Philippe Moreau1, Alfred L Garfall1, Niels W C J van de Donk1, Hareth Nahi1, Jesús F San-Miguel1, Albert Oriol1, Ajay K Nooka1, Thomas Martin1, Laura Rosinol1, Ajai Chari1, Lionel Karlin1, Lotfi Benboubker1, Maria-Victoria Mateos1, Nizar Bahlis1, Rakesh Popat1, Britta Besemer1, Joaquín Martínez-López1, Surbhi Sidana1, Michel Delforge1, Lixia Pei1, Danielle Trancucci1, Raluca Verona1, Suzette Girgis1, Shun X W Lin1, Yunsi Olyslager1, Mindy Jaffe1, Clarissa Uhlar1, Tara Stephenson1, Rian Van Rampelbergh1, Arnob Banerjee1, Jenna D Goldberg1, Rachel Kobos1, Amrita Krishnan1, Saad Z Usmani1. 1. 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.).
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: 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.).
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: 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.).
Authors: Raquel Jiménez-Segura; Laura Rosiñol; Ma Teresa Cibeira; Carlos Fernández de Larrea; Natalia Tovar; Luis Gerardo Rodríguez-Lobato; Esther Bladé; David F Moreno; Aina Oliver-Caldés; Joan Bladé Journal: Blood Cancer J Date: 2022-09-16 Impact factor: 9.812