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Original ArticleFree Preview

Teclistamab in Relapsed or Refractory Multiple Myeloma

List of authors.
  • Philippe Moreau, M.D.,
  • Alfred L. Garfall, M.D.,
  • Niels W.C.J. van de Donk, M.D., Ph.D.,
  • Hareth Nahi, M.D., Ph.D.,
  • Jesús F. San-Miguel, M.D., Ph.D.,
  • Albert Oriol, M.D., Ph.D.,
  • Ajay K. Nooka, M.D.,
  • Thomas Martin, M.D.,
  • Laura Rosinol, M.D.,
  • Ajai Chari, M.D.,
  • Lionel Karlin, M.D.,
  • Lotfi Benboubker, M.D.,
  • Maria-Victoria Mateos, M.D., Ph.D.,
  • Nizar Bahlis, M.D.,
  • Rakesh Popat, M.D., Ph.D.,
  • Britta Besemer, M.D.,
  • Joaquín Martínez-López, M.D., Ph.D,
  • Surbhi Sidana, M.D.,
  • Michel Delforge, M.D., Ph.D.,
  • Lixia Pei, Ph.D.,
  • Danielle Trancucci, M.Sc.,
  • Raluca Verona, Ph.D.,
  • Suzette Girgis, Ph.D.,
  • Shun X.W. Lin, Ph.D.,
  • Yunsi Olyslager, M.Sc.,
  • Mindy Jaffe, M.S.N.,
  • Clarissa Uhlar, Ph.D.,
  • Tara Stephenson, Ph.D.,
  • Rian Van Rampelbergh, M.D.,
  • Arnob Banerjee, M.D., Ph.D.,
  • Jenna D. Goldberg, M.D.,
  • Rachel Kobos, M.D.,
  • Amrita Krishnan, M.D.,
  • and Saad Z. Usmani, M.D.

Abstract

Background

Teclistamab is a T-cell–redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. In the phase 1 dose-defining portion of the study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma.

Methods

Download a PDF of the Research Summary.

In this phase 1–2 study, we enrolled patients who had relapsed or refractory myeloma after at least three therapy lines, including triple-class exposure to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. Patients received a weekly subcutaneous injection of teclistamab (at a dose of 1.5 mg per kilogram of body weight) after receiving step-up doses of 0.06 mg and 0.3 mg per kilogram. The primary end point was the overall response (partial response or better).

Results

Among 165 patients who received teclistamab, 77.6% had triple-class refractory disease (median, five previous therapy lines). With a median follow-up of 14.1 months, the overall response rate was 63.0%, with 65 patients (39.4%) having a complete response or better. A total of 44 patients (26.7%) were found to have no minimal residual disease (MRD); the MRD-negativity rate among the patients with a complete response or better was 46%. The median duration of response was 18.4 months (95% confidence interval [CI], 14.9 to not estimable). The median duration of progression-free survival was 11.3 months (95% CI, 8.8 to 17.1). Common adverse events included cytokine release syndrome (in 72.1% of the patients; grade 3, 0.6%; no grade 4), neutropenia (in 70.9%; grade 3 or 4, 64.2%), anemia (in 52.1%; grade 3 or 4, 37.0%), and thrombocytopenia (in 40.0%; grade 3 or 4, 21.2%). Infections were frequent (in 76.4%; grade 3 or 4, 44.8%). Neurotoxic events occurred in 24 patients (14.5%), including immune effector cell–associated neurotoxicity syndrome in 5 patients (3.0%; all grade 1 or 2).

Conclusions

Teclistamab resulted in a high rate of deep and durable response in patients with triple-class–exposed relapsed or refractory multiple myeloma. Cytopenias and infections were common; toxic effects that were consistent with T-cell redirection were mostly grade 1 or 2. (Funded by Janssen Research and Development; MajesTEC-1 ClinicalTrials.gov numbers, NCT03145181 and NCT04557098.)

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Funding and Disclosures

Supported by Janssen Research and Development. Dr. Usmani is supported by a career development award from the Leukemia and Lymphoma Society. Dr. Popat is supported by the Biomedical Research Centre of the National Institute for Health Research and University College London Hospitals.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Drs. Moreau and Usmani contributed equally to this article.

This article was published on June 5, 2022, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

We thank the patients who participated in the study and their families and caregivers; the physicians and nurses who cared for patients and supported this clinical trial; the staff members at the study sites and those involved in data collection and analyses; and Valerie Kinchen, Ph.D., and Linda Wychowski, Ph.D., of Eloquent Scientific Solutions, who provided medical writing support.

Author Affiliations

From the Hematology Clinic, University Hospital Hôtel-Dieu, Nantes (P.M.), Service d’Hématologie Clinique, Centre Hospitalier Lyon Sud, Pierre-Bénite (L.K.), and Service d’Hématologie et Thérapie Cellulaire, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire, Tours (L.B.) — all in France; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia (A.L.G.), and Janssen Research and Development, Spring House (R.V., S.G., S.X.W.L., C.U., T.S., A.B.) — both in Pennsylvania; the Department of Hematology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam (N.W.C.J.D.); Karolinska University Hospital at Huddinge, Stockholm (H.N.); Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada, Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Investigación Sanitaria de Navarra, Pamplona (J.F.S.-M.), Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona (A.O.), Hospital Clínic, August Pi i Sunyer Biomedical Research Institute, University of Barcelona, Barcelona (L.R.), University Hospital of Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro del Investigación del Cáncer, CIBERONC, Salamanca (M.-V.M.), and Hematological Malignancies Clinical Research Unit, Hospital 12 de Octubre Universidad Complutense, Centro Nacional de Investigaciones Oncológicas, CIBERONC, Madrid (J.M.-L.) — all in Spain; Winship Cancer Institute, Emory University, Atlanta (A.K.N.); the University of California, San Francisco, San Francisco (T.M.), Stanford University School of Medicine, Stanford (S.S.), and City of Hope Comprehensive Cancer Center, Duarte (A.K.) — all in California; Mount Sinai School of Medicine (A.C.) and Memorial Sloan Kettering Cancer Center (S.Z.U.) — both in New York; Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada (N.B.); Clinical Research Facility, National Institute for Health Research University College London Hospitals, NHS Foundation Trust, London (R.P.); the Department of Hematology, Oncology, and Immunology, University of Tübingen, Tübingen, Germany (B.B.); the University of Leuven, Leuven (M.D.), and Janssen Research and Development, Antwerp (Y.O., R.V.R.) — both in Belgium; Janssen Research and Development, Raritan, NJ (L.P., D.T., M.J., J.D.G., R.K.); and Levine Cancer Institute–Atrium Health, Charlotte, NC (S.Z.U.).

Dr. Moreau can be contacted at or at the Hematology Clinic, University Hospital Hôtel-Dieu, 1 Place Alexis-Ricordeau, 44000 Nantes, France. Dr. Usmani can be contacted at or at the Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065.