Results of ARI-0001 CART19 Cells in Patients With Chronic Lymphocytic Leukemia and Richter’s Transformation

Ortiz-Maldonado, Valentín; Frigola, Gerard; Español-Rego, Marta; Balagué, Olga; Martínez-Cibrián, Núria; Magnano, Laura; Giné, Eva; Pascal, Mariona; Correa, Juan Gonzalo; Martínez‐Roca, Alexandra; Cid, Joan; Lozano, Miquel; Villamor, Neus; Benítez‐Ribas, Daniel; Esteve, Jordi; López‐Guillermo, Armando; Campo, Elı́as; Urbano-Ispizúa, Álvaro; Juan, Manel; Delgado, Julio

doi:10.3389/fonc.2022.828471

Cited by 20 publications

(12 citation statements)

References 26 publications

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“…ARI-0001 are autologous T-cells transduced with a CD137-based CAR construct targeting CD19 and developed at the Hospital Clinic of Barcelona ( 106 ). The CAR-T product ARI-0001 was administered to six patients with RT (five patients with DLBCL-RT and one patient diagnosed with plasmablastic transformation), achieving CRs in three patients sustained at 1.4, 12.5, and 26.7 months after treatment, respectively.…”

Section: Treatment Of Dlbcl-rtmentioning

confidence: 99%

Biology and Treatment of Richter Transformation

Condoluci

Rossi

2022

Front. Oncol.

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Richter transformation (RT), defined as the development of an aggressive lymphoma on a background of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), represents a clinical unmet need because of its dismal prognosis. An increasing body of knowledge in the field of RT is arising from the recent development of preclinical models depicting the biology underlying this aggressive disease. Consistently, new therapeutic strategies based on a genetic rationale are exploring actionable pathogenic pathways to improve the outcome of patients in this setting. In this review, we summarize the current understandings on RT biology and the available treatment options.

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Section: Treatment Of Dlbcl-rtmentioning

confidence: 99%

Biology and Treatment of Richter Transformation

Condoluci

Rossi

2022

Front. Oncol.

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“…Another anti-CD19 CAR T cell product, ARI-0001, was approved by the Spanish Agency of Medicines and Medical Devices (AEMPS) under the hospital exemption approval pathway foreseen by the European Regulation [37]. The treatment of patients with CLL, including Richter's transformation, showed a response rate of 87.5% [38]; however, CD19-negative relapses occurred in 2 patients. In contrast to a centralized marketing authorization pathway which allows access to all member states, an advanced therapy medicinal product (ATMP) under hospital exemption approval is intended to be placed on the European market as a custom-made product used only in the member state where it was developed [39].…”

Section: First Car T Cell Products Are Approved By the Fda And Emamentioning

confidence: 99%

Treatment with Living Drugs: Pharmaceutical Aspects of CAR T Cells

Holzinger

Abken²

2022

Pharmacology

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Background: Adoptive therapy with genetically modified T cells achieves spectacular remissions in advanced hematologic malignancies. In contrast to conventional drugs, this kind of therapy applies viable autologous T cells that are ex vivo genetically engineered with a chimeric antigen receptor (CAR) and are classified as advanced therapy medicinal products. Summary: As “living drugs,” CAR T cells differ from classical pharmaceutical drugs as they provide a panel of cellular capacities upon CAR signaling, including the release of effector molecules and cytokines, redirected cytotoxicity, CAR T cell amplification, active migration, and long-term persistence and immunological memory. Here, we discuss pharmaceutical aspects, the regulatory requirements for CAR T cell manufacturing, and how CAR T cell pharmacokinetics are connected with the clinical outcome. Key Messages: From the pharmacological perspective, the development of CAR T cells with high translational potential needs to address pharmacodynamic markers to balance safety and efficacy of CAR T cells and to address pharmacokinetics with respect to trafficking, homing, infiltration, and persistence of CAR T cells.

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“…The ongoing ZUMA-8 Phase 1/2 trial is currently investigating the role of brexu-cel in this setting [ 78 ]. Additionally, promising activity has also been described in patients with transformed CLL/SLL (Richter syndrome) [ 72 , 79 , 80 , 81 ].…”

Section: Efficacy Of Autologous Car T Cell Therapy In Lymphomamentioning

confidence: 99%

CAR T-Based Therapies in Lymphoma: A Review of Current Practice and Perspectives

2022

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While more than half of non-Hodgkin lymphomas (NHL) can be cured with modern frontline chemoimmunotherapy regimens, outcomes of relapsed and/or refractory (r/r) disease in subsequent lines remain poor, particularly if considered ineligible for hematopoietic stem cell transplantation. Hence, r/r NHLs represent a population with a high unmet medical need. This therapeutic gap has been partially filled by adoptive immunotherapy. CD19-directed autologous chimeric antigen receptor (auto-CAR) T cells have been transformative in the treatment of patients with r/r B cell malignancies. Remarkable response rates and prolonged remissions have been achieved in this setting, leading to regulatory approval from the U.S. Food and Drug Administration (FDA) of four CAR T cell products between 2017 and 2021. This unprecedented success has created considerable enthusiasm worldwide, and autologous CAR T cells are now being moved into earlier lines of therapy in large B cell lymphoma. Herein, we summarize the current practice and the latest progress of CD19 auto-CAR T cell therapy and the management of specific toxicities and discuss the place of allogeneic CAR T development in this setting.

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Results of ARI-0001 CART19 Cells in Patients With Chronic Lymphocytic Leukemia and Richter’s Transformation

Cited by 20 publications

References 26 publications

Biology and Treatment of Richter Transformation

Biology and Treatment of Richter Transformation

Treatment with Living Drugs: Pharmaceutical Aspects of CAR T Cells

CAR T-Based Therapies in Lymphoma: A Review of Current Practice and Perspectives

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