Immunotherapy works in the brain!!! Surprise, surprise, surprise! NOT!!!

How long have I been yelling about this????  Let's just say it's been a while!

Here is a post from 2014 (NOT my first one on the topic that really explains the whole deal - with pictures and all!!!!!  Anti-PD1 in melanoma: T-cells, the brain, and EVERYWHERE ELSE!!!!

Here are about a zillion more posts with articles documenting response in the brain when immunotherapy is used:  Immunotherapy and melanoma brain mets

In the process of utilizing immunotherapy to treat those poor ratties with brain mets, we also learned that when immunotherapy is combined WITH radiation, the response is even better.  Which brings us to today.

Here is a link to Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. Tawbi, Forsyth, Algazi, Hamid, Hodi, et al. New England Journal of Medicine. August 23, 2018.  Which says in part:

METHODS  In this open-label, multicenter, phase 2 study, patients with metastatic melanoma and at least one measurable, nonirradiated brain metastasis (tumor diameter, 0.5 to 3 cm) and no neurologic symptoms received nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for up to four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks until progression or unacceptable toxic effects. The primary end point was the rate of intracranial clinical benefit, defined as the percentage of patients who had stable disease for at least 6 months, complete response, or partial response.  

RESULTS  Among 94 patients with a median follow-up of 14.0 months, the rate of intracranial clinical benefit was 57% (47 to 68); the rate of complete response was 26%, the rate of partial response was 30%, and the rate of stable disease for at least 6 months was 2%. The rate of extracranial clinical benefit was 56%. Treatment-related grade 3 or 4 adverse events were reported in 55% of patients, including events involving the central nervous system in 7%. One patient died from immune-related myocarditis. The safety profile of the regimen was similar to that reported in patients with melanoma who do not have brain metastases.  

CONCLUSIONS Nivolumab combined with ipilimumab had clinically meaningful intracranial efficacy, concordant with extracranial activity, in patients with melanoma who had untreated brain metastases. 

Now.  The sad thing is, immunotherapy, ipi/nivo in this case, does not work on anybody, anywhere, 100% of the time.  As you can see from the data above, outside the brain, 56% of these 94 patients gained clinical benefit.  In the brain, clinical benefit was attained in 57% of these patients.  Another sad point is that side effects are nothing to sneeze at, with grade 3/4 events reported in 55% of the patients and one passing due to inflammation of the heart.  Another very important point here, is that while the response numbers in the brain are basically the same as in the body, prior research demonstrates that when immunotherapy is combined with point specific radiation, like gamma knife or SRS, the response is better and more durable than with either treatment alone and the poor ratties in this study were required to have "at least one measurable, nonirradiated brain met".

And....we know this is real cause...oh, yeah!...We've gone mainstream!!!  Here's a link to a report on the findings in The New York Times, where Tawbi cedes the points I mentioned above and confirms that while these responses to immunotherapy alone were good, radiation is still a critical treatment component for most:  Immunotherapy Drugs Slow Skin Cancer That Has Spread to the Brain

("Skin Cancer"!!!?????  Really Denise Grady?  Seriously?  That is the description of MELANOMA you use and your editors approved to headline this story??????????????????)

Well, despite the ubiquitous "skin cancer" line, we've come a long way baby!!!!  Immeasurable thanks to all the ratties who have paved the way.  NOW!!  Let's stop pondering whether immunotherapy works in the brain!  Let's lose the old notion of "it can't cross the blood brain barrier" BS that one self-proclaimed expert on one particular melanoma forum has erroneously claimed - for YEARS!!!  Let's push all docs to realize that immunotherapy is enhanced when combined with radiation with no deleterious effects (at least no greater than the crappy crap that can go with melanoma and immunotherapy in the first place!!!) and move on to finding treatment solutions that work for greater than 50 odd percent of my melanoma peeps!!!!  Okay.  I'll breathe now.  Thanks J and F.  Thanks ratties.  Much love, c