Anti-CD19 CAR-T / University of Utah - LARVOL DELTA

PRODIGY: Pilot Study of Anti-CD19 Chimeric Antigen Receptor T Cells (CAR-T Cells) for the Treatment of Relapsed/Refractory CD19+ Malignancies (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: University of Utah | Trial completion date: Jan 2027 ➔ May 2027 | Trial primary completion date: Jan 2026 ➔ May 2026

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

Rethinking Surveillance: Low Incidence of Late-Onset Toxicities across CD-19 CAR T-cell Constructs Supports Reduced Monitoring (TCT-ASTCT-CIBMTR 2026) - "Introduction: Anti-CD19 chimeric antigen receptor T-cell therapy (CART) is an effective treatment for relapsed or refractory (R/R) large B-cell lymphoma (LBCL), with three FDA-approved constructs: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel). This is the largest real-world study to date examining late-onset CRS and ICANS associated with FDA-approved anti-CD19 CART. Results demonstrate a low risk of these toxicities occurring more than 14 days post-infusion across all constructs. These findings support the FDA's June 2025 label updates, reducing required monitoring for patients treated with these therapies."

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

Fludarabine Lymphodepletion Exposure Is Associated with Idecabtagene Vicleucel Toxicity in Relapsed and Refractory Multiple Myeloma Patients: Real-World Experience from the US Myeloma Immunotherapy Consortium (ASH 2023) - "Flu exposure, defined by the area under the curve (AUC), has been shown to predict rates of relapse after anti-CD19 CAR-T in B-cell acute lymphoblastic leukemia (Fabrizio et al, Blood Advances, 2022). These data highlight how standard BSA-based Flu dosing results in significant PK variability and overestimates Flu AUC, increasing the risk of CAR-T toxicities. Prospective validation of our model-based findings through measurement of Flu blood levels, CAR-T PK, and clinical outcomes is warranted."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Kidney Disease • Hematological Disorders • Hematological Malignancies • Leukemia • Multiple Myeloma • Nephrology • Oncology • Renal Disease

Outcomes of Chimeric Antigen Receptor (CAR) T-Cell Therapy in Extranodal (EN) B-Cell Non-Hodgkin Lymphoma (NHL): Results from a Multicenter Analysis (ASH 2024) - "Methods : We performed a retrospective multi-center analysis of pts with R/R aggressive B-cell NHL who had EN disease and received treatment with anti-CD19 CAR-T...99% (278 of 281 available) of pts received a commercial CD19 CAR (43% axicabtagene ciloleucel, 30% tisagenlecleucel, 25% lisocabtagene maraleucel, 2% brexucabtagene autoleucel), while the remaining 1% (n=3) received a bispecific or allogeneic CAR...Transfusion support (PRBC and platelets) and filgrastim beyond the first 30 days post CAR-T was needed in 18% (50 of 272 available), 20% (54 of 272 available), and 34% (93 of 272 available) of pts, respectively...TCT 2024). Further analysis including comparison of single-site versus multi-site EN disease as well as multivariate analysis of factors with significant impact on survival is ongoing."

Clinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T-Cell Large Granular Lymphocyte Leukemia

Real-World Early Outcomes of Second-Line Axicabtagene Ciloleucel (Axi-Cel) Therapy in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL) (ASH 2024) - P2, P3 | "Introduction In the Phase 3 ZUMA‑7 study (NCT03391466), axi-cel, an autologous anti-CD19 CAR T-cell therapy, showed superior event-free survival (EFS; Locke FL, et al...Lymphodepleting chemotherapy regimens were mostly cyclophosphamide plus fludarabine (75%) or bendamustine (22%)...To treat pts with any CRS and/or ICANS (n=398, 89%), tocilizumab, corticosteroids, and anakinra were given to 80%, 65%, and 18%, respectively...Despite a broader pt population beyond the ZUMA-7 and ALYCANTE trials, outcomes at median follow-up of 12 mo were consistent with those observed in ZUMA-7. DCL, SK, and MSOB contributed equally."

Clinical • Real-world • Real-world evidence • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • High-grade B-cell lymphoma • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • Thrombocytopenia

REAL-WORLD EFFECTIVENESS AND SAFETY OUTCOMES AMONG KEY SUBGROUPS OF SECOND-LINE (2L) AXICABTAGENE CILOLEUCEL (AXI-CEL) FOR PATIENTS WITH RELAPSED/REFRACTORY (R/R) LARGE B-CELL LYMPHOMA (LBCL) (EHA 2025) - "Background: Axi-cel is an autologous anti-CD19 CAR T-cell therapy that showed superiority vs historical standard of care for R/R LBCL in ZUMA-7. This is the largest real-world analysis of pts with R/R LBCL treated with L commercial axi-cel. No association was found between hepatic or pulmonary comorbidities and outcomes. Pts aged ≥65 y had a higher risk of ICANS while CV impairment and lower KPS were associated with shorter survival."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • B Cell Lymphoma • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia

Real-world outcomes of axicabtagene ciloleucel (axi-cel) for the treatment of relapsed/refractory (R/R) secondary central nervous system lymphoma (SCNSL). (ASCO 2025) - "Funded by U.S. National Institutes of Health, Kite, a Gilead Company Background: Axi-cel is an autologous anti-CD19 CAR T-cell therapy that demonstrated durable, long-term efficacy and manageable safety in R/R LBCL...Of 56 pts with CRS and/or ICANS, tocilizumab, corticosteroids, and anakinra were used in 68%, 73%, and 7% of pts, respectively... With 4-y median follow-up, this real-world study highlights the potential use of axi-cel as an option to treat this challenging group of pts. Further studies are needed to improve response durability."

Clinical • Real-world • Real-world evidence • CNS Disorders • CNS Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Oncology • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma • Thrombocytopenia

A Comparison of Survival in Younger Vs Older Patients Treated with CD19-Directed Chimeric Antigen Receptor T-Cell Therapy (CART) for Aggressive B-Cell Lymphoma (TCT-ASTCT-CIBMTR 2025) - "Methods We performed a multicenter, retrospective study of pts with R/R LBCL treated with anti-CD19 CART therapy across 14 US institutions from 2018-2024...Older pts were more likely to be treated with 4-1BB constructs (tisa-cel or liso-cel) rather than CD28 construct axi-cel (p< 0.01) and more likely to have an IPI of 3-5 at time of CART infusion (p=0.01)...For our oldest pts age ≥80, CART provides similar safety and therapeutic benefits comparable to younger pts and pivotal trials. CART should be prioritized as a curative option in these pts with consideration for functional status and toxicities."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Subsequent Malignant Neoplasms in Patients Previously Treated with Anti-CD19 CAR T-Cell Therapy. (PubMed, Blood Adv) - No abstract available

CAR T-Cell Therapy • Journal • Oncology

PRODIGY: Pilot Study of Anti-CD19 Chimeric Antigen Receptor T Cells (CAR-T Cells) for the Treatment of Relapsed/Refractory CD19+ Malignancies (clinicaltrials.gov) - P1 | N=6 | Recruiting | Sponsor: University of Utah | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • Enrollment open • Acute Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology