High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma

Author:

Dean Erin A.1ORCID,Mhaskar Rahul S.2ORCID,Lu Hong3,Mousa Mina S.4ORCID,Krivenko Gabriel S.5,Lazaryan Aleksandr5ORCID,Bachmeier Christina A.56ORCID,Chavez Julio C.1,Nishihori Taiga5ORCID,Davila Marco L.5ORCID,Khimani Farhad5,Liu Hien D.5ORCID,Pinilla-Ibarz Javier1,Shah Bijal D.1,Jain Michael D.57ORCID,Balagurunathan Yoganand8ORCID,Locke Frederick L.59ORCID

Affiliation:

1. Department of Malignant Hematology, H. Lee Moffitt Cancer and Research Institute, Tampa, FL;

2. Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, FL;

3. Tianjin Medical University Cancer Institute and Hospital, Tianjin, China;

4. Department of Diagnostic Imaging and Interventional Radiology,

5. Department of Blood and Marrow Transplant and Cellular Immunotherapy, and

6. Department of Pharmacy, H. Lee Moffitt Cancer and Research Institute, Tampa, FL;

7. Department of Oncologic Sciences, University of South Florida Morsani School of Medicine, Tampa, FL; and

8. Department of Biostatistics and Bioinformatics, and

9. Immunology Program, H. Lee Moffitt Cancer and Research Institute, Tampa, FL

Abstract

Abstract High metabolic tumor volume (MTV) predicts worse outcomes in lymphoma treated with chemotherapy. However, it is unknown if this holds for patients treated with axicabtagene ciloleucel (axi-cel), an anti-CD19 targeted chimeric antigen receptor T-cell therapy. The primary objective of this retrospective study was to investigate the relationship between MTV and survival (overall survival [OS] and progression-free survival [PFS]) in patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axi-cel. Secondary objectives included finding the association of MTV with response rates and toxicity. The MTV values on baseline positron emission tomography of 96 patients were calculated via manual methodology using commercial software. Based on a median MTV cutoff value of 147.5 mL in the first cohort (n = 48), patients were divided into high and low MTV groups. Median follow-up for survivors was 24.98 months (range, 10.59-51.02 months). Patients with low MTV had significantly superior OS (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.10-0.66) and PFS (HR, 0.40; 95% CI, 0.18-0.89). Results were successfully validated in a second cohort of 48 patients with a median follow-up for survivors of 12.03 months (range, 0.89-25.74 months). Patients with low MTV were found to have superior OS (HR, 0.14; 95% CI, 0.05-0.42) and PFS (HR, 0.29; 95% CI, 0.12-0.69). In conclusion, baseline MTV is associated with OS and PFS in axi-cel recipients with LBCL.

Publisher

American Society of Hematology

Subject

Hematology

Reference23 articles.

1. Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin’s lymphoma;Jain;Ther Clin Risk Manag,2018

2. Phase 1 results of ZUMA-1: a Multicenter Study of KTE-C19 Anti-CD19 CAR T cell therapy in refractory aggressive lymphoma;Locke;Mol Ther,2017

3. Fischer A . FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. October 18, 2017. https://www.fda.gov/news-events/press-announcements/fda-approves-car-t-cell-therapy-treat-adults-certain-types-large-b-cell-lymphoma. Accessed 16 January 2020.

4. The International Harmonization Project for response criteria in lymphoma clinical trials;Cheson;Hematol Oncol Clin North Am,2007

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