Cancer killed my young son, Zach. He fought hard against it for four years. His experience, his bravery, and most of all his absence make me question some of the critics of CAR-T therapy, a cutting-edge form of cancer immunotherapy. They say it is dangerous. I say I wish it had been around for Zach.
CAR-T therapy involves modifying a cancer patient’s own T cells so they recognize and kill cancer. Critics have seized on several deaths in a CAR-T clinical trial and are blaming companies for moving too fast in a race to bring the first CAR-T product to market. They were quick to spotlight the harrowing details of patients who died or experienced harmful side effects. CAR-T therapy was referred to in a STAT article as “terrifying,” “Frankensteinian T cells” whose treatment costs could “be enormous, with potential bills running hundreds of thousands of dollars.”
Zach experienced horrendous side effects from his chemotherapy, died from treatment-related complications, and the cost was astronomical — but all of this was with “standard” cancer therapy. In my view, the critics of CAR-T therapy are taking a myopic view of this incredibly powerful and exciting form of cancer treatment, one that holds great hope for desperate patients and their families.
Zach was diagnosed with acute myeloid leukemia (AML), an aggressive type of cancer, when he was just 5 years old. Although AML occurs far more often in adults, it is the second most common type of leukemia in children and one with a poor prognosis. Current treatments for AML are brutal, requiring multiple rounds of in-patient, pedal-to-the-metal chemotherapy that wipes out the immune system and leaves patients vulnerable to life-threatening infections. Treatment-related visits to the hospital and the intensive care unit are not uncommon.
I worked round-the-clock to comfort Zach as he suffered uncontrollable fevers, unrelenting nausea, hours-long nosebleeds, and skin burned from the inside-out — all side effects of the chemotherapy that was poisoning his healthy cells as well as his cancerous ones.
Zach struggled against AML for four years. He endured multiple rounds of intense chemotherapy, full-body radiation, and three bone marrow transplants. He died in an intensive care unit from transplant-related liver failure and blood loss. The cost of his four years of treatment was millions of dollars — not uncommon for young AML patients who receive one or more bone marrow transplants.
But know this: he died from a treatment option he had chosen to have. And he died with hope.
A chance at hope
Zach’s fight makes me passionate about speeding access to more targeted and curative cancer therapies. I, along with other patients and families running out of options, want scientists and companies to move faster. We understand that progress is not always pretty. But neither is cancer, nor many of the current treatments for it.
The harsh reality is that 10,000 Americans died from AML last year, and nearly 600,000 died from all cancers. Chemotherapy and radiation are highly toxic; bone marrow transplants, highly criticized in the early days, have notoriously high mortality and morbidity rates. And yet, over one million patients have received marrow transplants, and this Nobel Prize-winning therapy has saved countless lives and led the way in the discovery of immunotherapy.
Those who survive AML and other cancers can end up battling difficult and costly problems related to their cancer treatment as they get older, such as organ failure, infertility, graft vs. host disease, and even secondary cancers. This is especially problematic for childhood cancer survivors, who have years of life ahead of them.
CAR-T and other immunotherapies are a shining beacon of hope. Results in CAR-T clinical trials are promising, with complete remission often seen in some kinds of blood cancer. In childhood acute lymphoblastic leukemia, remission rates exceeding 90 percent have been reported. Many children and adults who were once facing certain death, like Emily Whitehead and Milton Wright, are alive today because of this new form of immunotherapy.
My family would have given anything for an option like CAR-T.
Zach participated in numerous clinical trials — he was a pioneer, of sorts. By its very definition, pioneering can be dangerous, and even deadly. We were always aware of the risks.
I believe that researchers and clinicians must be empowered to innovate and move full-speed ahead. When working at the cutting-edge of medicine, they need to follow strict safety measures and best practices, and certainly must be held accountable. But they also need to be given ample room to fail, learn, and refine. We accept injury and death as part of “standard” cancer treatments like the ones Zach endured. We need to do the same for experimental therapies such as CAR-T.
I’m not advocating for research run amok. Investigators, clinicians, cancer patients, and their family members must approach an experimental therapy responsibly, balancing risk versus reward. But patients and families are more than capable of weighing the risks of experimental therapies against one last chance at hope.
We also need investors to support firms developing next-generation cancer therapies. That means the media must provide balanced reporting. It’s fine to communicate safety issues in a clinical trial. But it’s also important to provide context. How many people has the treatment helped? What are the dangers and expense of the “standard” treatment?
And let’s not forget history. Countless patients, and even some researchers, were lost in the development of life-saving treatments like chemotherapy, radiation, and bone marrow transplant.
Here’s my bottom line: testing CAR-T therapies is giving hope to patients facing certain death. The idea that there are safer and less expensive alternatives often isn’t true. There will inevitably be stumbling blocks and risks associated with developing any new therapy — and some people will die. But with this risk comes the potential of incredible reward and new discoveries.
Sadly, there was simply no good path for Zach. He and our family chose to stand and fight, opting for a boundary-pushing, high-risk, 3rd bone marrow transplant. It didn’t save Zach, but we were grateful to have had the choice.
Despite the current safety concerns with CAR-T, I can say with confidence that Zach and my family would have chosen it had it been available then. That’s a choice thousands of Zachs are waiting for today.
Julie Guillot is a former IT/business operations executive who now advocates and raises funds for the Children’s Oncology Group and other organizations to accelerate less toxic, more curative treatments for pediatric cancer. The Children’s Oncology Group receives funding from the National Cancer Institute and pharmaceutical companies.
I was fortunate to be enrolled in a JCAR 017 trial for my DLBC NHL. It was my fourth recurrence and only 8 months post autologous SCT. If not for Juno’s CAR T therapy, I would not be alive today, in remission 10 months post treatment (which included cyclophosphamide and fludarabine).
We knew the risks going in and chose to take them.
Julie, I am so very sorry that your son passed away after such a brave fight. I wish CART would have been an option for him and I thank you for writing this honest article.
My nephew was taken to Seattle children’s hospital for treatment. The treatment failed. We took him all the way to Seattle from india to get him treated on PLAT 01 trial. It is a shame for Seattle children’s hospital to not report about the children and the treatment rate for PLAT 01 which they have stopped abruptly and now are taking patients for treatment under PLAT 02…. I do not know what problem they jad with PLAT 01 and why are they being so secret about it. ..I will also ask why are the US hospitals not using the bortezomib along with chemotherapy which is a effective drug and helps to get stubborn relapsed leukemia into remission with very little side effects … Tata cancer hospital which is a extraordinary hospital in treating cancer uses bortezomib as a agent along with FLAG and results jave been very encouraging. .
Thank you for sharing this moving and important story. I sit on 2 ACS research grant proposal panels, where proposals to study potential in you know therapies are considered. Your commentary on this issue is most appreciated. Thank you.
Sorry. That odd sentence should have read “immunotherapy.” There is no “one-size-fits-all” answer for whether a particular therapy suits a particular patient, and whether particular therapies need to be accelerated to market. Just keep in mind that there are huge risks of acceleration without proper clinical evidence that must be balanced with huge benefits for some patients.
Julie, as someone who is a cancer immunotherapy researcher as well as someone who has also lost a dear, dear relative (my own Mom died a brave but futile battle from colon cancer in 2010), I think for the most part that leading-edge researchers (like Juno, in the area of CAR-T) are indeed being very aggressive. The 3 CAR-T related deaths were due to a deadly combination of a couple of standard chemotherapy drugs (cyclophosphamide and fludarabine) where cerebral edema caused severe neuro toxicity in 3 out of just 10 patients. This is clearly unacceptable, and the FDA acted appropriately out of caution. In other areas of cancer immunotherapy like Adoptive Cell Therapy (ACT), patients have died from cross-reactive reactions where T cells looking for melanoma cancer cells and multiple myeloma cells instead homed in on almost identical-looking molecular markers (called ‘antigens’) in the patient’s heart muscles and instead killed 2 cancer patients by myocardial infarction. These treatments, as wonderful as they can be at times, depend on ruthless little assassins called CD8+ cytotoxic T cells. If a CD8+ T cell is off by just a single amino acid in its antigen target, the results can often be fatal. As an ACT researcher I am diligently working on ways to identify these kinds of anomalies up front, but this stuff is incredibly, incredibly complex, and God forbid, how I would react if despite my staff’s best intentions, one of our patients died because of one of these “anomalies”, especially if we rushed some sort of new treatment regimen (like Juno adding Fludarabine), as is often being done now. All of these treatments, both CAR-T and ACT, are by definition extremely, extremely risky. Those CD8+ T cells that killed those 2 cancer patients by myocardial infarction were so effective, so ruthless in their innate functionality, that they succumbed to death in just 5 days – 5 DAYS!!! Caution is indeed warranted until we can figure out these problems ahead of time. If anything, in my opinion, perhaps the FDA is not being cautious enough, and some of Trump’s candidates for head of the FDA basically want to throw all caution to the wind, which would be completely counterproductive.
Thank you Julie, your words are so important for us to hear. We (scientists) hear you, we are just as pationate and will do our best to honor your call to action for Zach. I too learned about this very battle as a younger brother, the loss of Andie at 13 years of age to ALL, has given me the justice and balance I need to face this very decision you so eloquently write.
From all of us in cell therapy , thank you!
Please keep in mind that these standards were developed for a reason. We don’t want companies to start praying on your desperation for a cure in order to cut corners. If a balance can be struck that increases access while maintaining strong disincentives to cheat patients, we should.
Julie, thank you for the incredibly moving story about your son Zach. I’ve got a 13 year old who is fighting ALL, and a 42 year old brother who is fighting stage 4 lung cancer. I read scientific literature every day to educate myself about any new treatment that could possibly help my brother or my son. Thank you so much for so eloquently giving voice to my feelings in your article
CD19 CAR is specific to ALL. Please seek guidance from investigator Stephen Grupp at CHOP. He treated Emily Whitehead.
I agree with this article, my daughter who is 14, just received her second bone marrow transplant, she has been battling AML, I had asked about immunotherapy options and was basically told that is not a current option.
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