Point-of-care CAR T-cell therapy as salvage strategy for out-of-specification tisagenlecleucel

Abstract

Tisagenlecleucel (tisa-cel) is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for patients with relapsed/refractory large B-cell lymphoma. Outcomes of patients with out-of-commercial specification (OOS) CAR T products are not well characterized. We therefore assessed 37 adult patients who underwent leukapheresis for tisa-cel therapy in a single center. In nine (24%) patients, manufactured tisa-cel was considered OOS. Three of them (33%) received tisa-cel after institutional review board approval; 2/9 (22%) did not receive tisa-cel due to disease progression; and 4/9 (44%) received academic point-of-care (POC) CAR T-cell as salvage therapy, at a median of 35 days following OOS notification. Three of those four patients achieved a complete response. In univariate analysis, risk factors for OOS were ≥ 4 prior therapies or previous bendamustine exposure. In conclusion, we report high OOS incidence of 24% in real-life setting. Forty-four percent of those patients received POC CAR T-cell as salvage therapy.

Keywords:

• Chimeric antigen receptor
• CAR-T
• OOS
• point of care
• Tisa-cel
• production failure

Acknowledgments

The authors acknowledge the kind support of all physicians and laboratory team of the Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center.

Previous Publication

This work was presented in part at the European Hematology Association 2021 Virtual Congress and the 16th International Conference on Malignant Lymphoma (Lugano, Switzerland).

Disclosure statement

R. S. served as a consultant for Medexus and MyBiotics. A. S. served on scientific advisory board for Jazz, Gilead, Novartis, Abbvie, Bristol-Myers Squibb and Medac. A. A. reports honoraria from Gilead, Novartis, Takeda, Roche, Bristol-Myers Squibb, and Sanofi. The authors report there are no competing interests to declare.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.