Hazim S. Ababneh, Andrea K. Ng, Jeremy S. Abramson, Jacob D. Soumerai, Ronald W. Takvorian, Matthew J. Frigault, Chirayu G. Patel
{"title":"代谢参数预测嵌合抗原受体T细胞治疗复发/难治性大B细胞淋巴瘤的存活率和毒性。","authors":"Hazim S. Ababneh, Andrea K. Ng, Jeremy S. Abramson, Jacob D. Soumerai, Ronald W. Takvorian, Matthew J. Frigault, Chirayu G. Patel","doi":"10.1002/hon.3231","DOIUrl":null,"url":null,"abstract":"<p>CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for patients with relapsed/refractory large B-cell lymphoma (LBCL). However, data available concerning the impact of the prognostic value of quantitative 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) parameters on the CAR T-related outcomes and toxicities are limited. Therefore, we aimed to evaluate the predictive value of pre- and post-CAR T metabolic parameters on survival and toxicities following CAR T-cell therapy. Fifty-nine patients with PET/CT scans done pre-and post-CAR T infusion were retrospectively identified and analyzed in a single institution database of LBCL patients treated with commercial CD19-targeted CAR T-cell therapy. The median follow-up was 10.7 months [interquartile range (IQR): 2.6–25.5 months]. The overall response (complete response-CR and partial response) and CR rates post-CAR T were 76% (<i>n</i> = 45) and 53% (<i>n</i> = 31), respectively. On univariate analysis, low pre-CAR T total lesion glycolysis (TLG) and metabolic tumor volume (MTV) predicted improved overall response post-CAR T (OR = 4.7, <i>p</i> = 0.01, OR = 9.5, <i>p</i> = 0.03, respectively) and CR post-CAR T (OR = 12.4, <i>p</i> = 0.0004, OR = 10.9, <i>p</i> = 0.0001, respectively). High TLG pre-CAR T was correlated with cytokine release syndrome (CRS, OR = 3.25, <i>p</i> = 0.04). High MTV pre-CAR T was correlated with developing immune effector cell neurotoxicity syndrome (ICANS) events (OR = 4.3, <i>p</i> = 0.01), and high SUV pre-CAR T was associated with grade 3–4 neurological events (OR = 12, <i>p</i> = 0.01). High MTV/TLG/SUVmax post-CAR T were significantly associated with inferior Overall survival (OS). On multivariate analysis, high TLG pre-CAR T (HR = 2.4, <i>p</i> = 0.03), age ≥60 (HR = 2.7, <i>p</i> = 0.03), and bulky disease (≥5 cm) at the time of apheresis (HR = 2.5, <i>p</i> = 0.02) were identified to be independent prognostic factors for inferior PFS. High MTV post-CAR T was identified as the most prognostic factor associated with inferior OS.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 1","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Metabolic parameters predict survival and toxicity in chimeric antigen receptor T-cell therapy-treated relapsed/refractory large B-cell lymphoma\",\"authors\":\"Hazim S. Ababneh, Andrea K. Ng, Jeremy S. Abramson, Jacob D. Soumerai, Ronald W. Takvorian, Matthew J. Frigault, Chirayu G. Patel\",\"doi\":\"10.1002/hon.3231\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for patients with relapsed/refractory large B-cell lymphoma (LBCL). However, data available concerning the impact of the prognostic value of quantitative 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) parameters on the CAR T-related outcomes and toxicities are limited. Therefore, we aimed to evaluate the predictive value of pre- and post-CAR T metabolic parameters on survival and toxicities following CAR T-cell therapy. Fifty-nine patients with PET/CT scans done pre-and post-CAR T infusion were retrospectively identified and analyzed in a single institution database of LBCL patients treated with commercial CD19-targeted CAR T-cell therapy. The median follow-up was 10.7 months [interquartile range (IQR): 2.6–25.5 months]. The overall response (complete response-CR and partial response) and CR rates post-CAR T were 76% (<i>n</i> = 45) and 53% (<i>n</i> = 31), respectively. On univariate analysis, low pre-CAR T total lesion glycolysis (TLG) and metabolic tumor volume (MTV) predicted improved overall response post-CAR T (OR = 4.7, <i>p</i> = 0.01, OR = 9.5, <i>p</i> = 0.03, respectively) and CR post-CAR T (OR = 12.4, <i>p</i> = 0.0004, OR = 10.9, <i>p</i> = 0.0001, respectively). High TLG pre-CAR T was correlated with cytokine release syndrome (CRS, OR = 3.25, <i>p</i> = 0.04). High MTV pre-CAR T was correlated with developing immune effector cell neurotoxicity syndrome (ICANS) events (OR = 4.3, <i>p</i> = 0.01), and high SUV pre-CAR T was associated with grade 3–4 neurological events (OR = 12, <i>p</i> = 0.01). High MTV/TLG/SUVmax post-CAR T were significantly associated with inferior Overall survival (OS). 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Metabolic parameters predict survival and toxicity in chimeric antigen receptor T-cell therapy-treated relapsed/refractory large B-cell lymphoma
CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for patients with relapsed/refractory large B-cell lymphoma (LBCL). However, data available concerning the impact of the prognostic value of quantitative 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) parameters on the CAR T-related outcomes and toxicities are limited. Therefore, we aimed to evaluate the predictive value of pre- and post-CAR T metabolic parameters on survival and toxicities following CAR T-cell therapy. Fifty-nine patients with PET/CT scans done pre-and post-CAR T infusion were retrospectively identified and analyzed in a single institution database of LBCL patients treated with commercial CD19-targeted CAR T-cell therapy. The median follow-up was 10.7 months [interquartile range (IQR): 2.6–25.5 months]. The overall response (complete response-CR and partial response) and CR rates post-CAR T were 76% (n = 45) and 53% (n = 31), respectively. On univariate analysis, low pre-CAR T total lesion glycolysis (TLG) and metabolic tumor volume (MTV) predicted improved overall response post-CAR T (OR = 4.7, p = 0.01, OR = 9.5, p = 0.03, respectively) and CR post-CAR T (OR = 12.4, p = 0.0004, OR = 10.9, p = 0.0001, respectively). High TLG pre-CAR T was correlated with cytokine release syndrome (CRS, OR = 3.25, p = 0.04). High MTV pre-CAR T was correlated with developing immune effector cell neurotoxicity syndrome (ICANS) events (OR = 4.3, p = 0.01), and high SUV pre-CAR T was associated with grade 3–4 neurological events (OR = 12, p = 0.01). High MTV/TLG/SUVmax post-CAR T were significantly associated with inferior Overall survival (OS). On multivariate analysis, high TLG pre-CAR T (HR = 2.4, p = 0.03), age ≥60 (HR = 2.7, p = 0.03), and bulky disease (≥5 cm) at the time of apheresis (HR = 2.5, p = 0.02) were identified to be independent prognostic factors for inferior PFS. High MTV post-CAR T was identified as the most prognostic factor associated with inferior OS.
期刊介绍：
Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged:
-Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders
-Diagnostic investigations, including imaging and laboratory assays
-Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases
-Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies
-Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems.
Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.
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