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3783 Impact of Obesity on Efficacy, Safety, and Expansion Kinetics of Chimeric Antigen Receptor-T (CAR T) Therapy in Patients with Relapsed or Refractory Large B Cell Lymphoma (LBCL)

Program: Oral and Poster Abstracts
Session: 905. Outcomes Research—Lymphoid Malignancies: Poster II
Hematology Disease Topics & Pathways:
Research, Biological therapies, Clinical Practice (Health Services and Quality), Lymphomas, non-Hodgkin lymphoma, Clinical Research, health outcomes research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, B Cell lymphoma, Diseases, Therapies, Immunotherapy, Lymphoid Malignancies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Anmol Goyal, MD1*, Sushma Bharadwaj, MD, MS1, Dasom Lee, MD2*, Eric Lau, DO3, Mark P. Hamilton, MD4, Alexandria Jensen, PhD5*, Bita Sahaf, PhD, MSc6*, Shriya Syal, MS6*, Sunita Patil6*, Juancarlos E Cancilla6*, Theresa Latchford7*, Wen-Kai Weng, MD, PhD1, Melody Smith, MD, MS8, Matthew J. Frank, MD, PhD1, David B. Miklos, MD, PhD1 and Saurabh Dahiya1*

1Division of Blood and Marrow Transplantation & Cellular Therapy, Stanford University, Palo Alto, CA
2Division of Hematology, Stanford University, Stanford
3Division of Blood and Marrow Transplantation & Cellular Therapy, Stanford University, Mountain View, CA
4Division of Blood and Marrow Transplantation & Cellular Therapy, Stanford University School of Medicine, Palo Alto, CA
5Quantitative Sciences Unit, Stanford University, Palo Alto, CA
6Cancer Correlative Science Unit, Stanford University, Palo Alto, CA
7Stanford Health Care, Stanford, CA
8Division of Blood and Marrow Transplantation & Cellular Therapy, Stanford University, Stanford, CA

Introduction: Obesity causes low-grade inflammation and immune escape, where T-cells lose their ability to infiltrate tumors. However, such T-cell exhaustion, characterized by increased expression of inhibitory checkpoint receptors, has led to better responses to immune checkpoint blockade therapy in patients with higher body mass index (BMI) (Wang Nature Medicine, 2019). Previous studies have shown no significant association of obesity with safety or efficacy of Chimeric Antigen Receptor T-cell (CAR T) therapy in hematologic malignancies (Faruqi Blood Advances, 2022). However, data on the impact of BMI on outcomes in LBCL and CAR T expansion kinetics is limited. We conducted a single-site study to investigate the effect of obesity on efficacy and safety outcomes, healthcare utilization, and CAR T expansion in patients with relapsed/refractory LBCL treated with Axicabtagene Ciloleucel(axi-cel).

Methods: 189 patients with relapsed/refractory LBCL who were consecutively treated with axi-cel from 12/2017 to 5/2022 were included in the study. BMI was calculated on the day of apheresis. Patients were then divided into three BMI categories based on CDC guidelines: underweight/normal (≤24.99kg/m2), overweight (>25kg/m2 and ≤29.99kg/m2), and obese (>30kg/m2). Response was assessed using the Lugano 2014 criteria, and toxicities via the CTCAE version 5.0 and ASTCT grading. CAR T expansion was measured by real-time flow cytometry with anti-idiotype-FMC63 conjugated to Dylight 650. 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 results were transformed using a base-10 logarithm. Continuous outcomes were compared using a Kruskal-Wallis test, categorical outcomes using Chi-square tests, and time-to-event outcomes using the Kaplan-Meier estimator and the log-rank test. Statistical significance was determined at p < 0.05. All analyses were conducted in R 4.3.0.

Results: Out of 189 patients, 46% (n=87) were in the underweight/normal group, 29% (n=56) in the overweight, and 24% (n=46) were obese. Baseline demographics and clinical characteristics between groups were similar except for gender (p=0.009).

Complete response (CR) and overall response (ORR) including partial response (PR) and CR were compared among these cohorts. Neither complete response nor overall response was found to be significantly different amongst the BMI categories for their best response within 12 months of CAR T infusion (p=0.9886 and 0.802, respectively).

Median progression-free survival (PFS) was 14.6 months (IQR 4.93, 44.81) for the underweight/normal weight cohort, 14.89 months (IQR 5.82, 40.07) for the overweight cohort, and 28.37 months (IQR 3.88, NA) for obese; but was not statistically significant (p=0.8004) [Figure 1]. Median overall survival (OS) was 44.81 months (IQR 18.18, NA) for the underweight/normal weight cohort and 40.07 months (IQR 23.18, NA) for the overweight category. This was not achieved for the obese category, and no statistical difference was found (p=0.3478).

When cytokine release syndrome (CRS) or immune cell-associated neurologic toxicity syndrome (ICANS) events were compared among these groups, there was no significant difference in either overall incidence or when graded as severe (›3), based on BMI category. Similarly, no significant differences were found in healthcare utilization variables, including length of hospital stay, ICU admissions, tocilizumab, anakinra or steroid use.

Differences in day 7 and day 14 CAR T expansion were not statistically significant (p=0.754 and 0.355, respectively). For AUC calculations, there was no statistically significant difference amongst the BMI categories (CD4: p=0.8284, CD8: p=0.8695, CD4 + CD8: p=0.8820) [Figure 2].

Conclusion: Contrary to the effect of obesity on response to therapies like checkpoint inhibitors we demonstrate that BMI does not significantly impact patients treated with CAR T. Weight has been central to chemotherapy dosing for lymphoma, but despite weight-based dosing for axi-cel, correlative studies on CAR T expansion kinetics did not indicate any significant difference. These findings suggest that obesity may not substantially influence the outcomes or dosing considerations of CAR T therapy, supporting the use of CAR T therapy as an effective treatment option for lymphoma patients, regardless of their BMI.

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

*signifies non-member of ASH