Cholangiocarcinoma Foundation
Kasia Lazar, Jack Martynow, and Maria Martynow at the 2019 Cholangiocarcinoma Foundation Annual Conference. Credit: Matt Barr/Cholangiocarcinoma Foundation

Melinda Bachini, 52, never intended to be a patient advocate for a disease few people have ever heard of, let alone pronounce.

Melinda Bachini
Melinda Bachini

But a Dec. 1, 2009, diagnosis of cholangiocarcinoma, also known as bile duct cancer, changed everything for the Billings, Montana, mother of 6. That day, the 41-year-old paramedic — who had been experiencing fatigue as well as abdominal and right-shoulder pain — learned she had a tumor on her liver measuring 13 by 9 centimeters, and that surgery was her only option.

A biopsy showed the mass was malignant. Three weeks later, during a 6-hour operation, doctors removed 65% of Bachini’s liver, with subsequent tests confirming her diagnosis of cholangiocarcinoma.

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“Thankfully, your liver grows back, and you regenerate rather quickly. Unfortunately, 3 months after my first checkup, the cancer had returned, in my lungs. It was stage IV terminal cancer,” she said. “I had done enough research to know that if I wanted to beat this, we needed to find something new.”

Bachini’s oncologist found a clinical trial seeking patients, but her health insurance provider refused to reimburse the standard of care that the trial required. So she became an activist.

“We went to the Montana state capital in Helena and told legislators our story. That was the first time I advocated for anything,” she recalled. “Eventually, they did pass a law saying that if cancer patients entered a clinical trial, the insurance had to cover those costs. But I didn’t do the trial because I didn’t want to put my family in a financial burden.”

After struggling with the rashes, hearing loss, fatigue, and hand-foot neuropathy caused by 3 different chemotherapy regimens — a weekly cocktail of gemcitabine/cisplatin, then cisplatin alone, and finally docetaxel — Bachini had had enough.

“At that point, I decided no more chemo, and that I wanted a better quality versus quantity of life. Though I didn’t want to give up, there really wasn’t any option,” she said. “That’s when I stumbled on a clinical trial at [the National Cancer Institute (NCI), a division of the US National Institutes of Health].

CCF Born Out of Personal Tragedy

Known as GITIL (gastrointestinal tumor infiltrating lymphocytes), the trial was led by Steven Rosenberg, MD, PhD, chief of the NCI’s surgery branch, and began in March 2012. Bachini was the ninth patient recruited for the trial, the first with cholangiocarcinoma to participate — and the first among all participants to have a response.

Rosenberg removed 4 tumors from Bachini’s lungs, took T cells, harvested those cells, and infused 42 billion of them back into her bloodstream intravenously. Despite the vomiting, ensuing baldness, and other side effects, the procedure significantly shrank her tumors.

The return of those tumors necessitated a second surgery in September 2013. But this time, Rosenberg’s team infused more than 120 billion T cells, 95% of them of the type that would attack her specific mutation. That resulted in the overall shrinkage of her cancer by 50% to 60%, with no other treatments — just her immune cells working to keep the cancer at bay.

Cholangiocarcinoma Foundation
Caitlin Fortuna and her daughter with Mindy Cooper at the 2019 Cholangiocarcinoma Foundation Annual Conference.
Credit: Matt Barr/Cholangiocarcinoma Foundation

Bachini is relatively healthy today, 11 years after her diagnosis of cholangiocarcinoma, a disease that affects only 3 out of 100,000 Americans. . The success of her immunotherapy made headlines in The New York Times and The Wall Street Journal.

She’s now a full-time patient advocate for the Cholangiocarcinoma Foundation (CCF), which has 12 employees and is based in Salt Lake City, Utah. Most of the charity’s $2.7 million annual budget goes to research and advocacy on behalf of people with cholangiocarcinoma.

CCF staff comes from 9 states, and its International Cholangiocarcinoma Research Network has 184 members representing more than 50 countries.

“My job is to represent patients, help them find second opinions, and connect them with support networks. I do lots of public speaking, bringing awareness to cholangiocarcinoma and serving on national panels,” Bachini said. “I do whatever I can to bring the patient’s voice to the table.”

The CCF has 15,300 followers on Facebook, 2615 on Twitter, 2155 on Instagram, 1115 on YouTube, and 946 on LinkedIn.

Part of the National Organization for Rare Disorders’ Rare Cancer Action Network, the CCF was founded by Stacie Lindsey of Herriman, Utah, after her brother, Mark, died of the disease in 2006 at the age of 39.

“When Mark was diagnosed in 2005, there was no standard of care and only 4 clinical trials for cholangiocarcinoma. All had been closed for lack of accrual; they just couldn’t get enough people,” said Lindsey, now the foundation’s CEO. “There was nothing outside of PubMed, not one thing on the Internet. We were desperate to connect to other families.”

Cholangiocarcinoma: An Underreported Disease

At present, some 150 clinical trials for the disease are ongoing, and there are many more in the solid tumor area for which cholangiocarcinoma patients might qualify.

“A lot of patients are misdiagnosed in the initial phase, so they think they have gallbladder cancer or cancer of unknown primary (CUP). So we know the numbers aren’t right, even in Europe,” said Lindsey. About 8000 Americans are diagnosed with cholangiocarcinoma annually, with the 5-year survival rate for all types of intrahepatic bile duct cancer averaging 9%.

Reported prevalence varies around the world, with the highest rate seen in Southeast Asia, where in some regions it reaches 71.3 per 100,000;  that’s because locals consume raw, pickled, fermented, or undercooked fish contaminated with a parasite known as a liver fluke. The ones most closely related to cholangiocarcinoma risk are called Clonorchis sinensis and Opisthorchis viverrini; according to the CCF, around 10% of chronically infected patients with these parasites will eventually develop cholangiocarcinoma.

Reham Abdel-Wahib, MD
Reham Abdel-Wahib, MD, chief scientific officer of the Cholangiocarcinoma Foundation. Credit: Cholangiocarcinoma Foundation.

Egyptian oncologist Reham Abdel Wahid, MD, PhD, is the CCF’s research director and chief scientific officer. Based in Houston, Texas, she did a 5-year research fellowship at MD Anderson, and formerly chaired the foundation’s international research network.

“Unfortunately, this disease is definitely underestimated, because there’s an issue with coding,” she said. “Most patients present with general symptoms — fever, weight loss, jaundice. Sometimes, they’re diagnosed as having metastasis of unknown origin, and then later the disease is confirmed as CUP.”

In the United States, about 20% of cholangiocarcinoma cases arise from primary sclerosing cholangitis (PSC), in which inflammation of the bile duct (cholangitis) leads to the formation of scar tissue, or sclerosis. This is the disease subset that eventually claimed the life of Robert Redford’s son, James Redford. The 58-year-old filmmaker and activist was awaiting a liver transplant when he died in October 2020.

Targeted Therapies in the Pipeline

The good news, Dr. Wahid said, is that “more than 50% of cholangiocarcinoma patients have at least one actionable mutation in their tumors. This means the mutation has a drug that can target it.”

In April 2020, the US Food and Drug Administration (FDA) approved Incyte’s pemigatinib (Pemazyre), an oral kinase inhibitor, to treat adults with locally advanced or metastatic cholangiocarcinoma. The therapy is specifically for patients with an FGFR2 mutation, marking the first targeted therapy ever for people with this disease. Wahid said she expects the FDA to approve another 1 or 2 similar drugs this year.

On March 1, 2021, Agios submitted a New Drug Application to the FDA for Tibsovo (ivosidenib tablets) as a potential treatment option for patients with previously treated IDH1-mutated cholangiocarcinoma, the company announced.

“A lot of work has been done over these past 10 years, and lots of clinical trials,” Dr. Wahid said. “Chemo is highly toxic and many patients suffer, so for us this was one of the biggest achievements in cholangiocarcinoma ever.”

Over the years, participation in CCF’s annual conference has grown sharply. The first gathering in 2014 attracted 59 participants and 17 speakers. The most recent event, held virtually March 31-April 2, 2021, due to coronavirus concerns, featured 1647 registrants from 53 countries, 46 posters, 19 sponsors, and 56 speakers. The next one, in February 2022, will take place in Salt Lake City.

Asked what’s next for herself, Bachini replied that even though her tumors are shrinking, she’s still not cured.

“There are still a couple of spots left in my lungs that we keep an eye on. I get scans and blood work every 6 months at the NCI,” she said. “I still have some side effects from the chemo like neuropathy and ringing in my ears. But I can live with that.”

She added: “My quality of life is great. That’s why it’s really important for me to advocate for others and find a way to pay it forward.”