The safety and clinical effects of administering a multiantigen-targeted T cell therapy to patients with multiple myeloma

Premal D. Lulla, Ifigeneia Tzannou, Spyridoula Vasileiou, George Carrum, Carlos A. Ramos, Rammurti Kamble, Tao Wang, Mengfen Wu, Mrinalini Bilgi, Adrian P. Gee, Shivani Mukhi, Betty Chung, Linghua Wang, Ayumi Watanabe, Manik Kuvalekar, Mira Jeong, Yumei Li, Shamika Ketkar, Matthew French-Kim, Bambi GrilleyMalcolm K. Brenner, Helon E. Heslop, Juan F. Vera, Ann M. Leen

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Multiple myeloma (MM) is an almost always incurable malignancy of plasma cells. Despite the advent of new therapies, most patients eventually relapse or become treatment-refractory. Consequently, therapies with nonoverlapping mechanisms of action that are nontoxic and provide long-term benefit to patients with MM are greatly needed. To this end, we clinically tested an autologous multitumor-associated antigen (mTAA)-specific T cell product for the treatment of patients with high-risk, relapsed or refractory MM. In this study, we expanded polyclonal T cells from 23 patients with MM. T cells whose native T cell receptors were reactive toward five myeloma-expressed target TAAs (PRAME, SSX2, MAGEA4, Survivin, and NY-ESO-1) were enriched ex vivo. To date, we have administered escalating doses of these nonengineered mTAA-specific T cells (0.5 × 107to 2 × 107cells/m2) to 21 patients with MM, 9 of whom were at high risk of relapse after a median of 3 lines of prior therapy and 12 with active, relapsed or refractory disease after a median of 3.5 prior lines. The cells were well tolerated, with only two transient, grade III infusion-related adverse events. Furthermore, patients with active relapsed or refractory myeloma enjoyed a longer than expected progression-free survival and responders included three patients who achieved objective responses concomitant with detection of functional TAA-reactive T cell clonotypes derived from the infused mTAA product. c 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Original languageEnglish (US)
Article numbereaaz3339
JournalScience translational medicine
Volume12
Issue number554
DOIs
StatePublished - Jul 29 2020

ASJC Scopus subject areas

  • Medicine(all)

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