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.

Surveillance CT scan and more

Today I had my first surveillance CT scan since suspending my immunotherapy in June. The process was identical to most of my prior 40+ scans: drink the contrast; have an IV placed and my labs drawn (only one blown vein); have the scans of my neck, chest, abdomen and pelvis; visit with the medical staff; then drink lots of Diet Coke to wash the contrast out of my system. According to Lindsey, Dr. Maughan’s PA, the preliminary scan readings showed no tumors or other metastatic activity. Yay! I've become pretty blasé about the whole process. A scan shows what's already happening in my body, and that's nothing to be afraid of. I'll continue these scans for every 12 weeks for (probably) the rest of my life. I fully expect that, at some point, a scan will show that my metastatic tumors have returned. At that point, I'll confer with my medical team and we'll determine the best therapy. Maybe that will work, maybe it won't. But it's nothing to get chuffed about right now. I’m just happy to continue my NED (no evidence of disease) status.

Speaking of NED’s excellent adventure, I've abandoned my plans to build a house. I made that decision in mid-July after two realizations: First, Jennifer's doctors told me that she was continuing to decline, and that there was virtually no chance that she ever would be able to leave assisted living and live with me at home. So the reason for me to design and build a home that could accommodate Jennifer (walker/wheelchair friendly, no accessible stairs, the ability to restrict access to dangerous places like the kitchen, and controls on exterior doors) no longer existed. Second, my efforts to find a contractor who would agree to build my house for less than a million dollars were not going well. I received quotes from four different contractors. I learned that the demand for housing in Utah was so great that the building trades could name their price and get it. Construction labor costs went up more than 25% in 2019, and the increases this year are on track to be even greater. After dozens meetings with those four different builders, I realized in early July that the compromises I was making to keep down the costs had turned the planned house into something I was no longer interested in building.

Serendipitously, a week after these two revelations, the owner of the house next door to Chelsea, Josh, and the grandkids, announced that he was being transferred back East to help build pharmaceutical plants for manufacturing Coronavirus drugs. I proposed that I buy his house, and in 30 seconds we agreed on a price and shook hands on the deal. I closed late last month. It was the easiest house purchase ever, since it was an all-cash deal. The title company came to my house and needed only two signatures. It’s a 40 year old split entry, which along with disco and bell bottoms was all the rage in the 1970s. Upstairs are two bedrooms, one bath, a living room, and dining room/kitchen in about 950 square feet. Downstairs is another 950 SF with two bedrooms, a bathroom, a family room, small kitchenette, laundry room, and storage area. There is a two car garage separated by a covered breezeway. Out back there is a 12x12 deck and a concrete patio. It sits on an acre of land. The house was recently renovated, with a new roof and siding and a new kitchen. It is unpretentious and is sufficient for my needs.

Spencer accepted my invitation to move into the basement. I have a bedroom and office upstairs, and he has a bedroom and office downstairs. In the past two weeks I’ve yanked out an old freestanding wood burning stove and the stone surrounding it and drywalled it up, gaining about 40 SF in the living room; had carpet installed; arranged for replacement windows; had a washer and dryer delivered and installed; and most importantly, added a hot tub. I have missed having a spa and have been using the new one every day. I also got a hot tub for the Slade’s to thank them for letting me park my fifth wheel next to their house for the past two years. I’ve listed the trailer for sale, and once that’s gone I’ll probably sell my diesel dually. I’m thinking of getting a Gladiator, since I miss having a convertible but want something that can pull my boat.

I feel like I’m staggering through 2020. It’s been a crazy year, between the Coronavirus and the quarantine of assisted living facilities cutting me off from Jennifer for months. Yesterday I was talking with my daughters about how much of Jennifer’s recent decline has been due to her frontotemporal dementia, as opposed to the decrease activity and interaction due to the quarantine. I think it’s a combination of the two, but even when I was able to start seeing her again regularly in July, she continued to decline. She now requires substantial assistance with virtually all of her activities of daily living. Her speech has slowed and interactions typically consist of her repeating the last thing that was said. She struggles with movement: her gait is an uncertain slow shuffle, and she cannot meaningfully engage in physical therapy. She needs assistance in getting up from sitting. In the middle of the night she sometimes slowly rolls out of bed onto the floor. The staff at Layton Park has suggested that she meets the criteria for hospice care, which means that she would have an additional level of care and increased frequency of visits by dedicated specialists. Hospice care also gives the staff more latitude in how they can help her. The nurse at Layton Park warned that, if we did not agree to allow Jennifer to enter hospice care, there soon would come a time that they could no longer legally provide the level of care that Jennifer needed, but would instead have to transfer her to a skilled nursing facility. They stressed that they were not trying to transfer her but needed to comply with the state and county regulations regarding long-term care facilities, especially because the government had stepped up its auditing during the Coronavirus. We agreed to have Jennifer evaluated by the hospice care service, and they agreed that Jennifer met their requirements.

One of the requirements of hospice is that the patient is diagnosed with a condition that could lead to death within six months. The hospice nurse and social worker said that Jennifer’s FTD qualified, even though she could live for much longer. They urged us as a family not to focus on that, but to instead see how her entering hospice would provide greater care. It took a little while for us to come around to it, but I think we’ve all acknowledged that this is in Jennifer’s best interest. But it’s another milestone in Jennifer’s decline that no one was eager to see.

Only four more months of this annus horribilis. Perhaps by the end of the year we will be relieved from this plague that has been scouring over our country and driving people to distraction. But enough about national politics. Hopefully life will get back to normal in 2021. I’m just biden time until then.

Update 6 weeks after therapy suspension

Nivolumab (Opdivo) has a half life of about 25 days. Doctors generally agree that a drug in the body needs to go through five half lives before it is considered to be completely out of the system. For nivolumab, that's 125 days. So far, 39 days have passed since my last infusion, so I'm not even one-third of the way to having the drug totally flushed from my body. Not surprisingly, little has changed with my side effects: I still have a rash on my face and scalp, and the skin on the back of my calves and around my groin remain increasingly sensitive. My GI tract is still loose. My cuts and abrasions take longer to heal. These are the same side effects that I've had since I resumed my nivolumab therapy in early 2018. I likely won't know until late in the year whether the side effects will dissipate as the drug exits my system.

I've also wondered when my metastatic tumors will return Not if. I am assuming that the tumors will come back. The only question is when. Strangely, my family has not been enthusiastic about my invitation to form a pool of guesses for the mets return date. I guess that they don't share my black humor that comes with living with a diagnosis of death.

In non-cancer news, my life continues to stagger along in this unremittingly weird year. Coronavirus is like the bad house guest who never leaves. For me personally it meant welcoming my fifth grandchild, but spending less time with the grandkids from mid-March until mid-May, when Chelsea and Josh got more comfortable with expanding their quarantine. I drove to California three times to help support Spencer during his hiking the Pacific Crest Trail. I drove to Denver over Memorial Day weekend to be with Kirsten after the long-expected but still-painful death of our standard poodle, Nephi, after sixteen and a half years of living with our family. It meant my joining Garrett in rereading the 14 books of the Wheel of Time. It meant lots of rides on my Fat Boy. It meant seeing much less of Jennifer, as her long term care center followed county guidelines and forbade any visits not deemed medically necessary. Recently I have been deemed an essential medical worker in helping her resume her physical therapy. She continues to slowly decline and her frontotemporal dementia gradually destroys her short term memory. As a cynical teenager, my friends and I would tell each other, "life sucks, then you die." How pathetically prophetic.

I'm done with Opdivo (for now)

Today is my last Opdivo infusion in 2020. This second round of nivolumab therapy has lasted for 28 months, with a total of 30 infusions. As of today I’ll be on surveillance, with CT scans of my neck, chest, abdomen, and pelvis every 12 weeks. The consensus opinion of my medical team is that, since I’ve had no evidence of disease for a year, and since I continue to show evidence of dermal toxicity and increased sensitivity in my GI system, the risks of side effects outweigh the justification for continuing therapy. So I’m back into the game of watchful waiting, knowing that my metastatic cancer likely will return at some point. Having ridden the cancer roller coaster for 9 years, I’ve accepted this fate. I’m no longer living life from scan to scan, fearful of what the future might hold. Instead, I’m living life one day at a time, trying to do the next right thing.

Before my infusion, I had another full set of CT scans. Lindsey (the PA who works with Dr. Maughan) said that they looked to be unremarkable, but we’ll wait for the radiologist’s results to be sure. I’ve lost count of exactly how many scans I’ve had, but I’m pretty sure it’s over 40. Years ago I remember wondering if the radiation exposure from all of those scans would give me cancer. Now I’m past all of that. The benefit of the scans clearly outweighs the risks.

Summer has been arriving in fits and starts. We had 80 degree weather in mid-March – enough to persuade me to get out the Harley – then had two months of cold. By mid-May the weather had warmed enough to de-winterize the boat and take the grandkids out on Pineview reservoir. Then last weekend we had snow down to 6000 feet. I think that was winter’s last gasp, and now we’re barreling into summer heat with a vengeance.

The Coronavirus pandemic is slowing down for the summer. Utah is gradually reopening, but it will be some time before things get back to normal. Church and other large public gatherings are still banned. Wearing facemasks in public is strongly encouraged. I still can’t visit Jennifer at Layton Park. I expect that people will gradually be less socially distant until Fall, when there likely will be a second wave of infections that will sweep the Northern Hemisphere. I wonder when it will be safe to fly again. And I’m still slightly amazed that I can even think about the possibility of flying.

Infusion 73 and a lesson in patient advocacy

Yesterday I had infusion #73. Everything went smoothly. My labs were unremarkable. I'll have one more infusion next month, then I'll suspend my therapy and be on surveillance with scans every 12 weeks. I wonder how long it will take for the rash on my face, scalp, and other portions of my body to go away. I wonder if my GI tract will settle down. Stay tuned for some crappy reading.

I'm a Patient Advocate on the Bladder Cancer Task Force on the Genitourinary Steering Committee, sponsored by the National Cancer Institute of the National Institute of Health. That mouthful is sometimes abbreviated as BCTF GUSC NCI NIH. Most of the BCTF members are bladder cancer clinicians and researchers at NCI centers. Three of the committee members have been active in my care: Dr. Andrea Apolo at the NIH NIC; Dr. Noah Hahn at Hopkins; and Dr. Betsy Plimack at Fox Chase. Every month the BCTF has an online meetings, primarily to evaluate proposed clinical trials, and to help set research priorities in bladder cancer research. My job as a patient advocate is to review proposed clinical trials and speak for the people who will be on the pointy end of the needle.

Today the BCTF had its May meeting. The entire agenda was dedicated to how to improve clinical trials from the patient advocate's point of view. More than 30 people were on the call. Stephanie Cooper Greenberg, the other patient advocate on the BCTF, and I, led the discussion on the following points:

Topics of most interest to BC patients:

#1: Greatest need for a better supply of BCG and BCG alternatives. This includes whether shorter or lower doses are acceptable, and whether BCG maintenance has been proved to be effective.

#2: Bladder preservation above all; MIBC patients continue to feel stampeded to RC

#3: Patient desire for Immunotherapy or other therapeutics early on for NMIBC

#4: Trials that acknowledge different variants of BC: i.e: upper track disease, adenocarcinoma, etc. There is a need for more “niche” trials.

Impediments to trial accrual

-       Trials are not often available locally – they often require herculean efforts to be part of a trial – travel long distances with frequent visits, which come with a financial burden that is not reimbursed.

-       Some trials require a lot of visits and therapies where showing up may no longer be possible

-       Existing clinical trial paradigms permit many patient visits to be moved out of central NCI’s to local clinics and virtual visits, including labs, CT’s, some drug administration, patient assessment, and surveillance.

Trials in a COVID world

-       How can trials achieve accrual when patients can’t or don’t want to come to the clinic?

-       How can visits for treatments and surveillance be minimized? Fewer infusions of existing or new treatments? Are there low interpersonal contact options that minimize the risk of COVID exposure? For example: a urine cytology or FISH test that could be done at home? Or done in the clinic instead of higher interpersonal contacts like cystoscopy and TUR-BT?

-       How can you incorporate telemedicine and treatment at home (oral drugs or other possibilities) into trial protocols? Trials can have home-based telemedicine consult and enrollment, when the patient has more time to think and absorb the information

-       Not all trials will be able to move forward in the next 18-24 months: create trials that are high impact that save lives

We had a good discussion. Committee members observed that they had rapidly pivoted to telemedicine during the ongoing coronavirus restrictions, and we considered whether and how to make permanent some of those changes. We also discussed the need to better communicate to patients the fact that BCG was far and away the best treatment for non-muscle invasive bladder cancer, as well as the emerging data on bladder preservation and trimodal therapy. It seemed to be a good discussion.

Infusion 72 in a pandemic

When I arrived at Huntsman Cancer Center's Farmington Campus this afternoon , I noticed that the staff had gotten more consistent with their mask standards since my last visit. All staff were wearing procedure masks over their noses and mouths, although most had not tightened the nose band to restrict air gaps. My temperature was taken when I entered, my hands washed with a liberal dose of cleaner, and I was interrogated regarding my potential exposure to COVID-19. Four weeks of panic about the Coronavirus seems to have made a bit of an impression. Utah's total number of cases is only about 2600, with 21 deaths, so the risks for me personally remain very low. I continue to have mixed feeling about the one-size-fits-all response to the pandemic, but understand the public health priorities. 

I am grateful that the personal impact of the Coronavirus restrictions has been relatively small. The biggest thing is that I have not been able to personally visit with Jennifer, since all long-term care facilities have been locked down for weeks. I fully support that decision, but it is strange to go from seeing her daily to only being able to waive to her through the doorway or window. The small grace, perhaps, is that Jennifer's temporal abilities have been so adversely affected by her frontotemporal dementia that she doesn't clearly recall the fact that I have been unable to spend time with her. She continues to slowly decline, and lives very much in the moment, frequently unable to regulate the impulses shooting through her brain.

I likewise have limited my interaction with my daughter, son-in-law, and grandchildren, even though they live next door. Chelsea has dual concerns: she continues her medical practice as a hospitalist, caring for admitted patients at the local hospital, and is in her last weeks of her pregnancy with grandchild no. 5. We're in agreement to limit the risk of potential exposure both ways. I still get together with my two sons on a regular basis to share meals and play family games (several variations of Settlers of Catan, Azul, and Dominion).

The pandemic shutdown also has caused us to cancel the Utah's 2020 BCAN Walk to Fight Bladder Cancer, which had been scheduled for May 30. Salt Lake County's event's staff called me last week to warn that the county had cancelled all events through May 11, and would almost certainly cancel all events through the end of May. BCAN also had advised us to pull the plug on in-person walks in May, and to publicize a virtual walk on May 2. You're welcome to make a donation under my team (Team Kbros), or an individual donation. Thanks!

Back to today's infusion. Maybe it was the masks, but it took 4 sticks by three different nurses before they get a good blood return (on the back of my left hand, which will likely leave a painful bruise). Oh well. The lab said that first set of blood draws were unusable because the blood had coagulated. Eventually all got straightened out, and my labs were perfect, as usual. I spoke with Lindsey, the PA, who had consulted with Dr. Maughan. She confirmed that present plan to go through June, then suspend therapy. She let me know that, if I was not comfortable with coming into the cancer center because of Coronavirus fears, they would be ok with my not having my last three scheduled infusions. We kicked around the pros and cons, and I decided that I'd go forward with today's treatment since I was already here. I also said that I was leaning towards going forward with my treatments in May and June, as we previously planned, since the risk of COVID-19 infection was very low. Lindsey also noted that the rash on my face and scalp was getting more visible, and that continued to reinforce the decision to suspend therapy soon.

The lab rapidly prepared my dose of nivolumab, and I had it pumped into my hand in the usual 30 minutes. I'd forgotten how much more temperature-sensitive it is to pump fluids through the veins in the hand as opposed to the arm. This was my 72nd infusion of Opdivo, and my 28th during this round of therapy. I'm glad the drug continues to work, but I'm not going to miss these events.

Clear CT; what it means to have multipe rounds of NED

The results of Thursday's CT scans of my neck, chest, abdomen, and pelvis were posted last night in MyChart. All were unremarkable, which I find to be remarkable. No evidence of disease anywhere. Yay!

Reality check: My doctors and I still assume I've got microscopic metastatic cancer lodged in my body. The rule of thumb is that a mets patient needs to have no detectable cancer for five years before we can start using that ambiguous and nontechnical word - "cured." I'm nine months into my latest experience with No Evidence of Disease (NED). Since I was diagnosed, I've had four periods of being NED: May 2012-August 2013; January-August 2014; June 2015-February 2018; and the one I'm currently experiencing, which started in June 2019. The longest NED period I've had was two years and eight months.

Each mets diagnosis is a bitch slap from death. I remember each of them. The first time - May 15, 2012 - was the hardest. Then time passes and hope slowly rebuilds, then gets crushed. Each cycle makes it more difficult to let hope rebuild. At this point, I don't expect to be cured. I'm just stretching out time, going from therapy to therapy, and trying to find joy in each day.

Infusion #71: The edge of normalcy

I'm living at the edge of normalcy. The global overreaction to the coronavirus had made us all islands. On Tuesday March 17 the governor of Utah issued an order (unconstitutional in my view) that forbids the gathering of more than 10 people, plus limited the visits to long-term care centers to essential personnel only, so I can't visit Jennifer. Everyone seems socially distant and uncertain. Most everything is closed: churches, schools, restaurants, ski areas. Funerals are forbidden. My NIH patient advocate meetings that were supposed to take place next week have been cancelled. So has next month's immunotherapy conference in Dallas. I had scheduled the SLC BCAN Walk for Saturday, May 30, but it's almost certain that will be postponed. Some grocery stores are open but the last time I went into one the lines were wrapped around the store and the tension was so palpable that I just wanted to get out.

Most of the receptionists and techs at Huntsman Cancer Center's Farmington campus are wearing masks, but many were improperly fitted, pulled down so the mask is not not covering the nose, or just hanging from an ear. Ineffectively wearing masks turns them into nothing more than comfort items. A woman in gloves and mask was wiping down chairs, tables, and other surfaces with a rag. She wiped down a dozen chairs before spraying some more antiseptic on the cloth. I wonder if she's spreading the virus instead of killing it. Strangely enough, no one took my temperature or vitals when I entered HCI, or did my CT's, or labs. I was asked if I'd knowingly been in contact with a person diagnosed with  COVID-19 (no, there's only about 50 in the entire state), or traveled outside the US in the past 30 days. I replied, "No, except Wuhan China." The tech asking the questions didn't acknowledge the obvious lie, although the receptionist sitting at the next desk snorted and pulled up her mask. I smiled and lightly coughed in her direction, and grinned as she slowly rolled her chair farther away from me.

Fortunately, some things remain the same. I still have metastatic cancer. That's a relief. Every 4 weeks I have an infusion of nivolumab. That's comforting. Every 12 weeks I have a CT scan of my neck, chest, abdomen, and pelvis, just as I've had for the past 8 years. Routine in times of uncertainty. Today's barium sulfate smoothie is ambiguously named "berry". Maybe a pun on the radioactive isotope?

I'd been told that the doctors and PAs were working remotely, but that either Dr. Maughan or Lindsey (the PA) would review my scans and labs, then give me a call. At this point, I as familiar with the process as they are. The nurse who was taking me back to the infusion area turned me around when I told her no one had taken my temperature. She grabbed the dermal sensor and slapped it on my head (98.1), then took me back to the infusion chair. She told me that my labs were perfect and that she'd released my nivolumab. While I waited for my immunotherapy medicine to arrive from the pharmacy, she hung a bag of saline to help push the radioactive contrast from my system. Not quite as effective as my usual method of flushing (4 liters of Diet Coke, accompanied by a Five Guys burger and fries), but with all sit down restaurants shuttered, I'll have to improvise. 

My infusion was routine, as I've come to expect. My infusions are scheduled through June, then I'll go on surveillance and wait and see when and where my tumors return. Maybe the coronavirus will have run its course by then. Or maybe we'll be deep in the forthcoming recession with 30% unemployment and most things in short supply. But at least I'll still have cancer!

<cough, cough>

I'm planning to suspend nivolumab in June; Infusion #70

In the past several weeks, my oncologist Dr. Maughan and I exchanged the following emails:

Me to Dr. Maughan, 12/20/19

Sorry I missed you [at clinic today]. Today with Lindsey I raised the question of how long I should stay on nivolumab therapy. It will be two years in March. My first regimen under Noah [Hahn] lasted 22 months. I was off therapy for 15 months before the tumors reappeared. I’d appreciate if if in the next couple of months you would give some thought to the question, perhaps discussing it with Noah, Andrea Apolo, and your HCI group. I doubt that there will be a clear empirical answer, but rather it likely will be a judgment call. I’d be interested to see if there is a collective consensus.

Dr. Maughan to me, 1/8/20

I too have been thinking about that issue (ie. Duration of n-th treatment with nivolumab). I typically think of 2 years as reasonable based on the results of prior studies. Planning to hear what they think at NIH and JHU. Will keep you updated.

Dr. Maughan to me, 1/27/20

I recently heard back from Noah and Andrea about the duration of nivolumab. Both agree that not much data on this topic—well not great data anyhow. Both typically follow a 1 year strategy, meaning discontinuing nivolumab 1 year after observing a complete response. As discussed in clinic, since there is no great data I can be supportive of many options here. However, I also recommend stopping nivolumab after 1 year. Let me know your thoughts on how you wish to proceed. 

Me to Dr. Maughan, 1/29/20

Thank you. With the consensus being to suspend therapy, I’m ok with that decision. The next question is timing - I’m not sure when to start measuring my last CR - would it be after my radiation treatment in June 2019, or the NED scan in September 2019, or another date? And once on surveillance, I’d continue with CT scans every 12 weeks, right?

Dr. Maughan to me, 1/29/20 

No great answer regarding the timing of when to start calculating the time from. The general consensus is starting from completion of radiation therapy though, which is also my recommendation. You are correct regarding the surveillance. I suggest repeat scans and clinic visits every 12 weeks.

Me to Dr. Maughan, 1/30/20

Ok, I’ll plan to continue monotherapy through June 2020, then switch to surveillance barring any adverse developments. 

*** 

Today was my first infusion after completing this email exchange. This morning was a bluebird day, so I drove up to Snowbasin and went skiing for three hours. The parking lot of the ski area is only a three mile detour from my drive from home to Huntsman's Farmington campus, so it was an easy decision. The snow was wonderful - there's been more than 280 inches so far this season - and the groomers were nice. I started on the Strawberry gondola and followed the sun, ending with a ride on the John Paul lift and a run down the Grizzly Olympic downhill. A recent New York Times article gave glowing reviews to Snowbasin and another local resort, Powder Mountain, so the secret is out. 

I checked into HCI, then realized that I was still wearing my base layer thermals and a long sleeve quick dry shirt, which would make it difficult to access my arm for blood draws and my infusion. I shed my thermal top and rolled up the sleeve of my quick dry short, and the nurse got my vein with the first stick. I got my labs drawn, then met with Lindsey, the PA who assists Dr. Maughan. She said that my labs were perfect - "the best I've seen all day" - and said that she'd read in my charts about my emails with Dr. Maughan and the decision to suspend my nivolumab infusions through June. Last week I saw Dr. Apolo at the 2020 ASCO conference, and she reiterated her agreement with going on surveillance this summer. 

So why suspend my treatments, you ask? Didn't I already try that back in December 2016, after 22 months of nivolumab, only to have metastatic tumors reappear only 15 months later? Yes, all true. But the concern is that the longer I stay on nivolumab, the greater risk I have to trigger and autoimmune disorder. I've been gradually seeing an increase in skin rashes and looser bowel movements - both indicators that my T cells are getting more twitchy and willing to attack normal tissue. I currently have no detectable disease (not the same thing as being cured - that's an entirely different kettle of fish). And since my cancer seems to be responsive to nivolumab, if and when my disease returns, I'd likely try it again. 

And if nivolumab doesn't work, there are other therapies that are being developed. One of the more exciting announcements coming out of ASCO was that a new combination therapy of pembrolizumab and enfortumab vedotin-ejfv (Padcev). The recent press release said that an astonishing 93% of patients with metastatic bladder cancer in a phase 1 clinical trial had tumor shrinkage, with a significant percentage having durable complete responses. This is an amazingly promising result, better than any other therapy for mets BC, including single drug immunotherapy. P+EV will now be tested in a phase 3 clinical trial. Hopefully it proves to be as good as indicated. 

While I was getting my infusion, Dr. Maughan came over to chat. We had missed seeing each other at ASCO, so I got his thoughts on the updates. Like me, he was impressed with the promise of P+EV, but wanted to see it hold up in the phase 3 trial. I also told him that NIH was flying me to DC at the end of March for a conference of patient advocates, and asked him to think about how Huntsman could better implement patient advocates in both its research and clinical settings. I also said that I was working on scheduling the SLC BCAN walk for May 30. I'll post more about the walk next month.

Notes from NCI GUSC Meetings at 2020 GU ASCO

Yesterday I attended several meetings sponsored by NIH's National Cancer Institute (NCI) in conjunction with the GU ASCO in San Francisco. Here are my notes:

Genitourinary Steering Committee (GUSC) Session

Discussion of “platform trials” in GU cancers by screening by biomarker and stratifying therapy based upon classifications. A platform trial is single overarching protocol developed to evaluate multiple hypotheses. FDA defines a master trial as“[A trial designed to] study multiple targeted therapies in the context of a single disease in a perpetual manner, with therapies allowed to enter or leave the platform on the basis of a decision algorithm”. Siden, et al., Reportingof master protocols towards a standardized approach: A systematic review, Contemp Clin Trials Commun. 2019 Sep; 15: 100406, quoting FDA Draft Guidance on Efficient Clinical Trial Designs (2017)). It’s similar to the UK’s STAMPEDE trial. Gilson, et.al, Incorporating Biomarker Stratification intoSTAMPEDE: an Adaptive Multi-arm, Multi-stage Trial Platform, Clin Oncol (R Coll Radiol). 2017 Dec; 29(12): 778–786. At the meeting, some researchers think platform trials are an exciting opportunity, but other researchers say those type of trials are very complex to implement and run. The discussion was inconclusive.

We also reviewed the recent and forthcoming clinical trials for the GU cancers: bladder, prostate, and kidney.

Bladder Task Force Session

Jason Efstathiou: We want to increase the visibility of patient advocacy. At a future meeting, maybe they’ll have a presentation from the patient advocates, and a checklist of things to consider from a patient advocate standpoint when designing clinical trials.

Jason also reviewed of chart of bladder bancer clinical trial concepts evaluated by GUSC. Generally, we’ve been successful in bringing trials forward. We’ve had some more recent trials that have had problems with accrual, and we’re trying to understand why. In looking at the chart of trials for all BC cancer types, virtually all types have pending or planned trials. There is some overlap, especially on the trimodal side.

Matt Milowsky: Current clinical trials planning meeting (CTPM) priorities: NCI wants to focus on biomarkers in NMIBC (where most patients are at). The majority of our trials are NMIBC. Do we stick with that? (Note: COXEN and CALGB 90601 are mets trials). I observed that BC has a high mutation burden with lots of biomarkers, and how in 2012 Dr. Apolo told me that they would identify the mutations, but didn’t know what to do about them. I said that my impression was that not a lot had changed in the past 8 years. I asked whether it’s even reasonable to tease out and test single biomarkers with BC, which typically has dozens of mutations (unlike most prostate cancers, for example). This triggered a good discussion on unmet needs, especially on HG NMIBC that is unresponsive to BCG. Bill Shipley pointed out how the median age of BC is (about age 73) among the oldest of common cancers. It would be great to develop therapies that don’t necessarily require RC, given the harsh recovery time. We wrapped up with a goal of sharpening the CTPM goals and providing greater communication and coordination between research groups.

Before and after the meetings, I spoke with several committee members, including Jason and Matt, co-chairs, and other committee members. I will be following up with to see how I can sharpen the role of patient advocates on the committee. I also spoke with Andrea Apolo, the NIH doctor who has been following my case since April 2012. It's been a couple of years since we had seen each other in person, and was delighted to see that I was not dead yet. I thanked her for her continuing role in keeping me alive, and looked forward to many more years of pleasant surprises. 

My next infusion in next week. I'll update my status then.  

Skiing into infusion #69

This morning I wend skiing with my brother at the Canyons at Park City. I have a season pass at Snowbasin, but he had a free guest pass so went to his "home" resort. We spent the morning on the groomers -- the off-piste stuff was pretty skied out. At about 1 pm I we called it a day and I drove down to the Huntsman Cancer Center's Farmington location for my monthly infusion - lucky number 69!

After labs and vitals, I met with my oncologist, Dr. Ben Maughan. I had not spoken with him for about three months, although we'd traded emails. The question of the moment is whether I should suspend my treatments in March, since it will have been two years since I resumed my nivolumab treatments, He acknowledged that there is an emerging consensus that two years of therapy is probably enough for the body's immune system to learn how to break the PD-1/PD-L1 link and destroy the cancer cells that were using that camouflage. I noted my concern that my rash on my face was getting worse (reflecting likely immunotherapy-induced dermal toxicity), and we shared a laugh about my visit to the dermatologist who likely had no idea what that was. I also reported how the frequency of my loose bowel movements was slowly increasing, also a potential signal of systemic toxicity.

On the other hand, I reminded him of how I'd already tried going off treatment in December 2016, after 22 months of nivolumab infusions as part of the clinical trial at Johns Hopkins. My disease-free status lasted 15 months before my tumors returned. While we agreed that was bad, we also agreed that the fact that I have had a complete response once I resumed treatment was a very good sign. Dr. Maughan allowed that it might be possible that, between the immunotherapy and the radiation treatments to zap the persistent tumor in my supraclavicular node, it may be possible that I have no more metastatic disease in my body. Maybe, I allowed. But probably not.

I've always assumed that even if immunotherapy wiped out the PD-L1 mediated mutation, some other mutation would assert itself and start growing. Mybe, said Dr. Maughan. But not necessarily. He said that more recent research has suggested that immunotherapy  can permanently change how a body responds to multiple types of tumor growth, not just those on the PD-1 pathway. The longer-term progression-free survival (PFS) rates of renal cell carcinoma patients and melanoma patients who have been on immunotherapy suggest that about 40% of patients have a long-term PFS. Immunotherapy was used on those cancers before it was used on bladder cancers, and the survival curves tend to taper out and flatten as the years progress. Maybe I could be one of those patients who have a long PFS after ending treatment and going on surveillance.

I asked whether he had heard from Dr. Apolo or Dr. Hahn on the question, and he said that he had not. I said that we'd probably all be together at GU ASCO next month, and we could talk more than. Dr. Maughan was delighted to hear that NIH was picking up the tab for me to attend ASCO, as well as having me fly out to DC in March for a patient advocate training meeting. We agreed to wait and see what the other members of my medical team thought about staying on treatment or suspending treatment and going on surveillance. I'm in no rush to make the decision.