Granulocyte-macrophage colony-stimulating factor for newly diagnosed glioblastoma.

in Neoplasia (New York, N.Y.) by Caineng Cao, Le Wang, Feng Jiang, Qifeng Jin, Ting Jin, Shuang Huang, Qiaoying Hu, Yuanyuan Chen, Yongfeng Piao, Yonghong Hua, Xinglai Feng, Yi Zhou, Xiaozhong Chen

TLDR

  • The study combined hypofractionated IMRT, temozolomide, and GM-CSF to treat patients with newly diagnosed glioblastoma (GBM), achieving a 6-month progression-free survival rate of 68.3%.
  • The combination therapy was found to be safe and effective, with significant changes in cytokine levels and immunity markers observed after GM-CSF administration.
  • Future studies may explore the therapeutic potential of GM-CSF and its potential as an adjunct therapy to enhance treatment outcomes for GBM patients.

Abstract

There is a clear need to improve the efficiency of therapeutic strategy for patients with newly diagnosed glioblastoma (GBM). The purpose of this study was to evaluate the feasibility of hypofractionated intensity-modulated radiation therapy (IMRT), temozolomide and granulocyte-macrophage colony-stimulating factor (GM-CSF) for patients with newly diagnosed GBM. Patients were treated with hypofractionated IMRT (15 × 3.5Gy to the high-risk region and 15 × 3.0Gy to the low-risk region), temozolomide (75 mg per square meter of body-surface area per day, from 1 week before the beginning of radiotherapy to the last day of radiotherapy) and GM-CSF [200μg (equivalent to 125 μg/m² calculated dose) subcutaneously injected daily for 2 weeks, starting from the second week of radiotherapy]. The primary endpoint was 6-month progression free survival (PFS). Between June 2016 and Feburary 2020, 41 patients were enrolled. During concomitant chemoradiotherapy, no grade 3 or 4 hematologic toxicities were observed and grade 3 non-hematologic toxicities were documented in 5 patients (12.2 %) due to GM-CSF. All patients completed both radiotherapy and concomitant temozolomide as planned. Only five patients (12.2 %) discontinued concomitant GM-CSF because of toxicity. At a median follow-up of 33.1 months (IQR 23.0-51.2), the 6-month PFS rate was 68.3 % (95 % CI: 54.0-82.6). The median overall survival of all patients was 16.7 months (95 % CI: 10.5-22.9). Compared with pre-GM-CSF, the concentrations of TNF-α (p = 1.9615E-10) and IL-18 (p = 6.8467E-8) were increased after GM-CSF, while the proportion of CD19 (p = 0.000015), the concentrations of IgG (p = 0.000015) and CXCL12 (p = 0.000257) were decreased. The combination of hypofractionated IMRT, temozolomide and GM-CSF for GBM was feasible and safe. ClinicalTrials.gov Identifier: NCT02663440.

Overview

  • The study aimed to evaluate the feasibility of a new therapeutic strategy for patients with newly diagnosed glioblastoma (GBM) by combining hypofractionated intensity-modulated radiation therapy (IMRT), temozolomide, and granulocyte-macrophage colony-stimulating factor (GM-CSF).
  • The study included 41 patients with newly diagnosed GBM who received a combination of hypofractionated IMRT, temozolomide, and GM-CSF from June 2016 to February 2020.
  • The primary endpoint was 6-month progression-free survival (PFS) rate, and the study aimed to answer the question of whether this new combination therapy is effective and safe for GBM patients.

Comparative Analysis & Findings

  • The 6-month PFS rate was 68.3% (95% CI: 54.0-82.6), which suggests that the combination therapy is effective in controlling tumor growth.
  • The median overall survival of all patients was 16.7 months (95% CI: 10.5-22.9), indicating that the therapy has a positive impact on patient survival.
  • The study found significant changes in cytokine levels and immunity markers after GM-CSF administration, suggesting that GM-CSF plays a role in modulating the immune response.

Implications and Future Directions

  • The study's findings support the feasibility and safety of the new therapeutic strategy, which could be explored further in larger, randomized controlled trials.
  • Future studies could focus on investigating the role of GM-CSF in modulating the immune response and exploring its potential as an adjunct therapy to enhance treatment outcomes.
  • The study's results could also inform the development of personalized immunotherapy strategies for GBM patients, taking into account individual differences in immune response and tumor biology.
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