Technology advances melanoma diagnosis, treatment

New technology on the market and in development offers the potential to revolutionize the detection of melanoma. Photography, dermoscopy, in vivo confocal microscopy and immunotherapy all hold promise thanks to recent advances, according to an expert who spoke about this topic at the 73rd annual meeting of the American Academy of Dermatology in San Francisco earlier this year.

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“Melanoma is one of the most deadly cancers once it spreads, and millimeter for millimeter, it’s more aggressive than just about any other cancer,” says dermatologist Sancy Leachman, M.D., Ph.D., who is professor and chair of dermatology and melanoma, as well as skin cancer research program director at Oregon Health & Science University’s Knight Cancer Institute.

“New technology has the potential to allow us to detect more potentially lethal cancers and treat them,” Dr. Leachman says.

The key to success is using diagnostic technology to expand upon human powers of perception, Dr. Leachman says, “We only have the capacity with our sense of sight and touch to observe certain things. We reach a limit of detection, and we just can’t do better,” she says. “So we rely on technology to enhance our senses. That’s the fundamental thing: We’re trying to see things that our eye can’t see.”

NEXT: Monitoring lesions

Monitoring lesions

On the photography front, new DermSpectra photo booths allow dermatologists to monitor the entire bodies of patients over time and track suspicious skin lesions in high resolution. “You don’t have to do a close-up photo,” Dr. Leachman says. “You can just magnify the photo you’ve got to see what those moles look like.”

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The booths are expensive at almost $200,000 each, Dr. Leachman says, but they offer dermatologists the ability to better track changes in the skin than traditional photography. “They have multiple cameras and they’re automated, telling a person how to stand so it gets the same images every single time.”

Caption: Video of mechanism of action of CLBS20 (formerly NBS20

NEXT: Diagnostic technology

The CLBS20 cell therapy manufacturing process takes place at at PCT, a Caladrius company. Photos: Caladrius Biosciences

Diagnostic technology

Other types of technology are geared toward helping dermatologists determine whether a lesion is cancerous.

One strategy expands on traditional dermoscopy by using different colors of light, including wavelengths out of the visible range known as hyperspectral light, to analyze a mole at different levels. Each wavelength penetrates the skin at a slightly different depth, Dr. Leachman says, allowing for better evaluation of invasive, potentially malignant cells.

The MelaFind system, which uses this form of technology, has been both high-profile and controversial. Some news stories have offered unquestioned claims about its value as a melanoma-finding tool. But news outlets, including The New York Times, have cast doubt by quoting experts who fear its use is risky because it could lead physicians to not biopsy suspicious moles.

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James Spencer, M.D., MS, a Dermatology Times board member and dermatologist in St. Petersburg, Fla., who’s familiar with the MelaFind technology, expects that the technology will be most popular outside the dermatologist’s office.

“The utility is going to be more for family practices,” he says. “Dermatologists are still pretty good at finding melanoma by visual inspection. The utility for the dermatologist is that it probably helps you do fewer biopsies by reassuring you that something is OK.”

NEXT: Another promising type of technology

The CLBS20 cell therapy manufacturing process takes place at at PCT, a Caladrius company. Photos: Caladrius Biosciences

Another promising type of technology, in vivo confocal microscopy, is already on the market. “This allows you to put a microscope on the surface of the skin and look at the cells within the lesion without having to cut it out,” Dr. Leachman says. “It’s like doing a non-invasive biopsy.”

Dr. Spencer says the confocal microscopy technology is “very promising since the person doesn’t get a scar.” 

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Nevisense, another technology in development, utilizes “electrical impedance” by measuring how easily electrical current travels through a lesion. “The idea is that Nevisense may be able to contribute toward more accurate detection of melanoma by using it on lesions that are clinically atypical,”[i] Dr. Leachman says. “If you’ve got a malignant lesion, studies have shown that it often has a different impedance than a benign lesion.”

There are caveats that puncture some of the hype about new forms of technology to detect melanoma. Some of these forms of technologies are still in development. And they can be pricey, Dr. Leachman says, with the confocal microscopes in particular running about $100,000.

NEXT: Practical use

Practical use

For now, she says, the diagnostic technology holds tremendous promise, but “we’re in the transition period of figuring out how they will be most useful in actual practice.”

What if melanoma is detected and diagnosed? Biopharmaceutical company Caladrius Biosciences - formerly known as NeoStem - hopes its developmental immune-cell therapy medication CLBS20 (also known as NBS20) will be a godsend for patients with state III recurrent or stage IV metastatic melanoma.

CLBS20 is a therapeutic vaccine that targets cancer-initiating stem cells.

Robert Dillman, M.D., vice president of oncology at Caladrius Biosciences and inventor of the technology that became CLBS20.“They only make up a small portion of any mass of melanoma, but they’re important to metastases or recurrence of disease,” says Robert Dillman, M.D., vice president, oncology at Caladrius Biosciences and inventor of the technology that became CLBS20.

The problem: “The immune system does not readily recognize these cells unless it’s induced to,” Dr. Dillman says. That’s where CLBS20 comes in. First, the patient's cancer cells are grown outside the body, irradiated, and then combined with immune cells called dendritic cells that are derived from the peripheral blood. The cell product is admixed with a growth factor that stimulates white blood cells and is injected.

According to the company, the more recent of two phase 2 trials compared the treatment to inactivated tumor cells in 42 randomized patients. At two years, 72 percent of patients who got the treatment survived compared with 31 percent of the control patients. Side effects included mild to moderate reactions at the injection site.[ii]

Norm Beegun, an attorney in the Los Angeles area, believes in the potential of CLBS20. He underwent the treatment in the early years of its development after being diagnosed with stage IV metastatic melanoma at the age of 56.

Norm Beegun, a patient who’s taken the experimental drug CLBS20. Photo Courtesy Todd Dubnicoff: CIRM

When diagnosed, he had a tumor in the lower left lobe of the lung that was “the size of a mango.” He says his chances of surviving for five years were 3-4 %. During the next year and a half, he also experienced metastases to the bowel and liver.

Mr. Beegun is now 70, and 13 years have passed since his diagnosis in 2002. “It’s been remarkable. For the last 11 years I’ve been cancer-free,” Mr. Beegun says, who remains active and both hikes and skis.

“There’s been no metastasis, and I’m in remission,” he says. “These have been some of the best years of my life. I’ve really appreciated every moment.”

Caladrius Biosciences has moved CLBS20 into phase 3 trials with support from a $17.7 million grant from the distinguished California Institute for Regenerative Medicine. “Our goal is to randomize 250 patients by the end of 2016,” Dr. Dillman says. “By the end of 2017, we may have enough events to perform an interim analysis that could lead to a biologics license application with FDA in 2018.”

The company hopes that the technology will become a weapon against other types of solid tumor cancer. Mr. Beegun will be watching. “I know how deadly melanoma is,” he says. “I’m very hopeful about this trial and where it’s headed.”

NEXT: References

References: Dr. Leachman received an honorarium for serving as a Medical and Scientific Advisory Board member for Myriad Genetics and Castle Biosciences.

[i] Malvehy J, Hauschild A, Curiel-Lewandrowski C, et al. Clinical performance of the Nevisense system in cutaneous melanoma detection: an international, multicentre, prospective and blinded clinical trial on efficacy and safety. Br J Dermatol. 2014 Nov;171(5):1099-107.

[ii] Dillman RO, Cornforth AN, Depriest C, et al. Tumor stem cell antigens as consolidative active specific immunotherapy: a randomized phase II trial of dendritic cells versus tumor cells in patients with metastatic melanoma. J Immunother. 2012 Oct;35(8):641-9.