A rare blood cancer called histiocytosis has found a glimmer of hope in experimental targeted therapy. This story is about a remarkable journey and the potential it holds for a brighter future.
Meet Joey Carlsen Martinez, a 34-year-old dad who, three years ago, was battling a devastating disease. Erdheim-Chester disease, a rare form of histiocytosis, had taken a toll on his body, leaving him with crushing fatigue, excruciating joint pain, and memory loss. He relied on a wheelchair to get by.
But today, thanks to an innovative drug treatment, Joey's life has transformed. "Today, I have a mostly normal life," Joey shares. "I still get tired quickly, but I manage. I go grocery shopping, cook dinner, and take care of my family. I'm incredibly grateful for every moment."
The secret behind Joey's turnaround is a novel targeted drug called ulixertinib. His doctor, Dr. Eli Diamond, a neuro-oncologist and early drug development specialist, is the lead author of a groundbreaking paper published in Cancer Cell. This paper details the outcomes of Joey and four other patients, all of whom were the first to receive ulixertinib for histiocytosis, a family of rare diseases.
The MSK study revealed that four out of five patients with histiocytosis showed improvement with ulixertinib. Based on these promising results, a larger phase 2 clinical trial is now underway at MSK and two other hospitals.
Dr. Diamond, an internationally recognized expert in histiocytosis treatment, has led the development of the only two drugs approved by the FDA for this condition: vemurafenib (Zelboraf) and cobimetinib (Cotellic).
"The patients in this study were treated under a single-patient investigational new drug (IND) application," Dr. Diamond explains. "We essentially design an individual clinical trial for each participant. For rare diseases like histiocytosis, this approach allows us to evaluate potential treatments in a small but impactful way."
Histiocytosis is a group of rare diseases affecting only a few hundred people in the United States annually. It can strike patients of any age, including children. The disease occurs when the body produces an excess of histiocytes, a type of white blood cell, which can accumulate and form tumors in various parts of the body. Symptoms range from bone and joint pain to general fatigue and malaise, skin issues, blurred vision, and even problems with the brain, including balance and memory loss.
Joey experienced these symptoms on and off for nearly a decade before being diagnosed with Erdheim-Chester disease at 29. Today, he leads a mostly normal life, thanks to a clinical trial at MSK.
"I finally learned what was wrong two months after my wife discovered she was pregnant with our first child," Joey recalls. "It was a wild time, especially since no one seemed to know much about this disease."
Joey, a Washington state resident, was fortunate to find a doctor in Seattle familiar with histiocytosis treatment. He tried three different therapies, which helped with some symptoms but caused severe side effects, especially nausea and vomiting. Running out of options, Joey heard about Dr. Diamond and made the journey to New York to visit MSK.
The development of ulixertinib for histiocytosis treatment stems from new discoveries about the ERK gene and MEK protein. Laboratory mouse models and other studies have shown that histiocytosis is driven by mutations in a cell-signaling pathway involving the MEK protein. These mutations lead to uncontrolled cell growth and, ultimately, cancer. MEK is implicated not only in histiocytosis but also in several other cancer types, particularly melanoma.
The two previous drugs approved for histiocytosis target genes within the MEK pathway to block histiocyte growth. Ulixertinib, the new drug, also acts on this pathway but focuses on a different gene: ERK.
Research in Dr. Omar Abdel-Wahab's lab has been instrumental in deepening our understanding of histiocytosis and finding new ways to combat it. Dr. Abdel-Wahab, along with Dr. Benjamin Durham, a former trainee and member of his lab now at the Rutgers Cancer Institute, is a co-senior author of the new paper.
"Drugs that block ERK have been studied for various cancers, but some patients experience notable side effects at high doses," Dr. Diamond explains. "With histiocytosis, ulixertinib works at very low doses, allowing patients to avoid most side effects."
For Joey, the primary side effect of ulixertinib has been an acne-like rash. He continues to take the drug daily. Initially, he had to travel frequently to MSK, but now Dr. Diamond coordinates with doctors in Seattle, enabling Joey to have scans and blood tests closer to home. He periodically visits MSK, where Dr. Diamond and his Seattle oncologist collaborate to adjust Joey's dosage based on his disease levels and treatment side effects.
Joey and his wife recently celebrated their sixth wedding anniversary. While he's unable to work full-time, he's grateful to be home with his daughters. "I can't imagine a better situation where I'd get to spend so much time with my girls every day," he says. "It's a blessing."
Joey actively participates in support groups for Erdheim-Chester patients and enjoys helping others, especially those newly diagnosed. "The Erdheim-Chester community is incredible," he says. "I'm grateful to them, to Dr. Diamond, and to the entire MSK team."
MSK's leadership in developing histiocytosis treatments stems from a dedication to fundamental lab research. Fifteen years ago, Dr. Abdel-Wahab developed the first-ever mouse models for studying histiocytosis. These models have been instrumental in learning more about the genes and proteins driving the disease and testing experimental therapies to block them.
Patient samples sent to MSK by histiocytosis specialists worldwide have also contributed to a better understanding of these rare diseases. Several of these specialists are co-authors on the Cancer Cell paper.
"Our work in histiocytosis and the impact it's had on patients worldwide is a testament to the importance of funding basic and translational lab research," Dr. Abdel-Wahab says.
This story highlights the potential of experimental targeted therapy for histiocytosis, offering a ray of hope for patients and their families. It's a reminder that, even in the face of rare diseases, dedicated research and innovative treatments can make a world of difference.
