澳大利亚Peter MacCallum癌症中心Michael J. Dickinson团队研究了Glofitamab治疗复发或难治性弥漫性大B细胞淋巴瘤的疗效与安全性。相关论文于2022年12月11日发表在《新英格兰医学杂志》上。

复发或难治性弥漫性大B细胞淋巴瘤（DLBCL）患者预后较差。Glofitamab是一种双特异性抗体，可将T细胞招募到肿瘤细胞中。

在1-2期临床研究的2期部分，研究组招募了复发或难治性DLBCL患者，这些患者之前至少接受过两种治疗。患者接受obinutuzumab预处理以缓解细胞因子释放综合征，随后接受固定持续时间的glofitamab单药治疗（共12个周期）。根据独立审查委员会的评估，主要终点为完全缓解。关键次要终点包括缓解持续时间、存活率和安全性。

在155名入选患者中，154名接受了至少一剂研究治疗（obinutuzumab或glofitamab）。根据独立审查，在12.6个月的中位随访中，39%的患者完全缓解。该结果在52名之前接受过嵌合抗原受体T细胞治疗的患者中保持一致（35%的患者完全缓解）。中位完全缓解时间为42天。

在12个月时，大多数（78%）的患者仍持续完全缓解。12个月无进展生存率为37%。9%的患者因不良事件而停用glofitamab。最常见的不良事件是细胞因子释放综合征（63%的患者）。62%的患者发生了3级或更高级别的不良事件，4%的患者发生3级或更低级别的细胞因子释放综合征，3%的患者出现3级或更高级别的神经系统事件。

研究结果表明，glofitamab治疗DLBCL有效。超过一半的患者出现了3级或4级的不良事件。

附：英文原文

Title: Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma | NEJM

Author: Michael J. Dickinson, M.B., B.S., D.Med.Sc.,, Carmelo Carlo-Stella, M.D.,, Franck Morschhauser, M.D., Ph.D.,, Emmanuel Bachy, M.D., Ph.D.,, Paolo Corradini, M.D.,, Gloria Iacoboni, M.D.,, Cyrus Khan, M.D.,, Tomasz Wróbel, M.D.,, Fritz Offner, M.D., Ph.D.,, Marek Trněny, M.D.,, Shang-Ju Wu, M.D., Ph.D.,, Guillaume Cartron, M.D., Ph.D.,, Mark Hertzberg, M.B., B.S., Ph.D.,, Anna Sureda, M.D., Ph.D.,, David Perez-Callejo, Ph.D.,, Linda Lundberg, Ph.D.,, James Relf, M.D.,, Mark Dixon, M.Sc.,, Emma Clark, M.Sc.,, Kathryn Humphrey, B.Sc.,, and Martin Hutchings, M.D., Ph.D.

Issue&Volume: 2022-12-11

Abstract:

Background

The prognosis for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is poor. Glofitamab is a bispecific antibody that recruits T cells to tumor cells.

Methods

In the phase 2 part of a phase 1–2 study, we enrolled patients with relapsed or refractory DLBCL who had received at least two lines of therapy previously. Patients received pretreatment with obinutuzumab to mitigate cytokine release syndrome, followed by fixed-duration glofitamab monotherapy (12 cycles total). The primary end point was complete response according to assessment by an independent review committee. Key secondary end points included duration of response, survival, and safety.

Results

Of the 155 patients who were enrolled, 154 received at least one dose of any study treatment (obinutuzumab or glofitamab). At a median follow-up of 12.6 months, 39% (95% confidence interval [CI], 32 to 48) of the patients had a complete response according to independent review. Results were consistent among the 52 patients who had previously received chimeric antigen receptor T-cell therapy (35% of whom had a complete response). The median time to a complete response was 42 days (95% CI, 42 to 44). The majority (78%) of complete responses were ongoing at 12 months. The 12-month progression-free survival was 37% (95% CI, 28 to 46). Discontinuation of glofitamab due to adverse events occurred in 9% of the patients. The most common adverse event was cytokine release syndrome (in 63% of the patients). Adverse events of grade 3 or higher occurred in 62% of the patients, with grade 3 or higher cytokine release syndrome in 4% and grade 3 or higher neurologic events in 3%.

Conclusions

Glofitamab therapy was effective for DLBCL. More than half the patients had an adverse event of grade 3 or 4.

DOI: 10.1056/NEJMoa2206913

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2206913