ASCO-2021 Express: Recurrent glioblastoma, Nivolumab combined with standard bevacizumab can benefit older patients

Trials using anti-PD1 in recurrent glioblastoma (rGBM) have shown limited efficacy.
VEGF is a highly up-regulated pro- angiogenic growth factor in GBM , which contributes to tumor-related immunosuppression .
Preclinical data indicate that anti-vascular endothelial growth factor therapy has a potential dose effect on immune regulation.
Therefore, the combination of anti-PD1 and anti-vascular endothelial growth factor may be a promising treatment for rGBM.

Manmeet Singh Ahluwalia of Harvard University, et al.
randomly (1:1) 90 patients with GBM who relapsed for the first time to receive nivolumab (240 mg intravenously, the second week) and the standard dose of bevacizumab (10 mg/kg; Arm A) or low-dose (3 mg/kg; arm B) intravenously, the second week.

Stratification factors include the extent of resection, age, performance status, and MGMT methylation status.
Using CITE-seq's single-cell RNA sequencing technology, blood samples of 8 responders and 8 non-responders were analyzed before and 8 weeks after treatment.
The progression-free survival (PFS) and overall survival (OS) of the two groups of patients were compared.

They found that 90 patients (median age 60.
6 years, range 27.
4-86.
4, 67.
8% male) were enrolled between May 2018 and January 2020.
The median follow-up time for patients was 7.
7 months.

35 of the 88 patients were MGMT methylated (2 are uncertain).
There was no significant difference in overall OS between group A and group B (1 year: 41.
1 vs 37.
7%, P = 0.
14), while group A who was older than 60 years had better OS ( 1 year: 46.
2% vs 23.
8%; medium Number of digits: 10.
6 vs 5.
9 months; P = 0.
046).

For patients ≤60 years of age, there was no difference in OS between the two groups (at 1 year: 35.
6% vs 56.
4; median 8.
0 vs 12.
4 months; P = 0.
90).

The blood samples of 16 patients were analyzed by CITE-seq single-cell RNA sequencing method, baseline and 8 weeks after treatment.
Standard-dose bevacizumab-treated patients had reduced bone marrow-derived suppressor cells and inflammatory response gene characteristics at 8 weeks.
The most common toxicities (>20%) included fatigue (45.
6%), proteinuria (34.
4%), diarrhea (28.
9%), hypertension (23.
3%) and increased lipase (21.
1%).

The side effects of grade 3-4 are hypertension (7.
8%), fatigue (5.
6) and other non-neurological side effects, including deep vein thrombosis , PE, infection and abnormal liver function.

The significance of this study is that the overall PFS and OS rates of nivolumab and standard or low-dose bevacizumab appear to be similar compared to the historical benchmark of bevacizumab.

Nivolumab combined with standard bevacizumab may benefit older patients, but not younger patients.