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2125 Analysis of PET-CT Derived Radiomic Biomarkers with Efficacy, Safety, and Expansion of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed or Refractory Large B-Cell Lymphoma (LBCL)

Program: Oral and Poster Abstracts
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Biological therapies, adult, Lymphomas, Clinical Practice (Health Services and Quality), B Cell lymphoma, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, cell expansion, aggressive lymphoma, Therapies, Adverse Events, Lymphoid Malignancies, Technology and Procedures, Study Population, Human
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Sushma Bharadwaj, MD, MS1, Eric Lau, DO2, Ayesha Hashmi, MBBS3*, Mark P. Hamilton, MD4, Alexandria Jensen, PhD5*, Anmol Goyal, MD1*, Mallika Marar, MD, MBA3*, Caroline Lee, MD4*, Snegha Ananth, MBBS1, Bita Sahaf, PhD, MSc6*, Jayasindhu Mallampet1*, Zachary Ehlinger7*, Shriya Syal, MS6*, Sunita Patil6*, Henry Guo, MD, PhD8*, Melody Smith, MD, MS9, Wen-Kai Weng, MD, PhD1, Matthew J. Frank, MD, PhD1, Michael S. Binkley, MD, MS10*, David B. Miklos, MD, PhD1 and Saurabh Dahiya1*

1Division of Blood and Marrow Transplantation & Cellular Therapy, Stanford University, Palo Alto, CA
2Division of Blood and Marrow Transplantation & Cellular Therapy, Stanford University, Mountain View, CA
3Department of Radiation Oncology, Stanford University, Stanford, CA
4Division of Hematology and Oncology, Stanford University, Palo Alto, CA
5Quantitative Sciences Unit, Stanford University, Palo Alto, CA
6Cancer Correlative Science Unit, Stanford University, Palo Alto, CA
7Center for Cancer Cell Therapy, Stanford University, Stanford, CA
8Department of Radiology, Stanford University, Palo Alto, CA
9Division of Blood and Marrow Transplantation & Cellular Therapy, Stanford University, Stanford, CA
10Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA


In LBCL, the presence of bulky disease is known to be an adverse prognostic factor, indicating poorer outcomes. The ZUMA-1 clinical trial (Neelapu, NEJM 2017) showed that high tumor burden, as measured by the sum of the product of diameters (SPD), was associated with lower durable response after Chimeric Antigen Receptor T-Cell Therapy (CAR T). Radiomic biomarkers such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been recently studied to assess three-dimensional measurement of tumor activity and metabolic volume in LBCL. There is a paucity of understanding on the impact of radiomic biomarkers on outcomes and CAR T expansion kinetics in LBCL CAR T recipients. We studied the association of these radiomic biomarkers with efficacy, toxicity, and CAR T expansion in this single institution retrospective study of patients with LBCL who received axi-cel.


189 patients with relapsed or refractory LBCL who were treated with axi-cel from 12/2017 to 5/2022 were studied. The closest PET-CT scan to CAR T leukapheresis date was identified for each patient. After excluding cases with unavailable pre-apheresis PET-CT scans, 172 patients were included in the statistical analysis. Two reviewers independently used a semi-automated contouring software (MIM, v. 7.1.2) to measure maximum standardized uptake value (SUV Max), mean SUV, total MTV and TLG values of malignant lesions. CD19 CAR T expansion was measured by real-time flow cytometry with anti-idiotype-FMC63 conjugated to Dylight 65013. Areas under the curve (AUCs) were calculated for CAR T expansion in the 28 days following infusion using the linear trapezoidal method on raw values, and the results were transformed using a base-10 logarithm. Patients were categorized into high and low biomarker groups based on whether their values exceeded or were below the respective median. For univariate analyses, continuous variables were compared using a Mann-Whitney U-test, categorical using a Chi-square test, and time-to-event using a log-rank test. Within a multivariable framework, regressions (linear, logistic, Cox) were fit to control for potential confounders.


Median duration of follow up was 33 months (IQR: 17.9, 44.7). MTV was highly correlated with TLG (r=0.87). High MTV was associated with bulky disease defined as >10cm (p<0.01), high IPI at apheresis (p<0.04), bridging treatment (p<0.01), pre-lymphodepletion lactate dehydrogenase (p<0.01), and autologous stem cell transplant (p=0.02).

Complete response (CR) rate was greater for those in the low MTV group (79.3%) compared to high MTV group (52.3%), (p<0.01), as well as those with high TLG (77.9%) compared to low TLG group (46%), (p<0.01). Low MTV was significantly associated with better progression free survival (PFS) in a univariate analysis (p=0.03); median PFS was 33.5 months (IQR 3.06, 39.55) for low MTV versus 6.1 months (IQR 6.38, NA) for high MTV. Low MTV was also significantly associated with better overall survival (OS) in a univariate analysis (p<0.01); median OS was not reached for the low MTV group but was 31.8 months for the high MTV group (IQR 16.5, NA) (Figure 1). After multivariable regression analysis, PFS was no longer different by MTV biomarker level (p= 0.07), but OS was still significantly different (p= 0.01). Neither PFS nor OS were significantly associated with the binary TLG variable.

The proportion of cytokine release syndrome (CRS) or immune cell associated neurologic toxicity syndrome (ICANS) of any grade or severe grade ICANS were significantly higher for the high MTV and TLG groups as compared to their respective low groups. Length of stay was significantly longer for those in the high MTV and TLG groups (Table 1).

A higher day 14 CAR T cell expansion was seen in the high TLG as compared to the low group (0.89 vs 0.63 cells/μL, p=0.002). However, there was no statistically significant difference in CAR T expansion as measured by AUC between the high and low MTV or TLG cohort.


Our study demonstrates poor outcomes for efficacy, safety, and healthcare utilization endpoints in patients with high tumor bulk as measured by volumetric tumor assessment on PET-CT. Furthermore, we show a differential peripheral day 14 CAR T expansion with higher expansion seen in patients with higher tumor bulk. Strategies like tumor debulking prior to CAR T therapy and earlier referral in patients with high tumor bulk may improve clinical outcomes.

Disclosures: Hamilton: Kite Pharma: Other: Advisory Board. Marar: Bristol Myers Squibb: Consultancy. Smith: BMS: Consultancy; A28: Membership on an entity's Board of Directors or advisory committees. Frank: Cargo Therapeutics: Consultancy, Other: Travel Support; Gilead Sciences: Consultancy, Other: Travel Support; Roche/Genentech: Current holder of stock options in a privately-held company; Allogene: Consultancy; Kite, a Gilead Company: Research Funding; Adaptive Biotechnology: Consultancy; EcoR1: Consultancy; BRVLH: Consultancy. Miklos: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria; Fate Therapeutics: Research Funding; NA: Patents & Royalties: cGVHD patent holder for Ibrutinib as cGVHD therapy but no compensation; Genentech: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Umoja: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Adaptive Biotechnologies: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Miltenyi: Consultancy, Research Funding; Navan Technologies: Consultancy, Current holder of stock options in a privately-held company, Honoraria; Mustang Bio: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; Legend Biotech: Consultancy, Honoraria; Juno Therapeutics: Consultancy, Honoraria, Patents & Royalties: rights to royalties from Fred Hutch for patents licensed to Juno, Research Funding; Incyte: Consultancy, Honoraria; A2 Biotherapeutics: Consultancy, Current holder of stock options in a privately-held company, Honoraria; 2Seventy Bio: Research Funding; Allogene: Research Funding; Adicet: Research Funding; Janssen: Consultancy, Honoraria, Other: Travel support; Bioline Rx: Membership on an entity's Board of Directors or advisory committees. Dahiya: Kite, a Gilead Company: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Incyte: Consultancy; Bristol Myers Squibb: Consultancy.

*signifies non-member of ASH