Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study
Abstract
Abstract Talquetamab, a G protein–coupled receptor class C group 5 member D–targeting bispecific antibody for relapsed/refractory multiple myeloma (R/R MM), plus daratumumab, may lead to deeper and more durable responses than either therapy alone. In the phase 1b TRIMM-2 study, patients with R/R MM (at least 3 previous lines of therapy or double refractory to a proteasome inhibitor and an immunomodulatory drug) received subcutaneous talquetamab 0.4 mg/kg weekly (QW; “QW cohort”) or 0.8 mg/kg every other week (Q2W cohort) plus daratumumab 1800 mg per the approved schedule. The primary end point was safety. Secondary end points included overall response and duration of response. Progression-free survival was an exploratory end point. Sixty-five patients (median 5 previous lines of therapy; 61.5% triple-class refractory; 24.6% bispecific antibody exposed) received talquetamab plus daratumumab (QW, n = 14; Q2W, n = 51; median follow-up of 18.6 months). Most common adverse events were oral events, skin events, cytokine release syndrome, and infections. Grade 3 or 4 events occurred in 81.5%. Two patients had dose-limiting toxicities, both in the Q2W cohort (grade 3 stomatitis/oral mucositis, and grade 3 maculopapular rash). Responses occurred in 71.4% (QW cohort) and 82.4% (Q2W cohort) of patients. Median progression-free survival was 23.3 and 21.2 months, respectively, in each cohort. Pharmacodynamic results suggest the immunomodulatory action of daratumumab contributes to a conducive environment for talquetamab by reducing immunosuppressive cells. Talquetamab plus daratumumab demonstrated promising efficacy outcomes in patients with heavily pretreated disease, with a safety profile consistent with each agent as monotherapy. This trial was registered at www.clinicaltrials.gov as #NCT04108195.
Article Details
Authors (26)
Ajai Chari
University of California San Francisco, San Francisco, California, United States
Niels W. C. J. van de Donk
Bhagirathbhai Dholaria
Katja Weisel
María-Victoria Mateos
Hartmut Goldschmidt
Internal Medicine V, Hematology, Oncology and Rheumatology, German-Speaking Myeloma Multicenter Group Study Group, Heidelberg University Hospital and National Center for Tumor Diseases, Heidelberg, Germany
Thomas G. Martin
Daniel Morillo
From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) — all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) — all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary’s Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) — all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d’Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.)...
Donna Reece
Princess Margaret Cancer Centre, Toronto
Paula Rodriguez-Otero
Manisha Bhutani
Atrium Health Levine Cancer Institute, Charlotte, North Carolina, United States
Anita D’Souza
11Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI
Albert Oriol
Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Spain
Laura Rosiñol
Hospital Clínic de Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona
Nizar J. Bahlis
Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada
Deeksha Vishwamitra
Johnson & Johnson, Spring House, Pennsylvania, United States
Sheri Skerget
15Johnson & Johnson, Spring House, PA
Raluca I. Verona
15Johnson & Johnson, Spring House, PA
Kalpana Bakshi
15Johnson & Johnson, Spring House, PA
Lijuan Kang
Johnson & Johnson, Los Angeles
Thomas J. Prior
15Johnson & Johnson, Spring House, PA
Lien Vandenberk
16Johnson & Johnson, Antwerp, Belgium
Jaszianne Tolbert
Johnson & Johnson, Spring House, PA
Sangmin Lee
M. Damiette Smit
17Johnson & Johnson, Leiden, The Netherlands
Ralph Wäsch
18Department of Medicine I, Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany