Today, we're laying the foundation with the help of Dr. Osama Rahma, a medical oncologist in the Center for Immuno-Oncology at Dana-Farber and an Assistant Professor of Medicine at Harvard Medical School. We'll walk through the basics of immunotherapy, what it is, who can benefit from it and what the future holds for this groundbreaking treatment.
MEGAN: Thanks for joining us, Dr. Rahma.
DR. RAHMA: Sure. Thank you for having me.
MEGAN: Starting with the basics, can you define immunotherapy?
DR. RAHMA: So, immunotherapy is a form of cancer treatment that's intended to empower the immune system against cancer either by energizing the immune cells and make them work against cancer or by lifting the break off the immune system to make it work.
MEGAN: What are the different types of immunotherapy?
DR. RAHMA: Yeah, so that we consider the next step, which is defining immunotherapy as two big categories. One is the active immunotherapy and another which is the adoptive immunotherapy. So the active immunotherapy uses one type of treatment that's called cancer vaccines, which have been in trials for many decades now and it actually energizes the immune cells again and make that immune system respond against each tumor.
The other form of that is monoclonal antibodies — they actually lift the break off the immune system that the tumor places on the immune system and, therefore, the immune system is active again and is powerful again against cancer.
The other form of immunotherapy, which is the adoptive immunotherapy, has gotten a lot of attention recently with the CAR T-cells and those are immune cells that are taken from the patients and they're energized or engineered in the lab to be infused back to the patient to fight the cancer cells, and it could be also taken out of the tumor itself and it would be modified, so it can be injected back to the patient and go after the cancer cells.
MEGAN: What kind of cancers are responding to immunotherapy?
DR. RAHMA: So currently there are a few cancers that are showing responses, mainly melanoma where this story started. Melanoma patients have about a 30 percent chance of responding to one drug and about 50-60 percent chances of responding to a combination of two drugs.
Other cancers that are showing responses are lung cancer, head and neck cancer. Also, bladder cancers start to show responses, in addition to a new subset of cancers where the FDA had approved immunotherapy for, based on what you call biomarkers, a certain type of labels that the cancer has and it could be any cancer to have that, and those are called MSI-high tumors that respond to immunotherapy.
As far as the CAR T-cells and the adoptive immunotherapy, those have been approved mainly in hematological cancers such as non-Hodgkin lymphoma and ALL or acute lymphoblastic leukemia.
MEGAN: What are the common side effects of immunotherapy for cancer patients?
DR. RAHMA: So the way we think about side effects in immunotherapy is completely different than in chemotherapy or targeted therapy. So once you activate the immune system, it could go in the wrong direction. It could go anywhere in your body. It could go through the skin or you can see a rash or it could go after the liver where it can cause inflammation in the liver, what we call hepatitis, or it could go after the colon. It shows or it causes inflammations in the bowel – that's called colitis, results in diarrhea, upset stomach — and also it could go after the lung, which is the most dangerous part, which we see pretty much in less than 3 percent of the cases. Those are pneumonitis that is caused by immunotherapy and patients would have shortness of breath and other symptoms that they may end up in the hospital with, but we have also medication that reverses the side effects of immunotherapy such as steroids.
MEGAN: If someone is interested in a clinical trial involving immunotherapy, what steps should they take?
DR. RAHMA: So, we, among other major institutions in the country, we run our drug development program with immunotherapy where we basically combine drugs that are already established and maybe approved by FDA and we combine those with other immunotherapy drugs. Those are one of the promising tools to actually identify the right target and to identify the right subset of patients.
So Dana-Farber, the Center for Immuno-Oncology, which was established a few years ago, welcomes patients to contact us and call us for availability for immunotherapy clinical trials, and we treat all kinds of cancers — so this is not just one or two types of cancer. It all depends on what available studies we have. So the right thing is to call us and we will try to identify the right study for patients.
MEGAN: What are researchers at Dana-Farber doing to further develop immunotherapy's ability to fight cancer?
DR. RAHMA: Sure, so obviously immunotherapy doesn't work for everyone. In general, it's about 20-30 percent of patients who will respond to immunotherapy — depends on what type of disease it is or what type of cancer. So we're working to identify or discover what we call "biomarkers." So those are maybe labels in the DNA of the tumor or maybe in the blood of the patient. They can tell us why some patients respond and others don't.
We have trials that are designed to have a biopsy before the treatment and a biopsy on the treatment and, that way, we can tell what changes we have due to immunotherapy drugs, and we can actually look at responders and non-responders and compare those to each other and figure out why some patients are responding and others are not.
Also, we're studying the resistance mechanism of these drugs, so some patients may respond and later on they stop responding — is that because of certain changes in their genomics? Is that because of certain changes in their blood inflammatory levels or what we call cytokines, and others? So we're studying those.
Finally, we're looking to overcome such resistance by combining the drugs and mainly immunotherapy drugs, and we believe that's probably the future for immunotherapy development so we can have more patients responding to these promising therapies.
I think the most important message is that there are cancers that have shown responses, but there are many cancers that they have not and we call those "cold tumors" versus "hot tumors" — hot tumors are the tumors that respond. We're actively studying those cold tumors and we're actively trying to make those tumors hot so they can respond to immunotherapy.
The perfect example is pancreatic cancer and ovarian cancer, and patients may read that these tumors don't respond, but we encourage them to contact us because we are very actively looking for ways to make things work in these types of tumors. We're looking to turn cancer eventually to a chronic disease where immunotherapy can just contain cancer rather than what we have seen with chemotherapy where you can shrink the tumor and it grows again.
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