Dual Targeting of Extramedullary Myeloma with Talquetamab and Teclistamab

Author(s): Shaji Kumar, M.D.¹; María-Victoria Mateos, Ph.D.^2,3,4,5; Jing Christine Ye, M.D.⁶; Shebli Atrash, M.D.⁷; Hila Magen, M.D.⁸; Hang Quach, M.D.⁹; Michael P. Chu, M.D.¹⁰; Suzanne Trudel, M.D.¹¹; Joshua Richter, M.D.¹²; Paula Rodríguez-Otero, M.D., Ph.D.¹³; Hun Chuah, M.D., Ph.D.¹⁴; Moshe Gatt, M.D.¹⁵; Eva Medvedova, M.D.¹⁶; Shahzad Raza, M.D.¹⁷; Dok Hyun Yoon, M.D., Ph.D.¹⁸; Tadao Ishida, M.D., Ph.D.¹⁹; Jeffrey V. Matous, M.D.²⁰; Laura Rosiñol, M.D., Ph.D.²¹; Koichi Onodera, M.D., Ph.D.²²; Emma Scott, M.D.²³; Christoph Heuck, M.D.²³; Jenny Zhang, Ph.D.²³; Todd Henninger, Ph.D.²⁴; Lisa O’Rourke, M.S.²³; Payal Thakkar, M.S.²⁴; Mariacristina Festa, M.S.²⁵; Lin Huang, Ph.D.²³; Jiangxiu Zhou, Ph.D.²³; Mikihiro Takamoto, M.P.H.²⁶; Lixia Pei, Ph.D.²⁴; Jiashen Lu, Ph.D.²⁷; Nicholas Au, Pharm.D., Ph.D.²³; Maria Krevvata, Ph.D.²³; Saad Z. Usmani, M.D.²⁸; Yael C. Cohen, M.D.²⁹; the RedirecTT-1 Investigators Study Group*;

Source: DOI: 10.1056/NEJMoa2514752

Dr. Anjan Patel's Thoughts

This is a very impressive signal in a notoriously difficult population—seeing a 79% response rate and median progression-free survival (PFS) of 15.4 months in true extramedullary, triple-class–exposed myeloma is better than expected. Toxicity is real and management-intensive, but the depth and durability of response make this dual-bispecific approach feel like a meaningful advance.

BACKGROUND

Patients with plasmacytomas that are noncontiguous with bone marrow (true extramedullary myeloma) are high risk for disease progression or relapse. Phase 1 of the RedirecTT-1 study showed promising efficacy with dual-antigen targeting of myeloma with talquetamab (anti–G protein–coupled receptor family C group 5 member D) plus teclistamab (anti–B-cell maturation antigen) in patients with triple-class–exposed relapsed or refractory multiple myeloma, including those with true extramedullary myeloma.

METHODS

In this phase 2 study, we investigated talquetamab plus teclistamab exclusively in patients with drug-resistant, true extramedullary myeloma. The primary end point was overall response, evaluated with the use of functional imaging. Secondary end points included the duration of response, progression-free survival, overall survival, and safety.

RESULTS

A total of 90 patients were enrolled in the study and received treatment (median follow-up, 12.6 months). A response occurred in 79% of the patients (95% confidence interval [CI], 69 to 87). Among the patients with a response, the percentage with a response duration of least 12 months was 64% (95% CI, 48 to 76). 12 months, progression-free survival was 61% (95% CI, 50 to 71), and overall survival was 74% (95% CI, 63 to 83). Common adverse events of any grade included oral symptoms, such as dysgeusia, dry mouth, and dysphagia (in 87% of the patients); cytokine release syndrome (in 78%); and nonrash skin effects (in 69%). Grade 3 or 4 adverse events (most commonly hematologic events) occurred in 76% of the patients; 31% had grade 3 or 4 infection. A nonfatal adverse event led to discontinuation of one or both agents in 6% of the patients. Among 10 deaths that occurred during follow-up, 5 were due to infection and 5 were considered to be related to the study treatment.

CONCLUSIONS

Most patients with drug-resistant, true extramedullary myeloma had a response with talquetamab plus teclistamab. The incidence of adverse events of grade 3 or above was high and was consistent with previous observations for each agent as monotherapy. (Funded by Johnson & Johnson; RedirecTT-1 ClinicalTrials.gov number, NCT04586426.)

Author Affiliations

¹Mayo Clinic Rochester, Rochester, MN; ²University Hospital of Salamanca, Salamanca, Spain; ³Institute for Biomedical Research of Salamanca, Salamanca, Spain; ⁴The Salamanca Cancer Research Center, Salamanca, Spain; ⁵Centro de Investigacion Biomedica en Red Cancer, Salamanca, Spain; ⁶M.D. Anderson Cancer Center, University of Texas, Houston; ⁷Levine Cancer Institute–Atrium Health, Charlotte, NC; ⁸Chaim Sheba Medical Center, Ramat-Gan, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel; ⁹University of Melbourne, St. Vincent’s Hospital, Melbourne, VIC, Australia; ¹⁰Alberta Health Services, Edmonton, Canada; ¹¹Princess Margaret Cancer Centre, Toronto; ¹²Mount Sinai Medical Center, New York; ¹³Cancer Center Clínica Universidad de Navarra, Cima, Pamplona, Spain; ¹⁴Royal Perth Hospital, Perth, WA, Australia; ¹⁵Hadassah Medical Cener, Hebrew University of Jerusalem, Jerusalem, Israel; ¹⁶Knight Cancer Institute, Oregon Health and Science University, Portland; ¹⁷Taussig Cancer Institute, Cleveland Clinic, Cleveland; ¹⁸Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; ¹⁹Japanese Red Cross Medical Center, Tokyo; ²⁰Colorado Blood Cancer Institute and Sarah Cannon Research Institute, Denver; ²¹Hospital Clínic de Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona; ²²Tohoku University Hospital, Sendai-shi, Miyagi, Japan; ²³Johnson & Johnson, Spring House, PA; ²⁴Johnson & Johnson, Raritan, NJ; ²⁵Johnson & Johnson, Leiden, the Netherlands; ²⁶Johnson & Johnson, Tokyo; ²⁷Johnson & Johnson, Shanghai; ²⁸Memorial Sloan Kettering Cancer Center, New York; ²⁹Tel Aviv Sourasky (Ichilov) Medical Center, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel

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