In my last treatment post, Uncharted Waters: waiting for a treatment plan, I outlined three treatment options:
- Plan A: IDH2 Inhibitor
- Plan A-: Immunotherapy
- Plan B: Reirradiation and CCNU chemotherapy
Over the past few weeks we have been waiting for two factors to determine which treatment plan I could do: insurance coverage and my genetic test results.
Two weeks ago I received a phone call from an unknown number in Florida. At first, I almost didn’t pick up my phone because I thought it was one of those fake cruise ship calls. I decided to answer, and a joyful sounding woman named Dee introduced herself. I almost hung up the phone because I was 99% sure this was a cruise ship call (…unknown Florida number, a woman named Dee, and Dee sounding way too joyful to be real).
Yet right when I was about to press the red button on my phone, Dee introduced herself as a patient advocate with Accredo pharmacy. My hairs stood up, heart racing, and I jumped off the couch trying to find something to write with. Accredo is a pharmacy that handles specialty drugs, and in 2015, they were the ones who shipped my chemotherapy to me every month (i.e. this wasn’t a cruise ship solicitor)!
Once I had a paper and pen in hand, Dee started to explain that she was calling about the IDH2 Inhibitor, Enasidenib (… the Plan A drug I mentioned in my last treatment post). She said that my insurance had approved the drug, and they were ready to deliver it to me.
I was stunned. My doctors and I thought we’d have to apply for compassionate care use from the FDA and pharmaceutical company…a three to four week process. To give the quicker route a shot, Dr. Wen had submitted a prescription for the drug, but none of us thought my insurance would actually cover it. Well…they did! And within two days I had the drug shipped to me.
Since accessing the IDH2 inhibitor was no longer an issue, regardless of the genetic testing results, I would be able to do one of Dr. Wen’s experimental treatment approaches: the inhibitor or immunotherapy. All we needed were the genetic results to determine which of the two treatments I could do.
Genetic Test Results:
During my surgery in May, a sample of my tumor was collected for genetic sequencing. The tumor was compared with a normal sample of my blood to test for mutations. This test at UCSF is called the UCSF 500 Cancer Gene Test. It is one of the most comprehensive genetic tests in the country that looks at 479 genes closely connected to cancer. For more information on the test, UCSF has their own site explaining what they do: https://gmi.ucsf.edu/cancer/#testing
On June 29th, after having a follow-up MRI, I finally received my genetic results. First, my tumor is not hypermutated. Hypermutation can sometimes occur in a subset of gliomas following treatment with temozolomide (…the chemotherapy I did in 2015), and would suggest immunotherapy treatment (plan A-). Instead, my results came back with five specific pathogenic alterations (i.e. abnormal changes that can lead to cancer):
- BRAF p.L597R (mutant allele frequency 42%)
- HRAS p.G13R (mutant allele frequency 44%)
- IDH2 p.R172K (mutant allele frequency 52%)
- TERT c.-124C>T (mutant allele frequency 49%)
- Chromosomes 1p & 19q co-deletion (mutant allele frequency N/A)
So what do all these letters and numbers mean?
Well to start, Chromosome 1p & 19q co-deletion and TERT are mutations characteristic of the type of tumor I have (…an oligodendroglioma). In other words, these mutations are like a fingerprint of my tumor, and pretty much expected to be there.
How about the IDH2? Well, from the genetic sequencing we did during my 2014/2015 recurrence, we already knew that I had this mutation. The UCSF 500 results not only confirmed that I have the rare form of this mutation (IDH2 but NOT IDH1), but also that the mutant allele frequency is high (i.e. it is commonly found in my tumor).
How about the BRAF and HRAS mutations? This is where things get a bit interesting. These are two new mutations I did not previously have. (…It’s important to note that the last time I did sequencing in 2014 was for tumor tissue collected during my 2004 surgery).
BRAF and HRAS are part of the MAP kinase signal transduction cascade. For my medical school friends you can check out this DIAGRAM or this VIDEO for more info. For everyone else, the MAP kinase pathway (…or MAPK for short), is a cellular pathway that allows a signal from outside a cell to cause the cell to undergo cellular division. BRAF and HRAS are proteins that are part of this pathway. When they are mutated, they can cause uncontrolled cellular division, which can lead to cancer.
These mutations have been found in various cancers like melanoma. Similar to how the IDH2 inhibitor was developed for leukemia, drug inhibitors have also been developed for BRAF and HRAS mutations in melanoma. One of these drugs is a MEK inhibitor since MEK is an important part of this cellular pathway. In other words, there are already drugs available to theoretically target tumors that have the BRAF and HRAS mutations.
While BRAF, HRAS, MAPK pathway alterations are not typically seen in oligodendrogliomas, they have been found to occur in IDH-mutant, diffuse gliomas, and may be associated with recurrences (i.e. the situation I am in now).
So what do we do with these results? We know IDH mutations are common drivers of gliomas, and one of the primary mutations in my tumor. Thus, it makes sense to try the IDH2 inhibitor, Enasidenib, as our first treatment. While I start this drug, a genomics team at Dana Farber is going to look at the BRAF and HRAS mutations to determine how likely it is that they are contributing to my tumor growth. If the IDH2 inhibitor does not work (i.e. my tumor keeps growing) then we may consider a MEK inhibitor related to the BRAF and HRAS mutations.
Now that we have all the genetic results out of the way, what’s next?
Plan A is a go! …actually it already started!
Since I had the IDH2 inhibitor with me, I took my first pill yesterday, July 2nd. From now on, I will take the drug every night around 10pm until we find evidence on my MRI scans that it is not working or the side effects become too significant. If you remember from my last post, this drug is meant to stop tumor growth. It will not shrink anything. The hope is that during my next MRI in two months, and in subsequent MRIs, we see no change.
Additionally, I will have to get blood tests every two weeks to monitor the side effects. Fortunately, this drug is relatively well-tolerated. However, the known side-effects are for people with Leukemia since that is who the drug is intended for. Thus, I’ll be monitored closely because I am one of a handful of people to use this drug for a brain tumor. Most likely I may experience some nausea, change in taste, and change in appetite.
Luckily, I am able to do this treatment in the Bay Area, and currently writing this post from my new place in Oakland! Dr. Wen (a.k.a. Yoda) is still the captain of my ship and coordinating my overall treatment. I am incredibly privileged that I also have access to a fantastic physician, Dr. T, at UCSF. She and her team will oversee the day-to-day aspects of my treatment.
It was an odd feeling to take pill #1 of the Enasidenib (…also called Idhifa) last night. With so much waiting over the past month and a half, I thought I’d be eager to start treatment. I thought I’d be excited that Plan A, the treatment route we’d been hoping for, had come to fruition. But mostly I felt unease, likely because all of this feels so surreal. Hypothetically, the best case scenario is that I am on this drug indefinitely until there is a cure. That concept, one of complete uncertainty, is hard to grasp.
Yet as I said in my speech at the Bay Area Brain Tumor Walk, I already know how to deal with uncertainty…I’ve been doing it my entire life. This isn’t some inherent strength of mine; rather, it is rooted in the privileges I’ve been afforded: unconditional love and support from my family and friends as well as access to the world’s best medical resources.
While I plan to do more writing on this topic, I want to take a moment to address this idea of access. When I was working on a community health survey at a rural medical clinic in Indonesia, a woman came to the clinic with a brain tumor. She had been diagnosed at the closest “city” a couple hours away, and had been experiencing symptoms. The doctors said she needed to go to Jakarta, the capital, to get a MRI.
…She went home…because she couldn’t afford the cost of transportation…
I can schedule MRIs with the click of an email to my doctor. I have insurance that is covering an experimental treatment that wasn’t even intended for brain tumors. I have two of the world’s top medical institutions going out of their way to work with each other to coordinate my care so that I can continue with my life here in the Bay Area. I have information from next-generation genetic sequencing technology that can be used to help determine future treatments…treatments I will likely have few challenges getting access to.
The comparison to the woman in Indonesia is extreme, but similar disparities exist here in the United States. Insurance coverage, access to diagnostic tests, access to treatments, access to specialists, the list goes on and on.
I am in the top 1% of 1% regarding my level of access to medical resources. Yes, I advocate strongly for myself, but my access is largely due to where I was born. No one’s health, or access to care, should be determined by this.
So…tonight I’ll take pill #2. The next day I’ll take pill #3. Then 4, 5, 6, and so on. Recognizing the privilege I have to go with Plan A (…regardless if it works) doesn’t negate the physical and emotional struggles I, my caregivers, and those around me experience as part of this journey. It does, however, come with a responsibility that with each pill I take, I try to transform my access…my privilege…into some value for others.