Teclistamab in Relapsed or Refractory Multiple Myeloma

Author(s): 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.

Source: DOI: 10.1056/NEJMoa2203478

The Bi-specific antibody era has started full-force with impressive results and reasonable toxicities, in different hematological neoplasms. Community oncology adoption of Bi-specific antibody will be successful, once standard operating procedures are in place, and multidisciplinary training takes place insofar as management of CRS. I am optimistic as to the uptake of this class of drugs in 1-2 years, pending payer coverage issues.

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, 77.8% 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. opens in new tab and NCT04557098. opens in new tab.)

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.).

Results from the randomized phase III DREAMM-7 study of belantamab mafodotin (belamaf) + bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd) in relapsed/refractory multiple myeloma (RRMM).

Triplet second line therapy shows superiority over daratumumab bortezomib and dexamethasone. This regimen is now used in first line with lenalidomide in some patients as quadruplet therapy, hence this second line regimen with Blantamab could be a second line option. The eye exam is still a pain and it is also more toxic.

Ciltacabtagene Autoleucel, an Anti–B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up

CAR-T for myeloma, impressive response rate, overall survival not reached.

Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA

MRD status in MM has unquestionable prognostic informational value, however many questions remain as how to address positive / negative MRD results. Should we de-escalate or stop Rx? When? Can we escalate Rx if + MRD? Which regimen, how long? It will be another few years till objective data are available. I do see value in at least having identification of clonality established upfront for tracking.