CAR-based Cellular Therapy: clinical ePoster

A087 - FEASIBILITY OF MANUFACTURING TISAGENLECLEUCEL IN PATIENTS LESS THAN 3 YEARS OF AGE WITH RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA (ID 576)

Authors
  • L. Eldjerou
  • C. Acker
  • D. Howick
  • L. Clough
  • M. Fuchs
  • F. Salmon
  • J. Willert
  • R. Tiwari
  • M. Robson

Abstract

Background:
Tisagenlecleucel is an autologous chimeric antigen receptor (CAR)-T cell therapy approved for the treatment of patients (pts) up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory or in ≥ 2nd relapse; however, pts < 3 years of age at screening were excluded from tisagenlecleucel clinical trials.

Methods:
Eligible pts were < 3 years of age at time of the request for commercial tisagenlecleucel, with manufacturing data after August 30, 2017 (first FDA approval of tisagenlecleucel).

Results:
Among 31 pts, the median age was 15 months (range, 3-35) and median body weight 10.2 kg (range, 6.0-15.6) at leukapheresis (14 pts < 10 kg and 17 pts ≥ 10 kg). Thirty-three leukaphereses were performed in 31 pts (Table; 2 pts underwent repeat leukapheresis for second manufacturing attempt), with a median of 1 leukapheresis day required to meet adequate cell counts (range, 1-6; Table). The acceptance criteria for tisagenlecleucel manufacture were met in 29/33 leukapheresis materials; 2/3 that did not meet acceptance criteria were unsuccessful. Following the first manufacturing attempt in 30 pts, 26/30 (86.7%) were successful and 4/30 experienced manufacturing failure (2 pts < 10 kg and 2 pts ≥ 10 kg). Of the 4 manufacturing failures, 2 successfully underwent repeat leukapheresis and remanufacturing and 2 did not undergo a second attempt. For 2 of the 4 manufacturing failures, the leukapheresis material did not meet acceptance criteria (pts were unable to undergo additional days of leukapheresis). The median manufactured cell dose in the final product was 4.0x106 CAR+ viable T cells/kg (range, 0.37x106 -4.0x106), median % cell viability was 87.6% (range, 66.7%-95.7%), and median CAR+% expression was 10% (range, 2.7%-25.6%). Measures to optimize leukapheresis in young pts with low weight, particularly < 10 kg, include raising hematocrit to 40% with blood transfusion, appropriate size central venous catheter, blood prime of the apheresis instrument, prevention of hypothermia during collection, close monitoring of vital signs and electrolytes, partial rinse back, and allowing > 1 day of leukapheresis to meet acceptance criteria.

Conclusions:
Leukapheresis and tisagenlecleucel manufacturing in pts with r/r ALL < 3 years of age and low weight are feasible and do not present manufacturability risk compared with clinical trial experience in patients ≥ 3 years of age.

 

 

Leukapheresis completed
N= 33
(n=31)

Pts<10 kg
N= 15
(n=14)

Pts≥10 kg
N= 18
(n=17)

Pts failed first manufacturing attempt
(n= 4/30)

Leukapheresis Procedure

# Leukapheresis days, median (range) 1 (1-6) 2 (1-3) Collapse