Teclistamab in Multiple Myeloma with One to Three Previous Lines of Therapy.

Methods

We randomly assigned patients with relapsed or refractory multiple myeloma who had previously received one, two, or three lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide, to receive teclistamab or the investigator's choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd).

我们随机分配了既往接受过一、二或三线治疗（包括抗CD38单克隆抗体和来那度胺）的复发或难治性多发性骨髓瘤患者，接受teclistamab治疗或研究者选择的泊马度胺、硼替佐米和地塞米松（PVd）或卡非佐米和地塞米松（Kd）。

Antimicrobial prophylaxis and immune globulin replacement were recommended.

建议使用抗菌预防和免疫球蛋白替代疗法。

The primary end point was progression-free survivalas assessed by an independent review committee.

主要终点是独立评审委员会评估的无进展生存。

Results

A total of 296 patients were assigned to teclistamab and 297 to PVd or Kd.

共有296名患者被分配接受teclistamab治疗，297名患者被分配接受PVd或Kd治疗。

At the interim analysis (median follow-up, 17.3 months), teclistamab significantly improved progression-free survivalas compared with PVd or Kd (estimated 18-month progression-free survival, 69.8% vs. 26.9%; hazard ratiofor disease progression or death, 0.29; 95% confidence interval[CI], 0.23 to 0.38; P<0.001).

在中期分析中（中位随访时间为17.3个月），与PVd或Kd相比，teclistamab显著改善了无进展生存期（估计18个月无进展生存率，69.8%对比26.9%；疾病进展或死亡的风险比为0.29；95%置信区间[CI]，0.23至0.38；P<0.001）。

The percentage of patients with a complete response or better was higher with teclistamab than with PVd or Kd (65.9% vs. 16.8%, P<0.001).

与PVd或Kd相比，使用teclistamab治疗的患者中完全缓解或更好的患者比例更高（65.9%对比16.8%，P<0.001）。

Overall survivalwas improved with teclistamab as compared with PVd or Kd (estimated 18-month overall survival, 79.2% vs. 68.6%; hazard ratiofor death, 0.60; 95% CI, 0.43 to 0.83; P = 0.002).

与PVd或Kd相比，使用teclistamab治疗的患者总生存期有所改善（估计的18个月总生存率为79.2%对比68.6%；死亡风险比为0.60；95%置信区间为0.43至0.83；P=0.002）。

Adverse events of grade 3 or 4 occurred in 84.9% of teclistamab recipients and in 76.3% of PVd or Kd recipients, with grade 5 adverse events in 6.5% and 3.5%, respectively.

3级或4级不良事件发生在84.9%的teclistamab接受者和76.3%的PVd或Kd接受者中，其中5级不良事件分别发生在6.5%和3.5%的人群中。

Cytokine release syndrome, mostly of grade 1 or 2, occurred in 66.0% of teclistamab recipients, and immune effector cell-associated neurotoxicity syndrome occurred in 4.1%.

66.0%的teclistamab接受者发生了主要为1级或2级的细胞因子释放综合征，而4.1%的接受者发生了免疫效应细胞相关的神经毒性综合征。

Grade 3 or 4 infection occurred in 41.6% of teclistamab recipients and in 29.0% of PVd or Kd recipients.

在接受teclistamab治疗的患者中，41.6%出现了3级或4级感染，而在接受PVd或Kd治疗的患者中，这一比例为29.0%。

Conclusions

Among patients with multiple myeloma and one to three previous lines of therapy, teclistamab significantly improved progression-free and overall survivalas compared with PVd or Kd.

在经历了一至三线治疗的多发性骨髓瘤患者中，与PVd或Kd相比，teclistamab显著提高了无进展生存期和总生存期。

Infections of grade 3 or 4 were common.

3级或4级感染很常见。

(Funded by Johnson & Johnson; MajesTEC-9 ClinicalTrials.gov number, NCT05572515.).

(由强生公司资助；MajesTEC-9临床试验注册号，NCT05572515。)