Correlation of patient type and inflammation biomarkers with clinical outcomes in JCAR017 treatment – ASH 2017 Oral Abstract #193

On Saturday December 9^th, 2017 during an oral abstract session at the 59^th Annual meeting American Society of Hematology (ASH), Tanya Siddiqi of the City of Hope National Medical Center in Duarte, CA presented a retrospective analysis of the TRANSCEND NHL 001 phase I clinical trial (NCT02631044). The objective of this analysis was to better predict and determine patient outcomes based on a variety of correlative variables. This session was moderated by Daniel Persky, University of Arizona Cancer Center in Tucson, AZ, and Jean L Koff, Winship Cancer Institute of Emory University in Atlanta, GA.

This abstract (#193), “Patient Characteristics and Pre-Infusion Biomarkers of Inflammation Correlate with Clinical Outcomes after Treatment with the Defined Composition, CD19-Targeted CAR T Cell Product, JCAR017,” was presented during Oral Session: 627. “Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas).” Data from the live session at ASH are used and therefore may supersede information in the pre-published abstracts.

Treatment

• Eligible patients had one of the following: R/R DLBCL NOS (de novo or transformed from indolent lymphoma), PMBCL, FL grade 3B, or MCL and adequate organ function
• Patients received lymphodepletion, with fludarabine and cyclophosphamide, followed by a single dose of JCAR017 at one of two dose levels (DL1, 5 × 10⁷cells; DL2, 1 × 10⁸ cells)
• Clinical endpoints were best overall response, durable response at month 3, any grade neurotoxicity (NT), any grade cytokine release syndrome (CRS), and Gr 3-4 NT

Efficacy

• 54 patients in the DLBCL cohort were evaluable for efficacy
• Of the 54 DLBCL patients evaluated for efficacy, 76% achieved best overall response of CR/PR
  • 51% remained in CR/PR at 3 months
• Pre-CAR T-cell analyses associated with best ORR included lower values of ferritin, LDH, CXCL10, G-CSF, and IL-10
• Those associated with durable response at 3 months were lower ferritin, CRP, LDH, CXCL10, IL-8, IL-10, IL-15, MCP-1, MIP-1β, TNF-α, and higher pre-CAR T cell hemoglobin and albumin (P < 0.05 for each)

Safety

• 55 pts in the DLBCL cohort and 4 MCL patients were evaluable for safety
• Of the 59 safety patients, CRS developed in 32% (30% Gr 1-2, 0% Gr 3, 2% Gr 4); NT was observed in 20% (5% Gr 1-2, 10% Gr 3, 5% Gr 4)
• Patient factors that correlate with any grade CRS and NT were poorer performance status [e.g. ECOG PS2] (P=0.03) and higher disease burden (P<0.05) as measured by the sum of the products of diameters [SPD] on imaging
• Pre-CAR T-cell clinical labs and cytokines associated with the occurrence of any grade NT were higher serum LDH, ferritin, and CRP, and higher plasma IL-6, IL-8, IL-10, TNF-α, IFN-α2, MCP-1, and MIP-1β (P<0.05 for each)
• Higher pre-CAR T infusion plasma IL-8, IL-10, and CXCL10 were also associated with Gr 3-4 NT (P<0.05 for each)

The authors concluded that low tumor burden and low inflammatory state are associated with improved toxicity profile and a more durable response. These data suggest that treating patients earlier in the treatment continuum, or using a panel of clinical and laboratory biomarkers to risk stratify patients for potential early intervention, may mitigate risk of toxicity and further improve durability of response.