New blastic plasmacytoid dendritic cell neoplasm (BPDCN) treatment improves outlook for many patients

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare type of acute leukemia that impacts about 500-1,000 people in the U.S. each year. It mainly affects older patients, but can affect people of any age.

Blastic plasmacytoid dendritic cell neoplasm springs from a rare immune cell that is usually found in the skin, bone marrow, blood, lymph nodes and spleen. Because it affects almost every part of the body and its name has changed so many times over the past four decades, BPDCN can be difficult to understand, recognize, diagnose and treat.

This aggressive disease has had historically few treatment options and a poor prognosis. But a new treatment option -- a targeted therapy drug called tagraxofusp -- has demonstrated clinical improvement for patients in a recently completed major clinical trial.

Naveen Pemmaraju, M.D., led the clinical trial for this new drug. He recently spoke with us about what makes the disease so hard to treat and what the new medication means for patients. Here’s what he had to say.

What are the symptoms of blastic plasmacytoid dendritic cell neoplasm?

BPDCN affects patients’ skin, bone marrow, lymph nodes and blood. Since it affects almost every single part of the body, blastic plasmacytoid dendritic cell neoplasm symptoms can be difficult to recognize, making the disease difficult to diagnose. Practically every BPDCN patient gets skin lesions. They often appear on, arms, legs, face and neck, but can show up anywhere on the body. In addition, the disease can cause swollen lymph nodes and a swollen spleen that can lead to stomach pain. So it combines features of leukemia, lymphoma and skin cancer.

Beyond the difficulty diagnosing the disease, why has the prognosis for BPDCN been so poor?

The theory is that it’s typically treated with chemotherapies borrowed from other diseases like acute leukemias and lymphoma. These powerful drugs are usually intended for younger patients, but when treating BPDCN, they’re typically given to older patients with a disease that has a different biology.

What’s changed in blastic plasmacytoid dendritic cell neoplasm treatment?

Cancer cells all have markers on their surface that bond with other markers and proteins or molecules in the body. This is called recognition. In some cases, these proteins and complexes can fuel the growth of some cancers.

On BPDCN cells there’s a marker called CD123. Tagraxofusp, a targeted therapy we’ve helped develop and study, attaches to that marker and then kills the cancer cells. The results are very encouraging. Over 90% of patients who received tagraxofusp as their first treatment had a major response. That means that the skin lesions and/or bone marrow lesions disappeared. A paper we recently published in the New England Journal of Medicine shows that we’re more than two years into our study, and we still haven’t reached the median length of survival for these patients. So we’ve apparently at least doubled the survival time when comparing to this historic expectation for our patients. The U.S. Food and Drug Administration approved tagraxofusp for treatment of BPDCN in December 2018; it’s now considered one of the standard treatments for this disease.

Stem cell transplants are often used to treat leukemia. Is that an option for BPDCN?

Because tagraxofusp is so new, we don’t know if it ultimately is a cure or not. We need longer term follow-up to monitor and see. If a patient responds well to tagraxosfusp, we want to take the next steps to kill any remaining cancer cells. This is called consolidation therapy.

If someone is young and fit enough, a stem cell transplant has historically been our best option for adding to the treatment of aggressive leukemias like BPDCN. If you have someone who can go for a potential cure through a stem cell transplant, you go for it, if they are healthy/fit enough to withstand this intensive approach.

What’s next for blastic plasmacytoid dendritic cell neoplasm research?

While we’ve made important progress in treating the disease, there are a lot of questions we still have to answer. If a patient has a major response, are they functionally cured, meaning the cancer cells are still present but in such small numbers the disease isn’t impacting the patient’s day-to-day life? Are they actually cured, meaning the disease has been wiped out of their body? How many patients are getting to the five-year point in remission? If patients are given this therapy, do you give them repeated cycles of the same drug or switch to or add another one? And for those patients who are able to undergo a stem cell transplant, is that really the best option? These are the important questions. I am eagerly awaiting the data so I can give the best information to my patients and their loved ones.

What advice would you give to someone who’s been recently diagnosed with blastic plasmacytoid dendritic cell neoplasm?

Ask a lot of questions. That’s important in any new cancer diagnosis, but it’s especially important with rare diseases and rare cancers. Remember, it’s your body and your life -- don’t hesitate to seek out a second or third opinion at a major academic cancer center like MD Anderson.

Also, remember that you are not alone. Thanks to the internet, there’s so much information out there about BPDCN. Look up and research everything you can, but remember to discuss it all with your doctor to sort out fact from fiction. Familiarize yourself with the doctors and teams, such as me and my team at MD Anderson, who specialize in treating patients with rare cancers like BPDCN and who are conducting clinical trials and doing active research to develop new and better treatments.