New Trial Shows Promise in Treatment of Cutaneous T-Cell Lymphoma

When Susan Thornton developed a rash around her waist she wasn’t sure what to make of it. It was a little itchy, but didn’t hurt; however, it wasn’t going away either. Five dermatologists later, over the course of a year, she learned the startling truth: It was cancer.

Then 31 years old, Thornton was diagnosed with cutaneous T-cell lymphoma (CTCL), a subset of non-Hodgkin lymphoma.

“I went into that last dermatologist appointment thinking ‘OK, maybe this one will have a different topical thing that I can do,’” said Thornton, whose disease led her to the Cutaneous Lymphoma Foundation (CLF), for which she now serves as CEO. “I had no anticipation of coming out with a rare cancer diagnosis. In fact, I was on my lunch hour and it totally freaked me out. I had to leave for the day.”

CTCL is a rare blood cancer of the skin, making up approximately six cases per one million annually. It generally affects men more than women and is usually first diagnosed in people between the ages of 50 and 60. Although treatable, CTCL is incurable and often associated with reduced quality of life for patients and survivors.

Road to New Therapies

Much like many cancers, treatment options for CTCL are based on a patient’s health, age and stage of the disease. For patients with early-stage disease skin-directed therapies, such as topical lotions, alone may help, while both skin-directed and systemic therapies may be better for those with advanced disease. According to the Leukemia & Lymphoma Society, allogeneic stem cell transplantation — stem cells from a donor — should be considered in patients with advanced disease who may be resistant to therapy.

Currently, the systemic therapies approved for treatment have determined 30 to 45 percent objective response rates (ORR), with low complete response rates.

A recent study published in The Lancet shows promising results with Adcetris (brentuximab vedotin), an antibody-drug conjugate focused on targeting CD30 — a protein that sits on the surface of the cell and is used by medical professionals to identify particular types of malignancies. Adcetris is not yet approved for the treatment of CTCL.

The randomized phase 3 trial compared Adcetris versus physician's choice of methotrexate or bexarotene, two chemotherapy agents. Between August 2012 and July 2015, 131 patients were enrolled from 52 centers in 13 countries. Researchers randomly assigned them to either the Adcetris group (66 patients) or physician’s choice (65 patients). The primary endpoint was an ORR lasting at least four months.

At a median follow-up of 22.9 months, 56.3 percent of patients in the Adcetris group achieved an ORR lasting at least four months (36 of 64 patients) compared with 12.5 percent (eight of 64 patients) with physician's choice. Progression-free survival (PFS) was 16.5 months with Adcetris versus just under four months with the standard arm.

“This study is practice changing in terms of it really gives us a brand new therapy, in what is otherwise a very difficult disease,” Miles Prince, M.D., a hematologist at Peter MacCallum Cancer Centre in Melbourne, Australia, and lead author on the study, said in an interview with CURE. “Fundamentally, the problem with CTCL is that very few treatments work for a long period of time. This is clearly the most active drug that we’ve had in CTCL in terms of response rate and PFS.”

The authors noted adverse events and four deaths; one death was thought to be treatment related and three due to progression of disease. In the Adcetris group, 41 percent of patients experienced grade 3-4 adverse events compared with 47 percent in the physician’s choice group. Peripheral neuropathy was seen in 67 percent of patients in the Adcetris group compared with just 6 percent of patients in the physician's choice group.

“Neuropathy can cause problems with sensation, numb fingers and hands, and sometimes it can be quite painful,” said Prince. “If they continue the drugs too long, neuropathy can be severe and last for months and months, and sometimes it doesn’t go away. It’s important for patients to let their doctors know they are experiencing it.”

Prince added that perhaps lowering doses or giving it less frequently could lower the risk of neuropathy.

Other common side effects of treatment for CTCL include skin irritation and inflammation, redness, rash, itching, burning sensation (like sunburn), fatigue and depression.

An Isolating Disease

In addition to the treatment side effects, patients with CTCL also experience a change in appearance, which can lead to emotional challenges.

Since CTCL involves the skin, patients may experience lesions that look like eczema or psoriasis, rashes that won’t go away, raised patches and, in advanced stages, patients can develop tumor-type lumps.

“As my disease progressed, I had tumors, rashes, red scaly patches on my face. It can be excruciatingly itchy,” said Thornton. “It feels like you have ants crawling on your skin from the inside out and there is nothing to alleviate the itch except trying to get the disease under control.”

To help with itching and irritation, the CLF recommends taking an oatmeal bath, applying moisturizer, switching to mild laundry detergent and wearing loose-fitted clothing.

In some cases, embarrassment from the physical changes will lead patients to seclude themselves from others and change how they dress. For example, Thornton said some people refuse to wear shorts, bathing suits or short-sleeves in the summer.

“It’s frightening and isolating. You feel very alone,” she said. “It’s hard for people to wrap their heads around it and it’s hard to explain.”

Thornton recalled an experience she had while food shopping: “At one point I had a lesion on my neck and was standing in the grocery store line and the clerk said to me, ‘Eww! What is that on your neck?’ and I thought, ‘Are you kidding me? Did you really just ask me that?’ He was a young kid. He wasn’t thinking. I was comfortable at that time, and was able to say, ‘It’s a rare form of cancer.’”

She added, “But it took me a good 10 years to get to that point.”

What the Future Holds

According to Prince, experts in CTCL now must optimize immune-based treatments since chemotherapy doesn’t have a strong role in treating the disease.

“Treatments are getting less toxic and becoming more targeted, and remissions are getting longer,” he said. “I don’t think there will be a cure in the next 10 years, but there will be a number of treatments that will suppress the disease.”

He added that there needs to be a focus on getting a better understanding about the biology of CTCL.

“There are new targets on the surface of the cell,” Prince said. “So, just like we described CD30, there are other proteins on the surface, which could potentially be targeted with new antibody treatments.”

As for Thornton, she hopes to help other patients and survivors by promoting awareness and education through her role at the CLF, while she continues to fight her slow-progressive disease.

“I’ve experienced the full spectrum,” she said. “I’ll have it [CTCL] forever, until we figure out how to not have it forever.”