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Immune profiling of patients with extranodal natural killer/T cell lymphoma treated with daratumumab.
Qing, Min; Zhou, Tianyuan; Perova, Tatiana; Abraham, Yann; Sweeney, Cheryl; Krevvata, Maria; Zhang, Xiaokang; Qi, Ming; Gao, Grace; Kim, Tae Min; Yao, Ming; Cho, Seok-Goo; Eom, Hyeon Seok; Lim, Soon Thye; Yeh, Su-Peng; Kwong, Yok Lam; Yoon, Dok Hyun; Kim, Jin Seok; Kim, Won Seog; Zhou, Longen; Attar, Ricardo; Verona, Raluca I.
Afiliación
  • Qing M; Janssen Research & Development, Shanghai, China.
  • Zhou T; Janssen Research & Development, Shanghai, China.
  • Perova T; Janssen Research & Development, LLC, Spring House, PA, USA.
  • Abraham Y; Janssen Research & Development, LLC, Beerse, Belgium.
  • Sweeney C; Johnson & Johnson (Ireland), Dublin, Ireland.
  • Krevvata M; Janssen Research & Development, LLC, Spring House, PA, USA.
  • Zhang X; Janssen Research & Development, Beijing, China.
  • Qi M; Janssen Research & Development, LLC, Spring House, PA, USA.
  • Gao G; Janssen Research & Development, Shanghai, China.
  • Kim TM; Seoul National University Hospital, Seoul, South Korea.
  • Yao M; National Taiwan University Hospital, Taipei, Taiwan.
  • Cho SG; Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
  • Eom HS; National Cancer Center, Goyang-si, South Korea.
  • Lim ST; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
  • Yeh SP; China Medical University Hospital, Taichung, Taiwan.
  • Kwong YL; Queen Mary Hospital, Pok Fu Lam, Hong Kong.
  • Yoon DH; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Kim JS; Yonsei University College of Medicine, Severance Hospital, Seoul, South Korea.
  • Kim WS; Division of Hematology/Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea.
  • Zhou L; Janssen Research & Development, Shanghai, China.
  • Attar R; Janssen Research & Development, LLC, Spring House, PA, USA.
  • Verona RI; Janssen Research & Development, LLC, Spring House, PA, USA. Raluca.verona@gmail.com.
Ann Hematol ; 103(6): 1989-2001, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38233570
ABSTRACT
Natural killer/T cell lymphoma (NKTCL) is a highly aggressive, heterogeneous non-Hodgkin lymphoma resulting from malignant proliferation of cytotoxic natural killer (NK) or T cells. Previous studies demonstrated variable expression of CD38 on NKTCL tumors. Daratumumab, a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, was hypothesized to be a novel therapeutic option for patients with relapsed or refractory (R/R) NKTCL. In the phase 2 NKT2001 study (ClinicalTrials.gov Identifier NCT02927925) assessing the safety and efficacy of daratumumab, a suboptimal overall response rate was seen in R/R NKTCL patients. One patient, whose tumors did not express CD38, responded to treatment, suggesting that the immunomodulatory activities of daratumumab may be sufficient to confer clinical benefit. To understand the suboptimal response rate and short duration of response, we investigated the immune profile of NKTCL patients from NKT2001 in the context of daratumumab anti-tumor activity. Tumor tissue and whole blood were, respectively, analyzed for CD38 expression and patient immune landscapes, which were assessed via cytometry by time-of-flight (CyTOF), multiparameter flow cytometry (MPFC), clonal sequencing, and plasma Epstein-Barr virus (EBV)-DNA level measurements. Changes observed in the immune profiles of NKTCL patients from NKT2001, including differences in B and T cell populations between responders and nonresponders, suggest that modulation of the immune environment is crucial for daratumumab anti-tumor activities in NKTCL. In conclusion, these findings highlight that the clinical benefit of daratumumab in NKTCL may be enriched by B/T cell-related biomarkers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfoma Extranodal de Células NK-T / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Hematol Asunto de la revista: HEMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfoma Extranodal de Células NK-T / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Hematol Asunto de la revista: HEMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania