Making Time for Innovation: Myeloma Expert Sets Brisk Pace of Discovery

Shaji K. Kumar, MD

Working in the laboratory and the clinic, Shaji K. Kumar, MD, has made a discovery: that there aren’t enough hours in a day.

That’s why the translational researcher, who spends his time solving the mysteries of multiple myeloma (MM), is determined to make every moment count.

So far, his plan is working.

The 42-year-old, who joined the Division of Hematology at the Mayo Clinic in Rochester, Minnesota, in 2003, was named a professor at the school’s College of Medicine in September 2012, in recognition of his achievements.

The doctor’s level of involvement was also reflected in December 2012 at the annual meeting of the American Society of Hematology (ASH), where he was listed as a coauthor of 45 abstracts or posters scheduled for presentation.

Through that work and more, Kumar has provided new insights about subgroups of patients with MM and a blood disease that is noncancerous yet similar—amyloidosis— and how the conditions should best be treated. In both diseases, he has conducted studies that have helped identify patients whose prognoses are either better or worse than average, based on biomarkers or response to stem cell transplant.

Specifically, the doctor and his colleagues came up with a new staging system for patients with amyloidosis; identified a group of patients with MM who tend to survive longer after autologous stem cell transplant; described a subgroup of patients with amyloidosis who should not undergo stem cell transplant because of a high risk of early mortality; and demonstrated that younger patients with MM tend to have poorer outcomes, and need novel treatments to prolong their survival.

In addition to unraveling the intricacies of the two diseases, Kumar investigates new therapies to treat them. For instance, in a clinical trial whose results drew attention at ASH (abstract 332), the doctor and his colleagues demonstrated that the proteasome inhibitor MLN9708, administered along with lenalidomide and dexamethasone in previously untreated patients with MM, showed comparable efficacy—with greater convenience and tolerability—than the typical results for a standard drug in the same class, bortezomib, used in a similar combination regimen.

To manage his schedule, which includes seeing patients and teaching residents and fellows, Kumar is focused on effectively organizing his time⎯not in order to work less, but as a means of getting more done.

That’s because his career is a labor of love for Kumar, even when he finds it difficult to strike a balance between his professional life and time with his wife and two daughters.

New Agents on His Roster

“It’s a lot of work, but I’ve enjoyed every bit of it,” Kumar said. “It’s hard to say it’s a sacrifice when you enjoy what you’re doing.”Kumar spends about half his working hours providing patient care, tending both to outpatients who have MM or amyloidosis, and to inpatients with those diseases who undergo stem cell transplant.

When it comes to conducting research, the doctor splits his time between his lab, which includes a staff of three and a rotation of fellows, and clinical trials.

In some cases, the trials are “homegrown,” investigating ideas generated in Kumar’s lab. For example, a phase I/II clinical trial now accruing (NCT00918333) will move a combination of panobinostat and everolimus from the doctor’s lab to patients with recurrent MM, non-Hodgkin lymphoma, or Hodgkin lymphoma, to evaluate the efficacy and side effects of the pairing. Panobinostat is a histone deacetylase inhibitor that also may modulate angiogenesis- related genes, while everolimus inhibits the key regulatory kinase mTOR, according to the National Cancer Institute. The hypothesis is that the two drugs may block some of the enzymes necessary for the growth of cancer cells.

The rest of Kumar’s trials look at drugs, or drug combinations, developed in other labs, including proteasome inhibitors and novel compounds. The doctor is especially excited about an investigational cyclindependent kinase inhibitor, dinaciclib, which he’s testing alone (NCT01096342) and in combination with bortezomib and dexamethasone (NCT01711528) in patients with refractory MM.

Finally, Kumar is pursuing long-term, grant-supported research projects, including one funded by the National Institutes of Health (NIH) concerning the onset and biomarkers for progression of monoclonal gammopathies, the umbrella of diseases that includes MM. The aim is to “identify the markers that predict why somebody would go from having gammopathy of undetermined significance to having MM,” he said. “If we know who will get it, maybe we can intervene early or figure out ways to try and prevent that progression or transition from happening.”

In a project funded by the Multiple Myeloma Research Foundation and set to stretch into 2020, Kumar will assess the relationship between outcomes, treatment regimens, and molecular profiles in patients with newly diagnosed MM

Academic Stardom in India

One goal “is to figure out how to improve the survival of patients with high-risk MM,” Kumar said. “There are 15% to 20% of patients with MM who don’t live beyond two or three years after diagnosis, and the medications we have now tend to stop working very fast—the myeloma just breaks through. We’re trying to understand why they behave the way they do by developing clinical trials looking at combinations and approaches for those patients.”Growing up in Aluva, India, Kumar was always fascinated by the field of medicine.

“Right from the beginning,” he recalled, “it seemed like something fun and intriguing at the same time.”

The son of a homemaker and a chemical engineer, and particularly good at math and physics, Kumar became one of 45 students countrywide chosen annually to attend the All India Institute of Medical Sciences in New Delhi, the top medical school in India.

“Clearly, being able to go to that medical school was a turning point,” said Kumar, who had previously graduated as a premed major from Union Christian College, in his hometown. “Being able to go there really opened up doors for me.”

Kumar graduated from the medical school with an MB BS in 1991 and stayed on to complete an internship, followed by a residency in internal medicine. As part of those programs, Kumar took care of several patients with cancer, sparking his interest in oncology and motivating him to work in a cancer hospital during his time as a senior resident, from 1996 to 1997.

“I found it quite challenging, but at the same time I felt that we were really helping people,” he said.

After completing his residencies and earning his MD, Kumar set his sights on coming to the United States to pursue oncology.

“The field was still quite in its infancy in India,” he said, “with very few options for training, and treatments out of reach for the vast majority of patients.”

To pursue his specialty, the doctor knew he’d be required to complete another residency in America. He applied to the Mayo Graduate School of Medicine, in Rochester, was selected, and arrived in 1997 to begin a two-year clinical residency in internal medicine. Kumar followed that with a fellowship in hematology/oncology at the school from 1999 to 2003.

“I showed up for the interview in the middle of a snowstorm,” recalled Kumar, who’d only seen a hint of snow once before, in northern India. “Culturally, it was a big change, too, but Rochester being a small city softened the impact of moving out of India to a different country. The Mayo Clinic is also very diverse ethnically and culturally, so it was a lot easier to get used to the place. Now my wife and I feel more at home here than back home.”

Kumar was named an assistant professor of Medicine and Oncology at Mayo in 2002, and a year later, as a Mayo Foundation Scholar, spent 18 months in a lab at the Dana-Farber Cancer Institute in Boston, Massachusetts. There, the doctor conducted research on myeloma, which he had already chosen as his field of interest.

“Mayo in Rochester is one of the bestknown institutions in the world for myeloma, and we have a large group of people interested in this disease,” he said. “When I started my internship there, that was when I got interested in myeloma.”

The doctor added that his two mentors at Mayo, S. Vincent Rajkumar, MD, and Morie A. Gertz, MD, helped spark his interest in studying the disease.

Shaji K. Kumar, MD . . .

• Is 42 years old.
• Graduated from medical school alongside his wife, Seema Kumar, MD, and now works with her at the Mayo Clinic; she’s a pediatric endocrinologist.
• Enjoyed the book Getting Things Done: The Art of Stress-Free Productivity, by David Allen. “You always think you figure out your own ways of doing things efficiently, but this book gives a different perspective about how you can organize—not by recycling all the things you have to do, but by making a checklist in your mind,” Kumar said. “It’s been helpful.”
• Cites as a favorite movie The Pursuit of Happyness, starring Will Smith, about a single dad bringing up his son. “There were some valuable lessons in there in terms of persistence and hope, and the fact that you always have to think positive and work hard,” Kumar said.
• Appreciates the wisdom in the saying “A goal without a plan is only a wish.”
• As hobbies, enjoys photography and building “souped-up, state-of-the-art” computers.
• Has never held a job outside the field of medicine.
• Is part of the Eastern Cooperative Oncology Group’s Myeloma Committee, and is on the steering committee of the Multiple Myeloma Research Consortium, a nonprofit that facilitates early-stage clinical trials by bringing together researchers and industry.
• Believes that funders should prioritize cancer research that can be applied directly to patient care, and that they should encourage scientists and institutions to work more collaboratively in order to drive swifter results.

Lessons Learned From Patients

Back in the fold at Mayo, Kumar earned the positions of senior associate consultant in the Division of Hematology and associate professor of Medicine several years later. He moved up the ladder to consultant in 2008, and to professor last year.Having risen through the ranks at the institution, Kumar has learned some valuable lessons about cancer patients.

“The thing that has always struck me is that, when confronted with a disease that is potentially or almost always fatal, the majority of the patients find courage that even they didn’t know they had,” he said. “It takes a lot of time to come to terms with that, but most of the patients eventually accept this and really want to do their best to try and beat the disease.”

Dealing with such prognoses isn’t easy for doctors, either, Kumar said.

Oncologists who care for cancer patients “tend to open up and learn more about them,” he said, “and that’s a double-edged sword, because you get close and then you lose them. But you really get a sense of what they want in life, and can try to strike a balance between that and the reality of what they can look forward to.”

Kumar likes to pass along that message to the students he teaches.

“Early in their careers, they don’t always take into account what the patients want,” he said of the residents and fellows. “You have to get a sense of how much patients are willing to sacrifice, or the quantity versus quality of life they are striving for, before you set out on a path of treatment.”

Kumar also leaves his students with an additional piece of wisdom.

“Not everybody necessarily wants to do research, but it’s important,” he said. “When you’re treating the patient in front of you, you’re just touching one patient. When you research, you touch a lot more patients. Doing research opens up new vistas and makes you think more, and think beyond just doing one thing at a time. You learn a new language, so when you’re taking care of patients and read about a new development, you’re able to interpret that information in a better fashion.”

In his own research, Kumar isn’t looking forward to any specific breakthroughs, but to “a series of small steps” that will move him closer to his goal.

“My aim is to continue to improve the survival of patients with myeloma,” he said, “by helping to develop better, safer treatments so that patients can live a normal life—not just in lifespan, but in quality.”