T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma

Syed Abbas Ali, Victoria Shi, Irina Maric, Michael Wang, David F. Stroncek, Jeremy J. Rose, Jennifer N. Brudno, Maryalice Stetler-Stevenson, Steven A. Feldman, Brenna G. Hansen, Vicki S. Fellowes, Frances T. Hakim, Ronald E. Gress, James N. Kochenderfer

Research output: Contribution to journalArticlepeer-review

Abstract

Therapies with novel mechanisms of action are needed for multiple myeloma (MM). B-cell maturation antigen (BCMA) is expressed in most cases of MM. We conducted the first-inhumans clinical trial of chimeric antigen receptor (CAR) T cells targeting BCMA. T cells expressing the CAR used in this work (CAR-BCMA) specifically recognized BCMAexpressing cells. Twelve patients receivedCAR-BCMAT cells in this dose-escalation trial. Amongthe 6 patients treated on the lowest 2 dose levels, limited antimyelomaactivity and mild toxicity occurred.Onthe third dose level, 1 patient obtained a very good partial remission.Twopatients were treatedon the fourth dose level of 9 3 106 CAR1 T cells/kg body weight. Before treatment, the first patient on the fourth dose level had chemotherapyresistant MM, making up 90% of bone marrow cells. After treatment, bone marrow plasma cells became undetectable by flow cytometry, and the patient'sMMentered a stringent complete remission that lasted for 17 weeks before relapse. The second patient on the fourth dose level had chemotherapy-resistantMMmaking up80%of bone marrow cells before treatment. Twenty-eight weeks after this patient received CAR-BCMA T cells, bone marrow plasma cells were undetectable by flow cytometry, and the serum monoclonal protein had decreased by >95%. This patient is in an ongoing very good partial remission. Both patients treated on the fourth dose level had toxicity consistent with cytokine-releasesyndrome including fever, hypotension, and dyspnea. Both patients hadprolonged cytopenias. Our findings demonstrate antimyeloma activity of CAR-BCMA T cells.

Original languageEnglish (US)
Pages (from-to)1688-1700
Number of pages13
JournalBlood
Volume128
Issue number13
DOIs
StatePublished - Sep 29 2016

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma'. Together they form a unique fingerprint.

Cite this