Immune profiling of patients with extranodal natural killer/T cell lymphoma treated with daratumumab
Journal
Annals of hematology
Date Issued
2024-01-18
Author(s)
Qing, Min
Zhou, Tianyuan
Perova, Tatiana
Abraham, Yann
Sweeney, Cheryl
Krevvata, Maria
Zhang, Xiaokang
Qi, Ming
Gao, Grace
Kim, Tae Min
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
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.
Subjects
Biomarkers; Daratumumab; Immune profiling; Natural killer/T cell lymphoma
SDGs
Type
journal article