Kirkwood Helped Chart Course of Adjuvant Immunotherapy in Melanoma

Jason Harris
Published: Monday, Nov 12, 2018
John M. Kirkwood, MD
John M. Kirkwood, MD
For a time, John M. Kirkwood, MD, thought he might become a professional musician.

His mother, 2 sisters, and 2 brothers have worked as professional musicians, and he was as fascinated with music as he was with science. Kirkwood wanted to pursue both his passions in college, which is how a New York City kid wound up going to college in rural Ohio.

“I was intrigued by the possibility that a place would mix music and science and allow me to pursue the music that I thought might be an option to give serious consideration,” he says of his time at Oberlin College in the late 1960s. “It served me well because I could really get deeply into music and then decide the science was even more driving.”

Kirkwood, 70, still pulls out the viola from time to time, although less frequently lately, since he’s become busier. He used to play in 5 orchestras, and groups of musicians would join him at his wooded 40-acre property outside Pittsburgh to play the orchestral and baroque music he loves so much.

Someone heading past the property at the right time in the morning and evening might find him riding a strange contraption, a bicycle specially adapted to train the German shepherds his wife breeds and trains to compete in a sport called Schutzhund, a German word meaning “protection dog.” The sport focuses on 3 areas: tracking, obedience, and protection work.

“That’s how every day starts and every day ends,” he says, adding that he finds the routine invigorating.

A Groove that Used to be a Rut

Kirkwood entered Oberlin College’s Senior Scholar program before his junior year and left the school to study immunology with a pioneer in cancer immunotherapy who became one of his mentors, Lloyd J. Old, MD, at what was then the Sloan-Kettering Cancer Institute. Kirkwood never made it back to Ohio, and the idea of a career in music took a back seat to his growing interest in oncology.

Instead, he stayed in New York and eventually matriculated at Yale School of Medicine, where he went to work in the laboratory of Richard K. Gershon, MD, professor of pathology, immunology, and biology and another giant in the field of immunotherapy.

Kirkwood received his medical degree from Yale in 1973 and founded the Yale Melanoma Unit alongside Aaron B. Lerner, MD, PhD, and Stephan Ariyan, MD, MBA, 5 years later. He led that unit until 1986, when the University of Pittsburgh Cancer Institute (UPCI) recruited him as professor and chief of the Division of Medical Oncology. He was named the school’s vice chairman for clinical research 10 years later.

Today, Kirkwood is the Thomas and Sandra Usher Professor of Medicine, Dermatology and Translational Science at the University of Pittsburgh School of Medicine and codirector of the UPMC Hillman Cancer Center Melanoma and Skin Cancer Program. In the 44 years since he began his career, he has seen melanoma become a growing field of research.

“This is a groove now. It once was a rut,” he says. “Melanoma, for many people, was a rut some wanted to get out of and people avoided.”

Kirkwood played no small part in changing the field’s reputation. He was the lead author on the pivotal ECOG EST 1684 trial published in 1996 that led to the approval of high-dose interferon alfa-2b for adjuvant treatment of deep primary (T4) or regionally metastatic (N1) melanoma.1

ECOG EST 1684 was the first randomized, controlled trial of interferon alpha-2b to show a significant benefit for overall survival (OS) and relapse-free survival in patients with high-risk melanoma. Results from that study showed that interferon alpha-2b increased median disease-free survival from 1 to 1.7 years and OS from 2.8 to 3.8 years. Compared with observation, a median follow-up of 6.9 years, interferon alpha-2b treatment induced a 42% improve-ment in the percentage of patients who were continuously disease-free compared with observation (37% vs 26%).

Kirkwood also serves as the principal investigator of the National Cancer Institute’s Specialized Program of Research Excellence in skin cancer at UPMC. The program’s goal is to improve the understanding of molecular and immunologic mechanisms of cancer progression and to validate prognostic and predictive biomarkers for personalized treatment of advanced melanoma and cutaneous T-cell lymphoma (CTCL).

The program will evaluate (1) the prognostic and predictive value of the proinflammatory response and markers of immune suppression in relation to ipilimumab and interferon alpha adjuvant therapy (leveraging an ECOG-led adjuvant trial); (2) an engineered, 3-antigen dendritic cell vaccine and interferon alpha boost in patients with metastatic melanoma; (3) a phase I study of anti–PD-1 antibody MK-3475 and peginterferon alfa-2b for advanced melanoma; and (4) a new personalized microneedle vaccination technology for patients with melanoma and CTCL.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of ImmunotherapyAug 13, 20191.5
Advances in™ Melanoma: Exploring BRAF/MEK in Adjuvant and Neoadjuvant SettingsSep 28, 20191.5
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