Falchi Lorenzo, Rahman Jahan, Melendez Lauren, Douglas Monifa, Amador Walter Ramos, Hamlin Paul, Kumar Anita, Hoehn Daniela, Lin Ya-Hui, Gao Qi, Roshal Mikhail, Ewalt Mark D, Dogan Ahmet, Greenbaum Benjamin, Salles Gilles A, Vardhana Santosha A
Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY.
Weill Cornell Medical College, New York, NY, USA.
medRxiv. 2024 Jul 5:2024.07.02.24309792. doi: 10.1101/2024.07.02.24309792.
Leveraging endogenous tumor-resident T-cells for immunotherapy using bispecific antibodies (BsAb) targeting CD20 and CD3 has emerged as a promising therapeutic strategy for patients with B-cell non-Hodgkin lymphomas. However, features associated with treatment response or resistance are unknown. To this end, we analyzed data from patients treated with epcoritamab-containing regimens in the EPCORE NHL-2 trial (NCT04663347). We observed downregulation of CD20 expression on B-cells following treatment initiation both in progressing patients and in patients achieving durable complete responses (CR), suggesting that CD20 downregulation does not universally predict resistance to BsAb-based therapy. Single-cell immune profiling of tumor biopsies obtained following one cycle of therapy revealed substantial clonal expansion of cytotoxic CD4+ and CD8+ T-cells in patients achieving CR, and an expansion of follicular helper and regulatory CD4+ T-cells in patients whose disease progressed. These results identify distinct tumor-resident T-cell profiles associated with response or resistance to BsAb therapy.
利用内源性肿瘤驻留T细胞，通过靶向CD20和CD3的双特异性抗体（BsAb）进行免疫治疗，已成为B细胞非霍奇金淋巴瘤患者一种有前景的治疗策略。然而，与治疗反应或耐药相关的特征尚不清楚。为此，我们分析了EPCORE NHL-2试验（NCT04663347）中接受含epcoritamab方案治疗患者的数据。我们观察到，在疾病进展的患者和实现持久完全缓解（CR）的患者中，治疗开始后B细胞上CD20表达均下调，这表明CD20下调并非普遍预示对基于BsAb的治疗耐药。对治疗一个周期后获得的肿瘤活检样本进行单细胞免疫分析发现，实现CR的患者中细胞毒性CD4+和CD8+T细胞大量克隆扩增，而疾病进展的患者中滤泡辅助性和调节性CD4+T细胞扩增。这些结果确定了与BsAb治疗反应或耐药相关的不同肿瘤驻留T细胞谱。
