The following article features coverage from the American Society of Hematology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Administration of a third-generation anti-CD19 chimeric antigen receptor (CAR) T-cell (CAR-T) therapy appeared feasible and showed no major safety concerns for patients with CD19-positive relapsed or refractory lymphoid malignancies. The initial results of the Heidelberg CAR trial 1 (HD-CAR-1) were presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.

Unlike second-generation CAR-T therapies, which have either a 4-1BB or CD28  costimulatory domain, third-generation CAR-T therapies appear to incorporate 2 or more signaling domains. Two other clinical trials (one of which is Identifier: NCT02132624) have evaluated third-generation anti-CD19 CAR-T therapies, and have reported “favorable” results, according to the study researchers.

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So far, the HD-CAR-1 trial ( Identifier: NCT03676504) has enrolled 10 patients with relapsed or refractory lymphoid disease to receive lymphodepleting therapy with fludarabine and cyclophosphamide followed by administration of anti-CD19 CAR-T.

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Among these 10 patients, 3 have B-lineage acute lymphoblastic leukemia, 2 have chronic lymphocytic leukemia, 2 have mantle cell lymphoma, 2 have diffuse large B-cell lymphoma, and 1 has transformed follicular lymphoma.

To date, all enrolled patients have undergone leukapheresis and 8 have received autologous anti-CD19 CAR-T, with 6 receiving only 106 CAR-T cells and 2 receiving 5 X 106 CAR-T cells. The CAR-T cells were manufactured successfully, with no production failures.

No patients had higher than grade 2 cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. One patient required treatment with tocilizumab. No patients had neurological side effects.

To date, 6 of the 8 treated patients have responded. The remaining 2 treated patients are not evaluable for a response yet, according to the data in the abstract.

“Leukapheresis and CAR-T cell manufacturing were effective for all patients enrolled in the HD-CAR trial to date,” the study researchers wrote in the abstract. “Patients responded clinically to treatment despite low numbers of administered CAR-T cells.”

Read more of Cancer Therapy Advisor‘s coverage of ASH’s annual meeting by visiting the conference page.


Schubert M-L, Schmitt A, Neuber B, et al. Third-generation CAR T cells targeting CD19 are associated with an excellent safety profile and might improve persistence of CAR T cells in treated patients. Presented at: 61st American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2019: Orlando, Florida. Abstract 51.