On Saturday December 9th, 2017 during an oral abstract session at the 59th 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.
- 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
- 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)
- 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.