In 1996, at just 37, the last thing Kathy Giusti expected to hear was that she had the fatal blood cancer multiple myeloma. An executive at Searle Pharmaceuticals and the mother of an 18-month-old daughter, Giusti was told she probably had 3 years to live. At the time, treatments for the disease were limited to the same alkylating agents available in the 1950s, and stem cell transplantation was just emerging as a potential therapy.

Diagnosed with the smoldering form of multiple myeloma, Ms. Giusti was given infusions of pamidronate disodium and put on a watch-and-wait approach. A graduate of the Harvard Business School, Giusti used her knowledge of the pharmaceutical industry and her business skills to launch the Multiple Myeloma Research Foundation (MMRF) in 1998. To propel the development of new drugs for the disease, Ms. Giusti founded the Multiple Myeloma Research Consortium (MMRC) 6 years later.

The results in money raised for research in multiple myeloma and success in new drug development for the disease are unprecedented. Since its inception, the MMRF has raised $195 million for research, funding more than 80 laboratories worldwide and 11 pharmaceutical and biotech companies.

Over the past 9 years, four new therapies have been FDA-approved for myeloma: bortezomib (Velcade), lenalidomide (Revlimid), thalidomide (Thalomid), and liposomal doxorubicin (Doxil). Through its research network (the MMRC), the MMRF has helped to accelerate development of two more agents, carfilzomib and pomalidomide, both of which could be approved by FDA later this year. Four more treatments are in late-stage clinical trials. While a better understanding of the genomics of myeloma cells and the development of more effective novel agents have extended median overall survival from 3 to 7 years, the 5-year relative survival rate remains one of the lowest of all cancers, at just 39%.

In 2006, Ms. Giusti underwent a syngeneic stem cell transplant using donor cells from her identical twin sister Karen Andrews, a cofounder of the MMRF, and she remains in remission. Last year, Ms. Giusti was named one of Time Magazine’s 100 Most Influential People in the World.

The ASCO Post talked with Ms. Giusti about the progress being made in multiple myeloma and new research initiatives launched by the MMRF.

Origins of the Foundation

Why did you launch the Multiple Myeloma Research Foundation?

Coming from the pharmaceutical industry, my hope was that we could attract scientists to the field of multiple myeloma, and the only way to do that was to provide funding for them. I wanted to extend my life long enough to see my daughter go to kindergarten or at least to remember me.

Novel Agents

What are some drugs in development that look effective for multiple myeloma?

We look at myeloma drug development as a portfolio. We tend to look at the next generation of drugs that we know are effective, such as the proteasome inhibitors, like bortezomib, and the immunomodulatory drugs, like thalidomide and lenalidomide. Carfilzomib is another effective proteasome inhibitor, and there is an additional one from ­Millennium called MLN9708, which is in phase II trials. The MMRC is facilitating a clinical trial of that drug in combination with lenalidomide and dexamethasone for newly diagnosed patients.

Building off of the immunomodulatory drugs, we have helped to support Celgene with its agent pomalidomide. There are other classes of drugs that we are testing that have been found to be synergistic with the two mainstay classes of proteasome inhibitors and immunomodulatory drugs. For example, the histone deacetylase inhibitors panobinostat and vorinostat (Zolinza), monoclonal antibodies like elotuzumab (HuLuc63) and Akt inhibitors like perifosine (KRX-0401).

What we are really trying to do now is understand a lot about our disease and the different pathways involved in disease onset and progression.

Building a Community

How is the MMRF able to be so effective in getting new drugs developed and fast-tracked for FDA approval?

The MMRF has been very successful at building a community. We are only as good as the partners that work with us, and we know that. And the partners that work with us are the pharmaceutical companies and biotech firms who look at our research models and understand the benefits they offer in speed and efficiency; the academic centers that have the scientists; and fellows, who we continually fund and bring into these models that we are constantly developing. In addition to the academic centers, we’re partnering with the community centers because—and this has been a big shift for us—so many patients are now being treated at the community level.

We are working on our 3-year strategic plan, and these plans are highly scientific, highly clinical, and highly translational. We build out how we raise our money and how we spend our money efficiently, because the question we are always asking is, what is going to have the greatest impact toward a cure?

Unique Organization

How is the MMRF structured differently from other disease foundations?

There are not a lot of foundations that have an MD as its Chief Medical Officer (as is the MMRF’s Dr. Michael N. Needle) and a team of experts with PhDs. But the big difference with us is that we actually design, build, and run the research models that we develop, and we’re constantly measuring them to see if the models are effective.

An example would be the Multiple Myeloma Research Consortium. We designed it, we built it, we brought everyone together, and we continue to fund it to make sure that the infrastructure for success is in place. Right now, the MMRC is overseeing more than 20 trials. We are opening clinical trials faster, and we always ask, are we accruing patients to them quickly enough? If not, we figure out what’s slowing us down—is it the protocol development or the contracting, and how do we fix it?

CoMMpass Study

The MMRF has just launched ­CoMMpass (Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile), a longitudinal study of 1,000 newly diagnosed patients. How many patients are enrolled so far, and what are the goals of the study?

We have 120 patients enrolled already, and we’re open in 40 study sites (themmrf.org/research-programs/commpass-study). The CoMMpass study is collecting and analyzing tissue samples and genetic information from newly diagnosed patients who will be followed over a 5-year period. The tricky part of CoMMpass is that we’re asking patients to give us that very first clean bone marrow aspirate before beginning treatment. There’s this window of time when patients are first diagnosed that can be challenging. Asking them to give bone marrow, enroll in the trial, and sign the consent forms can be difficult. That’s why it’s really important to work with community centers: They’re seeing those patients in that window of time.

We’ve come to understand that myeloma is not one disease; it’s a number of diseases. So we’re trying to understand the disease based on the molecular biomarkers of our patients’ tumor cells. And because we’re following these patients for a long time and sequencing their genomics at early diagnosis, at remission, and at relapse/progression, our hope is that we will start to understand why some patients relapse and become resistant to treatment. From there, we can look at what new drug targets and pathways might eventually emerge.

Looking Ahead

What does the future look like for patients with myeloma?

What we are starting to see is that a considerable number of patients don’t respond to the treatments that we have today. We would consider those patients to be at high risk. Then there are the patients who might only respond for a short period of time—they are high-risk in a different way. We don’t know why a drug only works for high-risk patients for a limited amount of time, so we need to understand that piece of the puzzle too.

There are many subtypes of myeloma. Each type has a different level of risk and may require a different combination of approaches, and we just don’t know the answers to that dilemma yet. Our hope is that the CoMMpass study will help generate the hypotheses that will lead us in the right direction, not just to more effective treatments for all patients, but also to a cure.■

Disclosure: Ms. Giusti is founder and CEO of the Multiple Myeloma Research Foundation.