Amanda Posner is enjoying life with her husband, Ben, and son, Andrew, after receiving an investigational treatment for leptomeningeal metastasis, a serious complication in which cancer spreads to the fluid around the brain and spine. She joined a clinical trial led by MSK neuro-oncologist Dr. Adrienne Boire, who has spent more than a decade researching and developing this therapy.
For Amanda Posner, it was a horrible start to the day.
She was asleep at a hospital in San Francisco where she had gone the night before after frightening symptoms — facial numbness, pain down her back, difficulty driving a car. Amanda had been battling stage 4 breast cancer for seven years, but these new developments so alarmed her oncologist that she insisted Amanda go straight to the hospital to get checked out.
Now a nurse practitioner was waking her at to tell her an MRI revealed she had leptomeningeal metastases (LM) — a devastating complication in which cancer spreads to the cerebrospinal fluid surrounding the brain and spinal cord. Although rare, LM is becoming more common as people live longer with metastatic cancer, especially breast and lung cancer.
Amanda, a doctor herself, knew the situation was dire: LM carries a median survival of three to four months. It can cause pain, seizures, difficulty thinking, and a loss of muscle control. There is no cure or effective therapy.
“I said, ‘What are you going to do about it?’ ” Amanda now recalls. “She said, ‘Well, nothing — but I thought you needed to know.’ I was just so upset to be woken up with that because I knew at that time it was like a death sentence.”
At , her oncologist, who had LM expertise herself, called Amanda. “You have to go to Memorial Sloan Kettering Cancer Center,” she said. “You have to go see Adrienne Boire at MSK, or you’re going to die.”
What happened next illustrates how new treatments for patients emerge years after scientists have studied them in a lab. This type of bench-to-bedside advance is possible at MSK, which unites basic and clinical research.
Traveling Cross-Country To Be Treated at MSK
For more than a decade, MSK neuro-oncologist Adrienne Boire, MD, PhD, has been studying how cancer spreads to the fluid around the brain and spine. Now she is leading a clinical trial testing a new treatment for LM. It was Amanda’s only hope. Within five days, she and her husband, Ben, and their 2-year-old son had picked up and moved across the country to her parents’ home in Connecticut. It was late 2022. She met with Dr. Boire a few days later.
Dr. Boire said she could enroll Amanda in the phase 1 trial, which involves giving a drug called deferoxamine (DFO) by intrathecal injection — delivering it directly into the cerebrospinal fluid.
“At the time, you just want to live. If I’m offered a chance to be here longer with my child, I’m going to take it,” Amanda says. “And Dr. Boire can be so positive and reassuring, telling me not to worry and that they could start the therapy right away.”
Lab Research Leads to Clinical Trial for Leptomeningeal Metastasis
Dr. Boire first set out to crack the mystery of LM in 2014. Frustrated by the lack of treatments for this daunting complication, she focused her research on how cancer cells spread to the leptomeningeal space and manage to survive.
Dr. Adrienne Boire
The brain and spinal cord are largely sealed off from the rest of the body by the blood-brain barrier, a network of blood vessels and tissue with closely spaced cells. In 2017, Dr. Boire and colleagues in the lab of Joan Massagué, PhD, studied human LM cells in mice. They found that a protein called C3 opens the membrane between the blood and spinal fluid and allows growth factors and nutrients from the blood to enter and sustain the cancer cells.
This discovery, however, did not fully explain how LM cells survived in the mostly barren environment. Immune cells also invade the spinal fluid and vastly outnumber the cancer cells, competing for the same nutrients. Yet some of the cancer cells persevere.
To find out how, Dr. Boire teamed with SKI computational biologist Dana Pe’er, PhD, a world-renowned expert in single-cell analysis, which uses new technologies to study cancer one cell at a time. This enables researchers to look at RNA rather than DNA within individual cells to determine which genes are expressed, or “turned on.”
How LM Cells Overtake Immune Cells
They found that LM cells reprogram themselves to produce a protein called lipocalin-2. This protein binds to iron, which LM cells need to survive. Dr. Boire’s team showed that increased lipocalin-2 levels enable the cancer cells to monopolize the iron, foiling the immune response that would normally destroy them. It’s like creating a much stronger magnet to pick up more paper clips.
Dr. Boire showed in mice that delivering chemical compounds called iron chelators directly into the spinal fluid deprived the cancer cells of their lifeline and slowed their growth. The chelators bind to the iron so less is available to all the cells, taking away the cancer cells’ survival advantage.
“It reminds me of when kids are fighting over a toy, and the parent says, ‘That’s it — I’m taking it away. Nobody gets it,’ ” Dr. Boire says.
Based on this finding, she launched a clinical trial in 2021 testing whether the iron chelator deferoxamine could be safe and effective treating LM in cancer patients. Patients receive the drug DFO through a small plastic tube called an Ommaya reservoir inserted into the ventricle which bypasses the blood-brain barrier.
Treatment Stops LM
Before starting the DFO, Amanda first received radiation therapy to reduce the amount of cancer spread throughout the leptomeningeal space. She went to the New York Proton Center for proton beam therapy, which is especially precise. Proton therapy involves the use of charged particles called protons, rather than the X-rays used in other forms of radiation therapy.
“In the past, the radiation treatment probably would have been limited to just the base of the skull or part of the nervous system that was causing trouble,” Dr. Boire says. “In recent years, collaborative clinical trials between radiation oncologists and neuro-oncologists at MSK showed you can safely do proton therapy to the entire brain and spinal cord. When Amanda came to MSK, we first treated her with proton therapy to get the tumor down to a manageable size.”
Amanda says, “After a few proton sessions, all the symptoms — mostly pain and numbness in my face, like a burning frostbite — just went away.”
In March 2023, Amanda then began her treatment with deferoxamine.
- To deliver the drug intrathecally, doctors implanted the Ommaya reservoir under her scalp, on the top-right side of her head.
- She received deferoxamine twice a week for a month, then once a week for month.
- She then transitioned to once every two weeks going forward, which she is continuing in addition to her other breast cancer treatment.
Amanda is able to get the treatment at Memorial Sloan Kettering Westchester in West Harrison, New York, which is much closer to home. Each session takes about 5 to 10 minutes.
The deferoxamine has not caused noticeable side effects, especially compared with other treatments. The proton therapy made her temporarily lose her hair and caused some memory loss. Her continued treatment for breast cancer carries the typical nausea and fatigue.
“One in a Billion in the Medical Community”
“We don’t use the ‘C’ word with our son, but we have to be honest with him,” Amanda explains. “We just say, ‘Mommy has to go get her medicine.’ Honestly, if I only got Dr. Boire’s treatment, I would be so lucky. It is miraculous.”
Amanda continues to live in Connecticut with her husband and son, who is now 5. The rest of her family lives nearby. Her parents, brother, and sister are all doctors, either retired or practicing. Although Amanda no longer practices medicine, she enjoys traveling — a trip to Italy last summer and an upcoming visit to Japan.
She knows this treatment is experimental and may not always control her cancer, but she is grateful for the extra time and for Dr. Boire, whom she calls “one in a billion in the medical community.”
“Women certainly do not get enough credit for running their own lab, seeing patients, and running a trial,” she says. “Dr. Boire is a phenomenal person from top to bottom, a scientist working at the highest level, doing meaningful clinical medicine, while being a mom. I’ve never met somebody in my career who was able to do that.”
Dr. Boire says her team hopes to publish results from the first phase of the trial soon. “Phase 1 trials are about looking at safety and dosage, but when we see patients like Amanda wildly outliving expectations, it’s pretty exciting,” she says. “Patients come to MSK from all over the country for the trial because there are vanishingly few clinical trials that study LM. If we have new therapies for LM, people will find us.”
