severe side effect- citokine releaze syndrome-ICI+SBRT_pazopanib

[Olga]

One awesome doctor published a report of a single ASPS case when they encountered and successfully managed the significant life threatening toxicity when combination SBRT+nivolumab (Opdivo)-pazopanib were used. I am attaching the full text article shared with my by the author.
Additionally he shared with me the timing of the events:

This is the timing of therapy leading up to the cytokine release:

Day #1 start radiation to tibial metastasis. 2500 cgy given in 5 doses over 9 days.
Day #3 start every other week nivolumab. Given again on Day #17.
Day #10 start pazopanib x 1 week (then held in anticipation of pin placement in tibia scheduled 1 week later).
Day #20 admitted for severe CRS.
As I can see, the pazopanib and Opdivo were given on the same day 17 and the patient was admitted with the severe toxicity on Day 20, 3 days later. Of interests is also the fact that the patient had a surgical procedure on a day 17 (pin placement in tibia)
Thenote:
C-reactive protein, which has
been shown to be a surrogate marker for IL-6 in CRS,5,6 was also elevated
to 4.97 mg/l (reference <0.30 mg/l) (Fig. 1). A cytokine profile
was obtained and results eventually demonstrated elevated levels of
IL-6, IL-8, IL-10, and interferon-gamma.
the treatment:
In addition to continuing broadspectrum
antibiotics, the patient received high-dose corticosteroids
and the IL-6 inhibitor tocilizumab1,2 Over the initial 48 hr of targeted
CRS therapy, fevers improved and C-reactive protein (CRP) declined.
there were reports that targeted CRS therapy (IL-6 inhibitor tocilizumab) might be enough to resolve the situation.