Article
Author: Herr, Megan M. ; Lin, Yi ; Parrondo, Ricardo D. ; Grajales-Cruz, Ariel F. ; Costello, Patrick ; Anderson, Larry D. ; Rossi, Adriana ; Goyal, Anmol ; Razzo, Beatrice M. ; Anwer, Faiz ; Julian, Kelley L. ; De Menezes Silva Corraes, Andre ; Shune, Leyla ; Vazquez-Martinez, Mariola ; Ferreri, Christopher J. ; Chen, Anna ; Cowan, Andrew J. ; Portuguese, Andrew J. ; Sborov, Douglas W. ; Lee, Hans C. ; Sidana, Surbhi ; Dima, Danai ; Banerjee, Rahul ; Lieberman-Cribbin, Alex ; Kaur, Gurbakhash ; Nadeem, Omar ; Castaneda Puglianini, Omar ; Pasvolsky, Oren ; Khouri, Jack ; Raza, Shahzad ; Sperling, Adam S. ; Garfall, Alfred L. ; Midha, Shonali ; Hwang, Wei-Ting ; Liu, Yuxin ; Richard, Shambavi ; Chhabra, Saurabh ; Davis, James A. ; Patel, Krina K. ; Afrough, Aimaz ; Bhurtel, Jenny ; Forsberg, Peter A. ; Hansen, Doris K. ; Susanibar-Adaniya, Sandra P. ; Voorhees, Peter M. ; Atrash, Shebli
Abstract:Teclistamab is an anti-CD3-/B-cell maturation antigen (BCMA) bispecific antibody approved for use in relapsed/refractory multiple myeloma. We undertook a retrospective study of post-approval, real-world outcomes with teclistamab in the US Multiple Myeloma Immunotherapy Consortium. Among 509 patients, 89% would have been ineligible for the MajesTEC-1 trial, primarily due to prior BCMA-directed therapy, cytopenias, or diminished performance status. Cytokine release syndrome occurred in 54% (1.4% grade ≥3) and immune effector cell–associated neurotoxicity syndrome in 11% (2.2% grade ≥3), with no fatal events. Infections occurred in 42% and contributed to death in 5%. Partial response (PR) or better was achieved in 53% and very good PR or better in 45%. With 10.1 months of median follow-up, the estimated median progression-free survival (PFS) was 5.8 months and 12-month overall survival was 61%. Independent predictors of less than very good PR and shorter PFS included BCMA-directed chimeric antigen receptor T-cell therapy in the previous 9 months, high disease burden, lymphopenia, and elevated ferritin.
Significance::T cell–engaging bispecific antibodies such as teclistamab represent an important new treatment modality for multiple myeloma and other blood cancers. This study evaluates the real-world safety and efficacy of teclistamab, including its activity in populations not represented in the initial phase I/II study, and identifies clinical variables associated with treatment response.See related commentary by Zweegman et al., p. 542