Seeing Cancer From All Sides: Richard M. Stone Is Giant of Cancer Care in Leukemia

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Partner | Cancer Centers | <b>Dana-Farber</b>

Driven by his mother’s advice and his father’s memory, Richard M. Stone, MD, rose to become a global leader in leukemia care and research.

Growing up, Richard M. Stone, MD, thought he was going to be an attorney like his father, but his direction in life changed when he was 15. His father, Benjamin, developed kidney cancer when Stone was just 5 years old, and 10 years later, the disease metastasized and took the man’s life.

Stone says he went from being middle class to poor rapidly after his father died. “And that sort of gave me the incentive to work hard,” he said.

Stone was an only child whose mother who was a homemaker. She demanded full effort in everything, telling him, “If you’re going to be an acorn, be the best one on the tree.” He grew up in Swampscott, Massachusetts, on the north shore of Boston and was born in a hospital that later became a supermarket—he jokes he was born in the dairy aisle.

After his father’s death, Stone worked at another supermarket and learned what it was really like to struggle financially and work hard. “Although I enjoyed picking cantaloupes for little old ladies, I knew that wasn’t going to be my life’s work.”

Later, he would receive a scholarship from Harvard University, where he majored in biochemistry. He gained a great appreciation for research as an undergrad and almost became an infectious disease specialist instead of an oncologist, although treating cancer was always in the back of his mind. He chose oncology because he liked the patients, and “of course my father’s memory was very strong—is very strong,” he noted.

A Life Studying Leukemia Wasn't Part of the Plan

“When I went to the Brigham and Women’s Hospital for my residency…I really wanted to take care of patients longitudinally. I wanted to take care of sick patients. I wanted to have intense relationships with the patients,” he explained. “I wanted to maybe do some good in the field.”

Stone is glad he ended up choosing oncology, although people not in the field often ask him, “How could you be an oncologist? All the patients die.” But to him, being an oncologist is about taking care of patients in their hour of need. He feels that oncologists should be there from diagnosis to death or diagnosis to cure.

When becoming a doctor, Stone knew he needed to focus on an intellectually challenging field and considered internal medicine. He knew surgery wasn’t the answer. He once fell asleep during a procedure while holding the retractor. “Plus, I was a bit of a klutz. I don’t think anybody would want me to be a surgeon,” he joked.

During his oncology fellowship at Dana-Farber Cancer Institute, Stone cared for a patient with acute promyelocytic leukemia (APL), an aggressive form of acute myeloid leukemia (AML), who was having trouble recovering from treatment. Stone became fascinated with the patient’s course of disease and wrote his first paper on APL under the tutelage of Robert J. Mayer, MD, who was an associate professor of medicine and director of the Dana-Farber Cancer Institute Fellowship Program, as well as the 2015 Giants of Cancer Care® award winner for gastrointestinal cancer.

After serving as chief resident at Brigham, Stone came back to Dana-Farber. By this time, Mayer was now in charge of both leukemia and gastrointestinal (GI) malignancies and wanted to focus more on GI patients. He asked Stone to oversee leukemia care and Stone said, “Absolutely.” Stone says leukemia was a good disease to work in because molecular understanding of the disease was advanced, thanks to the rapid ability to get patients’ cells and study them in the lab.

Doing Some Good in the Field

“For me, I’m certainly most proud of my work on FLT3 mutations and capitalizing on that for patient benefit. The story really highlights the way clinical research was done—how it’s a team effort,” he said.

Gary Gilliland, MD, PhD, now at Fred Hutchinson Cancer Research Center; James D. Griffin, MD, professor of medicine at Harvard Medical School and chair of the Department of Medical Oncology at Dana-Farber; and colleagues conducted research showing that 30% of patients with AML have the FLT3 mutation. “Then it was my job to take this very important scientific advance to the clinic. And that’s what it’s all about,” Stone said.

Stone was lead researcher on the phase 3 RATIFY trial (NCT00651261), one of the first, if not the first, to enroll patients based on their specific leukemia genotype. The study evaluated whether adding midostaurin (Rydapt), an oral multitargeted kinase inhibitor active in patients with the FLT3 mutation, to chemotherapy would prolong overall survival (OS) and event-free survival (EFS).

Investigators concluded that adding midostaurin to chemotherapy significantly extended both OS and EFS among patients with FLT3-mutated AML. The findings led to FDA approval of the drug, which is now the standard of care for this patient population.

“That was just the beginning of a whole field of FLT3 inhibitors. We have better drugs now, but I was there at the beginning—and I was very proud to be leading the key clinical trial,” Stone said.

“It’s not like being a lab researcher and discovering something new. It’s more like being a general and marshalling the troops toward an achievable goal,” he added. “I think being a good clinical researcher requires political skills in addition to statistical and biological knowledge.”

No one is an island in clinical research, and Stone is emphatic about his good fortune to work with “worldwide mentors,” especially Charles A. Schiffer, MD, and Richard A. Larson, MD.

“I interreacted and learned from incredibly devoted, clever, and wonderful people at [Dana- Farber] such as other faculty, fellows, and house staff,” he said. “Most importantly, I benefited immensely from teaming with the brilliant Dan DeAngelo, MD, PhD, who succeeded me as head of adult leukemia here, and my absolutely indispensable, dedicated, and caring nurse practitioner, Ilene Galinsky.”

Family Above All Else

Stone gives most of the kudos for his career and the upbringing of his 4 children to his wife, Jane Brown, MD. Brown, a pediatrician, was the key caretaker for their children while he was busy in his career going to meetings or delivering lectures. “She was a full-time pediatrician the whole time [raising the kids] and was extremely busy, so she deserves all of the credit for anything that I did,” he said.

Although his kids were raised by doctors, none became physicians. Stone thinks it might be because they grew up with a close-up view of how hard a doctor’s life can be. But he says they learned how important it is to assist people.

“They’re all doing things that I think are great in terms of giving back in a way that I don’t think I’ve done very well…other than the medical stuff,” Stone said. “They did it all on their own; I didn’t have much to do [with it].”

In 2018, Stone switched to the other side of the hospital bed when one of his twin daughters, Sarah, received a diagnosis of Hodgkin lymphoma at the age of 28. She had been complaining of itching for a while, and he and his wife had encouraged her to go to her primary care doctor.

After that visit, the doctor, one of Stone’s colleagues, texted him to say that Sarah would would need a neck ultrasound. In that moment, Stone already knew the implications. When his daughter came home, Stone put his hand on her neck and felt a large node. He asked why she hadn’t mentioned it. She thought it was just a pulled muscle.

“I felt very guilty, very stupid, and most importantly, I felt very worried about my daughter’s life,” Stone said.

Stone said it was hard to see care from the patient side of things. Although the family received great treatment, they still faced problems as any patient and their family would. He recalls a time when he went to pick up antinausea medication. The pharmacist said that the drug would cost $900 and that he’d have to wait for insurance company approval.

“I think it’s really important to see what our patients go through,” he said. “I wouldn’t wish that on any colleague, but it was a learning experience for me and to see how my daughter dealt with it.”

Sarah Stone responded well to treatment and is doing well today. Stone describes her as a “do-gooder,” working in peace research nationally and internationally. She is currently the director of a camp called Seeds of Peace, which brings children from the Middle East to the United States to play and live together. Prior to her diagnosis, she won the Goldberg Prize for Peace in the Middle East.

“That whole issue has nothing to do with me being a giant of cancer, that’s for sure. But it certainly was one more thing that shaped me in my later years,” he says.

One of the most important lessons Stone learned from his Jewish faith that he instilled in his children is “tikkun olam” or “repair the world.” He thinks all his kids are doing that in one way or another. His eldest son is head of public housing for the state of Massachusetts, one of his daughters “does something to do with making money. I ask her what she does, and she says I wouldn’t understand it,” he joked. And his youngest son lives in Washington state and works for the US Army Corps of Engineers.

“Most White Americans, as the cliché goes, are born on third base, and [if] they score a home run, they think they ran around all of the bases,” he said. “Those of us who were born on third base— and I was born on third base but went back to second for a while—it’s our duty to give back what we possibly can. I think that’s the most important thing I can [instill], and I’m glad to say that message was transmitted.”

The Future and a Legacy

Right now, Stone is busy serving as a doting grandfather to his first grandchild, Ethan, who was born in March 2020. It’s a new role that he is, understandably, incredibly excited about.

He is also involved in new leukemia trials. He is particularly excited about a phase 1 trial observing menin inhibitors in patients with MLL-rearranged and NPM1-mutant AML. This trial is based on seminal preclinical work led by Scott Armstrong, MD, PhD, chair of the Department of Pediatric Oncology at Dana-Farber, the David G. Nathan Professor of Pediatrics at Harvard Medical School, and president of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. The work is funded in part by a Specialized Programs of Research Excellence grant in leukemia, co-led by Stone and Benjamin Levine Ebert, MD, PhD, chair of medical oncology at Dana-Farber. Stone said investigators have already seen promising responses.

“The exciting part for me is that I get to talk to these amazing scientists about how we can translate [these discoveries] into people. It’s really [an] example of team science, bench to bedside science,” Stone said.

He would like to leave a professional legacy as a great oncologist who was devoted to patient care and clinical research. He emphasizes the importance of clinical trials in the field and that every patient, if possible, should be enrolled in a clinical trial. He mentions that the United States has “woefully low” enrollment in clinical trials and that improving participation is key to advancing the field.

“I’d like my legacy to be the importance of clinical trials in helping patients with often devastating malignancies because in my field alone, [we] couldn’t have made strides in [chronic myeloid leukemia], [acute lymphoblastic leukemia], and AML without the wonderful, brave patients who have gone on the clinical trials and made these advances possible,” Stone said, adding that he’d also like people to say, “He was a good teacher, developed and participated in team science, he mentored people, [and] he paved the way for the next generation.”