How my training helps me to address health disparities in multiple myeloma

Irene Ghobrial leads the Stand Up To Cancer’s Multiple Myeloma Dream Team, part of the research charity that investigates conditions that could lead to this type of bone marrow cancer, which kills 106,000 people annually. Ghobrial, a medical oncologist at the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, Massachusetts, describes her journey as an immigrant woman of colour to the United States. She explains why translational research is key to advancing personalized treatments and how her team addresses health disparities.

What challenges did you face as an early-career researcher after moving to the United States from Egypt?

I graduated in medicine from Cairo University in 1999 and moved to Detroit, Michigan, for training opportunities that were inaccessible to me in Egypt. I faced many challenges and mistreatment, sometimes driven by discrimination towards me as a woman and an immigrant. The chances of getting into elite training programmes when you belong to a minority group are slim. Sometimes, I was oblivious to these barriers, and not knowing about them helped me to persevere and persist.

Outlook: Multiple myeloma

I couldn’t have dreamt of this life when I was younger. Sometimes, I pinch myself and say, “I’m living the American dream, right?” — as an Egyptian immigrant and woman of colour who is now an associate professor of medicine at Harvard Medical School. But, as the saying goes, it took a village. My parents and mentors inspired me to dream big. And despite barriers to success faced by minority groups, the US system still allows people to thrive regardless of where they came from and who they are.

How has being an oncologist affected the way you conduct research?

In 2000, I worked in an immunology laboratory run by Karen Hedin at the Mayo Clinic in Rochester, Minnesota, looking at chemokine receptor signalling in immune cells. I’ve been in love with research ever since. As a clinician-researcher, you can take samples from your patients, do whole-genome sequencing, get the answers you need and use them to personalize treatment. This back-and-forth is gratifying and exciting.

How did you first get interested in multiple myeloma prevention?

Multiple myeloma is a cancer of plasma cells, white blood cells that make antibodies. In myeloma, these cells grow uncontrollably in the bones and produce an overabundance of abnormal immunoglobulin proteins.

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Myeloma develops in about 160,000 people every year worldwide. Although rare, it is the most common blood cancer in African Americans, who are twice as likely to have it as white Americans. They’re also likely to develop it at a younger age.

Myeloma might cause no symptoms in its early stages, but people with more-advanced forms of the disease can have bone pain, fractures, recurring infections, hypercalcaemia (higher-than-normal calcium levels) and anaemia.

The condition is not yet curable. But there are treatments to prevent and manage symptoms, slow disease progression and improve a person’s quality of life. Treatment might involve chemotherapy and other cancer-fighting drugs, as well as steroids, bone-modifying medications and bone-marrow transplants.

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I trained at Mayo with Robert (Bob) Kyle, whom I call the grandfather of myeloma, who influenced my interest in multiple myeloma. He named two of the precursor conditions that cause no symptoms but might develop into myeloma: monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM).

Unlike many of his peers in the 1970s, Bob didn’t dismiss these conditions simply because they seemed benign. Instead, he focused on understanding what causes them to develop into myeloma, and he emphasized that people with precursor conditions should be monitored closely.

How does your team apply its motto — ‘the fierce urgency of now’ — to its everyday work?

Our patients need our research to answer their health concerns, not in the next 10 or 15 years, but now. If we can diagnose and treat myeloma early, we can make a difference.

My team works fast and hard to sequence and do mass spectrometry to analyse patient samples and get the data back to them. Working this way takes a lot of effort — but it’s also a lot of fun.

My team is multidisciplinary and includes people with MDs or PhDs, as well as students. They work in biology, chemistry, bioinformatics, epidemiology, medicine and statistics. Every person on the team is complementary to the others.

Tell us more about the Multiple Myeloma Dream Team’s project.

Our team received a US$10 million award and began work in April 2018. Our study, called PROMISE, focuses on understanding these precursor conditions to predict the risk of developing myeloma. We will screen 30,000 individuals at risk of myeloma, including African Americans, people of African descent and people with first-degree family members who have had blood cancer.

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To help potential participants gain trust and confidence in our research, we educate them about multiple myeloma and its prevalence in African Americans, and explain that screening for precursor conditions can improve survival outcomes.

In July 2022, we screened 200 African American people at a health-fair event in Indianapolis. One woman was scared because she had a relative with myeloma. After convincing her, she took the test. Her results showed that she might have gone on to develop myeloma with kidney failure in a few weeks. We therefore referred her for standard myeloma therapy that week, which should protect her from developing myeloma and kidney damage.

What can you tell us about the PROMISE study’s findings so far, and their significance?

We published results¹ for the first 7,600 patients screened by mass spectrometry for monoclonal gammopathies, the abnormal immunoglobulins in the blood. We were surprised that 13% of the participants had MGUS, a high proportion compared with the 3–5% prevalence expected in the general population.

We also found that another 20% of participants had very low levels of these abnormal proteins, and we named this new precursor condition monoclonal gammopathy of indeterminate potential, or MGIP. Now, we’re trying to understand what MGIP is. So far, our findings suggest that it might be a sign of early B-cell malignancies — such as chronic lymphocytic leukaemia. If so, it’s possible that MGIP could be treated and cured in some people, before it progresses to later stages of blood cancers. It’s exciting that we have the potential of understanding MGIP better, to help prevent the progression of blood cancers.