The Rarefied World of Ocular Oncology

Dr. Brian P. Marr

Dr. Brian P. Marr

An estimated 3,000 adults in the United States will be diagnosed with primary intraocular melanoma this year. Relatively rare, cancers of the eye require the expertise of an ocular oncologist with experience in the diagnosis, treatment, and management of ocular tumors.

Brian P. Marr, MD, Director of Ophthalmic Oncology at NewYork-Presbyterian/Columbia University Irving Medical Center, is one of the few ocular oncologists in the country trained in all aspects of eye cancers and whose clinical experience in treating these diseases is among the most extensive. Dr. Marr’s focus on ophthalmic oncology began during an eight-year tenure in the Ocular Oncology Service at the Wills Eye Hospital in Philadelphia. There, he gained extensive knowledge treating intraocular tumors, and tumors of the eyelid, orbit, and conjunctiva in adults, children, and infants.

Dr. Marr, who joined NewYork-Presbyterian in May 2017 from Memorial Sloan Kettering Cancer Center, is a world leader in the clinical development of therapies for ocular melanoma. He also helped pioneer the technique of delivering intra-arterial chemotherapy and other treatments for intraocular retinoblastoma, the most common malignant cancer of the eye in children, sparing them enucleation. The treatment regimen is now being performed in countries throughout the world.

“I was drawn to ocular oncology because it offers a diverse range of challenging problems where I feel I can make a difference,” says Dr. Marr, whose expertise spans the full range of treatment options, including intraocular tumor resection, as well as advanced laser, radiation, and chemotherapy. “Patients with ocular tumors are not your average patients. They require more resources and more time. That is one of the great aspects of our program at the Harkness Eye Institute at Columbia. We have a full-service eye hospital, a full-service oncology program, and access to multiple other subspecialists throughout NewYork-Presbyterian working together for the benefit of each patient with eye cancer.”

Targeting Uveal Melanoma

Dr. Marr has developed a strong belief that the best research be used to help his patients, rather than his best patients be used to help his research. With that philosophy, he is pursuing clinical research in a number of areas, including uveal melanoma, the most common intraocular malignancy arising from melanocytes in the iris, ciliary body, or choroid. Early diagnosis and local treatment is critical, as survival correlates with the primary tumor size. However, approximately 50 percent of patients will develop metastatic disease, with a six- to 12-month survival from time of metastatic diagnosis.

Differential Diagnosis of Uveal Melanoma by Location
Iris Lesion Posterior Lesion
  Primary iris cyst   Choroidal nevus
  Iris nevus   Disciform degeneration
  Essential iris atrophy   Peripheral disciform degeneration
  Foreign body   Retinal pigment epithelium hypertrophy
  Peripheral anterior synechia   —
  Secondary metastasis   Hemangioma

“There hasn’t been a new therapy for primary treatment of this disease for over half a century,” says
Dr. Marr, who is currently the Principal Investigator for a multicenter phase 1b clinical trial for a first-of-its-kind, new class of drug treatment for primary uveal melanoma, collaborating with Richard D. Carvajal, MD, Director of Experimental Therapeutics and Director of the Melanoma Service at Columbia, and their colleagues internationally. “Uveal melanoma is considered rare — about 2,500 to 3,000 cases a year — but it is, in fact, the most common primary intraocular malignancy in adults. Biologically distinct from cutaneous melanoma, there are a number of underlying somatic gene alterations in uveal melanoma associated with a variable prognosis that are currently being investigated in clinical drug development.”

In February 2017, the FDA cleared an investigational new drug application for light-activated AU-011 in primary uveal melanoma. AU-011 is a targeted therapy administered through an intravitreal injection and consists of viral nanoparticle conjugates that bind to cancer cells in the eye. The drug is then activated with an ophthalmic laser, destroying the membranes of tumor cells. The clinical trial is evaluating the drug’s safety, immunogenicity, and preliminary efficacy in two dose levels. Interim data reported in November 2017 showed that AU-011 was well-tolerated, patients had stable disease, and vision was preserved. The investigators hope that AU-011 will be able to be used for small primary melanomas early on.

“Early detection of ocular melanoma, combined with the administration of AU-011 as a potential vision-sparing therapy, could transform the treatment of patients with this devastating disease,” says Dr. Marr, who is the Principal Investigator for the AU-011 clinical trial nationally and at Columbia — the only site in New York participating in the trial. “Because these eye diseases are so rare, many times I end up trying to borrow other technologies to apply in treatment. That’s why I’m so excited about this clinical trial. It has potential and we’re fortunate to be able to offer it to our patients.”

Dr. Marr points to the dual goals of the new drug — to preserve both life and vision. “The problem with my group of patients is that, pardon the vernacular, cancer sucks, right? But going blind sucks, too. I need to manage both simultaneously,” he says. “Some people would rather die than lose their vision and vice versa. So, I have a twofold challenge to address because of the sensitivity of the organ. I can cure a lot of cancer now, but then I end up blinding people. I’d like to be able to not do that. This new drug may avoid the long-term side effects typically seen with current treatments.”

Dr. Marr is also investigating immune markers within uveal melanoma that are specific to this diagnosis and that have already been explored in investigations of skin melanoma. “Uveal melanoma is genetic-specific and breaks down to about four subsets of this disease. Some of them have infiltrating lymphocytes. In skin melanoma, if this occurs it is a good sign. Uveal melanoma is the exact opposite in that it’s a bad sign. So, we are trying to discover what the discrepancy is. There are a few targetable processes within that immune pathway that have recently been published by colleagues at Columbia and elsewhere. We’re going to try to pick apart those areas to see if certain drugs can target that pathway and whether it makes a difference if we turn it on or off. If it does, then maybe we can subselect patients with this type of immune signaling to target their specific tumor makeup so that they might have a better likelihood of doing well.”

Dr. Marr emphasizes that though he is among few specialists in the field of ocular oncology, he does not work alone. “There are so many nuances in eye cancers,” he says. “For example, if I am treating a primary tumor in the eye that starts to spread elsewhere, I bring in neurosurgery, ENT, plastic surgery, and others to help manage the patient’s care. I am like the quarterback who helps guide everything that is uncommon to most people, but common to me.”

Reference Articles
Carvajal RD, Schwartz GK, Tezel T, Marr B, Francis JH, Nathan PD. Metastatic disease from uveal melanoma: Treatment options and future prospects. British Journal of Ophthalmology. 2017 Jan;101(1):38-44.
Krantz BA, Dave N, Komatsubara KM, Marr BP, Carvajal RD. Uveal melanoma: Epidemiology, etiology, and treatment of primary disease. Clinical Ophthalmology. 2017 Jan 31;11:279-89.
Abramson DH, Marr BP, Francis JH. Intra-arterial chemotherapy for retinoblastoma. JAMA Ophthalmology. 2016 Oct 1;134(10):1202.

For More Information
Dr. Brian P. Marr | [email protected]