At the 2025 Congress of the European Hematology Association (EHA 2025), held from 12 to 15 June, the preliminary results from the global, multi-centre open-label non-randomised Phase II RedirecTT-1 clinical trial (NCT04586426) were presented on 15 June. This trial evaluated the safety and efficacy of the combination of Johnson & Johnson’s (J&J’s) Tecvayli (teclistamab), an anti–G protein–coupled receptor family C group 5 member D (GPRC5D)-directed CD3 bispecific T-cell engager (BiTE) and Talvey (talquetamab), an anti–B-cell maturation antigen (BCMA)-CD3 BiTE, in treating patients with relapsed/refractory (r/r) multiple myeloma (MM) and extramedullary disease (EMD) who are already triple-class exposed (TCE) including proteasome inhibitor (PI), immunomodulatory drugs (IMiD), and an anti-CD38 monoclonal antibody.
EMD is defined as soft tissue/organ-associated plasmacytomas that have no contact with bony structures. It represents an aggressive form of MM and occurs when myeloma cells spread and form tumours (plasmacytomas) in areas such as soft tissues and organs. EMD is commonly observed in haematologic malignancies such as MM, with a prevalence of roughly 6%–20% in r/r MM. The current standard of care (SOC) for patients with r/r MM with EMD includes combination regimens with PI, IMiD, or anti-CD38 monoclonal antibodies and may also involve chimeric antigen receptor (CAR)-T cell therapy or radiotherapy. Despite the promising efficacy of these advanced therapies, patients with MM and EMD consistently show lower response rates and shorter durations of remission across clinical trials compared to those with r/r MM without EMD. This highlights a significant unmet need for more effective therapeutic options in this high-risk population. According to GlobalData’s Multiple Myeloma: Epidemiology Forecast to 2032 report, the number of diagnosed prevalent cases of MM in the eight major markets (8MM: US, France, Germany, Italy, Spain, UK, Japan, and China) is projected to increase from 328,151 in 2025 to 352,348 by 2032 at an annual growth rate of 1.12%.
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The RedirecTT-1 trial is the largest EMD study to date, with 90 patients enrolled who were TCE. The investigational combination of Tecvayli and Talvey demonstrated a robust overall response rate (ORR) of 78.9% (95% CI: 69.0–86.8), with 54.4% achieving a complete response or better. Notably, high response rates were maintained even among patients previously treated with BCMA CAR-T (ORR: 83.3%, 95% CI: 58.6–96.4) and anti-FcRH5 bispecifics (ORR: 75.0%, 95% CI: 34.9–96.8). At a median follow-up of 13.4 months, 66.2% of responders remained in remission, indicating the potential for deep and sustained responses. Progression-free survival at one year was 61.0%, while 64.1% of patients maintained their responses, with a median duration of response of 13.8 months. Overall survival data had not yet matured, but the one-year survival rate was reported at 74.5%. Discontinuations due to adverse events (AEs) were infrequent; only four patients discontinued Talvey. Most cases of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were Grade 1 and 2. 10 patients (11.1%) experienced Grade 5 AEs, five of which were infection-related, consistent with infection rates observed in monotherapy studies involving BCMA-targeting bispecifics.
The impressive results from the first oncology study to combine two bispecific antibodies are likely to reshape the SOC for patients with r/r MM and EMD. This dual-antigen targeting strategy enhances tumour cell recognition in a biologically and genetically heterogeneous patient population, helps overcome treatment resistance, and reduces the risk of relapse caused by antigen escape, particularly in those with EMD. Despite the strong efficacy and durability of response, the high incidence of Grade 3 and 4 infections and infection-related deaths highlights the need for careful consideration of dosing strategies and prophylactic interventions, including intravenous immunoglobulin, antibacterial, and antiviral therapies. In parallel, J&J is also advancing its BiTE portfolio through the Phase III MonumenTAL-6 clinical trial, which combines Tecvayli and Talvey, with results expected in 2026. J&J already dominates the MM market with Tecvayli, Talvey and its CAR-T cell therapy Carvykti (ciltacabtagene autoleucel), and is continuing to expand its pipeline. One of these assets, a trispecific T-cell engager, JNJ-79635322, is currently being evaluated in a Phase I clinical trial. It targets CD3, BCMA, and GPRC5D, and, if it progresses to later-stage trials and success, could become the first-in-class trispecific antibody in R/R MM. Its single-agent design offers a potential advantage in the overcrowded BiTE market, although it remains in early development. According to GlobalData’s analyst consensus forecast, Tecvayli and Talvey are projected to generate global sales of $4.4bn and $1.8bn. respectively by 2031.
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