Immunotherapy and coronavirus vaccines, and a CT scan

Twelve weeks have passed since my last set of scans, so it was time to get another dose of radiation. As usual, I drank a liter of barium sulfate, then went in for my blood work. A new nurse blew my veins in both arms then embarrassingly told me that I should go to CT and have them access a vein, do the scans, then leave the IV in so she could get a blood draw. It’s times like this that I regret having my port removed back in 2017. I ambled over to the CT area and the CT tech promptly did a good stick in my right arm inside the elbow, next to the blown vein. It’s always nice to have an experienced when placing and IV. I got the scans of my neck, chest, abdomen, and pelvis, then walked back to get my blood drawn for my labs and my appointment with Dr. Maughan.

 

I’d been wondering about the possible interactions between my immunotherapy and the newly developed COVID-19 vaccines. Both work by stimulating the immune system, and I wondered if there was any risk of interaction between the two. A few days before Thanksgiving, I emailed my oncologist, Dr. Ben Maughan:

In advance of my next appointment on December 10, I have two questions and a form:

1.  Coronavirus vaccine: Will there be any risk of interaction between the Pfizer or Moderna vaccine and my having had years of an anti-PD-L1 checkpoint inhibitor (Opdivo)? Will HCI offer early access for patients like me?

2. I continue to have a grade 1 rash and itching on my scalp and face, despite not having had Opdivo for more than 5 months. I was hoping that as the drug titrated out of my system, the rash would subside. What do the data suggest may be the durability of this side effect? Does it make sense for me to visit an HCI dermatologist to discuss? (I visited an IHC dermatologist at McKay Dee last year and she arrogantly dismissed any possibility that I had immunotherapy-induced dermal toxicity.)

3. My long-term disability insurance company asks that you fill out a form to confirm that you’re continuing to follow me for mets BC. The form is attached. All they care about is that am still under a physician care for mets BC; the functionality questions are irrelevant.

Happy Thanksgiving, and I’ll see you in a couple of weeks,

 

A few hours later, he responded:

I hope your Thanksgiving is a wonder time as well. I have to admit that I laughed and enjoyed the comment about your dermatitis. We will work on the form and get it back to you soon. Regarding the vaccine, we have no data (at least that has been published). There is a theoretical concern that vaccines will further stimulate the immune system and might lead to further autoimmune toxicities. The durability of the side effects can be very long (years) if there is a permanent change to the immune system which appears to be the case for you. This is why there is a theoretical risk in combination with vaccines (and so vaccines are often listed in the exclusion criteria of many clinical trials). Overall I suggest that the risk/benefit still strongly favors you getting the vaccine. Not sure how it will be distributed but with three companies (now AstraZeneca as well) manufacturing them I believe one will be available for you soon after approval. Team, please make a referral to UoU Dermatology. Also we need to fill this out. Can we do it tomorrow during clinic? 

 

I’ve done a bit or reading about the coronavirus vaccines. There is no data that I could find that shows whether cancer patients who have had immunotherapy are at greater risk for complications if they get the vaccine. This issue is complicated by the fact that both the Pfizer and Moderna vaccines are mRNA vaccines, which have never previously been used.  

Vaccines work by training the body to recognize and respond to the proteins produced by disease-causing organisms, such as a virus or bacteria. Traditional vaccines are made up of small or inactivated doses of the whole disease-causing organism, or the proteins that it produces, which are introduced into the body to provoke the immune system into mounting a response. mRNA vaccines, in contrast, trick the body into producing some of the viral proteins itself. They work by using mRNA, or messenger RNA, which is the molecule that essentially puts DNA instructions into action. Inside a cell, mRNA is used as a template to build a protein. An mRNA is like a proto-protein. To produce their mRNA vaccines, Pfizer and Moderna produced a synthetic version of the mRNA that the coronavirus uses to build its infectious proteins. This new mRNA is what is injected into the human body. The body reads the mRNA as instructions to build the coronavirus protein. These proteins are solitary, so they do not assemble to form the actual conronavirus. The immune system then detects these viral proteins and starts to produce a defensive response to them. (This article does a good job explaining mRNA viruses.)

My nivolumab is an anti-PD-L1 immunotherapy that uses my body’s immune system to attack my cancer cells, but it does not use mRNA. Instead, it uses a different type of protein that strips the cancer cell’s camouflage that tricks the immune system into not attacking the cancer cells. The mRNA vaccine’s methodologies and pathways are different from anti-PD1 and anti-PD-L1 cancer immunotherapy, so there does not appear to be an obvious conflict, at least based upon my review of the data. But I’m a lay person, and acknowledge that it has not been specifically tested in a population of immunotherapy cancer patients.

Happily, Dr. Maughan is not a lay person, but is immersed in the world of cancer therapies. Having primed the pump with my email, I asked him about his views. He said that, in the absence of data, all he could do was make a somewhat educated guess, guided by the following principles: Coronavirus in cancer patients: bad. Vaccines: good. The new mRNA vaccine: highly effective. Inoculating me against COVID-19: good. The only downside, he said (as he noted in his email) was that there was a theoretical chance that because both nivolumab and the mRNA coronavirus vaccine rev up the immune system, adding the mRNA vaccine to my system ran the risk of overstimulating my immune system. He had no data on which to assess the probabilities or risks. On balance, though, he thought that the benefits of getting the vaccine far outweighed the risks.

As we were meeting, the FDA's science advisory panel announced that it had approved Pfizer’s vaccine for emergency use. Doses are being distributed to all 50 states, and inoculations will start soon. As to when the vaccine might be available to me, he could only shrug. In the US, the CDC’s Advisory Committee on Immunization Practices (ACIP) said that the first people to get the vaccine should be health care workers and residents of long-term care facilities. The ACIP currently is debating who the next group should be, but it’s likely to include adults with certain underlying medical conditions, including cancer. The problem is, these recommendations do not have the force of law, but are instead recommendations. Each state will decide how to dispense its ongoing allotment of vaccines. Utah has said that it intends to follow the federal recommendations, but details have not been forthcoming. Dr. Maughan had been told by the University of Utah that the first people in line for the vaccines were front line medical workers and residents of long term care facilities, but he had no information of when those people (including himself) would be vaccinated, or when the next groups of people (perhaps including me) might have it available.  

The UK, which is the first country to approve the Pfizer vaccine, classified patients having immunotherapy or other continuing antibody treatments for cancer as “clinically extremely vulnerable.” Using the UK’s provisional priority list, such patients are placed in slot #4 for getting the vaccine, which is the same category as people over age 70. Whether the US, and the State of Utah, will follow suit remains to be determined. I told Dr. Maughan that I would look to him to advise me when I could get the vaccine, and he said that he would do so.

 

While we were talking about vaccines, the results of my CT scans were posted. The scans of my neck, abdomen, and pelvis were unremarkable. In my chest scan, however, the radiologist noted the presence of a new node measuring 9 mm in length located deep in my chest between my heart and thorax. The node did not “light up” in reaction to the contrast, suggesting that there was no active metastatic activity, but it’s still something to bear watching. It’s in a location that has not previously had metastatic growth, but since my cancer was in my lymph node system, it could pop up anywhere.

 

Dr. Maughan said that he did not recommend going back on monotherapy with nivolumab at this time, but that if I felt strongly to the contrary, he was ok with that too. I told him that the last time I’d gone off nivolumab, it was 15 months before my mets had returned. He said that there was no definitive indication that my mets were back now, and I reassured him that I was merely expressing my expectations that, at some point, my cancer would return. Dr. Maughan said that the ongoing data for nivolumab monotherapy did not point to a long-term durable remission (or “cure”, to use that wonderfully imprecise layperson term). The long-term duration for “no evidence of disease” (NED) for patients on single agent immunotherapy kept trending towards zero. But, he noted, the long-term data for combination therapies was much more promising. Those therapies could include Padcev, or ipi/nivo, or even ipi/nivo/cabo, as Dr. Andrea Apolo has been evaluating. I told Dr. Maughan that I fully expected that, once my mets returned, my next therapy would be a combination therapy, and I would look to him for his advice, along with Drs. Apolo and Hahn. Until then, I said, I was going skiing.