Correlation of immune fitness with response to teclistamab in relapsed/refractory multiple myeloma in the MajesTEC-1 study

Author:

Cortes-Selva Diana1,Perova Tatiana1,Skerget Sheri1,Vishwamitra Deeksha1,Stein Sarah1,Boominathan Rengasamy1,Lau Onsay1,Calara-Nielsen Karl1,Davis Cuc1,Patel Jaymala1,Banerjee Arnob1,Stephenson Tara1,Uhlar Clarissa1,Kobos Rachel2,Goldberg Jenna2,Pei Lixia2,Trancucci Danielle2,Girgis Suzette1,Wang Lin Shun Xin1ORCID,Wu Liviawati S.3,Moreau Philippe4,Usmani Saad Z.5,Bahlis Nizar J.6ORCID,van de Donk Niels W. C. J.7,Verona Raluca I.1ORCID

Affiliation:

1. 1Janssen Research & Development, Spring House, PA

2. 2Janssen Research & Development, Raritan, NJ

3. 3Janssen Research & Development, South San Francisco, CA

4. 4University Hospital Hôtel-Dieu, Nantes, France

5. 5Memorial Sloan Kettering Cancer Center, New York, NY

6. 6Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada

7. 7Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

Abstract

Abstract Teclistamab, an off-the-shelf B-cell maturation antigen (BCMA) × CD3 bispecific antibody that mediates T-cell activation and subsequent lysis of BCMA-expressing myeloma cells, is approved for the treatment of patients with relapsed/refractory multiple myeloma (R/RMM). As a T-cell redirection therapy, clinical outcomes with teclistamab may be influenced by patient immune fitness and tumor antigen expression. We correlated tumor characteristics and baseline immune profiles with clinical response and disease burden in patients with R/RMM from the pivotal phase 1/2 MajesTEC-1 study, focusing on patients treated with 1.5 mg/kg of teclistamab (N = 165). Peripheral blood samples were collected at screening, and bone marrow samples were collected at screening and cycle 3. Better clinical outcomes to teclistamab correlated with higher baseline total T-cell counts in the periphery. In addition, responders (partial response or better) had a lower proportion of immunosuppressive regulatory T cells (Tregs), T cells expressing coinhibitory receptors (CD38, PD-1, and PD-1/TIM-3), and soluble BCMA and a T-cell profile suggestive of a more cytolytic potential, compared with nonresponders. Neither frequency of baseline bone marrow BCMA expression nor BCMA-receptor density was associated with clinical response to teclistamab. Improved progression-free survival was observed in patients with a lower frequency of T cells expressing exhaustion markers and immunosuppressive Tregs. Overall, response to teclistamab was associated with baseline immune fitness; nonresponders had immune profiles suggestive of immune suppression and T-cell dysfunction. These findings illustrate the importance of the contribution of the immune landscape to T-cell redirection therapy response. This trial was registered at www.ClinicalTrials.gov as #NCT03145181/NCT04557098.

Publisher

American Society of Hematology

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3