ASH Highlights and Commentary: Additional Topics of Interest

J. Zurko, N. Epperla, -. Im, ran Nizamuddin, P. Torka, K. David, T. Ollila, B. Hess, Jonathon B. Cohen, R. Ferdman, Jieqi Liu, Sayan Mullick, Chowdhury, Kaitlyn L. O'Shea, Jason T. Romancik, R. Bhansali, E. Harris, M. Sorrell, R. Masel, L. Fitzgerald, C. Galvez, J. Winter, B. Pro, Léo, I. Gordon, A. Danilov, N. Shah, G. Shouse, Vaishalee, P. Kenkre, S. Barta
{"title":"ASH Highlights and Commentary: Additional Topics of Interest","authors":"J. Zurko, N. Epperla, -. Im, ran Nizamuddin, P. Torka, K. David, T. Ollila, B. Hess, Jonathon B. Cohen, R. Ferdman, Jieqi Liu, Sayan Mullick, Chowdhury, Kaitlyn L. O'Shea, Jason T. Romancik, R. Bhansali, E. Harris, M. Sorrell, R. Masel, L. Fitzgerald, C. Galvez, J. Winter, B. Pro, Léo, I. Gordon, A. Danilov, N. Shah, G. Shouse, Vaishalee, P. Kenkre, S. Barta","doi":"10.6004/jadpro.2022.13.2.12","DOIUrl":null,"url":null,"abstract":"884 Outcomes and Treatment Patterns in Patients With Aggressive B-Cell Lymphoma After Failure of Anti-CD19 CAR T-Cell Therapy Joanna C. Zurko, MD, Narendranath Epperla, MD, MS, Imran Nizamuddin, MD, Pallawi Torka, MD, Kevin A. David, MD, Thomas A. Ollila, MD, Brian T. Hess, MD, Jonathon B. Cohen, MD, MS, Robert Ferdman, MD, Jieqi Liu, MD, Sayan Mullick Chowdhury, DO, PhD, Kaitlyn O’Shea, PhD, Jason Romancik, MD, Rahul Bhansali, MD, Elyse Harris, MD, Mckenzie Sorrell, D.O., Rebecca Masel, Lindsey Fitzgerald, MD, Carlos Galvez, MD, Shuo Ma, MD, Jane N. Winter, MD, Barbara Pro, MD, Leo I. Gordon, MD, Alexey V. Danilov, MD, PhD, Deborah M. Stephens, Nirav N. Shah, MD, Geoffrey Shouse, PhD, Vaishalee P. Kenkre, MD, Stefan K. Barta, MD, MRCP, MS and Reem Karmali, MD, MSc Visit https://doi.org/10.1182/blood-2021-147433 for a complete list of contributor affiliations and full graphics. Background: Anti-CD19 chimeric antigen receptor T-cell therapy (CART) is a highly active therapy for relapsed/refractory (R/R) aggressive B-cell lymphoma. Nonetheless, most patients (pts) ultimately develop progressive disease (PD). There is little guidance on the optimal treatment approach(es) for these pts. We performed a multicenter retrospective analysis with a primary objective to assess treatment patterns and outcomes in pts with R/R aggressive B-cell lymphoma who develop PD after anti-CD19 CARTs. Methods: Pts with aggressive B-cell lymphoma treated with anti-CD19 CART between 2015 and 2020 across 12 US academic medical centers were included. Demographic and clinical characteristics were collected along with CART toxicities and response. Regimens administered as salvage post CART were assessed. Univariate analyses (UVA) were performed to determine impact of demographic and clinical variables on survival outcomes. All p-values were two-tailed. Survival curves were calculated using the KaplanMeier method. Results: A total of 400 pts received anti-CD19 CARTs and were included for analysis. For the entire cohort: median PFS and OS from time of CART infusion were 11 months [mo] and 27 mo respectively. On log-rank testing, pts who received ≥3 lines of pre-CART therapy and those with refractory disease pre-CART had significantly worse PFS (p=0.004 & 0.001) and OS (both p<0.001). With median follow-up 22.4 mo, 190 pts (48%) had PD after CART; demographic and clinical variables of pts with and without PD are detailed in Table 1. Biopsy to confirm PD and assess CD19 status was done in 69 pts (36%) with CD19 negative relapse seen in 11 (16%). Of pts with PD, median PFS and OS from time of PD was 83 days (in pts who received salvage) and 174 days (for all PD pts) respectively. Pts with PD were more likely to have elevated LDH (p=0.001) and extranodal disease (p=0.003) at apheresis. For pts with PD after CART: 125 (65.5%) received further therapies. Pts were more likely to receive salvage therapies if their best response to CART was CR (p=0.026) or PR (p=0.015). Response rates of select firstand second-line therapies and PFS of first line therapies received after CART failure are detailed in figure 1. ORR and CRs were highest for polatuzumab, bendamustine, & rituximab (pola-BR; 73% & 40%), followed by BTK inhibitors (BTKi; 50% & 38%), and bispecific antibodies (bsAb) (50% & 25%). Five of 7 pts who received a BTKi had non-germinal center (GC) cell of origin (COO; 1 unknown COO). On log-rank testing, pts with elevated LDH (p=0.003) at time of apheresis and those with intermediate/high IPI (p=0.013) had inferior PFS J Adv Pract Oncol 2022;13(suppl 2):25–32 https://doi.org/10.6004/jadpro.2022.13.2.12 Th is ar tic le is dis tri bu te d u nd er th e t er m s o f t he Cr ea tiv e C om m on s A ttr ibu tio n N on -C om m er cia l N on -D er iva tiv e L ice ns e, wh ich pe rm its un re str ict ed no nco m m er cia l a nd no nde riv at ive us e, dis tri bu tio n, an d r ep ro du cti on in an y m ed ium , p rov ide d t he or igi na l w or k i s p ro pe rly ci te d.","PeriodicalId":94110,"journal":{"name":"Journal of the advanced practitioner in oncology","volume":"13 1","pages":"25 - 32"},"PeriodicalIF":0.0000,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the advanced practitioner in oncology","FirstCategoryId":"0","ListUrlMain":"https://doi.org/10.6004/jadpro.2022.13.2.12","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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Abstract

884 Outcomes and Treatment Patterns in Patients With Aggressive B-Cell Lymphoma After Failure of Anti-CD19 CAR T-Cell Therapy Joanna C. Zurko, MD, Narendranath Epperla, MD, MS, Imran Nizamuddin, MD, Pallawi Torka, MD, Kevin A. David, MD, Thomas A. Ollila, MD, Brian T. Hess, MD, Jonathon B. Cohen, MD, MS, Robert Ferdman, MD, Jieqi Liu, MD, Sayan Mullick Chowdhury, DO, PhD, Kaitlyn O’Shea, PhD, Jason Romancik, MD, Rahul Bhansali, MD, Elyse Harris, MD, Mckenzie Sorrell, D.O., Rebecca Masel, Lindsey Fitzgerald, MD, Carlos Galvez, MD, Shuo Ma, MD, Jane N. Winter, MD, Barbara Pro, MD, Leo I. Gordon, MD, Alexey V. Danilov, MD, PhD, Deborah M. Stephens, Nirav N. Shah, MD, Geoffrey Shouse, PhD, Vaishalee P. Kenkre, MD, Stefan K. Barta, MD, MRCP, MS and Reem Karmali, MD, MSc Visit https://doi.org/10.1182/blood-2021-147433 for a complete list of contributor affiliations and full graphics. Background: Anti-CD19 chimeric antigen receptor T-cell therapy (CART) is a highly active therapy for relapsed/refractory (R/R) aggressive B-cell lymphoma. Nonetheless, most patients (pts) ultimately develop progressive disease (PD). There is little guidance on the optimal treatment approach(es) for these pts. We performed a multicenter retrospective analysis with a primary objective to assess treatment patterns and outcomes in pts with R/R aggressive B-cell lymphoma who develop PD after anti-CD19 CARTs. Methods: Pts with aggressive B-cell lymphoma treated with anti-CD19 CART between 2015 and 2020 across 12 US academic medical centers were included. Demographic and clinical characteristics were collected along with CART toxicities and response. Regimens administered as salvage post CART were assessed. Univariate analyses (UVA) were performed to determine impact of demographic and clinical variables on survival outcomes. All p-values were two-tailed. Survival curves were calculated using the KaplanMeier method. Results: A total of 400 pts received anti-CD19 CARTs and were included for analysis. For the entire cohort: median PFS and OS from time of CART infusion were 11 months [mo] and 27 mo respectively. On log-rank testing, pts who received ≥3 lines of pre-CART therapy and those with refractory disease pre-CART had significantly worse PFS (p=0.004 & 0.001) and OS (both p<0.001). With median follow-up 22.4 mo, 190 pts (48%) had PD after CART; demographic and clinical variables of pts with and without PD are detailed in Table 1. Biopsy to confirm PD and assess CD19 status was done in 69 pts (36%) with CD19 negative relapse seen in 11 (16%). Of pts with PD, median PFS and OS from time of PD was 83 days (in pts who received salvage) and 174 days (for all PD pts) respectively. Pts with PD were more likely to have elevated LDH (p=0.001) and extranodal disease (p=0.003) at apheresis. For pts with PD after CART: 125 (65.5%) received further therapies. Pts were more likely to receive salvage therapies if their best response to CART was CR (p=0.026) or PR (p=0.015). Response rates of select firstand second-line therapies and PFS of first line therapies received after CART failure are detailed in figure 1. ORR and CRs were highest for polatuzumab, bendamustine, & rituximab (pola-BR; 73% & 40%), followed by BTK inhibitors (BTKi; 50% & 38%), and bispecific antibodies (bsAb) (50% & 25%). Five of 7 pts who received a BTKi had non-germinal center (GC) cell of origin (COO; 1 unknown COO). On log-rank testing, pts with elevated LDH (p=0.003) at time of apheresis and those with intermediate/high IPI (p=0.013) had inferior PFS J Adv Pract Oncol 2022;13(suppl 2):25–32 https://doi.org/10.6004/jadpro.2022.13.2.12 Th is ar tic le is dis tri bu te d u nd er th e t er m s o f t he Cr ea tiv e C om m on s A ttr ibu tio n N on -C om m er cia l N on -D er iva tiv e L ice ns e, wh ich pe rm its un re str ict ed no nco m m er cia l a nd no nde riv at ive us e, dis tri bu tio n, an d r ep ro du cti on in an y m ed ium , p rov ide d t he or igi na l w or k i s p ro pe rly ci te d.
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ASH亮点和评论:其他感兴趣的主题
884抗CD19 CAR T细胞治疗失败后侵袭性B细胞淋巴瘤患者的预后和治疗模式Joanna C.Zurko,医学博士,Narendranath Epperla,医学博士、Imran Nizamuddin,医学博士;Pallawi Torka,医学博士:Kevin A.David,医学博士。Thomas A.Ollila,医学医学博士:Brian T.Hess,医学博士,医学博士Jason Romancik、医学博士Rahul Bhansali、医学博士Elyse Harris、医学主任Mckenzie Sorrell、医学博士Rebecca Masel、医学博士Lindsey Fitzgerald、医学博士Carlos Galvez、医学博士Shuo Ma、医学博士Jane N.Winter、医学博士Barbara Pro、医学博士Leo I.Gordon、医学硕士Alexey V.Danilov、医学博士Deborah M.Stephens、医学博士Nirav N.Shah、医学教授Geoffrey Shouse、医学博士Vaishalee P.Kenkre、医学博士Stefan K.Barta、医学博士MRCP和医学博士Reem Karmali访问https://doi.org/10.1182/blood-2021-147433以获取投稿人隶属关系的完整列表和完整的图形。背景:抗CD19嵌合抗原受体T细胞疗法(CART)是一种治疗复发/难治性(R/R)侵袭性B细胞淋巴瘤的高效疗法。尽管如此,大多数患者(pts)最终发展为进行性疾病(PD)。关于这些pts的最佳治疗方法,几乎没有什么指导。我们进行了一项多中心回顾性分析,主要目的是评估抗CD19 CART后发生PD的R/R侵袭性B细胞淋巴瘤患者的治疗模式和结果。方法:纳入2015年至2020年间在12个美国学术医疗中心接受抗CD19 CART治疗的侵袭性B细胞淋巴瘤患者。收集人口统计学和临床特征以及CART毒性和反应。评估了作为CART后救助站管理的团。进行单变量分析(UVA),以确定人口统计学和临床变量对生存结果的影响。所有p值都是双尾的。使用KaplanMeier方法计算存活曲线。结果:共有400名患者接受了抗CD19 CART治疗,并纳入分析。对于整个队列:CART输注后的中位PFS和OS分别为11个月和27个月。在对数秩检验中,接受≥3行CART前治疗的患者和CART前患有难治性疾病的患者的PFS(p=0.004&0.001)和OS(均<0.001)显著较差。中位随访22.4个月,190名患者(48%)在CART后出现PD;表1详细列出了患有和不患有帕金森病的患者的人口统计学和临床变量。69名患者(36%)进行了活检以确认PD并评估CD19状态,11名患者(16%)出现CD19阴性复发。在PD患者中,自PD发生时起,中位PFS和OS分别为83天(接受抢救的患者)和174天(所有PD患者)。PD患者在单采时更可能出现LDH升高(p=0.001)和结外疾病(p=0.003)。CART后PD患者:125例(65.5%)接受了进一步治疗。如果Pts对CART的最佳反应是CR(p=0.026)或PR(p=0.015),则他们更有可能接受挽救性治疗。选择的一线和二线治疗的有效率以及CART失败后接受的一线治疗的PFS如图1所示。polatuzumab、bendamustine和利妥昔单抗的ORR和CR最高(pola-BR;73%和40%),其次是BTK抑制剂(BTKi;50%和38%)和双特异性抗体(bsAb)(50%和25%)。接受BTKi治疗的7名患者中有5名患者有非生发中心(GC)来源细胞(COO;1名COO未知)。在对数秩检验中,单采时LDH升高的患者(p=0.003)和IPI中等/高的患者(p=0.013)的PFS较差,《肿瘤杂志》2022;13(补充2):25-32https://doi.org/10.6004/jadpro.2022.13.2.12这是Cr ea tiv e C om m on s A ttr ibu tio n n on-C om m cia l n on-d er iva tiv e l ice ns e的三个部分,即它的非结构化无nco m er cia l A和非私有化、三个部分、一个在一个y m d ium中的操作过程,以及它的内部或外部。
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