Mathematical Program Can Dictate Multiple Myeloma Therapy

Multiple myeloma is a rare type of cancer that affects plasma cells, a type of white blood cell found in bone marrow that makes antibodies to help the body fight infections. For those with the disease, malignant plasma cells accumulate in the bone marrow and crowd out healthy blood cells. Instead of producing helpful antibodies, the cancer cells produce abnormal proteins that can cause complications in addition to the cancer cells.

Currently, the goals of therapy are to control myeloma, stopping and reducing the symptoms of disease. And long-term control involves multiple sequential combinations of therapy following therapeutic successes and failures. Accordingly, when patients require treatment, choosing the correct therapy or combination of therapies can be crucial, as the cells can become resistant to drugs over time.

“We have several new therapies to help us treat multiple myeloma patients, which has vastly improved survival rates. Years ago, patients were only expected to survive two- or three-years past diagnosis. Now, patients are living on average seven to 10 years,” said Dr. Ken Shain, a physician scientist at Moffitt who treats and researches the disease.

Years ago, patients were only expected to survive two- or three-years past diagnosis. Now, patients are living on average seven to 10 years.

Dr. Ken Shain, medical oncologist and researcher

Shain says most doctors rely on their clinical experience to choose the right course of treatment, but because every patient’s disease is different, it can cause a lot of trial and error and wasted time.

“Patients do not have predictable responses to treatment. Our goal is to give the right patient, the right drug, at the right time, but to accomplish that we need to develop the right tools,” he said.

Moffitt has developed that tool to provide a more personalized approach to selecting multiple myeloma care. The Ex Vivo Mathematical Myeloma Advisor, or EMMA, can test a patient’s sensitivity dozens of drugs at one time, individually and in combination with one another.

The researchers behind the multiple myeloma EMMA platform

Each multiple myeloma patient has a bone marrow biopsy before starting treatment. If they would like to participate in EMMA, they can choose to have a portion of their biopsy sent for analysis.

Microscopes that capture live images of multiple myeloma cells for EMMA platform

In the lab, multiple myeloma cells are isolated from each biopsy and cultured overnight. The next day, the cells are dosed with 31 different multiple myeloma drugs. For the next five days, power digital microscopes snap live images of how the cells react to each drug every 30 minutes. The digital imagery is then used in combination with patient- and drug-specific mathematical models to predict how the individual will respond to the different therapies. The result is a three-month prediction of clinical response outlining which course of treatment is best for the patient.

“We are essentially testing all the possible therapy options—31 drugs individually and up to 127 different combinations—before a patient is treated in the clinic,” said Moffitt researcher Dr. Ariosto Silva, who worked with Shain on the platform. “It can eliminate the trial and error approach to therapy and personalize a patient’s treatment plan from the start to provide the best course of action.”

Roughly 25% of Moffitt’s multiple myeloma patients, about 120 to 140 patients annually, consent to have their cells analyzed by EMMA. The results are reviewed during the clinic’s weekly tumor board meetings and assist the medical team in making real-time decision on therapeutic management for those patients.

To date, EMMA has analyzed more than 600 patient samples with excellent accuracy. But the impact goes far beyond individual patients.

“Our initial goal is to take that one patient’s sample and look at the biomarkers in the cells to help determine which therapies their multiple myeloma will be more sensitive to, but cumulatively we will be able use all of this data to better understand the biology of the disease,” said Shain.

Collectively, the data provides insight at a patient level, including medical history, symptoms and demographical information, but also on broader scale, looking at the genetic and molecular characteristics of the disease, as well as the tumor microenvironment surrounding the malignant cells.

“We want to get the whole picture to learn what is driving the disease and how we can possible slow its progression,” said Silva.

The researchers say the data could help them develop new drugs and therapies for multiple myeloma patients in the future. It could also assist clinicians with designing clinical trials for patients with specific subtypes of the disease.

“We are also working to expand this to other cancers, beginning with hematologic malignancies such as lymphoma and leukemia. There could also be potential in solid tumors, like ovarian and breast cancers,” said Shain.

There are roughly 35,000 new cases of multiple myeloma diagnosed each year. It is still unclear what causes someone to develop the disease. Common risk factors include:

• Age – Risk increases with age, most are diagnosed in their mid-60s
• Sex – Men are more likely to develop the disease
• Race – Black people are more likely to develop the disease compared to other races
• Family History – Having an immediate family member with the disease increases a person’s risk
• Medical History – Monoclonal gammopathy of undetermined significance (MGUS) is a precursor to multiple myeloma