Originally published in the 2007 ASCO Daily News
Robert A. Kyle, MD, of Mayo Clinic, is “very surprised and very grateful” to be the 2007 recipient of the David A. Karnofsky Memorial Award. The award, named for one of the true pioneers in oncology, is bestowed upon individuals who, through their clinical research, have changed the way oncologists think about the general practice of oncology.
Honored throughout his career for his groundbreaking research, Dr. Kyle’s discovery of two significant hematologic entities (monoclonal gammopathy of undetermined significance and smoldering multiple myeloma) is considered fundamental to the contemporary understanding of hematology. These entities will serve as the subject of his Karnofsky Memorial Lecture, titled “The Key to Neoplasia,” which he will deliver during this morning’s Opening Session (9:30 AM–12:00 PM; Hall B1, North Building).
Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma are conditions coined by Dr. Kyle in 1978 and 1980, respectively. The first term refers to an abnormal, asymptomatic protein present in the blood of about 3% of the Caucasian population and 6% of the African-American population older than 50 years in the United States. Over time, this condition can develop into multiple myeloma, macroglobulinemia, or primary amyloidosis.
“Our research is focused on why and how one patient’s disease progresses while the next one’s does not. Ultimately, we would like to figure out some way to convert multiple myeloma or macroglobulinemia to a monoclonal gammopathy of undetermined significance,” Dr. Kyle explains. “Smoldering multiple myeloma is a condition in which a patient has a large monoclonal gammopathy of undetermined significance but does not exhibit the clinical features of multiple myeloma: anemia, bone destruction, kidney failure and the like.” Dr. Kyle and his colleagues at Mayo Clinic continue to investigate these important entities.
It was a combination of practical considerations that originally led Dr. Kyle to choose his specialty. Mayo Clinic, where he completed his residency, required students to complete six months of laboratory work or basic science. The laboratory options at the time were limited. One choice was pathology, “in which one would do autopsies for six months and then write a thesis,” he says. A second option was physiology, specifically, the emerging science of cardiovascular physiology.
“Cardiac surgery was just being introduced,” Dr. Kyle recalls. “Believe it or not, the resident who took his basic science in physiology was personally catheterized — heart catheterization. This is hard to believe today, but it was the practice at that time, and I knew of people who actually had chills and fever following their cardiac catheterization.”
As neither pathology nor physiology proved appealing, Dr. Kyle chose to complete his laboratory requirement in a third track: hematology. “[It] was one of my weaknesses,” he confesses. “I’d had very little of it in medical school. I thought I would kill two birds with one stone: I would fulfill my basic science requirement and learn another discipline.”
Another factor directed his choice of specialty during his residency: Dr. Kyle was selected for service in the Air Force during the “doctor draft” at the time of the Cold War. “At the Air Force Hospital, there were three fully trained internists, and none of them had any experience in hematology,” he explains.
Although it was pragmatism that guided him to select hematology, Dr. Kyle found that he had an aptitude for the field. As the specialty developed, several opportunities to conduct exciting and innovative science emerged. While completing an elective course in clinical hematology, an attending consultant encouraged Dr. Kyle to investigate gamma spikes in the electrophoretic patterns of patients with multiple myeloma and macroglobulinemia. He reviewed Mayo Clinic’s archive of 6,500 serum protein electrophoretic patterns and developed a formula by which the height and width of the spike could be used to determine the nature of the anomaly — specifically, whether it represented myeloma or an inflammatory process. This was at a time when immunoelectrophoresis was not yet available as a clinical test.
Although his research in hematology has been and continues to be groundbreaking, Dr. Kyle believes that great strides are still waiting to be made. He anticipates seeing scientists and clinicians “getting at the more basic aspects of the plasma cell proliferative disorders, to understand the genetics and the gene profiling features of these entities.” Personalized medical care will be the next major breakthrough, in his opinion.
“One would hope to come to a time,” Dr. Kyle notes, “when one could more intelligently tailor treatment for the individual patient, to determine if the newly diagnosed patient who required therapy would be an individual who would respond to drug X, Y or Z.”
To improve patient care and clinical science, Dr. Kyle has initiated several programs at Mayo Clinic. He was responsible for establishing the institution’s dysproteinemia clinic. There, patients with myeloma, macroglobulinemia, primary amyloidosis and other hematologic disorders are treated by physicians who specialize in these conditions. “This allows for concentrated numbers of patients with particular diseases to be seen by a group of individuals who then have the opportunity [to] develop new protocols and new concepts concerning the treatment of those diseases,” he says.
In the 1960s, following considerable lobbying of the Mayo Clinic Board of Governors, Dr. Kyle was granted permission to create a special protein laboratory. “We performed immunoelectrophoresis and now, of course, we have switched to immunofixation,” he notes, “which identifies monoclonal protein in the patient’s serum or urine. This is essential for recognition and management of patients with monoclonal plasma cell disorders.”
Dr. Kyle has been an active participant in several oncology and hematology organizations. He is a current member of the Board of Directors of the International Myeloma Foundation, for which he also acts as Chair of the Scientific Advisory Board, and he also serves as Co-chair of the ASCO Bisphosphonates-Myeloma Expert Panel and as a Trustee and the Director of the Scientific Advisory Committee of the International Waldenstrom’s Macroglobulinemia Foundation.
He currently serves on the editorial boards of the journals Amyloidosis, Clinical Lymphoma and Myeloma and Blood Reviewsand has completed prior terms of service on those for Leukemia, Leukemia Research and the American Journal of Hematology. At Mayo Clinic, Dr. Kyle has been the William H. Donner Professor of Medicine and Chair of the Division of Hematology. He was the first President of the International Society of Amyloidosis and former Chair of the Myeloma Committee of the Eastern Cooperative Oncology Group and Secretary-General/Treasurer of the International Society of Hematology (Inter-American Division).
In addition to his considerable professional accomplishments, Dr. Kyle has been honored with more than 50 awards throughout his distinguished career, including the Mayo Clinic Distinguished Alumni Award and an honorary membership in the Royal Society of Pathologists, London.
He is the namesake for three prestigious awards given to oncology professionals in various specialties. The International Myeloma Foundation grants the Robert A. Kyle Lifetime Achievement Award to physicians who demonstrate “a singular dedication to and compassion for myeloma patients and treatment of their disease.” The Waldenstrom’s Macroglobulinemia Program presents the biannual Robert A. Kyle Award for important contributions to the therapy of that disease. Mayo Clinic Arizona presents the Robert A. Kyle Award for Excellence in Clinical Investigation to the physician at that institution who has conducted the most outstanding work in any field of research.
Beyond his extensive bibliography — which constitutes more than 1,800 published materials, as well as co-editor responsibilities for four editions of Neoplastic Disorders of the Blood and three editions of Myeloma: Biology and Management — Dr. Kyle has for more than 40 years served as coauthor for a special series of “Stamp Vignettes.” These biographic sketches of famous scientists who have been recognized on stamps were published first in the Journal of the American Medical Association and later in the Mayo Clinic Proceedings. Dr. Kyle, who himself collects stamps featuring medical subjects, received the Myrtle Watt Medical Journalism Award for his stamp-related writing.
His personal collection is extensive. “Until a few years ago, I had all of the stamps relating to blood transfusion and to cancer — probably 300 of each,” he notes proudly. “Then I have several hundred more of portraits … as well as stamps related to cardiology and to organ transplant. Someday, when I have more time, I should probably catalogue all of them.”
Dr. Kyle was involved in the United States Postal Service’s decision to issue a stamp recognizing blood donors. He has also served as President of the Medical Subjects Unit of the American Topical Association, which has recognized him as a “Distinguished Topical Philatelist.”
Brian G. M. Durie, MD, Chair of the International Myeloma Foundation and an ASCO member, praises Dr. Kyle’s expertise and dedication to both science and patient care.
“Dr. Kyle has brought a scientific rigor and integrity to clinical research, which provides a model for everyone. He has the most comprehensive knowledge of published research of anyone working in the field,” says Dr. Durie. “He brings that breadth of knowledge to the bedside and is able to provide management guidance with skill, elegance and a great humanity. His carefully measured advice is cherished by all who seek it.”