University of Iowa Health Care has developed a strong apparatus for researching and treating a rare and highly fatal cancer called uveal melanoma. One of the latest developments is a phase III clinical trial published in Annals of Oncology, in which Mohammed Milhem, MBBS, Clinical Professor of Hematology, Oncology, and Bloodand Marrow Transplantation, played a crucial role.
Context
Uveal melanoma is the most common form of ocular melanoma, developing in the eye’s pigmented cells. This disease is particularly fatal because it often metastasizes before it is detected; in most of these cases, people die within one year of diagnosis.
Although much remains unknown about the mechanism of this metastasis, Milhem’s study yielded promising findings for adult patients with the cell marker HLA-A∗02:01and who are diagnosed with unresectable or metastatic uveal melanoma. The five-year survival rate for this subset of patients doubled when they were treated with Tebentafusp, compared with the control group treated with the investigator’s choice therapy. Survival benefits persisted across all RECIST (Response Evaluation Criteria in Solid Tumors) categories, including patients with progressive disease or high tumor burden.
Tebentafusp is an immunotherapy called a bispecific T-cell engager (BiTE), which works by binding to a protein (CD3) on healthy T cells and a protein (gp100) on melanoma cells. It then joins these cells together so that the immune system can more effectively kill the tumor.
Collaborative care
Milhem said Iowa contributed so much to the study in part because the state currently has one of the highest incidence rates of uveal melanoma in the United States.“We have a very big referral basin, so we were able to contribute very strongly towards building the trial, getting this drug FDA approved, and helping it reach patients,” he said.
Addressing the need for accessible treatment, H. Culver Boldt, MD, Professor of Ophthalmology and Visual Sciences, established a center of excellence for ocular oncology care at the University of Iowa. Elaine Binkley, MD, who serves as co-Director of UI’s Ocular Oncology Service alongside Milhem, explained how the “collaborative team environment” between the Ophthalmology and Internal Medicine departments provides comprehensive care for the treatment of ocular tumors and metastatic disease.
“We serve patients from all of Iowa, western Illinois, and parts of Nebraska, Missouri, and Kansas as a regional referral center for ocular tumors,” she said. “We work extremely hard to provide personalized, high-quality ocular oncology care for our patients to control their primary tumors, which is a team approach involving ocular oncology, radiation oncology, and medical physics. We then send our patients for metastatic screening and treatment of metastatic disease to Drs. Milhem and [John] Reith.”
Indispensable to this process is ocular oncology coordinator Jennifer Menke. Binkley emphasized the effort Menke dedicates to coordinating patient care, particularly in minimizing travel burden for patients in rural areas.
This collaboration also advances new research beyond drug trials. An ongoing project led by Colin Kenny, PhD—a researcher in UI’s Holden Comprehensive Cancer Center—uses a zebrafish model to identify biomarkers in uveal melanoma. Pinning down these biomarkers could help prevent the cancer from spreading to the liver, a process which is often the difference between a patient living or dying.
“We are very fortunate to have scientists studying this disease in Iowa,” Binkley added. “Having excellent scientists like Dr. Kenny who study the disease and collaborate with clinicians and patients to focus on the most important questions in the field is essential to moving the treatment of the disease forward.”
[Read more about Kenny’s award-winning melanoma research.]
On the horizon
Collaboration will continue to shape what comes next. On the ocular oncology side, Binkley said the team is focused on maintaining its excellence in local tumor control and plaque brachytherapy using echographic techniques. They are also researching better treatments for the vision loss caused by radiation retinopathy—a condition that can develop following plaque brachytherapy—through participation in the DRCR Network’s Protocol AL clinical trial. In addition, they recently completed participation in the ATLAS-UM clinical trial, which studied prognostication in primary uveal melanoma tumors.
This same collaborative spirit drives the field on the systemic side, too—the very environment, Milhem says, that made UI’s role in the Tebentafusp trial possible. Milhem described the way Iowa’s clinicians and researchers foster this kind of environment, writing, “People across our organization share information and are receptive to debate and counterargument. We’re unafraid to get around a table and see things through different perspectives. There’s an emphasis on teams, not on individuals trying to make a name for themselves.”