Paving the Path to Progress in Multiple Myeloma Research

Nikhil C. Munshi, MD, stands out as a leader in multiple myeloma who exemplifies hard work and dedication. But beyond his career accolades, there is a deep passion for research and finding a cure for the disease, heavily inspired by his father, and carried out through the pursuit of knowledge.

“Many different people have contributed to my success,” said Munshi, a 2023 Giant of Cancer Care inductee in multiple myeloma. “This country provided me the opportunity. I have had good fortune to interact with many great people, and each one has helped me go a step further. Compassion, caring for people and patients, being humble, and remembering where you came from are great values my parents instilled [in me].”

His journey into medicine began in childhood as he observed the remarkable impact his father had on the lives of his patients and the admiration and love they had for him. These experiences left a lasting mark on his young mind. “Being interested in medicine came from an early age when [I saw my father] do what he did.”

Munshi, director of basic and correlative science at Jerome Lipper Multiple Myeloma Center; Kraft Family Chair, director of multiple myeloma immune effector cell therapy, senior physician at Dana-Farber Cancer Institute, and a professor of medicine at Harvard Medical School, noted that his interest in oncology came a little later in his career, sparked from his fascination with lab research, including DNA, RNA, and the role of cellular controls.

A Born Passion for Studying Hematologic Malignancies

Born and raised in Vadodara, India, Munshi began his academic endeavors at Maharaja Sayajirao University, also in India. Here, his mentors played a pivotal role in shaping his future by emphasizing the importance of research. Under their guidance, he found an interest in cytogenetics in blood cancers.

“It was great thinking on my mentor’s part to have me follow that path. This is what also brought my interest to blood cancers, even in those early times.”

Munshi has always been intrigued by how little is known regarding incurable forms of cancer, the short half-life of different therapies, and how much room for growth there is across oncology. He found himself drawn to both cell and molecular biology, seeking answers to the fundamental questions that go hand in hand with oncologic developments.

During medical school, his interests followed him through basic research, as well as research in laboratories, DNA, RNA, and what role cellular controls plays.

His background in neurological studies provided an added layer of intrigue, as he admires the intricacies of the brain, comparing it to “a remarkable machine”—a sentiment he still holds today.

“The fundamentals of cell division and cancer development from the interest in brain activity led me to being an oncologist,” Munshi said. “I must confess, in the neurological system, the brain is such an incredible organ, and more so today, where we can compare the brain with computers, and we realize how incredible the machine is.”

To explore his passion for cytogenetics, Munshi came to the United States, where he began as a research fellow at Johns Hopkins Cancer Center, now The Sidney Kimmel Comprehensive Cancer Center. Under the guidance of an incredible mentor, he experienced a sense of freedom to explore and take risks in his professional endeavors.

Mentoring the Munshi Way

This supportive environment was pivotal in honing his skills as a researcher and later shaped his approach as a mentor to his own students.

“I try to follow this in my own career with my own mentees. [My first mentor] provided incredible freedom to explore the risks and questions that would come to me. I had a project to do, but I was able to do 3 other projects that were not directly connected with my main project and in fact, were not common to that particular lab. But that ability to push [myself] and being encouraged helped me tremendously in many angles, and it has helped me become a good mentor.”

Munshi then delved deeper into research training at Indiana University, where he learned more about the importance of clinical trials. There, he found a mentor in Lawrence Einhorn, MD, an oncologist Munshi notes “is credited for curing testicular cancer” by developing cisplatin-based chemotherapy regimens that successfully treated patients with the once deadly disease.” Einhorn, a 2013 Giants of Cancer Care inductee in genitourinary cancers, taught him the fundamentals of finding a cure for cancer and how to do good clinical research. At Indiana University, Arun Srivastava, MD, introduced Munshi to virology and gene transfer, particularly the emerging concept of gene therapy, which was in its infancy in the 1980s. Munshi notes that he had the privilege of learning from a “true visionary” in Srivastava, who played a critical role in developing the adeno-associated virus vector for gene transfer. This early exposure to gene therapy fueled his interest in exploring its potential applications in oncology.

Developing Treatment Options in Multiple Myeloma

With his next milestone, Munshi found himself in Little Rock, Arkansas, where he joined an up-andcoming program focused on multiple myeloma. Munshi merged his interests in gene therapy and virology with his background in hematologic cancers and began shifting a focus to myeloma, which was considered incurable at the time.

Munshi was part of a program project grant, funded by the National Institutes of Health, that was focused on developing gene therapy in myeloma. As the program evolved, it became one of the leading centers for multiple myeloma research. The team’s efforts, combined with Munshi’s passion and expertise, led to groundbreaking developments in the understanding and treatment of patients with myeloma. His contributions to the field include an improved understanding and identification of the genomic changes in multiple myeloma, and developing new therapeutics, such as CAR T-cell therapy.

The once grim prognosis for patients began to change, with survival rates increasing over the years.

Colleague Mehmet K. Samur, PhD, described Munshi as “tirelessly focused on resolving the code of multiple myeloma.”

“His passion in science, his desire to understand the biology of multiple myeloma, his clinical leadership in new and novel clinical trials, and his leadership in the International Myeloma Society [IMS] have generated enormous resources for the field. Even with all these successes and contributions, his humble and humanitarian side always becomes happy with anything that helps patients with multiple myeloma. He is a real giant of cancer care, keeps his patients the topmost priority, and works with all his power to make it better,” Samur, research scientist, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, said.

Munshi later joined Dana-Farber Cancer Institute, where he partnered with Kenneth C. Anderson, MD, the 2014 Giant of Cancer Care inductee in multiple myeloma.

“We have been best partners and friends ever since. We have very complementary research. He had focused on how the microenvironment impacts myeloma, so I began to look at myeloma cells themselves. Over the last 25 years, we have made incredible progress.”

Together, the team explored the impact of the microenvironment on myeloma and the unique characteristics of myeloma cells. Throughout his career, Munshi and his team have also been involved in the preclinical and clinical work of numerous new therapeutics, including idecabtagene vicleucel (Abecma), ciltacabtagene autoleucel (Carvykti), NKTR-255, and more that helped to revolutionize myeloma treatment. The progress, he said, has been remarkable, with survival rates doubling and patients living even beyond 10 years.

One of the most impactful points of Munshi’s career, he said, has been further understanding the genomic changes in multiple myeloma and identifying these changes to help develop therapeutics.

“In the genomics field, we have looked at the mutational changes fundamental to the early stage of the disease and fundamental to the progression of the disease. We have described what makes myeloma cells unstable,” Munshi said.

Munshi’s contributions to the field can be broadly categorized into 3 key areas:

• Defining the genomic changes that underlie multiple myeloma by uncovering critical insights into the pathogenesis of the disease,
• Exploring the genomic evolution of myeloma cells and tracing the pathways that mediate disease progression, which has been essential in developing effective treatment strategies,
• Developing drugs that specifically target genomic instability, some of which are cellular therapies

Today, Munshi directs the CAR T-cell program at Dana-Farber. With over 2000 patients available for genome sequencing, the team is on the cusp of uncovering critical insights into myeloma, bringing them closer to the long-sought-after cure.

Munshi also serves as president of the IMS, reflecting his dedication to improving patient outcomes and ultimately finding a cure. Munshi works to promote the goals of IMS and encompass various educational aspects for both students and practitioners and does advocacy work involving interactions with regulatory authorities.

He said the current state of understanding and access to advanced technologies has brought us closer to achieving this ambitious goal as knowledge gained over the past 30 years provides a sense of optimism about the potential for a cure. Still, he noted that the only way to reach a cure is by bringing together diverse entities, including researchers, companies, and organizations like IMS, to work in unison.

“Having that collaborative angle is an important component to be successful here, and bringing people together with all various entities is what we need to begin to utilize for the purpose of succeeding in our ultimate goal.”

On top of the Giants of Cancer Care award, Munshi has been recognized numerous times, including with the Waldenström Lifetime Achievement Award given by IMS for the Most Distinguished Lifetime Achievement in Myeloma Research in 2013, the COMy Multiple Myeloma Excellence Award for Translational Research in 2019, and the Robert A. Kyle Lifetime Achievement Award in 2021. He was also given the Dr B.C. Roy National Award by the president of India.

“This is given to the most prominent person with a contribution to medicine, not just cancer, not just 1 disease, but it is given to contribution to medicine in general. It is given to 1 person of Indian origin,” Munshi said. “I was one of the first people who was awarded who did not live in India anymore, so it was incredible recognition and a very proud moment. Coming from India, there was an unbelievable recognition for me, my family, and for [my country].”

Family Ties

In addition to his father, Munshi admires the role his wife has played in his career success. Medha Munshi, MD, is an associate professor focusing on geriatric diabetes at Harvard Medical School. He spoke fondly of his wife’s influence on his personal and professional growth. “She’s very successful in her own right, but she has contributed to mine as well. It’s wonderful working in, almost, the same institution,” he said.

But Munshi’s passion to continue to learn extends beyond medicine. He often reminisces about his former role as a soccer coach for his son’s team.

“That was one of my favorite pastimes in the old days.” Today, he proudly displays photos of those precious memories on the walls of his office, symbolizing his dedication and commitment to nurturing the talents of his children on and off the field.

While Munshi believes playing soccer is important at a young age and watched games growing up, he never played in India. That didn’t stop him from becoming the best coach possible for his son, using any book he could get his hands on to learn.

As his children grew older and went to high school, Munshi remained a devoted coach and an avid spectator at their games. Now his journey in parenthood has evolved to the role of a grandparent, and Munshi’s eyes light up with joy when he talks about his new favorite pastime, playing with his 2 grandchildren.

“Truly, I would drop things at work and go with them. [They have] been one of the very important newer fairs in life: to be with the grandkids and have fun with them.”