{"id":4739,"date":"2017-12-06T11:05:03","date_gmt":"2017-12-06T16:05:03","guid":{"rendered":"http:\/\/blogs.shu.edu\/cancer\/?p=4739"},"modified":"2021-07-02T08:51:38","modified_gmt":"2021-07-02T12:51:38","slug":"car-t-cell-more-effective-than-standard-of-care-in-refractory-non-hodgkin-lymphoma","status":"publish","type":"post","link":"http:\/\/blogs.shu.edu\/cancer\/2017\/12\/06\/car-t-cell-more-effective-than-standard-of-care-in-refractory-non-hodgkin-lymphoma\/","title":{"rendered":"CAR T-cell more effective than standard of care in refractory Non-Hodgkin Lymphoma"},"content":{"rendered":"<p>The FDA granted approval of <a href=\"https:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/CellularGeneTherapyProducts\/ApprovedProducts\/UCM581226.pdf\" target=\"_blank\" rel=\"noopener\">axicabtagene ciloleucel (YESCARTA)<\/a> on October 25, 2017, two months following the approval of <a href=\"https:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/CellularGeneTherapyProducts\/ApprovedProducts\/UCM573941.pdf\" target=\"_blank\" rel=\"noopener\">tisagenlecleucel (KYMRIAH)<\/a> \u2013 both are anti-CD19-directed CAR T (chimeric antigen receptor T-cell) therapies that employ re-programmed autologous T-cells to fight cancer:<!--more--><\/p>\n<ul>\n<li>KYMRIAH is indicated for B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse;<\/li>\n<li>YESCARTA is indicated for use in patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL \u2013 <a href=\"http:\/\/www.lymphoma.org\/site\/pp.asp?c=bkLTKaOQLmK8E&amp;b=6300153\" target=\"_blank\" rel=\"noopener\">the most common form of NHL<\/a> \u2013 non-Hodgkin lymphoma), primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.<\/li>\n<\/ul>\n<div id=\"attachment_4742\" style=\"width: 2863px\" class=\"wp-caption aligncenter\"><a href=\"http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Figure-1.-CAR-T-structure.png\" data-rel=\"lightbox-image-0\" data-rl_title=\"\" data-rl_caption=\"\" title=\"\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-4742\" class=\"size-full wp-image-4742\" src=\"http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Figure-1.-CAR-T-structure.png\" alt=\"\" width=\"2853\" height=\"4200\" srcset=\"http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Figure-1.-CAR-T-structure.png 2853w, http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Figure-1.-CAR-T-structure-204x300.png 204w, http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Figure-1.-CAR-T-structure-768x1131.png 768w, http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Figure-1.-CAR-T-structure-696x1024.png 696w, http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Figure-1.-CAR-T-structure-624x919.png 624w\" sizes=\"auto, (max-width: 2853px) 100vw, 2853px\" \/><\/a><p id=\"caption-attachment-4742\" class=\"wp-caption-text\">Figure 1. The engineered receptor on CAR T cells binds to an antigen on cancer cells. After binding, components of the receptor inside the T cell provide signals that activate it.<br \/>Credit: Kite Pharma <a href=\"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2017\/yescarta-fda-lymphoma\" target=\"_blank\" rel=\"noopener\">https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2017\/yescarta-fda-lymphoma<\/a>.<br \/>The CAR T therapies are comprised of autologous T cells that are genetically modified using a lentiviral vector to encode an anti-CD19 chimeric antigen receptor (CAR). To prepare YESCARTA, a patient\u2019s own T cells are harvested and genetically modified ex vivo by retroviral transduction to express a chimeric antigen receptor (CAR) comprising a murine anti-CD19 single chain variable fragment (scFv) linked to CD28 and CD3-zeta co-stimulatory domains. The anti-CD19 CAR T cells are expanded and infused back into the patient, where they can recognize and eliminate CD19-expressing target cells. <a href=\"https:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/CellularGeneTherapyProducts\/ApprovedProducts\/UCM581226.pdf\" target=\"_blank\" rel=\"noopener\">https:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/CellularGeneTherapyProducts\/ApprovedProducts\/UCM581226.pdf<\/a>.<br \/>KYMRIAH is comprised of autologous T cells that are genetically modified using a lentiviral vector to encode an anti-CD19 chimeric antigen receptor (CAR). The CAR is comprised of a murine single-chain antibody fragment (scFv) specific for CD19, followed by a CD8 hinge and transmembrane region that is fused to the intracellular signaling domains for 4-1BB (CD137) and CD3 zeta. <a href=\"https:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/CellularGeneTherapyProducts\/ApprovedProducts\/UCM573941.pdf\" target=\"_blank\" rel=\"noopener\">https:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/CellularGeneTherapyProducts\/ApprovedProducts\/UCM573941.pdf<\/a><\/p><\/div>\n<p><strong><em>YESCARTA &#8211; \u00a0B-cell Lymphoma<\/em><\/strong><\/p>\n<p>The registration trial (ZUMA-1) for YESCARTA was a single-arm, open label study of 101 patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Eligible patients had refractory disease to the most recent therapy or relapse within 1 year after autologous hematopoietic stem cell transplantation (HSCT). Half of the patients (51%) had a complete response, that is, their cancers disappeared completely.<\/p>\n<div id=\"attachment_4743\" style=\"width: 705px\" class=\"wp-caption aligncenter\"><a href=\"http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-1.-YESCART-response-rates-ZUMA-1.png\" data-rel=\"lightbox-image-1\" data-rl_title=\"\" data-rl_caption=\"\" title=\"\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-4743\" class=\"size-full wp-image-4743\" src=\"http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-1.-YESCART-response-rates-ZUMA-1.png\" alt=\"\" width=\"695\" height=\"179\" srcset=\"http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-1.-YESCART-response-rates-ZUMA-1.png 695w, http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-1.-YESCART-response-rates-ZUMA-1-300x77.png 300w, http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-1.-YESCART-response-rates-ZUMA-1-624x161.png 624w\" sizes=\"auto, (max-width: 695px) 100vw, 695px\" \/><\/a><p id=\"caption-attachment-4743\" class=\"wp-caption-text\">Table 1. Response rates on ZUMA-1. <a href=\"https:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/CellularGeneTherapyProducts\/ApprovedProducts\/UCM581226.pdf\" target=\"_blank\" rel=\"noopener\">https:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/CellularGeneTherapyProducts\/ApprovedProducts\/UCM581226.pdf<\/a><\/p><\/div>\n<div id=\"attachment_4744\" style=\"width: 705px\" class=\"wp-caption aligncenter\"><a href=\"http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-2.-YESCARTA-durability-of-repsonse-on-ZUMA-1.png\" data-rel=\"lightbox-image-2\" data-rl_title=\"\" data-rl_caption=\"\" title=\"\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-4744\" class=\"size-full wp-image-4744\" src=\"http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-2.-YESCARTA-durability-of-repsonse-on-ZUMA-1.png\" alt=\"\" width=\"695\" height=\"338\" srcset=\"http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-2.-YESCARTA-durability-of-repsonse-on-ZUMA-1.png 695w, http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-2.-YESCARTA-durability-of-repsonse-on-ZUMA-1-300x146.png 300w, http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-2.-YESCARTA-durability-of-repsonse-on-ZUMA-1-624x303.png 624w\" sizes=\"auto, (max-width: 695px) 100vw, 695px\" \/><\/a><p id=\"caption-attachment-4744\" class=\"wp-caption-text\">Table 2. Durability of response on ZUMA-1. <a href=\"https:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/CellularGeneTherapyProducts\/ApprovedProducts\/UCM581226.pdf\" target=\"_blank\" rel=\"noopener\">https:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/CellularGeneTherapyProducts\/ApprovedProducts\/UCM581226.pdf<\/a><\/p><\/div>\n<p><strong><em>Standard of care in refractory B-cell lymphomas<\/em><\/strong><\/p>\n<p><a href=\"http:\/\/www.bloodjournal.org\/content\/early\/2017\/08\/02\/blood-2017-03-769620?sso-checked=true\" target=\"_blank\" rel=\"noopener\">SCHOLAR-1 is a study of patients with DLBCL<\/a> that pooled the outcomes from two previously conducted randomized trials\u00a0and databases from two large academic cancer centers:<\/p>\n<p style=\"padding-left: 30px\">SCHOLAR-1 pooled data from 2 phase 3 clinical trials (Lymphoma Academic Research Organization-CORAL and Canadian Cancer Trials Group LY.12) and 2 observational cohorts (MD Anderson Cancer Center and University of Iowa\/Mayo Clinic Lymphoma Specialized Program of Research Excellence). SCHOLAR-1 is the largest patient-level pooled retrospective analysis that characterizes response rates and survival for a population of patients with refractory DLBCL.<\/p>\n<p>The objective response rate was 26% with 7% of patients achieving complete responses to the next line of therapy; the median overall survival was 6.3 months. Twenty percent of patients were alive at 2-years.<\/p>\n<p><strong><em>YESCARTA vs standard of care<\/em><\/strong><\/p>\n<p>There are no randomized studies comparing YESCARTA to standard of care therapies in refractory DLBCL. However, using the results of ZUMA-1 and SCHOLAR-1<a href=\"https:\/\/academic.oup.com\/annonc\/article\/28\/suppl_5\/mdx376.026\/4109240\" target=\"_blank\" rel=\"noopener\">, Neelapu and colleagues compared the efficacy<\/a> of the treatments, adjusting for imbalances and key covariates.<\/p>\n<p style=\"padding-left: 30px\">The patients in the two studies were balanced for distribution of sex, disease type, and the proportion of patients with disease refractory to two consecutive lines of therapy. ZUMA-1 included more patients with three or more prior lines of therapy, with advanced, stage III-IV disease and less favorable International Prognostic Index scores. Also, more patients in ZUMA-1 had transformed follicular lymphoma or primary mediastinal large B-cell lymphoma, and more patients in SCHOLAR-1 had primary refractory disease.<\/p>\n<div id=\"attachment_4745\" style=\"width: 715px\" class=\"wp-caption aligncenter\"><a href=\"http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-3.-Patient-characteristics-ZUMA-1-vs-SCHOLAR-1.png\" data-rel=\"lightbox-image-3\" data-rl_title=\"\" data-rl_caption=\"\" title=\"\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-4745\" class=\"size-full wp-image-4745\" src=\"http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-3.-Patient-characteristics-ZUMA-1-vs-SCHOLAR-1.png\" alt=\"\" width=\"705\" height=\"702\" srcset=\"http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-3.-Patient-characteristics-ZUMA-1-vs-SCHOLAR-1.png 705w, http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-3.-Patient-characteristics-ZUMA-1-vs-SCHOLAR-1-150x150.png 150w, http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-3.-Patient-characteristics-ZUMA-1-vs-SCHOLAR-1-300x300.png 300w, http:\/\/blogs.shu.edu\/cancer\/files\/2017\/12\/Table-3.-Patient-characteristics-ZUMA-1-vs-SCHOLAR-1-624x621.png 624w\" sizes=\"auto, (max-width: 705px) 100vw, 705px\" \/><\/a><p id=\"caption-attachment-4745\" class=\"wp-caption-text\">Table 3. Patient characteristics \u2013 ZUMA-1 versus SCHOLAR-1. <a href=\"https:\/\/academic.oup.com\/annonc\/article\/28\/suppl_5\/mdx376.026\/4109240\" target=\"_blank\" rel=\"noopener\">https:\/\/academic.oup.com\/annonc\/article\/28\/suppl_5\/mdx376.026\/4109240<\/a><\/p><\/div>\n<p>The <em><strong>risk of death in ZUMA-1 was reduced by 77%<\/strong><\/em> relative to SCHOLAR-1 (p &lt; 0.0001). Moreover, YESCARTA<\/p>\n<p style=\"padding-left: 30px\">\u201cinduced remissions that last years in a significant proportion of patients, suggesting the possibility of cures in these patients, who typically do not survive beyond six months,\u201d said Neelapu.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The FDA granted approval of axicabtagene ciloleucel (YESCARTA) on October 25, 2017, two months following the approval of tisagenlecleucel (KYMRIAH) \u2013 both are anti-CD19-directed CAR T (chimeric antigen receptor T-cell) therapies that employ re-programmed autologous T-cells to fight cancer:<\/p>\n","protected":false},"author":2252,"featured_media":4650,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[1],"tags":[233,554,182,2104,1762,2107,1122,183,519,1877,1878,2106,806,1876,2108,1987,2105,2109],"class_list":["post-4739","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","tag-4-1bb","tag-acute-lymphoblastic-leukemia","tag-all","tag-axicabtagene-ciloleucel","tag-car-t-cell","tag-cd137","tag-cd28","tag-cd3","tag-chimeric-antigen-receptor-t-cells","tag-diffuse-large-b-cell-lymphoma","tag-dlbcl","tag-kymriah","tag-nhl","tag-non-hodgkin-lymphoma","tag-scholar-1","tag-tisagenlecleucel","tag-yescarta","tag-zuma-1"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/posts\/4739","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/users\/2252"}],"replies":[{"embeddable":true,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/comments?post=4739"}],"version-history":[{"count":4,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/posts\/4739\/revisions"}],"predecessor-version":[{"id":4750,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/posts\/4739\/revisions\/4750"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/media\/4650"}],"wp:attachment":[{"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/media?parent=4739"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/categories?post=4739"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/tags?post=4739"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}