Checkpoint Inhibitor Immunotherapy Update

When I wrote my previous blog post about checkpoint inhibitor immunotherapy, I didn’t realize that Phase 2 of the clinical trials were being released later on that day. Researchers at the University of Texas MD Anderson Cancer Center (here in the Lone Star State) performed clinical trial checkpoint inhibitor immunotherapy in 94 patients with melanoma that had spread to the brain. The results – more than half the patients had shrinkage of the best kind…

As noted in my previous post, T cells act like roving assassins, destroying anything deemed detrimental to the body. But because the body also doesn’t want the T cells to go rogue and start tearing up everything like a gang of rowdy hooligans after a World Cup victory, there are certain proteins that will “check” the action of the T cells. We make some of those internally. And unfortunately, tumor cells have found a way to synthesize those proteins as well. So what some immunotherapy drugs do is to block certain checkpoints on the T cell.

In this study, patients were given a combination of two immunotherapy drugs ipilimumab, which blocks the CTLA-4 checkpoint; and nivolumab, which inhibits activation of the PD1 checkpoint. (I had previously posted about CTLA-4, which were used in some of the first human immunotherapy clinical trials, if you’re at all interested in learning more.)

Researchers then followed up with the patients at nine months and then again around a year or so after starting the trial. At nine months, 59.5% of patients with brain tumors had not progressed. And at about a year and a half after treatment started, they found that over 50% of patients saw their melanoma brain lesions shrinking! The principal investigator and lead author of the study, Hussein Tawbi, M.D., Ph.D. stated, “As treatment for stage 4 melanoma has improved greatly in recent years, our patients with metastases to the brain have remained the group most in need, they’ve had the worst prognosis, so we are very excited about these results.”

Exciting news indeed! But one of the concerns about using immunotherapy is the potential for some wicked side effects. When you unleash the immune system’s full potential, you run the risk of triggering unintended immune-related diseases (although honestly, the side effects from radiation and chemo don’t seem like a walk in the park either). In this study, the researchers were obviously concerned with triggering an inflammatory response in the brain and the patients were closely monitored for that. In the end, only 5% of the patients had brain swelling. Thirty-six percent did experience some type of central nervous system side effect. But while it’s not 100% risk-free, being able to potentially shrink a melanoma lesion in the brain is really ground-breaking stuff.

Why do I say it’s ground-breaking? For one, most patients who have had their melanoma metastasize to the brain don’t get to participate in clinical trials. Why? Well, I’m going to quote directly from the article because honestly, I can’t say it any better.

“Historically, one reason patients with brain metastases had been excluded from clinical trials is that the blood-brain barrier, tight vascular construction, prevents drugs from reaching tumors. Since immunotherapy empowers T cells rather than treating tumors directly, the immune system cells can defeat the barrier, but there were concerns about immune-related side effects.”

Results like this clinical trial mean that more clinical trails will be performed. Are there risks to the patients? Of course, there are. But patients who participate may realize benefits as well. They have the opportunity to not only further our collective knowledge of how to treat and maybe someday beat prognoses that mean a death sentence, they have the potential to enjoy some longer quality time here with their families and friends as well. I have a huge amount of gratitude to every patient that helps us find better and more effective ways of treating disease.