Product characteristics associated with in vivo expansion of anti-CD19 CAR T cells in patients treated with axicabtagene ciloleucel (axi-cel).

Authors

Frederick Locke

Frederick Lundry Locke

H. Lee Moffitt Cancer Canter and Research Institute, Tampa, FL

Frederick Lundry Locke , John Rossi , Sattva Swarup Neelapu , Allen Xue , Marc Better , Xiao Zhang , Armin Ghobadi , Lazaros J. Lekakis , David Bernard Miklos , Caron Alyce Jacobson , Ira Braunschweig , Olalekan O. Oluwole , Tanya Siddiqi , Yi Lin , John Timmerman , Patrick Michael Reagan , Lynn Navale , William Y. Go , Jeffrey S. Wiezorek , Adrian Bot

Organizations

H. Lee Moffitt Cancer Canter and Research Institute, Tampa, FL, Kite Pharma, Inc., Santa Monica, CA, The University of Texas MD Anderson Cancer Center, Houston, TX, Washington University in St. Louis, St. Louis, MO, University of Miami, Miami, FL, Stanford University Medical Center, Stanford, CA, Dana-Farber Cancer Institute, Boston, MA, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, Vanderbilt University Medical Center, Nashville, TN, City of Hope Comprehensive Cancer Center, Duarte, CA, Mayo Clinic, Rochester, MN, University of California, Los Angeles, Los Angeles, CA, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY

Research Funding

Pharmaceutical/Biotech Company

Background: Axi-cel (formerly KTE-C19) is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy. ZUMA-1 is a multicenter, registrational trial of axi-cel in patients (pts) with refractory aggressive non-Hodgkin lymphoma. In a prespecified interim analysis, ZUMA-1 met its primary endpoint, with a 76% objective response rate and a 47% complete response rate (Blood 2016;128:LBA-6). Post-treatment CAR T cell blood levels were associated with objective response. Here, we describe novel associations between product characteristics and CAR T cell levels in pts. Methods: CAR T cell characteristics in axi-cel produced from 62 pts were analyzed by flow cytometry and modeled against CAR T cell levels. In vivo CAR T cell levels were measured by qPCR. T cell expansion during production (fold expansion/total days in culture) was compared with CAR T cell blood levels, using a partition analysis with expansion rates of ≥1 vs < 1. Wilcoxon 2-sample test and linear regression were used. Results: Axi-cel contained CCR7+ T cells (median, 42%; range, 15–73%), with naïve (CD45RA+/CCR7+; median, 12%; range, 1–57%), central memory (CD45RA−/CCR7+; median, 29%; range, 12–49%) phenotypes, and more differentiated CCR7− effector memory and effector T cells. On infusion, CAR T cells expanded rapidly, reaching peak levels within 2 weeks (median, 43 cells/μL; range, 1–1513), and were also measurable in all pts at 1 month (median, 2 cells/μL; range, 0.03–89). The CCR7+/CCR7− T cell ratio in axi-cel associated positively with peak (P=0.001) and cumulative (P=0.003) CAR T cell levels through 1 month. Axi-cel lots that expanded more rapidly during production (≥1.0-fold/d; n = 18/62) associated with higher cumulative levels of CAR T cells (P=0.03). Other product characteristics, eg, CD4/CD8 ratio or number of infused T cells, were not significantly associated with CAR T cell blood levels. Conclusions: An association was observed between CAR T cell expansion in vivo and both the T cell growth rate during production and product cell phenotype pretreatment. A key attribute of axi-cel product was the presence of CCR7+ naïve/central memory T cells, without upfront T cell subset selection. Clinical trial information: NCT02348216

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics—Immunotherapy

Track

Developmental Therapeutics and Translational Research,Immunotherapy

Sub Track

Biomarkers and Correlative Studies from Immunotherapy Trials

Clinical Trial Registration Number

NCT02348216

Citation

J Clin Oncol 35, 2017 (suppl; abstr 3023)

DOI

10.1200/JCO.2017.35.15_suppl.3023

Abstract #

3023

Poster Bd #

118

Abstract Disclosures