Prospective study of adoptive activated αβT lymphocyte immunotherapy for refractory cancers: development and validation of a response scoring system.


Journal

Cytotherapy
ISSN: 1477-2566
Titre abrégé: Cytotherapy
Pays: England
ID NLM: 100895309

Informations de publication

Date de publication:
01 2023
Historique:
received: 24 03 2022
revised: 03 09 2022
accepted: 25 09 2022
pubmed: 18 10 2022
medline: 28 12 2022
entrez: 17 10 2022
Statut: ppublish

Résumé

This prospective clinical study aimed to determine the efficacy and prognostic factors of adoptive activated αβT lymphocyte immunotherapy for various refractory cancers. The primary endpoint was overall survival (OS), and the secondary endpoint was radiological response. The authors treated 96 patients. Activated αβT lymphocytes were infused every 2 weeks for a total of six times. Prognostic factors were identified by analyzing clinical and laboratory data obtained before therapy. Median survival time (MST) was 150 days (95% confidence interval, 105-191), and approximately 20% of patients achieved disease control (complete response + partial response + stable disease). According to the multivariate Cox proportional hazards model with Akaike information criterion-best subset selection, sex, concurrent therapy, neutrophil/lymphocyte ratio, albumin, lactate dehydrogenase, CD4:CD8 ratio and T helper (Th)1:Th2 ratio were strong prognostic factors. Using parameter estimates of the Cox analysis, the authors developed a response scoring system. The authors then determined the threshold of the response score between responders and non-responders. This threshold was able to significantly differentiate OS of responders from that of non-responders. MST of responders was longer than that of non-responders (317.5 days versus 74 days). The validity of this response scoring system was then confirmed by internal validation. Adoptive activated αβT lymphocyte immunotherapy has clinical efficacy in certain patients. The authors' scoring system is the first prognostic model reported for this therapy, and it is useful for selecting patients who might obtain a better prognosis through this modality.

Sections du résumé

BACKGROUND AIMS
This prospective clinical study aimed to determine the efficacy and prognostic factors of adoptive activated αβT lymphocyte immunotherapy for various refractory cancers. The primary endpoint was overall survival (OS), and the secondary endpoint was radiological response.
METHODS
The authors treated 96 patients. Activated αβT lymphocytes were infused every 2 weeks for a total of six times. Prognostic factors were identified by analyzing clinical and laboratory data obtained before therapy.
RESULTS
Median survival time (MST) was 150 days (95% confidence interval, 105-191), and approximately 20% of patients achieved disease control (complete response + partial response + stable disease). According to the multivariate Cox proportional hazards model with Akaike information criterion-best subset selection, sex, concurrent therapy, neutrophil/lymphocyte ratio, albumin, lactate dehydrogenase, CD4:CD8 ratio and T helper (Th)1:Th2 ratio were strong prognostic factors. Using parameter estimates of the Cox analysis, the authors developed a response scoring system. The authors then determined the threshold of the response score between responders and non-responders. This threshold was able to significantly differentiate OS of responders from that of non-responders. MST of responders was longer than that of non-responders (317.5 days versus 74 days). The validity of this response scoring system was then confirmed by internal validation.
CONCLUSIONS
Adoptive activated αβT lymphocyte immunotherapy has clinical efficacy in certain patients. The authors' scoring system is the first prognostic model reported for this therapy, and it is useful for selecting patients who might obtain a better prognosis through this modality.

Identifiants

pubmed: 36253253
pii: S1465-3249(22)00816-7
doi: 10.1016/j.jcyt.2022.09.007
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

76-81

Informations de copyright

Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.

Auteurs

Atsushi Nonami (A)

Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan; Department of Medicine and Biosystemic Science, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: anonami@camiku.kyushu-u.ac.jp.

Ryu Matsuo (R)

Department of Health Care Administration and Management, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Kouta Funakoshi (K)

Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan.

Tomohiro Nakayama (T)

Department of Radiology, Saiseikai Fukuoka General Hospital, Fukuoka, Japan.

Shigenori Goto (S)

Department of Next-Generation Cell and Immune Therapy, Juntendo University School of Medicine, Tokyo, Japan.

Tadafumi Iino (T)

Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan.

Shigeo Takaishi (S)

Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan.

Shinichi Mizuno (S)

Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan; Division of Medical Sciences and Technology, Department of Health Sciences, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.

Koichi Akashi (K)

Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan; Department of Medicine and Biosystemic Science, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.

Masatoshi Eto (M)

Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

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