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

On Monday 3rd 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.

Reference:

1. Rossi J. Polyfunctional anti-CD19 CAR T cells determined by single-cell multiplex proteomics associated with clinical activity in patients with advanced non-Hodgkin’s lymphoma [Abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; 2017. Abstract nr [2990].