Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma

Luciano J Costa; Nizar J Bahlis; Aurore Perrot; Ajay K Nooka; Jin Lu; Charlotte Pawlyn; Roberto Mina; Gaston Caeiro; Alain Kentos; Vania Hungria; Donna Reece; Ting Niu; Anne K Mylin; Charlotte T Hansen; Raphael Teipel; Britta Besemer; Meletios A Dimopoulos; Elena Zamagni; Satoshi Yoshihara; Kihyun Kim; Chang Ki Min; Paul Geerts; Elena Van Leeuwen-Segarceanu; Agata Tyczynska; Juan Luis Reguera; Magnus Johansson; Markus Hansson; Mehmet Turgut; Mark Grey; Surbhi Sidana; Paula Rodriguez-Otero; Joaquin Martinez-Lopez; Hamza Hashmi; Robin Carson; Rachel Kobos; Weili Sun; Kristen Lantz; Anne Seifert; Deborah Briseno-Toomey; Lisa O'Rourke; Maria Rubin; Diego Vieyra; Lijuan Kang; Maria Victoria Mateos; MajesTEC-3 Trial Investigators

doi:10.1056/NEJMoa2514663

Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma

Luciano J Costa, Nizar J Bahlis, Aurore Perrot, Ajay K Nooka, Jin Lu, Charlotte Pawlyn, Roberto Mina, Gaston Caeiro, Alain Kentos, Vania Hungria, Donna Reece, Ting Niu, Anne K Mylin, Charlotte T Hansen, Raphael Teipel, Britta Besemer, Meletios A Dimopoulos, Elena Zamagni, Satoshi Yoshihara, Kihyun KimChang Ki Min, Paul Geerts, Elena Van Leeuwen-Segarceanu, Agata Tyczynska, Juan Luis Reguera, Magnus Johansson, Markus Hansson, Mehmet Turgut, Mark Grey, Surbhi Sidana, Paula Rodriguez-Otero, Joaquin Martinez-Lopez, Hamza Hashmi, Robin Carson, Rachel Kobos, Weili Sun, Kristen Lantz, Anne Seifert, Deborah Briseno-Toomey, Lisa O'Rourke, Maria Rubin, Diego Vieyra, Lijuan Kang, Maria Victoria Mateos, MajesTEC-3 Trial Investigators

Afdeling for Blodsygdomme CKO

Abstract

BACKGROUND: In a phase 1-2 trial, teclistamab, a bispecific antibody targeting CD3 on T-cell surfaces and B-cell maturation antigen on myeloma cells, showed durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma. Daratumumab, a monoclonal antibody targeting CD38 protein, has shown survival benefit in patients with multiple myeloma.

METHODS: In this phase 3 trial, we randomly assigned patients with one to three previous lines of therapy to receive combination therapy with teclistamab-daratumumab or daratumumab combined with dexamethasone plus the investigator's choice of pomalidomide (DPd) or bortezomib (DVd) - the DPd or DVd group. The primary end point was progression-free survival, as assessed by an independent review committee.

RESULTS: A total of 587 patients underwent randomization (291 to receive teclistamab-daratumumab and 296 to receive DPd or DVd). At a median of 34.5 months, progression-free survival was significantly longer with teclistamab-daratumumab than with DPd or DVd. The estimated 36-month progression-free survival was 83.4% in the teclistamab-daratumumab group and 29.7% in the DPd or DVd group (hazard ratio, 0.17; 95% confidence interval, 0.12 to 0.23; P<0.001). More patients in the teclistamab-daratumumab group than in the DPd or DVd group had a complete response or better (81.8% vs. 32.1%), an overall response (89.0% vs. 75.3%), and minimal residual disease negativity (10-5; 58.4% vs. 17.1%) (P<0.001 for all comparisons). Serious adverse events occurred in 70.7% of the patients in the teclistamab-daratumumab group and in 62.4% of those in the DPd or DVd group; death from adverse events occurred in 7.1% and 5.9%, respectively.

CONCLUSIONS: In patients with multiple myeloma who had received one to three previous lines of therapy, those in the teclistamab-daratumumab group had significantly longer progression-free survival than those in the DPd or DVd group. (Funded by Johnson & Johnson; ClinicalTrials.gov number, NCT05083169.).

Originalsprog	Engelsk
Tidsskrift	The New England journal of medicine
ISSN	0028-4793
DOI	https://doi.org/10.1056/NEJMoa2514663
Status	E-pub ahead of print - 9 dec. 2025

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10.1056/NEJMoa2514663

Citationsformater

Costa, L. J., Bahlis, N. J., Perrot, A., Nooka, A. K., Lu, J., Pawlyn, C., Mina, R., Caeiro, G., Kentos, A., Hungria, V., Reece, D., Niu, T., Mylin, A. K., Hansen, C. T., Teipel, R., Besemer, B., Dimopoulos, M. A., Zamagni, E., Yoshihara, S., ... MajesTEC-3 Trial Investigators (2025). Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. The New England journal of medicine. Advance online publication. https://doi.org/10.1056/NEJMoa2514663

Costa, LJ, Bahlis, NJ, Perrot, A, Nooka, AK, Lu, J, Pawlyn, C, Mina, R, Caeiro, G, Kentos, A, Hungria, V, Reece, D, Niu, T, Mylin, AK, Hansen, CT, Teipel, R, Besemer, B, Dimopoulos, MA, Zamagni, E, Yoshihara, S, Kim, K, Min, CK, Geerts, P, Van Leeuwen-Segarceanu, E, Tyczynska, A, Reguera, JL, Johansson, M, Hansson, M, Turgut, M, Grey, M, Sidana, S, Rodriguez-Otero, P, Martinez-Lopez, J, Hashmi, H, Carson, R, Kobos, R, Sun, W, Lantz, K, Seifert, A, Briseno-Toomey, D, O'Rourke, L, Rubin, M, Vieyra, D, Kang, L, Mateos, MV & MajesTEC-3 Trial Investigators 2025, 'Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma', The New England journal of medicine. https://doi.org/10.1056/NEJMoa2514663

@article{18519e82696e47589154771356a60f18,

title = "Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma",

abstract = "BACKGROUND: In a phase 1-2 trial, teclistamab, a bispecific antibody targeting CD3 on T-cell surfaces and B-cell maturation antigen on myeloma cells, showed durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma. Daratumumab, a monoclonal antibody targeting CD38 protein, has shown survival benefit in patients with multiple myeloma.METHODS: In this phase 3 trial, we randomly assigned patients with one to three previous lines of therapy to receive combination therapy with teclistamab-daratumumab or daratumumab combined with dexamethasone plus the investigator's choice of pomalidomide (DPd) or bortezomib (DVd) - the DPd or DVd group. The primary end point was progression-free survival, as assessed by an independent review committee.RESULTS: A total of 587 patients underwent randomization (291 to receive teclistamab-daratumumab and 296 to receive DPd or DVd). At a median of 34.5 months, progression-free survival was significantly longer with teclistamab-daratumumab than with DPd or DVd. The estimated 36-month progression-free survival was 83.4% in the teclistamab-daratumumab group and 29.7% in the DPd or DVd group (hazard ratio, 0.17; 95% confidence interval, 0.12 to 0.23; P<0.001). More patients in the teclistamab-daratumumab group than in the DPd or DVd group had a complete response or better (81.8% vs. 32.1%), an overall response (89.0% vs. 75.3%), and minimal residual disease negativity (10-5; 58.4% vs. 17.1%) (P<0.001 for all comparisons). Serious adverse events occurred in 70.7% of the patients in the teclistamab-daratumumab group and in 62.4% of those in the DPd or DVd group; death from adverse events occurred in 7.1% and 5.9%, respectively.CONCLUSIONS: In patients with multiple myeloma who had received one to three previous lines of therapy, those in the teclistamab-daratumumab group had significantly longer progression-free survival than those in the DPd or DVd group. (Funded by Johnson & Johnson; ClinicalTrials.gov number, NCT05083169.).",

author = "Costa, {Luciano J} and Bahlis, {Nizar J} and Aurore Perrot and Nooka, {Ajay K} and Jin Lu and Charlotte Pawlyn and Roberto Mina and Gaston Caeiro and Alain Kentos and Vania Hungria and Donna Reece and Ting Niu and Mylin, {Anne K} and Hansen, {Charlotte T} and Raphael Teipel and Britta Besemer and Dimopoulos, {Meletios A} and Elena Zamagni and Satoshi Yoshihara and Kihyun Kim and Min, {Chang Ki} and Paul Geerts and {Van Leeuwen-Segarceanu}, Elena and Agata Tyczynska and Reguera, {Juan Luis} and Magnus Johansson and Markus Hansson and Mehmet Turgut and Mark Grey and Surbhi Sidana and Paula Rodriguez-Otero and Joaquin Martinez-Lopez and Hamza Hashmi and Robin Carson and Rachel Kobos and Weili Sun and Kristen Lantz and Anne Seifert and Deborah Briseno-Toomey and Lisa O'Rourke and Maria Rubin and Diego Vieyra and Lijuan Kang and Mateos, {Maria Victoria} and {MajesTEC-3 Trial Investigators}",

note = "Copyright {\textcopyright} 2025 Massachusetts Medical Society.",

year = "2025",

month = dec,

day = "9",

doi = "10.1056/NEJMoa2514663",

language = "English",

journal = "The New England journal of medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

}

TY - JOUR

T1 - Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma

AU - Costa, Luciano J

AU - Bahlis, Nizar J

AU - Perrot, Aurore

AU - Nooka, Ajay K

AU - Lu, Jin

AU - Pawlyn, Charlotte

AU - Mina, Roberto

AU - Caeiro, Gaston

AU - Kentos, Alain

AU - Hungria, Vania

AU - Reece, Donna

AU - Niu, Ting

AU - Mylin, Anne K

AU - Hansen, Charlotte T

AU - Teipel, Raphael

AU - Besemer, Britta

AU - Dimopoulos, Meletios A

AU - Zamagni, Elena

AU - Yoshihara, Satoshi

AU - Kim, Kihyun

AU - Min, Chang Ki

AU - Geerts, Paul

AU - Van Leeuwen-Segarceanu, Elena

AU - Tyczynska, Agata

AU - Reguera, Juan Luis

AU - Johansson, Magnus

AU - Hansson, Markus

AU - Turgut, Mehmet

AU - Grey, Mark

AU - Sidana, Surbhi

AU - Rodriguez-Otero, Paula

AU - Martinez-Lopez, Joaquin

AU - Hashmi, Hamza

AU - Carson, Robin

AU - Kobos, Rachel

AU - Sun, Weili

AU - Lantz, Kristen

AU - Seifert, Anne

AU - Briseno-Toomey, Deborah

AU - O'Rourke, Lisa

AU - Rubin, Maria

AU - Vieyra, Diego

AU - Kang, Lijuan

AU - Mateos, Maria Victoria

AU - MajesTEC-3 Trial Investigators

PY - 2025/12/9

Y1 - 2025/12/9

N2 - BACKGROUND: In a phase 1-2 trial, teclistamab, a bispecific antibody targeting CD3 on T-cell surfaces and B-cell maturation antigen on myeloma cells, showed durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma. Daratumumab, a monoclonal antibody targeting CD38 protein, has shown survival benefit in patients with multiple myeloma.METHODS: In this phase 3 trial, we randomly assigned patients with one to three previous lines of therapy to receive combination therapy with teclistamab-daratumumab or daratumumab combined with dexamethasone plus the investigator's choice of pomalidomide (DPd) or bortezomib (DVd) - the DPd or DVd group. The primary end point was progression-free survival, as assessed by an independent review committee.RESULTS: A total of 587 patients underwent randomization (291 to receive teclistamab-daratumumab and 296 to receive DPd or DVd). At a median of 34.5 months, progression-free survival was significantly longer with teclistamab-daratumumab than with DPd or DVd. The estimated 36-month progression-free survival was 83.4% in the teclistamab-daratumumab group and 29.7% in the DPd or DVd group (hazard ratio, 0.17; 95% confidence interval, 0.12 to 0.23; P<0.001). More patients in the teclistamab-daratumumab group than in the DPd or DVd group had a complete response or better (81.8% vs. 32.1%), an overall response (89.0% vs. 75.3%), and minimal residual disease negativity (10-5; 58.4% vs. 17.1%) (P<0.001 for all comparisons). Serious adverse events occurred in 70.7% of the patients in the teclistamab-daratumumab group and in 62.4% of those in the DPd or DVd group; death from adverse events occurred in 7.1% and 5.9%, respectively.CONCLUSIONS: In patients with multiple myeloma who had received one to three previous lines of therapy, those in the teclistamab-daratumumab group had significantly longer progression-free survival than those in the DPd or DVd group. (Funded by Johnson & Johnson; ClinicalTrials.gov number, NCT05083169.).

AB - BACKGROUND: In a phase 1-2 trial, teclistamab, a bispecific antibody targeting CD3 on T-cell surfaces and B-cell maturation antigen on myeloma cells, showed durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma. Daratumumab, a monoclonal antibody targeting CD38 protein, has shown survival benefit in patients with multiple myeloma.METHODS: In this phase 3 trial, we randomly assigned patients with one to three previous lines of therapy to receive combination therapy with teclistamab-daratumumab or daratumumab combined with dexamethasone plus the investigator's choice of pomalidomide (DPd) or bortezomib (DVd) - the DPd or DVd group. The primary end point was progression-free survival, as assessed by an independent review committee.RESULTS: A total of 587 patients underwent randomization (291 to receive teclistamab-daratumumab and 296 to receive DPd or DVd). At a median of 34.5 months, progression-free survival was significantly longer with teclistamab-daratumumab than with DPd or DVd. The estimated 36-month progression-free survival was 83.4% in the teclistamab-daratumumab group and 29.7% in the DPd or DVd group (hazard ratio, 0.17; 95% confidence interval, 0.12 to 0.23; P<0.001). More patients in the teclistamab-daratumumab group than in the DPd or DVd group had a complete response or better (81.8% vs. 32.1%), an overall response (89.0% vs. 75.3%), and minimal residual disease negativity (10-5; 58.4% vs. 17.1%) (P<0.001 for all comparisons). Serious adverse events occurred in 70.7% of the patients in the teclistamab-daratumumab group and in 62.4% of those in the DPd or DVd group; death from adverse events occurred in 7.1% and 5.9%, respectively.CONCLUSIONS: In patients with multiple myeloma who had received one to three previous lines of therapy, those in the teclistamab-daratumumab group had significantly longer progression-free survival than those in the DPd or DVd group. (Funded by Johnson & Johnson; ClinicalTrials.gov number, NCT05083169.).

U2 - 10.1056/NEJMoa2514663

DO - 10.1056/NEJMoa2514663

M3 - Journal article

C2 - 41363801

SN - 0028-4793

JO - The New England journal of medicine

JF - The New England journal of medicine

ER -

Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma

Abstract

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