Can altering the microbiome improve how checkpoint inhibitors work?

Our new meta-analysis

There has been a lot of talk about the benefits of immune checkpoint inhibitors (ICIs), and to be fair, these drugs that have demonstrated meaningful improvements in overall survival in multiple cancer types, even ones that historically have been difficult to treat. One of the downsides of these drugs is that they don’t work for everyone.

The question then becomes how to maximize benefits. One of the solutions that has been suggested is to supplement ICI treatment with microbiome modulators or fecal microbiome transplants.

Anjali Bhatt, a medical student at Texas A&M looked into the evidence supporting the use of these interventions to reduce ICI resistance, and our new paper is out now.

Here is the key figure:

The Figure summarizes all studies on this topic. Based on the number of studies that are review articles, there seems to be a lot of “interest” about these types of interventions. But, in looking at studies that test the intervention, almost all are mice or observational studies, which are not adequate for determining whether something actually works in people. One would need to look at human interventional trials – preferably a randomized one.

Of the 3 interventional trials, only 1 was randomized. The sample sizes for the 3 studies were very small, ranging from 10 to 30 people. The response rates in the single arm trials were in the same ballpark as the response rate reported in the registration trial (without the microbiome modulator), and the response rate in the randomized study were not significantly different between the intervention and control arm.

In the end, it’s tragic that there is very little evidence to support the excitement these interventions have generated. A few simple RCTs are desperately needed.