Delving into the Latest Updates on CD19/CD20 CAR-T Cells(The Parker Institute For Cancer Immunotherapy) with Synapse

Overview

Basic Info

Drug Type

CAR-T

Synonyms

CD19/CD20 chimeric antigen receptor (CAR) T-cells

Target

CD19 x CD20

Mechanism

CD19 inhibitors(B-lymphocyte antigen CD19 inhibitors), CD20 inhibitors(B-lymphocyte antigen CD20 inhibitors), Cell replacements

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Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication

Chronic lymphocytic leukaemia refractoryDiffuse large B-cell lymphoma recurrentDiffuse large B-cell lymphoma refractory+ [8]

Inactive Indication-

Originator Organization

The Parker Institute For Cancer ImmunotherapyStartup

Active Organization

Jonsson Comprehensive Cancer Center

The Parker Institute For Cancer ImmunotherapyStartup

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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This phase I trial studies the side effects and best dose of CD19/CD20 chimeric antigen receptor (CAR) T-cells when given together with chemotherapy, and to see how effective they are in treating patients with non-Hodgkin's B-cell lymphoma or chronic lymphocytic leukemia that has come back (recurrent) or has not responded to treatment (refractory). In CAR-T cell therapy, a patient's white blood cells (T cells) are changed in the laboratory to produce an engineered receptor that allows the T cell to recognize and respond to CD19 and CD20 proteins. CD19 and CD20 are commonly found on non-Hodgkin?s B-cell lymphoma and chronic lymphocytic leukemia cells. Chemotherapy drugs such as fludarabine phosphate and cyclophosphamide can control cancer cells by killing them, by preventing their growth, or by stopping them from spreading. Combining CD19/CD20 CAR-T cells and chemotherapy may help treat patients with recurrent or refractory B-cell lymphoma or chronic lymphocytic leukemia.

Start Date04 Oct 2019

Sponsor / Collaborator

Jonsson Comprehensive Cancer Center

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100 Clinical Results associated with CD19/CD20 CAR-T Cells(The Parker Institute For Cancer Immunotherapy)

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100 Translational Medicine associated with CD19/CD20 CAR-T Cells(The Parker Institute For Cancer Immunotherapy)

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100 Patents (Medical) associated with CD19/CD20 CAR-T Cells(The Parker Institute For Cancer Immunotherapy)

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566

Literatures (Medical) associated with CD19/CD20 CAR-T Cells(The Parker Institute For Cancer Immunotherapy)

01 Sep 2024·Journal for ImmunoTherapy of Cancer

Neurofilament light chain levels as an early predictive biomarker of neurotoxicity after CAR T-cell therapy

Article

Author: Thieblemont, Catherine ; Carpentier, Antoine F ; Azoulay, Elie ; Bouvier, Amélie ; Allain, Vincent ; Ursu, Renata ; Cuffel, Alexis ; Di Blasi, Roberta ; Larue, Marion ; Caillat-Zucman, Sophie ; Maillard, Alexis

Immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant cause of morbidity associated with CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. Early prediction of patients who will develop ICANS would be crucial to better guide individualized management of high-risk patients, but specific predictive markers are still missing. Serum neurofilament light chain (NfL) levels are a sensitive indicator of neuroaxonal injury in neurological diseases. Elevated NfL levels at the time of CAR T-cell infusion have been associated with the severity of ICANS, but their utility for earlier identification of patients with subclinical neurological damage has not been evaluated.We studied all consecutive adult patients who received commercial CAR T cells for relapsed/refractory B-cell lymphomas at Saint-Louis Hospital between January 2019 and February 2023. Patients with pre-existing or current neurological disease were excluded. NfL levels were quantified in frozen serum collected at the time of the decision to treat (ie, the day of leukapheresis) and at the time of treatment (ie, the day of infusion).Of the 150 study patients, 28% developed ICANS of any grade, including 15.3% of grade 2–4. Receiving a CAR construct with a CD28 domain (58% of patients) was the strongest predictor of grade 2–4 ICANS. Serum NfL levels were significantly higher in patients with grade 2–4 ICANS than in those with grade 0–1 ICANS, both at the time of leukapheresis and infusion. In multivariate models, NfL above the cut-off value was independently associated with grade 2–4 ICANS at leukapheresis (NfL>75 pg/mL, OR 4.2, 95% CI 1.2 to 14.2, p=0.022) and infusion (NfL>58 pg/mL, OR 4.3, 95% CI 1.3 to 13.7, p=0.015).In conclusion, high NfL levels at the time of the decision to proceed with CAR T-cell manufacturing may represent an early surrogate of underlying loss of neuroaxonal integrity that increases the risk of subsequent neurotoxicity. Incorporating NfL levels into the decision-making process based on each patient’s risk profile could help determine the appropriate CAR product when possible, and guide the prophylactic or therapeutic management of ICANS.

01 Jul 2024·Clinical and Translational Radiation Oncology

Adaptive bridging radiation therapy for relapsed/refractory B-cell lymphoma patient undergoing CAR T-cell therapy: Case report

Article

Author: Pursley, Jennifer ; Patel, Chirayu G ; Ababneh, Hazim S ; Connor Johnson, P

Radiation therapy (RT) is utilized as a bridging strategy for patients with aggressive B-cell lymphoma prior to CD19-targeted chimeric antigen receptor (CAR T)-cell therapy. RT has been shown to provide local control without exacerbating the toxicities associated with subsequent CAR T-cell infusion. However, a consensus on the optimal radiation dose and fractionation for bridging purposes has yet to be established. We present a case of a patient with relapsed aggressive B-cell lymphoma who underwent bridging adaptive RT on a CT-linac prior to receiving CAR T-cell therapy. At month 6 post-CAR T infusion, the patient demonstrates no signs of disease recurrence or relapse, nor any unexpected toxicities attributable to the combined treatment. This underscores the feasibility and success of this innovative approach in treating lymphoma patients undergoing CAR T-cell therapy.

01 Jun 2024·Oncology and Therapy

Optimizing Real-World Outcomes in High-Risk Relapsed/Refractory (r/r) FL with CAR-T Cell Therapy: A Vodcast and Case Example

Article

Author: Hübel, Kai

Follicular lymphoma (FL) is often considered a chronic disease with frequent relapses, shortening both response duration and survival after every relapse. Selecting the most appropriate therapy at the right time within the treatment timeline is key to optimize outcomes. The aim of this vodcast, featuring Dr. Kai Hübel, is to outline the severity of FL by referring to a patient case as well as highlight chimeric antigen receptor (CAR)-T cells as an effective therapy in relapsed/refractory (r/r) FL. The patient was in their early 50s, diagnosed with FL in the early 2010s and presented with a third relapse. The patient complained of night sweats and fatigue but was still capable of self-care (Eastern Cooperative Oncology Group Performance Status Scale 2). The patient received eight cycles of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP), followed by irradiation and rituximab maintenance (first-line) and then received rituximab 4 × weekly, followed by rituximab maintenance (second-line). The patient relapsed during rituximab maintenance; the patient was rituximab refractory. The patient received six cycles of bendamustine/obinutuzumab followed by obinutuzumab maintenance. The patient relapsed during obinutuzumab maintenance, achieved a partial remission after irradiation and was switched to R/lenalidomide. Due to several high-risk features, CAR-T cell therapy was initiated. Dr. Hubel underlines how earlier treatment with CAR-T cell therapy would have been beneficial for this patient. Results of the ELARA trial as well as comparative studies have shown tisagenlecleucel to be more effective than standard of care in extensively pretreated r/r FL, including high-risk patients. In conclusion, CAR-T cell therapy is a promising therapy option for patients with multiply r/r FL. A vodcast feature is available for this article.

100 Deals associated with CD19/CD20 CAR-T Cells(The Parker Institute For Cancer Immunotherapy)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diffuse large B-cell lymphoma recurrent	Phase 1	US	The Parker Institute For Cancer ImmunotherapyStartup	04 Oct 2019
Diffuse large B-cell lymphoma recurrent	Phase 1	US	Jonsson Comprehensive Cancer Center	04 Oct 2019
Mantle cell lymphoma recurrent	Phase 1	US	The Parker Institute For Cancer ImmunotherapyStartup	04 Oct 2019
Mantle cell lymphoma recurrent	Phase 1	US	Jonsson Comprehensive Cancer Center	04 Oct 2019
Primary mediastinal large B-cell lymphoma recurrent	Phase 1	US	The Parker Institute For Cancer ImmunotherapyStartup	04 Oct 2019
Primary mediastinal large B-cell lymphoma recurrent	Phase 1	US	Jonsson Comprehensive Cancer Center	04 Oct 2019
Recurrent Chronic Lymphoid Leukemia	Phase 1	US	Jonsson Comprehensive Cancer Center	04 Oct 2019
Recurrent Chronic Lymphoid Leukemia	Phase 1	US	The Parker Institute For Cancer ImmunotherapyStartup	04 Oct 2019
Refractory Small Lymphocytic Lymphoma	Phase 1	US	Jonsson Comprehensive Cancer Center	04 Oct 2019
Refractory Small Lymphocytic Lymphoma	Phase 1	US	The Parker Institute For Cancer ImmunotherapyStartup	04 Oct 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04007029 (AACR2023) Manual	Phase 1	Non-Hodgkin's lymphoma refractory	11	CD19/CD20 CAR-T Cells	(aaryfonpdz) = Neurotoxicity was not observed mfxnycuzww (mhhfodfsds ) View more	Positive	14 Apr 2023
NCT04007029 (ASCO2022) Manual	Phase 1	Non-Hodgkin Lymphoma	9	Chimeric Antigen Receptor T-Cell Therapy+Cyclophosphamide+Fludarabine Phosphate+Tocilizumab	(bleuwsewys) = degmyzadop zpuyyujqgj (uxzsmpbrge ) View more	Positive	02 Jun 2022