AACR 2017 | Polyfunctional anti-CD19 CAR T-cells associated with clinical activity in patients with advanced Non-Hodgkin Lymphoma

On Monday 3^rd April at AACR 2017, during the “MS.CL10.01 - Clinical Biomarkers” session, John Rossi from Kite Pharma, Santa Monica, CA, gave a talk titled: “Polyfunctional anti-CD19 CAR T cells determined by single-cell multiplex proteomics associated with clinical activity in patients with advanced non-Hodgkin’s lymphoma.”

Rossi began the talk by providing some background on CD19 specific Chimeric Antigen Receptor (CAR) T-cell therapy:

• Anti-CD19 CAR T-cells have demonstrated clinical activity in advanced NHL (Kochenderfer Blood 2010 and JCO 2017)
• So far, the best correlate of objective response is expansion of CAR T-cells within 4 weeks post-infusion (Kochenderfer JCO 2017 and Locke AACR 2017)
• Pro-inflammatory, immune modulatory, immune effector, and chemokine signaling immune programs are initiated by anti-CD19 CAR T-cells (Rossi SITC 2016)
• No clear associations with clinical outcomes have been observed when evaluating bulk product

The talk then discussed how CAR T-cell polyfunctionality is quantified:

Rossi then went on to outline the recent results published by Kochenderfer et al. in the Journal of Clinical Oncology (NCT00924326), which found that anti-CD19 CAR T-cell therapy results in durable tumor regression in relapsed NHL patients:

• Total number of patients = 22 (n = 19 DLBCL; n = 2 FL; n = 1 MCL)
• Low dose conditioning therapy; 1–2x10⁶ CAR+ T-cells/kg
• Clinical response:
  • ORR = 73%; CR = 55%; PR = 18%
  • CRs ongoing = 11/12 (7–24 months+)
• Toxicities
  • ≥Grade 3 neurologic events = 55%
  • ≥Grade 3 hypotension by CTCAE3 = 18%
  • All toxicities completely resolved, most within 2 weeks

Following this, Rossi presented data indicating that pre-infusion single-cell CAR PSI and CAR PEAK levels in vivo and polyfunctional strength are significantly associated with objective response. However, pre-infusion product PSA is not significantly associated with expansion of CAR T-cells.

Before concluding the talk, John Rossi also presented data which indicated that IL-17a, IFN-γ, IL-8, IL-5, and MIP-1α drive CD4 polyfunctionality in responders.