Israeli Breakthroughs Credited for Early Progress in Treating Multiple Myeloma

Shlomit Norman was 42 when doctors diagnosed her with multiple myeloma — an incurable bone marrow cancer that rarely strikes people under the age of 65.

At the time, the youngest of her three boys was 10, and few patients with the disease survived for more than a couple of years.

“I told my best friend that she’d have to be in charge of my son’s bar mitzvah, because I didn’t think I’d be around by then,” recalled Norman, who lives in Haifa, Israel.

Leaders of AMEN, the Israel Association of Myeloma Patients, gather at Tel Aviv University for the group’s annual conference on May 24, 2019. (Photos courtesy of AMEN)

But thanks to some innovative treatments with roots in Israeli research, Norman managed to outlive her initial prognosis and today leads a relatively stable life 12 years later.

“For the first 10 years after I was diagnosed, I was in a partial remission after my first bone marrow transplant, and I had a fantastic quality of life,” she said. “But in 2016, I relapsed and had another transplant. Since then, I’m on maintenance medicine. Other than fatigue, and numbing in the hands and feet, I’m OK.”

About 13,000 Americans die every year from multiple myeloma (commonly referred to as myeloma), according to the American Cancer Society. However, the typical life expectancy for patients following diagnosis has increased from two years to about eight to 10.

Some people have lived for more than two decades with myeloma — a cancer in which the body produces too many plasma cells that “crowd out” other types of cells, such as platelets and red blood cells, which are necessary for optimal health.

Nobel Prize-winning discovery led to early treatments

A significant part of the global progress in treating multiple myeloma, which was first documented in 1844, stems from research conducted in Israel.

In 2004, Aaron Ciechanover and Avram Hershko, scientists at Haifa’s Technion-Israel Institute of Technology, won the Nobel Prize in Chemistry, along with American biologist Irwin Rose, for their discovery years earlier of the ubiquitin proteasome system, a pathway responsible for the degradation of proteins.

Israeli scientists Avram Hershko and Aaron Ciechanover work in their lab at Haifa’s Technion, in this 2005 file photo.

This discovery was crucial to the creation of a class of treatments called proteasome inhibitors — medications that slow the degradation of proteins and thereby inhibit the progression of the cancer, said Yael Cohen, MD, head of myeloma services at Tel Aviv’s Ichilov Hospital, also known as the Sourasky Medical Center.

Velcade (bortezomib), a treatment which came out of that research, was a “revolutionary drug, and it’s still used a first-line treatment for myeloma in most places around the world,” Cohen said.

The early work on proteasome inhibitors was groundbreaking even if the scientists didn’t fully realize all its implications at the time, said Mark Israel, MD, national executive director of the New York-based Israel Cancer Research Fund (ICRF), which helped fund Ciechanover’s research and raises millions of dollars every year for cancer research in Israel.

“When Ciechanover and Hershko got the Nobel Prize for something important, they had no idea they had discovered the target that works in multiple myeloma,” Israel said. “But if they had never done their work, everybody with the disease would still be dying quickly.”

Now second- and third-generation treatments have resulted from the same research, such as Kyprolis (carfilzomib), a selective proteasome inhibitor given to patients via an intravenous line, and Ninlaro (ixazomib), the first oral therapy for multiple myeloma.

Longer life expectancies

A more recent Israeli contribution to treating multiple myeloma was the invention of the CAR-T cell, based on early work by Zelig Eshhar of the Weizmann Institute of Science in Rehovot, south of Tel Aviv.

A T-cell is a type of white blood cell that helps the human immune system fight harmful microbes. CAR-T cells are specially modified T-cells designed to fight cancer.

Shlomit Norman chairs AMEN, the Israel Association of Myeloma Patients.

“Eshhar’s idea was to take a T-cell, modify it genetically and implant a hybrid receptor that can target the cancer antigen and have a component that activates the T-cell to kill the cancer cell,” Cohen said. “This was later developed for the treatment of leukemia and lymphoma, and we are now hoping to open CAR-T clinical trials in Israel to treat multiple myeloma in the next few months.”

Moshe Gat, MD, chairs the Israeli Multiple Myeloma Study Group, a gathering of 20 to 30 physicians who meet every few months to discuss current topics in myeloma. The group runs joint clinical trials, and advocates for better patient care and access to medication.

“When I was a fellow 15 years ago, the median survival for a patient with multiple myeloma was two and a half years,” Gat said. “Since then, it’s nearly quadrupled, and I don’t know what to say to a new patient since so many treatments are coming online.”

Help for myeloma patients in Israel

About 550 people in Israel are diagnosed with multiple myeloma each year, with roughly 3,500 patients living with the disease at any given time, according to Norman, who chairs AMEN- The Israeli Association of Myeloma Patients. The nonprofit, founded in 2005, advocates for multiple myeloma patients throughout the country. Its most recent annual meeting took place in May at Tel Aviv University.

“These days, people are living with myeloma much longer than they used to,” Norman said. “Even if they’re diagnosed with myeloma at the age of 40, they can still hope for many years of a good quality of life.”

The association offers support through monthly meetings, empowerment workshops and an active Facebook group with more than 600 members. Several months ago, it also launched a guide called “Living Well with Myeloma,” which takes newly diagnosed patients step-by-step through the medical process.

“It includes what you need to know, how to get a second opinion, and what your rights are. It’s already in Hebrew, and we’re looking for money to translate it into Russian and Arabic,” Norman said, noting that English-speaking patients already have access to a wealth of myeloma information online.

Scientists gather for the annual conference of AMEN, the Israel Association of Myeloma Patients, at Tel Aviv University in May 2019.

The most difficult thing about living with myeloma, Norman said, is the inevitability that her health will take a turn for the worse.

“For now, there’s no cure, so even when you’re in remission, you know it’s going to come back,” she said. “You don’t know when or how, but every physician you ask will say ‘you’re going to relapse.’ We always carry this fear.”

While the median age for a multiple myeloma diagnosis is 70, some patients get it much younger. It’s outdated thinking to view myeloma as a disease of the elderly, Norman said.

Myeloma is one of the many cancers that the ICRF is targeting through research.

“We’re trying to use the best minds in the world to ask the fundamental questions about cancer cells: How do they grow, how do they metastasize, how do they invade normal tissue and ultimately do things which make people sick and die?” Israel said. “We contribute to the fund of knowledge on which cancer interventions are based. This is where the investment really counts.”