Kathy Giusti’s “Fatal to Fearless” memoir tells the story of prevailing over multiple myeloma

(The Cancer Letter) – Sometimes in oncology, you get “beat-the-reaper” stories.

There is the classic story of John Mark Cleland, the first man whose metastatic testicular cancer was cured with combination chemotherapy containing cisplatin. He would live another 47 years.

And there is a story of Beth Garner, diagnosed with stage 4 colon cancer at age 25 in 2014 and, as a last-ditch effort, treated with a drug now known as Keytruda (pembrolizumab), which targeted her specific genetic mutation—MSI (microsatellite unstable)-H.

And there is Judy Orem, who, after running out of treatment options for chronic myeloid leukemia in 1998, enrolled in a phase I clinical trial of STI-571, a drug now known as Gleevec.

Kathy Giusti’s war on multiple myeloma is more than an example of the beat-the-reaper genre. Giusti, who was diagnosed with a smoldering multiple myeloma at age 37 in 1995, created a foundation that catalyzed the research that resulted in creation of the very treatments that ultimately saved her life.

Kathy Giuisti holding a copy of her book, “Fatal to Fearless: 12 Steps to Beating Cancer in a Broken System.”

Aiming to change the culture of research, the foundation Giusti started, the Multiple Myeloma Research Foundation, required researchers to share data and meet deadlines.

Giusti tells her story in “Fatal to Fearless: 12 Steps to Beating Cancer in a Broken Medical System.” In her blend of advice book, a crash course in cancer policy, and memoir, the memoir stands out as an extraordinary story of survival.

For patients and their caregivers, the book proposes a 12-step guide for staying afloat in what she describes as the “broken medical system” in the U.S.

Giusti calls her 12 steps a journey “from WTF to WTD.”

After getting a multiple myeloma diagnosis in 1996, Giusti started a journal she wasn’t sure she would be able to complete.

Said Giusti:

Back then, myeloma was so unbelievably fatal that the whole reason I’m able to write that personal narrative is because on my way out of Borders, where I was trying to learn everything I could about myeloma, I picked up that journal, because I was writing to our daughter Nicole.

That was really the start of it. I was writing to her, because it was the only way I could think of that she could remember me. I would just document everything we were doing together, and the places we were going, and anything that we were sharing.

And now here it is, 26 years later, and I have 26 journals, one for every year I never expected to live.

I really had to go back and read them, from cover to cover, in order to write the book. They really did give me a lot of insight into the toll that cancer really takes on a family when you’re trying to get through it. A whole different perspective.

Now Giusti has 26 volumes of journals, which she relied on in the writing of “Fatal to Fearless,” a story of good science, great timing, and all manner of luck.

Said Giusti:

Because I came from pharma, I actually had been through enough medical legal regulatory meetings to write beautiful newsletters and things like that that would not get me in trouble.

I was always writing like, okay, here’s the benefit, but here are the risks. I was so trained on that.

So, we were able to work with Celgene of thalidomide. Of course, Sol Barer was there back then, and we kept moving things off to Revlimid and Pomalyst.

And at the same time, there’s a beautiful story in the book about Julian Adams.

Again, the science is amazing, and sometimes, there’s just a tad of serendipity. Because on Velcade, when Julian was doing the very first trial, it was a phase I, it was all comers, and he happened to put a multiple myeloma patient into that phase I, and the patient went into a complete remission—and that changed everything.

At that point, Julian’s calling me, and, of course, we had a meeting—because we were always convening the myeloma community—we had a meeting ready to go and he just took it over.

They wrote the protocol, and we just saved so much time for patients. So, yeah, it was a really exciting time, and it kind of played to my strength, because I had been in pharma, so I loved that kind of work.

After her diagnosis, Giusti started the MMRF, which spearheaded the development of therapies, served on the National Cancer Advisory Board, and ran a science accelerator at Harvard Business School. And she raised two children, one of whom was born post-diagnosis.

Giusti acknowledges that she was extremely fortunate. At the time of diagnosis, she served as a pharmaceutical company executive at Searle Pharmaceuticals, a job that made her aware of how drugs are developed, how the academia operates, what advocacy can accomplish, the leadership drug development requires, and the nuts and bolts of drug regulation.

Giusti had excellent health insurance, a supportive husband, a supportive family, a network of friends. She even has an identical twin willing to donate bone marrow for a transplant.

When she started MMRF, Giusti had a business plan and demanded accountability from participating institutions. And she spearheaded building a tissue bank of bone-marrow samples and blood samples from patients with myeloma.

Said Giusti:

Where pharma started getting interested was realizing that we had a great biomarker. It’s so easy to follow a multiple myeloma patient in a clinical trial. All you have to do is follow our M spike. So, you could get trials done really quickly in myeloma. So, we were communicating that out.

Remember, the myeloma community back then was very small. There were like four to six academic centers actually working in myeloma. So, we did not have a loud voice at all.

Now, all of a sudden, our voice is getting louder. We’re spending a lot of time with NCI, down at FDA, we’re trying to build bridges. And I think the combination of knowing we had a biomarker, that novel drugs were starting to work, and the fact that it had such high unmet need meant that FDA would work with us to get these drugs approved.

I think that’s when pharma started saying, this is an interesting disease to take a look at.

In a 2008 profile of Giusti in The New Yorker, Jerome Groopman said her approach is “best suited to a disease such as myeloma, whose basic biology is at least partly understood.”

At the time, Kenneth Anderson, a myeloma researcher at Dana-Farber Cancer Institute (and Giusti’s physician) said to Groopman that the progress in developing treatments for the disease was in part due to MMRF.

“Myeloma now is a paradigm for new drug development, because of partnerships that occur between academics, large pharmaceutical companies, small biotech, the F.D.A., the National Cancer Institute, and foundations,” Anderson said at the time. “And, frankly, Giusti’s foundation has been a catalyst that created the urgency and awareness to make this progress possible.”

Though myeloma is still uncurable, the survival numbers are heading in the right direction.

Said Giusti:

Now, the five-year survival for myeloma—patients are living not the three years when I was diagnosed, but over 10 years. I mean, that is just a gift, because you think to yourself, “There’s always a lag in the data.”

I always say to people, if you’re going to get a cancer—and I’m so shocked to say this—but if you’re going to get one, you want to get one like myeloma, where there is just such an active pipeline and so much incredible progress.

It’s a reflection of the entire community. It’s never a situation where one person makes all that happen. It’s really just a lot of really good leaders, passionate about the patient and making a difference and being hungry to do it.

Myeloma had that. We really had it.

On March 15, for example, the FDA Oncologic Drugs Advisory Committee will review two multiple myeloma indications:

Carvykti (ciltacabtagene autoleucel), suspension for intravenous infusion, submitted by Janssen Biotech Inc. The proposed indication for this product is for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least one prior line of therapy, including a proteasome inhibitor, and an immunomodulatory agent, and are refractory to lenalidomide. Carvykti is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T-cell immunotherapy.

Abecma (idecabtagene vicleucel), suspension for intravenous infusion, submitted by Celgene Corp., a Bristol-Myers Squibb Co. The proposed indication is for the treatment of adult patients with relapsed or refractory multiple myeloma who have received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Abecma is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T-cell immunotherapy.

Giusti spoke with Paul Goldberg, editor and publisher of The Cancer Letter.