Clinical trial puts rare BPDCN leukemia in remission with diphtheria-based targeted therapy drug

When a small, painless lump began developing on Melissa Evans’ left arm near her elbow in late 2014, she didn’t give it much thought. The school cafeteria manager had always bruised fairly easily. She assumed she’d bumped it somehow, and that the growth would resolve on its own.

The 45-year-old never imagined that the lump would turn out to be an extremely rare form of leukemia called blastic plasmacytoid dendritic cell neoplasm (BPDCN) — or that the cure would be found in a clinical trial at MD Anderson using a drug made in part from a diphtheria-based toxin.

“It sounded really crazy,” says Melissa, “but the drug did exactly what it was supposed to do.”

Hometown providers defer to MD Anderson’s expertise

Melissa arrived at MD Anderson after a series of false starts. Once the lump grew to the size of a golf ball and started changing colors — from purple to blue and back again — her local doctor biopsied it. But both local oncologists that her doctor referred her to declined to treat it.

The first said it was because he knew what BPDCN was, but almost nothing beyond that. The second said that while she was familiar with BPDCN, she’d seen it only once. Both agreed that Melissa needed to be treated by someone with far more experience, and offered to work with her to find a suitable medical team.

“The way BDPCN was described to us was like a mixture of lymphoma and leukemia, with a little bit of skin cancer thrown in,” explains Melissa’s husband, Denny. “We understood it was pretty unusual. But we also kept hearing that it was very aggressive. So, we needed an expert — and fast. The second oncologist told us flat out that we needed to get to MD Anderson.”

Patient finds small town feel at big city hospital during BPDCN treatment

After calling for an appointment, Melissa and her husband made the nine-hour drive to Houston from their home in rural Mississippi. They found the size of the hospital a little intimidating.

“MD Anderson’s got more people on staff than the population of our entire town,” notes Melissa. “But everyone there makes you feel like you’re the only person they’re treating.”

They met with Naveen Pemmaraju, M.D., a leukemia expert who specializes is BPDCN and other unusual presentations of rare leukemias. He told them that BPDCN only affects about 500 to 1,000 people in the U.S. a year, so it’s extremely rare.

“He also said that I was one of the first females he’d ever seen with it and among the youngest adults to be diagnosed at that time,” Melissa says. “Most cases are found in much older men.”

Unusual disease presentation calls for innovative treatment plan

After completing Melissa’s examination, Pemmaraju made his treatment recommendation: a clinical trial involving a targeted therapy drug called SL-401, followed by a stem cell transplant under Muzzafar Qazilbash, M.D.

SL-401 combines a human protein called interleukin-3 (IL-3) with a genetically engineered toxin derived from the diphtheria bacterium — a pathogen that caused severe illness and death in thousands of children in the early part of the last century before a vaccine was developed.

“Bacteria have actually been used as a drug delivery mechanism for decades,” Pemmaraju explains. “Early scientists noticed that when they took the active component out of some really deadly bacterial toxins, they could use them to deliver medicine in a way that treated a particular disease or condition without causing a new infection.”

The clinical trial Pemmaraju led was designed to take advantage of this mechanism, by capitalizing on the unique qualities of the drug’s components.

“Scientists discovered back in the late 1970s that the diphtheria toxin could actually be an anti-neoplastic agent,” he explains. “A researcher named Dr. Arthur Frankel later found that if he combined a version of the diphtheria toxin with IL-3, BPDCN cells would absorb it more easily and die at an increased rate.”

Novel drug in clinical trial brings remission for BPDCN survivor

This novel therapy showed some very positive early results in clinical trials treating patients with BPDCN. And Melissa was one of the very first patients to begin receiving the drug through Pemmaraju’s clinical trial. After only four of the six recommended treatments with it, she showed no evidence of disease.

“If I’d stayed in Mississippi, I’d have just gotten only standard chemotherapy, which might have kept me in remission for a few years, before the cancer came back and possibly killed me,” Melissa marvels. “But that drug saved my life. And I never had any side effects.”

Melissa is unique in another way, too. Most BPDCN patients must obtain stem cells from a donor. But she is one of a handful of patients who could use her own, because the disease was restricted to just her skin.

“In order to achieve a cure with BPDCN, though, induction therapy with SL-401 — whether used with other drugs or not — must be consolidated with a stem cell transplant,” notes Qazilbash. “Without a stem cell transplant, relapse or recurrence is almost universal.”

Drug’s efficacy allows for faster completion of BPDCN treatment

Melissa did so well on the drug that she was able to receive her stem cell transplant a little early, on Nov. 4, 2014. She was released from the hospital the week before Christmas. She’s been disease-free ever since.

“I feel very blessed,” Melissa says. “We only found out later that Dr. Pemmaraju is considered one of world’s leading researchers on BPDCN. That really blew us away. It’s not like here in Mississippi, where even the specialists have only seen one case of it in their entire lives. He deals with this all of the time.”

Once experimental drug now approved by FDA for first-line BPDCN treatment

The drug previously known as SL-401 is now called tagraxofusp-erzs. It was approved by the Food and Drug Administration (FDA) for first-line treatment of BPDCN in December 2018. Pemmaraju says he still gets chills when he thinks about how effective the drug turned out to be for Melissa.

“BPDCN is a visual disease,” he says. “So, when you can actually see the skin lesions going away, it’s not just the patients who get excited. Physicians do, too. It’s exhilarating! And for a patient to have not just had immediate results, but enduring results — that’s astonishing. Back then, the median time for someone to stay in remission after BPDCN treatment was 8-14 months. For Melissa, it’s been almost seven years — and counting.”

“I went into the clinical trial hoping that even if it didn’t help me, it might help someone else,” Melissa says. “It’s exciting to know that it’s doing both.” 

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