Prognostic value of pre-infusion tumor growth rate for patients with lymphoma receiving chimeric antigen receptor T-cell therapy |
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| Institution: | 1. Department of Radiology, University Hospital, LMU Munich, Munich, Germany;2. Laboratory for Translational Cancer Immunology, Gene Center of the LMU Munich, Munich, Germany;3. German Cancer Consortium (DKTK) and Bavarian Center for Cancer Research (BZKF), partner site Munich, Munich, Germany;4. Department of Medicine III, University Hospital, LMU Munich, Munich, Germany;5. Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany;6. Comprehensive Cancer Center München-LMU (CCCMLMU), LMU Munich, Munich, Germany;1. Department of Laboratory Medicine and Pathology, Mayo Clinic Minnesota, Rochester, Minnesota, USA;2. Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix, Arizona, USA;1. Medical Sciences Program, University of Brasilia, Brasilia, Distrito Federal, Brazil;2. Program of Evidence for Health Policy and Technologies, Oswaldo Cruz Brasilia Foundation, Brasilia, Distrito Federal, Brazil;4. Interdisciplinary Biosciences Laboratory, Faculty of Medicine, University of Brasília, Brasília, Distrito Federal, Brazil;5. Epidemiology Surveillance, Federal District Health State Department, Brasília, Distrito Federal, Brazil;6. Faculty of Medicine, University of Brasilia, Brasilia, Distrito Federal, Brazil;1. Centre for Discovery in Cancer Research, McMaster University, Hamilton, Ontario, Canada;2. McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada;3. Department of Medicine, McMaster University, Hamilton, Ontario, Canada;1. University of Minnesota, Minneapolis, MN, United States of America;2. University of Cincinnati College of Medicine, Cincinnati, OH, United States of America;3. Massachusetts General Hospital, Boston, MA, United States of America;4. University of Virginia, Charlottesville, VA, United States of America;5. CIBMTR® (Center for International Blood and Marrow Transplant Research), Milwaukee, WI, United States of America;6. Rush University Medical Center, Chicago, IL, United States of America;7. Center for International Blood and Marrow Transplant, Milwaukee, WI, United States of America;8. University of North Carolina, Chapel Hill, NC, United States of America;9. Medical College of Wisconsin, Milwaukee, WI, United States of America;10. College of Medicine, Mayo Clinic, Phoenix, AZ, United States of America;1. George Washington Cancer Center, Department of Biochemistry & Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA;2. George Washington Cancer Center, Department of Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA;3. The Institute for Biomedical Sciences, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA;4. George Washington Cancer Center, Department of Microbiology, Immunology, and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA;5. George Washington Cancer Center, Department of Neurosurgery, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA;6. Center for Cancer and Immunology Research, Children''s National Hospital, Washington, DC, USA;1. Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;;2. Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;;3. Institute of Hematology, Zhejiang University, Hangzhou, China;;4. Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China;5. Shanghai YaKe Biotechnology Ltd.;6. Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China |
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| Abstract: | Background aimsChimeric antigen receptor T-cell therapy (CART) prolongs survival for patients with refractory or relapsed lymphoma, yet its efficacy is affected by the tumor burden. The relevance of tumor kinetics before infusion is unknown. We aimed to study the prognostic value of the pre-infusion tumor growth rate (TGRpre-BL) for progression-free (PFS) and overall survival (OS).MethodsConsecutive patients with available pre-baseline (pre-BL) and baseline (BL) computed tomography or positron emission tomography/computed tomography scan before CART were included. TGR was determined as change of Lugano criteria-based tumor burden between pre-BL, BL and follow-up examinations (FU) in relation to days between imaging exams. Overall response rate (ORR), depth or response (DoR) and PFS were determined based on Lugano criteria. Multivariate regression analysis studied association of TGR with ORR and DoR. Proportional Cox regression analysis studied association of TGR with PFS and OS.ResultsIn total, 62 patients met the inclusion criteria. The median TGRpre-BL was 7.5 mm2/d (interquartile range –14.6 mm2/d to 48.7 mm2/d); TGRpre-BL was positive (TGRpre-BL POS) in 58% of patients and negative (TGRpre-BL NEG, indicating tumor shrinkage) in 42% of patients. Patients who were TGRpre-BL POS had a 90-day (FU2) ORR of 62%, a DoR of –86% and a median PFS of 124 days. Patients who were TGRpre-BL NEG had a 90-day ORR of 44%, DoR of –47% and a median PFS of 105 days. ORR and DoR were not associated with slower TGR (P = 0.751, P = 0.198). Patients with an increase of TGR from pre-BL over BL to 30-day FU (FU1) ≥100% (TGRpre-BL-to-FU1≥100%) showed a significant association with shorter median PFS (31 days versus 343 days, P = 0.002) and shorter median OS after CART (93 days versus not reached, P < 0.001), compared with patients with TGRpre-BL-to-FU1<100%.ConclusionsIn the context of CART, differences in pre-infusion tumor kinetics showed minor differences in ORR, DoR, PFS and OS, whereas the change of the TGR from pre-BL to 30-day FU significantly stratified PFS and OS. In this patient population of refractory or relapsed lymphomas, TGR is readily available based on pre-BL imaging, and its change throughout CART should be explored as a potential novel imaging biomarker of early response. |
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