Fatal to Fearless, page 16
Maintenance Therapy, Recurrence, Repeat
In an effort to hold that M-spike at zero after the transplant, and erase the remaining spots on my PET scan, I stayed on Revlimid (a pill I could take at home), while seeing the doctor every eight weeks for continued monitoring. I was also back at the helm of the MMRF, which meant more days than I would like on the road. The travel and long hours led to respiratory infections that meant I would need to go off the Revlimid until I was better. I often asked Ken if I should just stay off because I kept getting sick; I felt like I was off more than I was on. His response: “There’s no data to answer that question.”
WTF!
“To be safe, you need to stay on,” he kept telling me.
It was another moment where the CEO in me thought: We can do something about this. The MMRF can build a database that starts to answer these kinds of patients’ questions.
Over the next few years, the organization took on building (and funding) one of the largest and most highly published datasets in cancer. We designed it with open access for any scientist in the field to use, breaking down a huge barrier in the broken healthcare system.
As CEO of the MMRF, I was on speed dial for many patients who were struggling.
“What stage are you?”
“Which drugs have you already been on?”
“Have you already done a transplant?”
“How long was your remission?”
“Where do you live?”
“Can you drive to an academic center?”
“Do you have any other illnesses?”
The new trifecta of drugs followed by a stem cell transplant remained a powerful combination for myeloma patients. But when relapse happened, and it almost always did, the cupboard was bare. We were working urgently with pharmaceutical and biotech companies to find the “next thing,” while scouring ClinicalTrials.gov to coach patients on what was out there now. It was no easy feat. A single search on clinicaltrials.gov could bring up fifty trials with endless eligibility criteria not written for patients to understand.
Another WTF!
Over time, we made it a priority at the MMRF to help patients learn about trials with a simpler search engine, emails, and a toll-free number.
It was in 2010, four years from my transplant, when Paul got the call from Ken Anderson again. Ken preferred that Paul relay any negative news to me in person. The blip began when Paul walked briskly into my office with that same determined step and his head lowered. He, too, knew that recurrence was sometimes even harder. He also knew I had used up my options. The cupboard was bare for me, too.
We placed the call to Anderson, who explained he did not like the ugly binucleated cells from my previous bone marrow biopsy. He was not panicking because my other tests looked okay and if this was something, at least we’d caught it early. Together, we looked at every single clinical trial available. Anderson knew most of them because Dana-Farber had since become the top center in myeloma at this point and he was often the principal investigator (the person running the trial). I knew them, too, searching nonstop for patients through the MMRF. We studied what was available in phase 1 or 2 or 3. Having supported many trials at the MMRF, I knew the risks and opportunities of each. It was a balance of getting the best therapy. But I also knew the later-phase trials offered more advantages because the researchers had already figured out the optimal dose and/or combination. I had become an expert in the vast, overwhelming world of clinical trials and regulatory efforts at the FDA.
Unfortunately, our efforts only confirmed what I already knew. I was standing in a desert between treatments I’d already used and ones not yet around. But Ken, functioning as both clinician and researcher, was thinking creatively. He recommended we focus on donor lymphocyte infusion (DLI) where we boosted my immune system with Karen’s fresh stem cells again, adding Revlimid at the same time to strengthen the response. This had never been done before. It would be a unique protocol. I would essentially be a “clinical trial of one.”
Once again, Karen, Paul, and I headed up to Dana-Farber, where the team harvested Karen’s healthy stem cells and gave them back to me in a nonceremonious infusion bag. I took the Revlimid pills alongside the infusion to boost the cells’ activity. Because we felt we’d caught this spike so early, we never told Nicole and David, nor the MMRF team or board. It was a relatively easy and uneventful treatment—far from the transplant experience as there was no chemotherapy involved.
Months later, following another bone marrow biopsy, we discovered that it had worked. Still, in the back of my mind, I wondered: How can we better track my remission? Is there a better, more sensitive way to detect signs of relapse? How can we know if there is even the tiniest handful of lurking cells we still need to get rid of? I approached Ken for some answers—not just for me, for all patients.
“I talk to patients every day, Ken. One day they’re in complete remission, then bang!, their M-spike is up and they’re desperate. If the M-spike only works so well, is there anything else we can use? Something to catch the myeloma cells the M-spike is missing? Something more sensitive, more precise?”
After a brief pause, Ken said, “There is one test called PCR. It’s labor-intensive and not for everyone. But it could work for you.” PCR (polymerase chain reaction) is a laboratory technology that generates multiple copies of a specific segment of DNA or RNA, making it possible to analyze small amounts of DNA with high precision and sensitivity. “We would have to know the genomic signature of your cancer cells to make it work, but we have that because we did your genomics years ago.” This was one more example where the right tests early led to a better result later.
“How do we make this happen?” I pressed on. Ken knew “not possible” was not an answer.
“We would need someone to take this on,” he said. “A researcher who knows this space and is willing to commit to following you over time. It would be another clinical trial of one.”
And with that Ken brought in one of his researchers, Dr. Kathy Wu. To this day, my mini-trial continues. And once again, the MMRF learned of the importance of understanding the entirely new and critically important field of minimal residual disease (MRD). We would become leaders in this space, too, working with the FDA, academia, and diagnostic companies to pursue early detection assays and diagnostics for patients. If MRD could be routinely tested, if patients knew the true depth of their response, they would know whether to discontinue therapy or be more aggressive. Because of PCR, I was ultimately able to safely go off maintenance therapy and fully get my life back again.
Accessing the Latest Treatments
Clinical trials are a tricky game. The only way to know them is to study them and consistently ask your doctor what might be right for you. But it’s a daunting task. Today, only 8 percent of patients are in a trial, mostly because they didn’t know one was available for them.* And even if one is nearby (often challenging because they are mostly conducted at academic centers), you have to first pass the eligibility criteria and then get to the site often for treatment and testing.
And clinical trials are not always the solution. When it came to my breast cancer, I’d had enough of the fear of relapse and had a definitive option in double mastectomy. My “third opinion,” a wonderful clinician at Dana-Farber, said to me, “Kathy, you spent your life helping to cure myeloma. Now you have an opportunity to do surgery and have a 99 percent chance of curing your breast cancer. Take it.”
I did. But when I did a quick search for breast cancer trials on clinicaltrials.gov, it yielded more than 12,000 studies. How is anyone supposed to figure out which of the 12,000 is the right trial for them, let alone how to get into it? And whether any of these 12,000-plus trials is even an option at all? Here are your WTDs for understanding and navigating trials when a clinical trial might be your best option.
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STEP 8: KNOW THE RIGHT TRIAL
WTDs
Know the Types of Trials
Phases 1 and 2 trials
Phase 3 trials
Phase 4 trials
Investigator-initiated trials
Know Where and How to Find Them
ClinicalTrials.gov
Patient and research foundations
Cancer centers
Ask your doctor
Know What to Look For
Trial design and protocols
Trial location
Time commitment
Eligibility criteria
Making your decision
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WTD 1: Know the Types of Trials
Clinical trials are research studies where people volunteer to test new treatments or therapies that may not be available through standard care. The treatment, while still being developed, is free. Often there is additional compensation and expenses are reimbursed. Trials are conducted in phases, based on how far along a treatment is in its development cycle. Each phase of a clinical trial has a specific purpose and participant group. The key phases of cancer trials are as follows:
Phase 1 and 2 trials Trials in phases 1 and 2 are frequently done at academic centers as they require detailed scientific information and can be labor intensive. This is where a potential treatment is tested first for its safety and ideal dosage (phase 1) and whether or not it even works (phase 2). These trials are often started in later-stage patients who have exhausted other treatment options and are willing to take the risk of being in a trial where the dosing and/or efficacy is still being determined.
Phase 3 trials By phase 3, the goal is to compare the new treatment against the current standard of care. Study participants are typically picked randomly (“randomized”) to receive either the standard of care or the new therapy. Phase 3 trials may be, but are not always, double-blinded, comparing standard of care with a new therapy. Neither you nor your doctor will know which therapy you’re getting. The beauty of phase 3 trials is that they tend to include large numbers of patients, and can be done in many places (around the world) at the same time as opposed to only at academic medical centers. This means you might be able to participate through a local community hospital or doctor’s office. If, during a phase 3 trial, the drug being tested demonstrates a statistically and clinically improved benefit over standard of care, all patients are moved to the new drug.
Phase 4 trials By phase 4, which is the safest type of clinical trial, the treatment has been FDA-approved and the study seeks more long-term data on effectiveness, quality of life, and cost issues on a larger and more diverse patient population. Drugs in this phase do not require you to formally participate in the ongoing study—you can still get them. Any compensation or reimbursement is generally much lower in phase 4 trials than it is in phases 1 to 3.
Investigator-initiated trials Investigator-initiated trials are run by nonpharmaceutical researchers working in a healthcare setting and hoping to test a new clinical practice or to compare the effectiveness of existing treatments. They are often designed to answer a question that the pharma company may not have asked.
WTD 2: Know Where and How to Find Them
To find clinical trials in cancer, there are several resources available:
ClinicalTrials.gov This site, spearheaded by the government, is the most frequently searched site for cancer trials. Every trial must “register” its information here and it can be a gold mine for patients. Still, it can be unwieldy and hard to maneuver.
Patient and research foundations Cancer.gov: NCI offers a custom tool for people to search NCI-supported trials at cancer.gov. You can also talk or chat with an information specialist to help you with your search.
Disease-specific foundations: Individual foundations often have a robust database of trials with a search engine. The organizations often pull from ClinicalTrials.gov but they curate the information to make it easier for you. In addition, the organization may be able to offer a coordinator or patient navigator to walk you through the process.
Cancer centers Many cancer centers conduct clinical trials and may have information on current trials available on their websites or through patient services. If you’re already going to a cancer center, it’s worth asking if they have any clinical trials that would be right for you.
Ask your doctor Your doctor or nurse may also have information on clinical trials that may be suitable for you and may help guide you on how to participate.
WTD 3: Know What to Look For
It’s important to note that participation in clinical trials is voluntary and involves a serious commitment on behalf of the patient. Here are a few things to think about before committing to be in a clinical trial:
Trial design and protocols A clinical trial “protocol” is basically the blueprint for a trial. It’s a detailed document that outlines a trial’s design, goals, methods, and procedures. Understanding the trial protocol can help you understand what to expect during the study and make an informed decision about whether to participate.
Trial location Is the study near you? Is it even feasible to get there? To see this, you must look at the full list of sites included. You may also be able to reach out to the principal investigator running the study. Their clinical coordinator can provide additional information.
Time commitment Clinical trials involve extensive time commitments. Is the treatment a pill you can take at home or do have to go to the center for an infusion or other procedure? How often do you have to go in for that treatment? How often do you have to go back to the center for testing?
Eligibility criteria Are you even eligible? Clinical trials have strict eligibility criteria, which could relate to your specific disease, your biology or genetics, your medical history (which you will need to provide), or your age, sex, gender, and ethnic background. Knowing all the inclusion and exclusion details is critical. Most of this will be in a study’s protocol, but protocols aren’t written for the average person to understand. So look for contact information to find someone who can review a full list of the requirements. Applying for a clinical trial is a detailed process that will involve filling out forms, supplying health records, and coming in for any prequalifying medical tests. It isn’t easy, but is worth it if it takes you one step closer to your cure.
Making your decision Like all treatments, deciding whether to participate in a clinical trial is a personal decision. You need to think about the benefits versus the risks, your current health needs, and, most important, your personal wants. Here are some considerations that may help you make an informed decision:
Benefits and risks: Before deciding to participate, review the trial’s information sheet, which includes details on the potential benefits and risks of participating, as well as the study’s goals and procedures.
Be realistic: Clinical trials can provide early access to treatments before they are available to the public. But it’s important to understand going in that not all trials are successful, and some may not provide any benefit.
Ask questions: You should feel free to ask questions about the trial and discuss any concerns with a trial representative. You may also want to seek support from family members or friends to help you make an informed decision.
Talk to your doctor: This is a must. Your doctor can help you understand whether a clinical trial is a good option for you and make sure it fits into your overall treatment plan.
IN CONVERSATION WITH MONICA BERTAGNOLLI
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Director of the National Cancer Institute
Monica M. Bertagnolli, MD, is a surgical oncologist, cancer researcher, and educator who has dedicated her life to pioneering scientific discovery to improve cancer prevention, early detection, and treatment. Dr. Bertagnolli leads the National Cancer Institute (NCI), the taxpayer-supported federal agency devoted to conducting and supporting cancer research. NCI is the largest funder of cancer research in the world and it coordinates and supports thousands of clinical trials across the country, so she was at the top of my list of people to speak to about these potentially life-saving studies.
Q.What should patients know about clinical trials?
A.Ask about them the moment you’re diagnosed so you know what’s possible for you should you be eligible to enter one at some point during your treatment. When I was diagnosed with breast cancer in 2022, one of the first things I asked my doctors was “Is there a study right for me?” And there was. I signed on to it, grateful for all the women before me who participated in trials to arrive at the life-saving treatments I received. The reason you want to ask about trials right away is because some are only open to newly diagnosed patients who have yet to be treated. Don’t be intimidated by the fact that trials are studying “experimental” therapies not FDA-approved yet. Some of the most cutting-edge, innovative science is being done in clinical trials—and they are designed to balance potential benefits and risks of being on the experimental treatment with the greater familiarity of being randomized to a conventional treatment. You might receive a life-saving drug that you won’t get elsewhere. And the data you add to the research will go on to save other lives. Unfortunately, we don’t have enough people participating in trials today, which limits our research and how fast we can find new therapies and potential cures. Part of my goal is to make it possible for everyone who wants to participate in cancer research to have a realistic opportunity to do so, even if you live in a rural area or far from an NCI-designated cancer center.
