Gemcitabine, carboplatin, and Epstein–Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial

Article

作者: Hasbullah, H.H. ; Wirasorn, K ; Lulla, P. ; Brenner, M.K. ; Sirachainan, E ; Samol, J. ; Horak, I ; Ding, C. ; Ang, M K ; Ho, G F ; Algazi, A ; Wang, H.-M. ; Liu, Y C ; Toh, H C ; Ho, K F ; Myo, A. ; Toh, H.C. ; Wang, W.-W. ; Yang, M-H ; Wirasorn, K. ; Lertbutsayanukul, C. ; Ho, G.F. ; Ho, K.F. ; Wirth, L J ; Low, S.H.J. ; Tan, S H ; Tho, L M ; Nadler, E ; Wang, H-M ; Ding, C ; Low, S H J ; Colevas, A.D. ; Hong, R.-L. ; Ang, S F ; Chitapanarux, I. ; Nadler, E. ; Chitapanarux, I ; Brenner, M K ; Tho, L.M. ; Tan, S.H. ; Ang, S.F. ; Hsieh, C Y ; Liu, Y.C. ; Lulla, P ; Ang, M.K. ; Hsieh, C.Y. ; Myo, A ; Ong, W S ; Lertbutsayanukul, C ; Sirachainan, E. ; Yang, M.-H. ; Colevas, A D ; Hong, R-L ; Samol, J ; Wirth, L.J. ; Wang, W-W ; Ong, W.S. ; Horak, I. ; Algazi, A. ; Hasbullah, H H

BACKGROUND:

Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment.

PATIENTS AND METHODS:

This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety.

CLINICALTRIALS:

gov identifier: NCT02578641.

RESULTS:

A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC + EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC + EBV-CTL subjects. The median OS was 25.0 months in the GC + EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% confidence interval 0.91-1.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL.

CONCLUSIONS:

GC + EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.

2022-08-01·Zhongguo shi yan xue ye xue za zhi

[Clinical Analysis of Post-Transplant Lymphoproliferative Disorder after Hematopoietic Stem Cell Transplantation in Severe Aplastic Anemia Patients].

Article

作者: Ding, Li ; Yan, Hong-Min ; Wang, Heng-Xiang ; Han, Dong-Mei ; Xue, Mei ; Zhu, Ling ; Li, Sheng ; Liu, Jing ; Zheng, Xiao-Li

OBJECTIVE:

To analyze the clinical characteristics of SAA patients with post-transplantation lymphoproliferative disease (PTLD) after allogeneic hematopoietic stem cell transplantation, and to improve diagnosis and treatment of PTLD.

METHODS:

The clinical data of 192 patients with SAA patients who underwent HSCT in a single center from September 2010 to September 2017 were analyzed retrospectively. All patients were received antithymocyte globulin（ATG） conditioning regimen and mesenchymal stem cell(MSC) infusion.

RESULTS:

Among 192 cases, PTLD occurred in 14 cases, the incidence was 7.29％， 9 of them were diagnosed by pathology， and 5 were diagnosed clinically. EBV infection occurred with a median time of 72（35-168） days, Viral load higher than 1×10⁴ copies/ml occured in all PTLD patients. The incidence of probable PTLD in patients ≤12 years old and ＞12 years old was 11.11%, 2.38%, respectively (P<0.01）. Univariate and multivariate analysis that the EBV infection, patients age≤12 years old, HLA-mismatch in URD-HSCT, grade II to IV aGVHD were the independent risk factors for PTLD. All PTLD patients were treated with rituximab(RTX) when EBV-DNA load higher than 1×10⁴ copies/ml, or reducted the use of immunosuppression(RIS), patients with poor therapeutic effect were treated combined with EBV-specific CTLs(EBV-CTL) and chemotherapy. All patients were treated effectively, and the total effective rate was 100％. The median follow-up time was 65(62-115) months, and the overall survival rate was 92.85%. One patients died of cerebral hemorrhage, 7 months after PTLD curred.

CONCLUSION:

The incidence of PTLD after HSCT with SAA who used ATG and MSC in conditioning regimen closely relates to EBV infection, age of patients≤12 years, HLA-mismatch in URD-HSCT, grade II to IV GVHD. Rituximab combined with RIS may reduce the incidence of PTLD, combined EBV-CTL and chemotherapy may be the useful and most important treatment for PTLD.

2021-12-01·Transplant international : official journal of the European Society for Organ Transplantation2区 · 医学

EBV‐specific cytotoxic T lymphocytes for refractory EBV‐associated post‐transplant lymphoproliferative disorder in solid organ transplant recipients: a systematic review

2区 · 医学

Review

作者: Wei, Lin ; Zhang, Jin‐Ming ; Liu, Jing‐Yi ; Sun, Li‐Ying ; Zhan, Hao‐Su

The use of Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs) in adoptive immunotherapy in hematopoietic stem cell transplantation (HSCT) patients with post-transplantation lymphoproliferative disorder (PTLD) has demonstrated safety and effectiveness. EBV-CTLs might also be the effective treatment of refractory PTLD of solid organ transplantation (SOT) recipients. Two independent assessors searched Pubmed, Embase, Cochrane Library, and Web of Science from their inception to November 2020. Eleven studies with 76 patients (42, 55% male) were included. We extracted the data and completed the quality assessments. Most of the studies were from Europe and the USA. Liver and kidney transplantation accounted for most of the transplant types. Thirty-five (46.1%) patients were diagnosed with monomorphic PTLD, and B lymphocyte type was the most common. All the patients received primary treatment for PTLD while it was ineffective. CTLs included autologous EBV-CTLs (15/76, 22%) and HLA-matched third-party EBV-CTLs (61/76, 78%). The response rate for EBV-CTL treatment of refractory PTLD was 66%. Of 50 patients, 36 achieved complete remission and 14 achieved partial remission. EBV-DNA level decreased in 39 patients. Adverse reactions were rare and mild. We conclude that adoptive therapy with EBV-specific CTLs is safe, well-tolerated, and effective in PTLD.

项与 Autologous Epstein-Barr virus-specific T-cell therapy(Atara Biotherapeutics, Inc.) 相关的新闻（医药）

2017-12-28

·GlobeNewswire

Atara Biotherapeutics to Host Corporate Update Conference Call on Friday, December 29, 2017, at 8:00 a.m. EST

– Company to announce FDA clearance to initiate two Phase 3 tabelecleucel clinical studies – SOUTH SAN FRANCISCO, Calif., Dec. 28, 2017 (GLOBE NEWSWIRE) -- Atara Biotherapeutics, Inc. (Nasdaq:ATRA), a leading off-the-shelf T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, today announced that it will host a live corporate update conference call and webcast on Friday, December 29, 2017, at 8:00 a.m. EST. Analysts and investors can participate in the conference call by dialing (888) 540-6216 for domestic callers and (734) 385-2715 for international callers, using the conference ID 2395468. The live webcast can be accessed on the Events and Presentations page in the Investors and Media section of the Atara website, www.atarabio.com . A replay of the webcast will be available on the Company’s website for 90 days following the live conference call. About Atara Biotherapeutics, Inc. Atara Biotherapeutics, Inc. ( @Atarabio ) is a leading T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases. The Company's off-the-shelf, or allogeneic, T-cells are bioengineered from donors with healthy immune function and allow for rapid delivery from inventory to patients without a requirement for pretreatment. Atara's T-cell immunotherapies are designed to precisely recognize and eliminate cancerous or diseased cells without affecting normal, healthy cells. Atara's most advanced T-cell immunotherapy in development, tabelecleucel (formerly known as ATA129), is being developed for the treatment of patients with rituximab-refractory Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (EBV+PTLD), as well as other EBV associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC). Phase 3 studies of tabelecleucel in EBV+PTLD following an allogeneic hematopoietic cell transplant (MATCH study) or solid organ transplant (ALLELE study) are expected to start in 2017, and a Phase 1/2 study of tabelecleucel in combination with Merck's anti-PD-1 (programmed death receptor-1) therapy, KEYTRUDA® (pembrolizumab), in patients with platinum-resistant or recurrent EBV associated NPC is planned for 2018. Tabelecleucel is also available to eligible patients with EBV associated hematologic and solid tumors through an ongoing multicenter expanded access protocol (EAP) clinical study. Allogeneic ATA188 and autologous ATA190, the Company's T-cell immunotherapies using a complementary targeted antigen recognition technology, target specific EBV antigens believed to be important for the potential treatment of multiple sclerosis (MS). A Phase 1 clinical study of autologous ATA190 in patients with progressive MS is ongoing. Atara also initiated a multinational, multicenter Phase 1 allogeneic ATA188 clinical study in patients with progressive or relapsing-remitting MS in October 2017. Atara's clinical pipeline also includes ATA520 targeting Wilms Tumor 1 (WT1) and ATA230 directed against cytomegalovirus (CMV). Forward-Looking Statements This press release contains or may imply "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. For example, forward-looking statements include statements regarding: the initiation of the Phase 3 studies of tabelecleucel in EBV+PTLD following an allogeneic hematopoietic cell transplant (MATCH study) or solid organ transplant (ALLELE study) in 2017; and the initiation of a Phase 1/2 study of tabelecleucel in combination with Merck's anti-PD-1 (programmed death receptor-1) therapy, KEYTRUDA® (pembrolizumab), in patients with platinum-resistant or recurrent EBV associated NPC planned for 2018. Because such statements deal with future events and are based on Atara Biotherapeutics' current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Atara Biotherapeutics could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including those discussed under the heading "Risk Factors" in Atara Biotherapeutics' quarterly report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 9, 2017, including the documents incorporated by reference therein, and subsequent filings with the SEC. Except as otherwise required by law, Atara Biotherapeutics disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise. INVESTOR & MEDIA CONTACTS: Investors: John Craighead, Atara Biotherapeutics 650-410-3012 jcraighead@atarabio.com Steve Klass, Burns McClellan 212-213-0006 x331 sklass@burnsmc.com Media: Justin Jackson, Burns McClellan 212-213-0006 x327 jjackson@burnsmc.com

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适应症	最高研发状态	国家/地区	公司	日期
多发性硬化症	临床2期	澳大利亚	QIMR Berghofer Medical Research Institute	2017-10-19
多发性硬化症	临床2期	澳大利亚	Atara Biotherapeutics, Inc.	2017-10-19
淋巴瘤	临床2期	-	Atara Biotherapeutics, Inc.	-
淋巴瘤	临床2期	-	Memorial Sloan Kettering Cancer Center	-