塔奎他单抗联合替西他单抗治疗复发或难治性多发性骨髓瘤

Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma.

作者信息

Cohen Yael C, Magen Hila, Gatt Moshe, Sebag Michael, Kim Kihyun, Min Chang-Ki, Ocio Enrique M, Yoon Sung-Soo, Chu Michael P, Rodríguez-Otero Paula, Avivi Irit, Quijano Cardé Natalia A, Kumar Ashwini, Krevvata Maria, Peterson Michelle R, Di Scala Lilla, Scott Emma, Hilder Brandi, Vanak Jill, Banerjee Arnob, Oriol Albert, Morillo Daniel, Mateos María-Victoria

机构信息

From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) - all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) - all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary's Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) - all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d'Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.), START Madrid-Fundación Jiménez Díaz Early Phase Unit, University Hospital Fundación Jiménez Díaz, Madrid (D.M.), and the University Hospital of Salamanca, Institute for Biomedical Research of Salamanca, the Salamanca Cancer Research Center, and Centro de Investígación Biomédica en Red Cáncer, Salamanca (M.-V.M.) - all in Spain; Janssen Research and Development, Spring House, PA (N.A.Q.C., A.K., M.K., M.R.P., E.S., B.H., J.V., A.B.); and Janssen Research and Development, Allschwil, Switzerland (L.D.S.).

出版信息

N Engl J Med. 2025 Jan 9;392(2):138-149. doi: 10.1056/NEJMoa2406536.

DOI:10.1056/NEJMoa2406536

PMID:39778168

Abstract

BACKGROUND

Talquetamab (anti-G protein-coupled receptor family C group 5 member D) and teclistamab (anti-B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class-exposed relapsed or refractory multiple myeloma.

METHODS

We conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study. Talquetamab at a dose of 0.8 mg per kilogram of body weight plus teclistamab at a dose of 3.0 mg per kilogram every other week was selected as the recommended phase 2 regimen. The primary objective was to evaluate adverse events and dose-limiting toxic effects.

RESULTS

A total of 94 patients received treatment, with the recommended phase 2 regimen used in 44. The median follow-up was 20.3 months. Three patients had dose-limiting toxic effects (including grade 4 thrombocytopenia in 1 patient with the recommended phase 2 regimen). Across all dose levels, the most common adverse events were cytokine release syndrome, neutropenia, taste changes, and nonrash skin events. Grade 3 or 4 adverse events, most commonly hematologic events, occurred in 96% of the patients. Grade 3 or 4 infections occurred in 64% of the patients. With the recommended phase 2 regimen, a response occurred in 80% of the patients (including in 61% of those with extramedullary disease); across all dose levels, a response occurred in 78%. The likelihood of patients continuing in response at 18 months was 86% with the recommended phase 2 regimen (82% among those with extramedullary disease) and 77% across all dose levels.

CONCLUSIONS

The incidence of grade 3 or 4 infections with talquetamab plus teclistamab was higher than has been observed with either therapy alone. A response was observed in a high percentage of patients across all dose levels, with durable responses with the recommended phase 2 regimen. (Funded by Janssen Research and Development; RedirecTT-1 ClinicalTrials.gov number, NCT04586426.).

摘要

背景

塔奎他单抗（抗G蛋白偶联受体C家族第5成员D）和替西他单抗（抗B细胞成熟抗原）是双特异性抗体，通过靶向CD3激活T细胞，已被批准用于治疗接受过三种药物治疗的复发或难治性多发性骨髓瘤。

方法

我们开展了一项塔奎他单抗联合替西他单抗治疗复发或难治性多发性骨髓瘤患者的1b-2期研究。在1期，我们在剂量递增研究中调查了五个剂量水平。选择每公斤体重0.8毫克的塔奎他单抗加每公斤体重3.0毫克的替西他单抗，每隔一周给药一次，作为推荐的2期治疗方案。主要目的是评估不良事件和剂量限制性毒性作用。

结果

共有94例患者接受了治疗，44例采用了推荐的2期治疗方案。中位随访时间为20.3个月。3例患者出现剂量限制性毒性作用（包括1例采用推荐的2期治疗方案的患者出现4级血小板减少症）。在所有剂量水平上，最常见的不良事件是细胞因子释放综合征、中性粒细胞减少、味觉改变和非皮疹性皮肤事件。96%的患者发生3级或4级不良事件，最常见的是血液学事件。64%的患者发生3级或4级感染。采用推荐的2期治疗方案时，80%的患者出现缓解（包括61%有髓外病变的患者）；在所有剂量水平上，缓解率为78%。采用推荐的2期治疗方案时，患者在18个月时持续缓解的可能性为86%（有髓外病变的患者中为82%），在所有剂量水平上为77%。