MAJESTEC-9: A PHASE 3 RANDOMIZED STUDY OF TECLISTAMAB MONOTHERAPY VS INVESTIGATOR’S CHOICE OF POMALIDOMIDE, BORTEZOMIB, AND DEXAMETHASONE OR CARFILZOMIB AND DEXAMETHASONE (PVD/KD) IN PATIENTS (PTS) WITH RELAPSED REFRACTORY MULTIPLE MYELOMA (RRMM)

@article{mina2026majestec9,
  title = {{MAJESTEC-9: A PHASE 3 RANDOMIZED STUDY OF TECLISTAMAB MONOTHERAPY VS INVESTIGATOR’S CHOICE OF POMALIDOMIDE, BORTEZOMIB, AND DEXAMETHASONE OR CARFILZOMIB AND DEXAMETHASONE (PVD/KD) IN PATIENTS (PTS) WITH RELAPSED REFRACTORY MULTIPLE MYELOMA (RRMM)}},
  author = {Roberto MINA and Cyrille TOUZEAU and Vania HUNGRIA and Ola LANDGREN and Divaya BHUTANI and Wenming CHEN and Swarup KUMAR and Chakra P CHAULAGAIN and Meletios A DIMOPOULOS and Nizar BAHLIS and Senem MARAL and Niels W.C.J. VAN DE DONK and Khalid SAJA and Raphael TEIPEL and Miki ANDO and Dai WANG and Susan WROBLEWSKI and Priya SHAH and Katherine CHASTAIN and Jayr SCHMIDT},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107889},
  url = {https://doi.org/10.1016/j.htct.2026.107889},
  note = {CC BY},
}

TY  - JOUR
TI  - MAJESTEC-9: A PHASE 3 RANDOMIZED STUDY OF TECLISTAMAB MONOTHERAPY VS INVESTIGATOR’S CHOICE OF POMALIDOMIDE, BORTEZOMIB, AND DEXAMETHASONE OR CARFILZOMIB AND DEXAMETHASONE (PVD/KD) IN PATIENTS (PTS) WITH RELAPSED REFRACTORY MULTIPLE MYELOMA (RRMM)
AU  - Roberto MINA
AU  - Cyrille TOUZEAU
AU  - Vania HUNGRIA
AU  - Ola LANDGREN
AU  - Divaya BHUTANI
AU  - Wenming CHEN
AU  - Swarup KUMAR
AU  - Chakra P CHAULAGAIN
AU  - Meletios A DIMOPOULOS
AU  - Nizar BAHLIS
AU  - Senem MARAL
AU  - Niels W.C.J. VAN DE DONK
AU  - Khalid SAJA
AU  - Raphael TEIPEL
AU  - Miki ANDO
AU  - Dai WANG
AU  - Susan WROBLEWSKI
AU  - Priya SHAH
AU  - Katherine CHASTAIN
AU  - Jayr SCHMIDT
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107889
UR  - https://doi.org/10.1016/j.htct.2026.107889
AB  - Background: Triplet and quadruplet regimens have greatly improved outcomes in newly diagnosed multiple myeloma, yet a high unmet need remains for more effective, broadly accessible treatments for anti-CD38- and lenalidomide- (Len) exposed/refractory RRMM. Teclistamab (Tec) is the most widely used BCMA×CD3 BsAb in heavily pretreated RRMM, with improved outcomes in earlier lines of therapy (LOTs). In MajesTEC-3, the synergistic Tec-daratumumab combination significantly improved progression-free and overall survival (PFS/OS) as early as first relapse. MajesTEC-9 (NCT05572515) is the first phase 3 study of Tec monotherapy in pts with 1–3 prior LOTs. Methods: Pts with RRMM and 1–3 prior LOTs including anti-CD38 and Len were randomized 1:1 to receive 28-day cycles (C) of Tec (C1–2: 2 step-up doses then 1.5 mg/kg QW; C3–6: 3 mg/kg Q2W or Q4W depending on response; C7+: 3 mg/kg Q4W) or investigator’s choice of PVd/Kd (21/28-day C). Primary endpoint was PFS by IRC; secondary endpoints included OS, complete response or better (≥CR), and safety. Results: 593 pts were randomized (Tec, n=296; PVd/Kd, n=297). Median (range) age: 70 (34–86) yrs; number of prior LOTs: 2 (1–3); Len refractory: 80%; anti-CD38 refractory: 85%; refractory to last LOT: 92%. With 17.3-mo median follow-up, Tec significantly improved PFS vs PVd/Kd (HR, 0.29; 95% CI, 0.23–0.38; P<0.0001); mPFS: NR vs 8.2 mo; 18-mo PFS rate: 69.8% vs 26.9%. OS was significantly improved with Tec vs PVd/Kd (HR, 0.60; 95% CI, 0.43–0.83; P=0.0020). Of 174 PVd/Kd pts who received subsequent treatment, 68.4% received BsAb or CAR-T. PFS favored Tec across all prespecified subgroups, including anti-CD38-refractory pts and Len-refractory pts. ≥CR rate was significantly higher with Tec vs PVd/Kd (65.9% vs 16.8%; OR, 10.42; 95% CI, 6.89–15.76; P<0.0001). At data cutoff, 65.3% of pts remained on Tec vs 24.0% on PVd/Kd (safety set: Tec, n=291; PVd/Kd, n=283). TEAEs were similar for Tec and PVd/Kd (99.7% vs 97.9%). Grade (Gr) 3/4 TEAEs (84.9% vs 76.3%) and Gr 5 TEAEs (6.5% vs 3.5%) were higher with Tec vs PVd/Kd, noting the median treatment duration was nearly doubled with Tec (13.1 vs 7.0 mo). Treatment discontinuation due to TEAEs was lower with Tec vs PVd/Kd (10.7% vs 13.1%). Gr 3/4 infections were higher with Tec vs PVd/Kd (41.6% vs 29.0%). Any-onset Gr ≥3 infections decreased over time. CRS occurred in 66.0% of pts with Tec (Gr 1/2: 48.8%/16.5%) and ICANS in 4.1% (Gr 1/2: 2.4%/1.4%). Conclusions: Tec monotherapy significantly improved PFS/OS vs standard of care (SoC) in this high unmet need population. CRS and infections were managed with established protocols. Results of phase 3 studies support Tec-based regimens as a SoC as early as second line, across all treatment settings and regardless of prior anti-CD38/Len exposure. Acknowledgments: This study was funded by Johnson & Johnson.
SN  - 2531-1379
SN  - 2531-1387
ER  -