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

Blood Advances - Tập 4 Số 14 - Trang 3268-3276 - 2020
Erin Dean1, Rahul Mhaskar2, Hong Lü3, Mina Mousa4, Gabriel Krivenko5, Aleksandr Lazaryan5, Christina A. Bachmeier5,6, Julio C. Chávez1, Taiga Nishihori5, Marco L. Davila5, Farhad Khimani5, Hien Liu5, Javier Pinilla‐Ibarz1, Bijal Shah1, Michael D. Jain5,7, Yoganand Balagurunathan8, Frederick L. Locke5,9
1Department of Malignant Hematology, H. Lee Moffitt Cancer and Research Institute, Tampa, FL;
2Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, FL
3Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
4Department of Diagnostic Imaging and Interventional Radiology
5Department of Blood and Marrow Transplant and Cellular Immunotherapy, and
6Department of Pharmacy, H. Lee Moffitt Cancer and Research Institute, Tampa, FL;
7Department of Oncologic Sciences, University of South Florida Morsani School of Medicine, Tampa, FL; and
8Department of Biostatistics and Bioinformatics, and
9Immunology Program, H. Lee Moffitt Cancer and Research Institute, Tampa, FL

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

Jain, 2018, Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin’s lymphoma, Ther Clin Risk Manag, 14, 1007, 10.2147/TCRM.S145039

Locke, 2017, Phase 1 results of ZUMA-1: a Multicenter Study of KTE-C19 Anti-CD19 CAR T cell therapy in refractory aggressive lymphoma, Mol Ther, 25, 285, 10.1016/j.ymthe.2016.10.020

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.

Locke, 2018

Cheson, 2007, The International Harmonization Project for response criteria in lymphoma clinical trials, Hematol Oncol Clin North Am, 21, 841, 10.1016/j.hoc.2007.06.011

Cheson, 2014, Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification, J Clin Oncol, 32, 3059, 10.1200/JCO.2013.54.8800

Ahmadzadehfar, 2011, Prognostic significance of the standardized uptake value of pre-therapeutic (18)F-FDG PET in patients with malignant lymphoma, Med Oncol, 28, 1570, 10.1007/s12032-010-9584-2

Malek, 2015, Metabolic tumor volume on interim PET is a better predictor of outcome in diffuse large B-cell lymphoma than semiquantitative methods, Blood Cancer J, 5, e326, 10.1038/bcj.2015.51

Song, 2016, High total metabolic tumor volume in PET/CT predicts worse prognosis in diffuse large B cell lymphoma patients with bone marrow involvement in rituximab era, Leuk Res, 42, 1, 10.1016/j.leukres.2016.01.010

Song, 2013, Clinical value of metabolic tumor volume by PET/CT in extranodal natural killer/T cell lymphoma, Leuk Res, 37, 58, 10.1016/j.leukres.2012.09.011

Guo, 2019, Prognostic value of baseline metabolic tumor volume and total lesion glycolysis in patients with lymphoma: a meta-analysis, PLoS One, 14, e0210224, 10.1371/journal.pone.0210224

Xie, 2014, Predictive value of F-18 FDG PET/CT quantization parameters in diffuse large B cell lymphoma: a meta-analysis with 702 participants, Med Oncol, 32, 446, 10.1007/s12032-014-0446-1

Meignan, 2014, Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients, Eur J Nucl Med Mol Imaging, 41, 1113, 10.1007/s00259-014-2705-y

Ilyas, 2018, Defining the optimal method for measuring baseline metabolic tumour volume in diffuse large B cell lymphoma, Eur J Nucl Med Mol Imaging, 45, 1142, 10.1007/s00259-018-3953-z

Lee, 2014, Current concepts in the diagnosis and management of cytokine release syndrome, Blood, 124, 188, 10.1182/blood-2014-05-552729

National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Published May 28, 2009; Revised Version 4.03 June 14, 2010. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed 10 May 2020.

Maziarz, 2019, Cytokine release syndrome and neurotoxocity by baseline tumor burden in adults with relapsed or refractory diffuse large B-cell lymphoma treated with tisagenleucleucel [abstract], Hematol Oncol, 37, 307, 10.1002/hon.117_2630

Wang, 2019, Role of fluorodeoxyglucose positron emission tomography/computed tomography in predicting the adverse effects of chimeric antigen receptor T cell therapy in patients with non-Hodgkin lymphoma, Biol Blood Marrow Transplant, 25, 1092, 10.1016/j.bbmt.2019.02.008

Borchmann, 2018, An updated analysis of JULIET, a global pivotal Phase 2 trial of tisagenlecleucel in adult patients with relapsed or refractory (r/r) diffuse large b-cell lymphoma (DLBCL) [abstract], HemaSphere, 2

Siddiqi, 2017, 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, Blood, 130, 193

Lee, 2019, ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells, Biol Blood Marrow Transplant, 25, 625, 10.1016/j.bbmt.2018.12.758

Maziarz, 2020, Grading of neurological toxicity in patients treated with tisagenlecleucel in the JULIET trial, Blood Adv, 4, 1440, 10.1182/bloodadvances.2019001305

Pennisi, 2020, Comparing CAR T-cell toxicity grading systems: application of the ASTCT grading system and implications for management, Blood Adv, 4, 676, 10.1182/bloodadvances.2019000952

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Blood Advances

Tập 4 Số 14

3268-3276

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