD19 CAR T-CELL THERAPY IN AGGRESSIVE B-CELL LYMPHOMA (EBMT 2026) - "Background: B-cell-directed immunotherapies (BCDI), such as CD19 chimeric antigen receptor T-cell therapy (CAR-T), antibody-drug conjugates including polatuzumab vedotin (pola), and bispecific antibodies (BSA) have revolutionized the treatment of large B-cell lymphoma (LBCL)...BCDI exposure (excluding rituximab) prior to CAR-T, including bridging therapy, was categorized as BSA, pola-based regimens, and other BCDI, including obinutuzumab, brentuximab vedotin, and loncastixumab tesirine...BCDI-exposed patients more often had ≥3 prior treatment lines (54.8% vs. 43.0%, p<0.001), more frequent axicabtagene ciloleucel usage (63.8% vs. 56.0%, p=0.012), and higher complete/partial remission (CR/PR) rates at lymphodepletion (40.2% vs. 29.1%, p<0.001).Three-year overall survival (OS) was numerically inferior with prior BCDI (41.3% vs. 49.7%, p=0.07), without differences in progression-free survival (PFS) (35.0% vs. 37.2%), relapse incidence (52.0% vs. 51.5%), or NRM (13.0%..."

CAR T-Cell Therapy • B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma

FC-GAMMA-RECEPTOR-ACTIVATION BY CIRCULATING IMMUNE COMPLEXES IN SYSTEMIC AUTOIMMUNE DISEASES AND ITS REDUCTION BY CD19-CAR T-CELL THERAPY (SSWC 2026) - "Our study reveals the presence of Fc-gamma-R-engaging cICs in CTDs and demon- strates that the bioactivity of cICs is correlated with clinical phenotypes and treatment outcomes."

CAR T-Cell Therapy • Immunology • Inflammation • Inflammatory Arthritis • Psoriatic Arthritis • Scleroderma • Seronegative Spondyloarthropathies • Sjogren's Syndrome • Systemic Sclerosis • TOP1

PERSISTING CD19.CAR-T CELLS IN COMBINATION WITH NINTEDANIB: CLINICAL RESPONSE IN A PATIENT WITH SYSTEMIC SCLEROSISASSOCIATED PULMONARY FIBROSIS AFTER 3 YEARS (SSWC 2026) - "The case suggests serological remission and improvement of pulmonary fibrosis as new goals in the treatment of SSc. References: (1) Merkt W, et al. Third-generation CD19.CAR-T cell-containing combination therapy in Scl70+ systemic sclerosis."

CAR T-Cell Therapy • Clinical • Combination therapy • Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

FC-GAMMA-RECEPTOR-ACTIVATION BY CIRCULATING IMMUNE COMPLEXES IN SYSTEMIC AUTOIMMUNE DISEASES AND ITS REDUCTION BY CD19-CAR T-CELL THERAPY (SSWC 2026) - "Our study reveals the presence of Fc-gamma-R-engaging cICs in CTDs and demon- strates that the bioactivity of cICs is correlated with clinical phenotypes and treatment outcomes."

CAR T-Cell Therapy • Immunology • Inflammation • Inflammatory Arthritis • Psoriatic Arthritis • Scleroderma • Seronegative Spondyloarthropathies • Sjogren's Syndrome • Systemic Sclerosis • TOP1

Hospital Exemption for 3rd Generation CD19.CAR T Cell Therapy in Germany (EHA-EBMT-CART 2026) - P1/2 | "Patients obtained the CAR-T-cells after standard conditioning with fludarabine and cyclophosphamide, and were followed-up clinically. This is interesting for various reasons: simplification of logistics, increased flexibility, development and clinical testing of own approaches, achievement of autarky by strengthening of know-how in vector design and production of genetically modified cells and thus cost reduction in the German healthcare system. Clinical Trial Registry : HD-CAR-1 trial (NCT03676504 (clinicaltrials.gov)."

CAR T-Cell Therapy • Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma

Zamtocabtagene Autoleucel (Zamto-Cel), a Tandem CD20-CD19 Directed CAR-T cell Therapy As Second-Line Treatment for relapsed/refractory Large B-cell Lymphoma: Primary analysis of the Randomized, Pivotal DALY 2-EU Study (TCT-ASTCT-CIBMTR 2026) - P2 | "Pts in the zamto-cel arm started lymphodepletion fludarabine + cyclophosphamide during manufacturing, followed by infusion of zamto-cel, target dose 2.5 × 10 6 CAR-T cells/kg body weight...For CRS, 29 38% pts received tocilizumab, 14 18% corticosteroids...4 . To understand the potential mechanistic advantages of a dual-targeting CD20/CD19 CAR-T construct in the treatment of r/r LBCL, as investigated in the DALY 2-EU trial"

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Respiratory Diseases • CD20

Patterns, risk factors and management of CD19-directed chimeric antigen receptor T-cell therapy failure in CNS lymphoma (ASH 2025) - "Notably,peripheral CD19+-B-cell aplasia suggested persistence of CD19-CAR T-cells in 93% of patients at PD.Salvage immune checkpoint inhibition (pembrolizumab, nivolumab), and lenalidomide with rituximab ortafasitamab yielded prolonged responses in a subset of patients, often exceeding 5 months... Our study identifies novel radiological risk factors for CD19-CAR failure in patients withCNSL, namely peripheral CE and LMD prior to CD19-CAR, which may guide prognostic stratification atbaseline. Outcome after CD19-CAR failure remains poor, underlining the need for rational salvagetreatments. In patients progressing after CD19-CAR therapy, we noted encouraging responses aftersalvage ICI and lenalidomide combined with rituximab/tafasitamab, which warrant further investigationin prospective studies."

CAR T-Cell Therapy • Clinical • IO biomarker • CNS Disorders • CNS Lymphoma • Hematological Malignancies • Lymphoma

Impact of prior B-cell-directed immunotherapy on the outcome of CD19 CAR T-cell therapy in aggressive B-cell lymphoma - an analysis of the EBMT and the GoCART coalition (ASH 2025) - "Introduction:Treatment outcomes of diffuse large B-cell lymphoma (DLBCL) and related large B-cell lymphoma (LBCL)have been revolutionized by novel B-cell-directed immunotherapies (BCDI), such as CD19-targetingchimeric antigen receptor T-cell therapy (CAR-T), polatuzumab vedotin (pola), and bispecific antibodies(BSA)...Here, wecompare outcomes of patients (pts) receiving BCDI (excluding rituximab) versus conventional treatmentsprior to CD19 CAR-T in a large European multicenter cohort.We collected retrospective data on the use and type of BCDI, as well as outcomes from 1154 adult ptsacross 38 European centers who received CD19 CAR-T between 2018 and 2023 for LBCL, identified in theEuropean Group for Blood and Marrow Transplantation (EBMT) registry...Twenty-four of 380 pts (6.3%) received BSA, 305 (80.3%)pola-based regimens, and 51 (13.4%) other BCDI (including obinutuzumab, 26 pts; brentuximab, 16 pts).The BCDI and non-BCDI groups were balanced for lymphoma diagnosis and..."

CAR T-Cell Therapy • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Mediastinal Large B-Cell Lymphoma

Fcγ-receptor-activation by circulating immune complexes in systemic autoimmune diseases and its reduction by CD19-CAR T-cell therapy. (PubMed, Rheumatology (Oxford)) - "Our study reveals the presence of FcyR-engaging cICs in CTDs and demonstrates that the bioactivity of cICs is correlated with clinical phenotypes and treatment outcomes."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Psoriatic Arthritis • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Seronegative Spondyloarthropathies • Sjogren's Syndrome • Systemic Sclerosis • TOP1

Clinical Presentation, Management and Outcome of Tumor inflammation-associated neurotoxicity (TIAN) in CNS lymphoma treated with CD19-CAR T-cell therapy (SNO 2025) - "Collectively, our work supports TIAN as a localized on-tumor, on-target neurotoxicity syndrome, closely related to pre-existing CNSL lesions and distinct from ICANS. CNS tumor volume at baseline may allow to identify patients at risk and may guide management."

CAR T-Cell Therapy • Clinical • Brain Cancer • CNS Lymphoma • CNS Tumor • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Clinical Presentation, Management and Outcome of Tumor inflammation-associated neurotoxicity (TIAN) in CNS lymphoma treated with CD19-CAR T-cell therapy (WFNOS 2025) - "Collectively, our work supports TIAN as a localized on-tumor, on-target neurotoxicity syndrome, closely related to pre-existing CNSL lesions and distinct from ICANS. CNS tumor volume at baseline may allow to identify patients at risk and may guide management."

CAR T-Cell Therapy • Clinical • Brain Cancer • CNS Lymphoma • CNS Tumor • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Clinical Presentation, Management and Outcome of Tumor inflammation-associated neurotoxicity (TIAN) in CNS lymphoma treated with CD19-CAR T-cell therapy (WFNOS 2025) - "Collectively, our work supports TIAN as a localized on-tumor, on-target neurotoxicity syndrome, closely related to pre-existing CNSL lesions and distinct from ICANS. CNS tumor volume at baseline may allow to identify patients at risk and may guide management."

CAR T-Cell Therapy • Clinical • Brain Cancer • CNS Lymphoma • CNS Tumor • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

The Ig Superfamily Ligand B7H6 Subjects Activated T Cells to NK Cell Surveillance and Limits CAR T Cell Persistence (ASH 2023) - P2 | "We then co-injected CD19.CAR T cells and patient-autologous NK cells in leukemia-engrafted mice and observed reduced CAR T cell persistence in the peripheral blood of mice with NK cell co-injection...We therefore analyzed tissue of patients that were treated with nivolumab and ipilimumab (NCT03416244)...We therefore suggest an alternative immune checkpoint that limits T cell expansion and persistence in physiological and cellular engineering contexts. Targeting the B7H6-NKp30 axis may offer a means to modulate T cell immunity across multiple disease entities."

CAR T-Cell Therapy • Clinical • IO biomarker • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammatory Bowel Disease • Leukemia • Lymphoma • Multiple Sclerosis • Oncology • T Cell Non-Hodgkin Lymphoma • CD4 • CD8 • GZMB • NCR3LG1

A Propensity Score-Matched Analysis on the Outcomes of Brexucabtagene Autoleucel from Zuma-2 Study and Allogeneic Stem Cell Transplantation from the EBMT Database in Relapsed and Refractory Post-Btki Mantle Cell Lymphoma (ASH 2023) - "Introduction Brexucabtagene autoleucel (brexu-cel), an autologous anti-CD19 CAR T-cell therapy, is approved in the US for the treatment of relapsed/refractory (r/r) mantle cell lymphoma (MCL) and in Europe for r/r MCL after ≥2 prior lines of therapies, including Bruton's tyrosine kinase inhibitor (BTKi)...Selection criteria to identify pts in the EBMT registry were: r/r MCL diagnosis and receipt of alloSCT from 2010 to 2020, age ≥18 years, prior treatment with anti-CD20, prior anthracycline- or bendamustine containing regimens, and prior BTKi...Despite efforts to match pts between the cohorts, the inherent limitations of this study, such as incongruent data sources and case selection bias, have to be considered. Additional analyses will be presented."

Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Lymphoma • Mantle Cell Lymphoma • Oncology • Transplantation

The CAR-Hematotox As a Risk Model to Predict Early Complications and Outcome after Bispecific T-Cell Engager Therapy in Relapsed/Refractory Multiple Myeloma (ASH 2024) - "The CAR-HEMATOTOX (HTX) score was originally developed to predict long-lasting neutropenia following anti-CD19 CAR T-cell therapy, but has since then emerged as a risk model for other immune-related toxicities, infections and survival across cellular immunotherapies...Methods : This retrospective observational study included 128 RRMM patients who had received at least one step-up dose of either standard-of-care teclistamab (n=70) or talquetamab (n=58) at two major German myeloma centers until June 2024...Moreover, a HTX ≥ 2 was associated with a significantly increased rate of CRS grade ≥ 2 (36% vs. 12%; OR 4.33; 95% CI 1.59-11.53; p=0.004) and tocilizumab administration (43% vs. 17%; OR 3.55; 95% CI 1.43-8.16; p=0.004)...Conclusion : Our study provides first evidence for the HTX score as a suitable model for risk stratification prior to BTCE therapy. Such scores can potentially influence clinical decision-making regarding inpatient step-up dosing, frequency of clinical..."

IO biomarker • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

Clonal Evolution of Lymphoid Malignancies Following the Mutagenic Impact of Radiotherapy (ASH 2024) - "Finally, we validated and refined the indel landscape of chemoRT by exposing TP53-mutant lymphoma cells (DHL-4) to cisplatin and RT, then performing 30x bulk WGS of 15 single-cell-derived colonies...All of these RT-unexposed cases had evidence of platinum/melphalan mutagenesis...One LBCL case had an irradiated neck node prior to CD19 CART...Here, we see that even a single resistant tumor cell from an RT-exposed lesion can seed systemic relapse. further underscoring the need to eradicate disease in entirety to avoid propagation of resistant subclones."

B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Plasmacytoma • RB1 • SOCS1 • TNFAIP3 • TP53