Apheresis for chimeric antigen receptor T-cell production in adult lymphoma patients.

Abstract

BACKGROUND:

To date, in-depth analysis of leukapheresis products as starting material for CAR T-cell manufacturing, specifically Tisagenlecleucel production, are scarce. In this study, we report on lymphapheresis data for production of Tisagenlecleucel for elderly and pretreated lymphoma patients.

STUDY DESIGN AND METHODS:

Spectra Optia from Terumo BCT, Lakewood, CO, was employed for apheresis using the cMNC program. Apheresis success was defined as meeting a target total nucleated cell (TNC) count of ≥2 × 109 , a CD3-positive lymphocyte count of ≥1 × 109 and an overall viability of ≥70% in the lymphapheresis product.

RESULTS:

Twenty-three patients (age 37-77 years) and 24 apheresis runs were evaluated. The median CD3-positive lymphocyte count in peripheral blood at the beginning of apheresis was 565 cells/μl (range: 70-1345 cells/μl). Circulating lymphoma cells were detected in one patient prior to apheresis. Target criteria were met in 21 of 23 patients. The median TNC count in the apheresate was 11.2 × 109 (range: 2.9 × 109 -47.4 × 109 ). The median CD3-positive lymphocyte count in the apheresate was 2.55 × 109 (range: 0.370 × 109 -6.915 × 109 ), which resulted in a median collection efficiency for CD3-positive lymphocytes of 63.7% (range: 9.56%-93.6%). No adverse events associated with the apheresis process were observed.

CONCLUSIONS:

Lymphapheresis with the Spectra Optia cMNC program provided a sufficient quantity of CD3-positive lymphocytes for CAR T-cell manufacturing for the majority of patients despite their heavy pretreatment and advanced age. Moreover, we are the first to advocate early pre-emptive lymphocyte collection in DLBCL-NOS patients intended to undergo treatment with Tisagenlecleucel.

• Authors: Dennis Christoph Harrer, Martin Heidenreich, Matthias Alexander Fante, Viktoria Müller, Viola Haehnel, Robert Offner, Ralph Burkhardt, Wolfgang Herr, Matthias Edinger, Daniel Wolff, Simone Thomas, Andreas Brosig
• Journal: Transfusion (Transfusion) Vol. 62 Issue 8 Pg. 1602-1611 (08 2022) ISSN: 1537-2995 [Electronic] United States
• PMID: 35851959 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.

Chemical References

• Receptors, Chimeric Antigen

Topics

• Adult
• Aged
• Blood Component Removal (methods)
• Humans
• Leukapheresis (methods)
• Lymphoma (therapy)
• Middle Aged
• Receptors, Chimeric Antigen
• T-Lymphocytes