ASCO Members Larry W. Kwak, MD, PhD, and Douglas J. Schwartzentruber, MD, made this year’s “Time 100” List

By Virginia Anderson, Senior Writer/Editor

October 2010 Issue: ASCO members Time magazine’s annual list of the 100 most influential people in the world (commonly called the “Time 100”) regularly features heads of state, business moguls, celebrities, and sports superstars. In 2010, the “Thinkers” category included Supreme Court Justice Sonia Sotomayor, Apple CEO Steve Jobs, activist author Michael Pollan, consumer advocate Elizabeth Warren—and two ASCO members. Larry W. Kwak, MD, PhD, and Douglas J. Schwartzentruber, MD, were recognized for their contributions to the field of cancer vaccine research with a place on the list. The exciting research results from their respective phase III trials were presented at the ASCO Annual Meeting in June 2009, and a related article appeared in Time in September 2009.

A Personalized Approach to Follicular Lymphoma

Dr. Kwak, of M. D. Anderson Cancer Center, has been interested in cancer research since a high school summer job in a research laboratory at the University of Kansas. His mentor, Albert Kim, MD, a member of the lab faculty, was a pathologist by training. “He would spend a couple hours with me at the end of every day, teaching me about the immune system and disease,” Dr. Kwak said. “He introduced me to the idea that one could harness the immune system to fight cancer.”

He began investigating the use of a vaccine for patients with follicular lymphoma during his fellowship at Stanford University. “I vividly recall personally making multiple vaccines for patients from scratch using their own lymphoma cells, going to the clinic to treat the patients, and then finally back to the laboratory to do human tumor immunology experiments using patient blood samples,” Dr. Kwak said.

He refined the idiotypic vaccine as he progressed in his career to an independent laboratory at the National Cancer Institute (NCI; where a successful phase II trial was completed) and then as Chair of the Department of Lymphoma/Myeloma at M. D. Anderson. In 2000, the multicenter phase III trial began.

“I was very confident that this investigator-initiated trial would be successful because the academic investigators were faithful to the design of the phase II trial,” he said. “For example, a major lesson from this trial, which has implications for future cancer vaccine trials, is that vaccines are likely to work best in patients who have a low tumor burden. The decision to retain the design of restricting the vaccine to patients who achieved and remained in a complete remission after standard chemotherapy was critical to its success.”

A door to more opportunities
He hopes that his inclusion on the Time 100 list will help give the field of cancer vaccines “the scientific recognition that it deserves,” but he is realistic about the amount of research that is still required. “With our positive clinical trial, I think we finally have our foot in the door for a lymphoma vaccine. That opens up a whole host of opportunities for further optimizing the therapy and really bringing it to reality for patients,” he said. “We still have work to do, as this vaccine is not yet available to patients on a large scale. It has a very exciting promise, and while we have completed the bench-to-clinic translation, the task that remains is to bring it to the bedside. Generous support from the Leukemia & Lymphoma Society and two SPORE grants in Lymphoma and Myeloma we recently received are helping to make this possible.”

Being selected for the Time 100 came as a surprise, and he noted that he was “flattered to be recognized for a 20-year commitment to the discovery and development of cancer vaccines. There is so much promising cancer research being accomplished by many outstanding investigators. I am proud to represent physician–scientists in the field of oncology.”

Family, faith keep him balanced
His children, however, remained unimpressed. “When I shared the news at home, my kids said, ‘Dad, you probably just barely made it. You’re probably number 100.’ We count on them to keep us honest,” he said.

Dr. Kwak considers his investment in his family to be his greatest accomplishment, even beyond his important work in oncology. He and his wife, Ruth, have been married for 26 years and have three sons and a daughter. He has fond memories of coaching their sports teams and attending their music recitals. Together, they enjoy traveling to far-flung destinations like Singapore, Italy, France, and Costa Rica.

Along with his family, reading and religious faith help Dr. Kwak balance the demands of his career, but he considers oncology to be a vocation: “One of my patients once told me, at a particularly difficult time during development of the lymphoma vaccine, that I am an instrument of God. For me the work has been a calling, and that has kept me focused and humbled.”

The importance of mentoring
Mentoring the next generation of researchers is also an important aspect of his work, particularly in encouraging the 10 trainees who currently work in his lab. “This is a truly exciting time for the field of cancer vaccines, and not just in lymphoma. There is more and more emerging evidence for the role of the immune system in controlling many types of cancer,” he noted.

He is also quick to recognize his own mentors, including Ronald Levy, MD, Dan L. Longo, MD, and especially Waun Ki Hong, MD. “One is never too old to seek out wise counsel,” Dr. Kwak said. “For the past six years, I have been benefiting from Dr. Hong’s advice on how to recruit and lead a world-class academic department of 20 faculty, all focused on lymphoma or myeloma patient care and research.”

As he continues to lead investigations into lymphoma and myeloma vaccines, Dr. Kwak is achieving the goal he set for himself during his high school summer job in Kansas. “I knew that my passion was to have a career as both a physician and a scientist,” he said. “My eventual vision was to make medical discoveries in a research laboratory and then be able to translate these discoveries to patients myself.”

Improving Melanoma Outcomes

While Dr. Kwak was pioneering the follicular lymphoma vaccine, Dr. Schwartzentruber—who was also at NCI—was developing his own investigation into a vaccine that could improve outcomes for patients with melanoma.

His 10-year phase III trial examined the use of a peptide vaccine in combination with interleukin-2. “We were excited to get the results,” Dr. Schwartzentruber said. “There is benefit to patients, but it’s a small incremental step of benefit. More important is the proof of principle that vaccines can play a role in the treatment of metastatic cancer.”

The research began at NCI but continues now at Dr. Schwartzentruber’s current institution, Goshen Center for Cancer Care, in Indiana. Although Goshen is his hometown, it was the strong commitment to integrated, multidisciplinary patient care that he found most appealing about the practice.

“We talk a lot about multidisciplinary care in oncology, but to see it work as well as it does here is a different story,” he explained. “The patient-centered approach is truly multidisciplinary, where all of the needs—not only the physical, but the emotional, spiritual, and social needs—of patients are really addressed. This institution made a financial commitment to make it happen because these services are not reimbursable services, and the consequence is patient satisfaction. We are consistently ranked above 95% nationally in patient satisfaction. I was totally intrigued and caught up in wanting to be part of that model of care.”

“A mentor is for life”
He salutes the mentors who spurred his interest in patient care and research, including Jay L. Grosfeld, MD, a pediatric surgeon at Indiana University. “It was in his laboratory that I got a research start that developed my passion for cancer care. That was an initial defining moment,” Dr. Schwartzentruber noted.

He also praised Steven A. Rosenberg, MD, PhD, of NCI, who impressed upon him “the importance of clinical trials, how to conduct them, and the research methods,” he said. “This particular peptide vaccine was developed by Dr. Rosenberg and his team in the Surgery Branch of the NCI. Through his mentoring and financial support as my branch chief, I was able to initiate the phase III trial, which I was then able to conclude here in Goshen. He continues to give valuable advice and support—a mentor is for life.”

Next steps
Dr. Schwartzentruber serves as Medical Director of the Goshen Center for Cancer Care and continues to see patients with cutaneous malignancies in his role as a surgical oncologist. His melanoma vaccine research is ongoing, and he is a strong proponent of community practice participation in clinical trials. “We say that 80% of cancer care is delivered in community centers, so that’s where we really need to promote clinical trials and get patients enrolled in studies,” he said. “Every new patient that comes to Goshen is considered for a clinical trial.”

The next step for the melanoma vaccine, he believes, will be expanding its applicability to a larger patient population. The current iteration is only effective in a particular human leukocyte antigen (HLA) type, present in about 50% of the Caucasian population. Dr. Schwartzentruber hopes to successfully move a more broadly effective version of the vaccine through phase II trials and into a new randomized phase III investigation.

If that were not enough to keep him busy, Dr. Schwartzentruber is dedicated to time spent with his family. He enjoys annual ski trips and vacations with his wife and their two children (a daughter, 21, and a son, 19), and celebrates holidays and special occasions with extended family members still living in Goshen, including his parents and brother. He is active in his church, which he also describes as a “family.” And when he needs a few quiet moments, he takes his fishing pole to his backyard, which is bordered by a small river.

A community achievement
When Dr. Schwartzentruber learned that he had been selected for the Time 100 list, he said, “I thought they had made a mistake. I still think ‘why me,’ over many other deserving oncologists who are focused on clinical trials and finding new treatments. You pursue cancer research to find truth. You certainly don’t do it for the recognition. That there was recognition in this case is humbling and unexpected.”

He considers the recognition to be a community achievement. The economy of Elkhart County, where Goshen is located, was heavily vested in the production of recreational vehicles and was hit particularly hard during the recession. “It felt good to have some positive news after all the talk of recession and unemployment. The community is very proud of this accomplishment, and it speaks to our collective effort,” he said. “This effort began at the NCI, but it was transported and accomplished and continued here in Goshen, a city of about 35,000 people in northern Indiana.”

Read the article “A Shot at Cancer,” by Alice Park, which led to Dr. Kwak and Dr. Schwartzentruber’s selection for the Time 100 list
Read a brief essay on Dr. Kwak and Dr. Schwartzentruber, written by Olympic swimmer and cancer survivor Eric Shanteau