Data from Phenotypic Composition of Commercial Anti-CD19 CAR T Cells Affects <i>In Vivo</i> Expansion and Disease Response in Patients with Large B-cell Lymphoma

Abstract

&lt;div&gt;AbstractPurpose:&lt;p&gt;In clinical trials, the expansion and persistence of chimeric antigen receptor (CAR) T cells correlate with therapeutic efficacy. However, properties of CAR T cells that enable their &lt;i&gt;in vivo&lt;/i&gt; proliferation have still to be consistently defined and the role of CAR T bag content has never been investigated in a real-life setting.&lt;/p&gt;Experimental Design:&lt;p&gt;Residual cells obtained after washing 61 anti-CD19 CAR T product bags were analyzed to identify tisagenlecleucel/Tisa-cel and axicabtagene ciloleucel/Axi-cel phenotypic features associated with postinfusion CAR T-cell &lt;i&gt;in vivo&lt;/i&gt; expansion and with response and survival.&lt;/p&gt;Results:&lt;p&gt;While Tisa-cel was characterized by a significant enrichment in CAR&lt;sup&gt;+&lt;/sup&gt;CD4&lt;sup&gt;+&lt;/sup&gt; T cells with central memory (&lt;i&gt;P&lt;/i&gt; &lt; 0.005) and effector (&lt;i&gt;P&lt;/i&gt; &lt; 0.005) phenotypes and lower rates of CAR&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; with effector memory (&lt;i&gt;P&lt;/i&gt; &lt; 0.005) and naïve-like (&lt;i&gt;P&lt;/i&gt; &lt; 0.05) phenotypes as compared with Axi-cel, the two products displayed similar expansion kinetics. &lt;i&gt;In vivo&lt;/i&gt; CAR T-cell expansion was influenced by the presence of CAR T with a CD8&lt;sup&gt;+&lt;/sup&gt; T central memory signature (&lt;i&gt;P&lt;/i&gt; &lt; 0.005) in both Tisa-cel and Axi-cel infusion products and was positively associated with response and progression-free survival (&lt;i&gt;P&lt;/i&gt; &lt; 0.05).&lt;/p&gt;Conclusions:&lt;p&gt;Our data indicate that despite the great heterogeneity of Tisa-cel and Axi-cel products, the differentiation status of the infused cells mediates CAR T-cell &lt;i&gt;in vivo&lt;/i&gt; proliferation that is necessary for antitumor response.&lt;/p&gt;&lt;/div&gt;