CAR-based Cellular Therapy: clinical ePoster

A099 - CHALLENGES IN PROVIDING GOOD LEUKAPHERESIS PRODUCTS FOR THE PRODUCTION OF CAR T CELLS FOR PATIENTS WITH RELAPSED/REFRACTORY NHL OR ALL (ID 936)

Authors
  • F. Korell
  • S. Laier
  • S. Sauer
  • S. Jaramillo-Segura
  • E. Lasitschka
  • K. Veelken
  • H. Hennemann
  • M. Schubert
  • T. Sauer
  • P. Pavel
  • C. Müller-Tidow
  • P. Dreger
  • M. Schmitt
  • A. Schmitt

Abstract

Background:
In patients with relapsed or refractory B-lineage acute lymphoblastic leukemia (ALL) or B-cell non-Hodgkin's lymphoma (NHL) therapy with chimeric antigen receptor T (CAR-T) cells has proven to be highly effective. As starting material for the production of CAR-T cells T lymphocytes from the patients are mandatory. To harvest sufficient lymphocytes, leukapheresis as first step in the production process has to be performed. This constitutes a challenge to the treating physicians with regard to timing of the apheresis in heavily pretreated patients suffering from rapid progressive disease and being treated by drugs with negative impact on T cells.

Methods:
Data from 45 adult patients suffering from r/r DLBCL (68%), PMBCL (2%), MCL (4%), FL (2%), CLL (4%), ALL (13%) or multiple myeloma (5%) who received a leukapheresis for CAR-T cell production were analyzed. Apheresis procedures were effective using the Spectra Optia_ device. Peripheral blood counts pre- and post-apheresis, as well as leukapheresis product parameters were assessed. Further important tasks were the analysis of the medication used prior to apheresis and the optimization of the apheresis procedure. Fourteen leukapheresis products were produced for clinical trials including 11 patients in our in-house production HD-CAR-1 study.

Results:
All patients qualified for leukapheresis due to the following criteria: hemoglobin > 8g/dl, platelets > 75/nl, ANC > 1/nl, ALC > 0.3/nl, negative PCR for HBV, HCV, HEV and HIV; no active GvHD, no florid infection, no severe impairment of cardiac or pulmonary function. Leukapheresis was feasible in all patients and could be performed through peripheral venous access using the Spectra Optia_ device without any serious side effects. In total we performed 48 leukaphereses. 45 patients received a single apheresis and in three patients a later second apheresis was required due to infectious complications or electrolyte disturbance leading to a manufacturing failure.
CAR T cell production was feasible for 44 of 45 patients. A mean blood volume of 11.8 (range 5.8-15) L was processed over a time of 238 (120-326) minutes. The leukapheresis product contained a mean of 11.8 x 10^9 (0.9-34.1 x 10^9) total nucleated cells and 4.9 x 10^9 (0.4 - 23.2 x 10^9) CD3+ T cells with a viability of 99.9 (99.6 - 100) % in a mean volume of 235 (136 - 310) ml with a hematocrit of 3 (1.1 - 7.4) %.

Conclusions:
Leukapheresis was feasible in all patients in an out-patient setting. To harvest a sufficient number of lymphocytes for CART cell production, a minimum of 12 -15 L total blood volume should be processed in patients with an ANC 1-3/nl and ALC 0.3-1/nl. We established therefore a standardized procedure for the apheresis handling and developed a recommendation list for the timing of the medication before apheresis.

Disclosure:

MS: Apogenix: Funding for collaborative research. Hexal: Financial support for research on biosimilars, travel grants. Kite: Financial support of educational activities and conference, travel grants. Co-PI of clinical trials on CAR-T cells. MSD: Ad board member, PI of clinical trials on letermovir. Novartis: Collaborative research grant. Co-PI of clinical trials on CAR-T cells. TolerogenixX: Co-Founder and shareholder.
AS: TolerogenixX: Co-Founder and shareholder, Mallinckrodt-Therakos: research grant, Jazz: travel grant.
PD: Advisory boards Novartis, Kite/Gilead

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