A novel treatment using CAR-T cells is showing promise for treating multiple myeloma. Understanding the treatmet requires a short course in cell therapy (see sidebar). 

Liedtke explains that the treatment uses the patient’s own T cells, which reside in the body after eradicating the cancer.

Her expertise in CAR-T cells derives from her connection with Crystal Mackall, MD, Ernest and Amelia Gallo Family Professor of Pediatrics and Internal Medicine, and founder of the Stanford Center for Cancer Cell Therapy.

For most of us, a common cold or a stomach bug is a nuisance, but usually in a matter of days the body’s immune system will fight off the invading disease-causing agents and we’ll get back to normal. In more serious situations, the immune system even defeats pneumonia, endocarditis, and other severe health threats.

But that’s not the case for the 20,000 to 30,000 Americans who are diagnosed with multiple myeloma each year. Multiple myeloma is a form of cancer that affects plasma cells, the white blood cells in the bone marrow that produce antibodies to fight disease and infection.

Current treatment options include chemotherapy, radiation therapy, specialized drugs, and stem cell transplants. Despite advances in these approaches, the average American will succumb to multiple myeloma about seven to 10 years after being diagnosed with the disease.

“While we can treat the disease well initially, almost every single patient with multiple myeloma relapses, and every time the disease comes back, it becomes more resistant to therapies, making it even harder to treat,” says Michaela Liedtke, MD, associate professor of hematology.

A novel treatment using CAR-T cells is showing promise for treating multiple myeloma. Understanding the treatmet requires a short course in cell therapy (see sidebar).

Liedtke explains that the treatment uses the patient’s own T cells, which reside in the body after eradicating the cancer.

Her expertise in CAR-T cells derives from her connection with Crystal Mackall, MD, Ernest and Amelia Gallo Family Professor of Pediatrics and Internal Medicine, and founder of the Stanford Center for Cancer Cell Therapy.

Liedtke’s research on the subject was part of a study published in the May 2, 2019 issue of The New England Journal of Medicine.

“With this new CAR-T cell technology, known as BB 2121, ultimately the hope is that it will cure the disease and make it go away forever,” Liedtke proclaims.

“If any other cancer cells should develop in the future—if a relapse should ever occur—then the CAR-T cells should be ready to address that relapse or alternatively additional CAR-T cells could be infused. That’s the theoretical context,” she says.

In fact, CAR-T cell technology has proven to be effective in treating acute lymphoblastic leukemia (ALL), especially in children.

“There are studies using similar CAR-T cells showing that half to two-thirds of children with relapsed ALL, another hematological cancer, can be cured of their disease,” she says.

What Are CAR-T Cells?
T cells, part of the immune system that defends the body against infections, can become compromised when a patient develops a malignancy. One way to overcome that is to remove the T cells from the patient’s body and “re-educate” them in the laboratory. That is, each T cell is given a chimeric antigen receptor (CAR), which is why these engineered biological units are known as CAR-T cells.

After the T cells have been converted to CAR-T cells, they are reintroduced into the patient’s bloodstream and circulate in the body. The CAR-T cells are able to recognize, hunt for, and bind to certain characteristics on the surface of cancer cells before destroying them.

The CAR-T cells become very prolific and recreate themselves in great numbers. These expanded numbers of CAR-T cells circulate throughout the body and continue to hunt for myeloma cells until all the malignant cells are destroyed.

Liedtke’s research on the subject was part of a study published in the May 2, 2019 issue of The New England Journal of Medicine.

“With this new CAR-T cell technology, known as BB 2121, ultimately the hope is that it will cure the disease and make it go away forever,” Liedtke proclaims.

“If any other cancer cells should develop in the future—if a relapse should ever occur—then the CAR-T cells should be ready to address that relapse or alternatively additional CAR-T cells could be infused. That’s the theoretical context,” she says.

In fact, CAR-T cell technology has proven to be effective in treating acute lymphoblastic leukemia (ALL), especially in children.

“There are studies using similar CAR-T cells showing that half to two-thirds of children with relapsed ALL, another hematological cancer, can be cured of their disease,” she says.

What Are CAR-T Cells?
T cells, part of the immune system that defends the body against infections, can become compromised when a patient develops a malignancy. One way to overcome that is to remove the T cells from the patient’s body and “re-educate” them in the laboratory. That is, each T cell is given a chimeric antigen receptor (CAR), which is why these engineered biological units are known as CAR-T cells.

After the T cells have been converted to CAR-T cells, they are reintroduced into the patient’s bloodstream and circulate in the body. The CAR-T cells are able to recognize, hunt for, and bind to certain characteristics on the surface of cancer cells before destroying them.

The CAR-T cells become very prolific and recreate themselves in great numbers. These expanded numbers of CAR-T cells circulate throughout the body and continue to hunt for myeloma cells until all the malignant cells are destroyed.

Weissman and his colleagues later developed the Hu5F9-G4 antibody that blocks the CD47 protein, prompting macrophages to engulf and devour cancer cells.

For this clinical trial, participants were administered a combination of Hu5F-G4 and the rituximab antibody that has been shown to amplify positive “eat me” signals.

The antibody combination was used to treat people with two types of non-Hodgkin’s lymphoma: diffuse large B-cell lymphoma and follicular lymphoma.

“It’s very exciting to have a potentially new class of immunotherapy like this,” says Advani. “For the first time we have an antibody that activates macrophages against cancer and appears to be safe for use in humans.”

A novel immunotherapy combination appears safe for use in patients with a type of blood cancer called non-Hodgkin’s lymphoma. Not only that, but half of the 22 people enrolled in an early clinical trial of the therapy had a positive response, and about one-third went into complete remission from their cancer.

The therapy combines Hu5F9-G4 (an experimental antibody developed by researchers at Stanford) and a commercially available anti-cancer antibody called rituximab.

“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” says Ranjana Advani, MD, professor of medicine at Stanford. Advani is the lead author of a paper describing the results of the phase-1 trial that was published in The New England Journal of Medicine.

Some patients showed signs of a transitory anemia or reactions at the injection site, but there were few other significant side effects to the treatment, according to the paper.

Although there are many things that can kill cancer cells, the real test of a therapy is whether it can kill the cancer cells without harming normal cells. Advani says she was particularly pleased that the researchers observed only minor side effects in the participants.

How the Combination Works
In 2010, researchers led by Irving Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, showed that the CD47 protein that covers nearly all cancer cells acts as a “don’t eat me” signal to immune cells called macrophages.

Weissman and his colleagues later developed the Hu5F9-G4 antibody that blocks the CD47 protein, prompting macrophages to engulf and devour cancer cells.

For this clinical trial, participants were administered a combination of Hu5F-G4 and the rituximab antibody that has been shown to amplify positive “eat me” signals.

The antibody combination was used to treat people with two types of non-Hodgkin’s lymphoma: diffuse large B-cell lymphoma and follicular lymphoma.

“It’s very exciting to have a potentially new class of immunotherapy like this,” says Advani. “For the first time we have an antibody that activates macrophages against cancer and appears to be safe for use in humans.”

A Personal Trial
Clinical trial participant Michael Stornetta, a retired Santa Rosa businessman who said he had never previously been sick with anything worse than colds, flus, and the usual childhood maladies, was hit with follicular lymphoma over five years ago. He said that after attempting multiple therapies with “varying degrees of success,” he was referred to the Hu5F9-G4 trial at Stanford.

In October of 2017, he drove with his wife and son to Stanford to view the first scans that would reveal whether the experimental treatment was working. The scans showed that his cancer was significantly reduced. By strange coincidence, the very day he learned that he had lost his house in a devastating wildfire, he also learned that the treatment was working.

A Personal Trial
Clinical trial participant Michael Stornetta, a retired Santa Rosa businessman who said he had never previously been sick with anything worse than colds, flus, and the usual childhood maladies, was hit with follicular lymphoma over five years ago. He said that after attempting multiple therapies with “varying degrees of success,” he was referred to the Hu5F9-G4 trial at Stanford.

In October of 2017, he drove with his wife and son to Stanford to view the first scans that would reveal whether the experimental treatment was working. The scans showed that his cancer was significantly reduced. By strange coincidence, the very day he learned that he had lost his house in a devastating wildfire, he also learned that the treatment was working.

A Growing Population
As of 2019, the population of cancer survivors in the United States has grown to 17 million people. Improved treatments and earlier detection methods mean that people live longer after a cancer diagnosis than ever before—many decades, in some cases. That growing population has led to the emergence of cancer survivorship as a niche field within medicine.

In recent years, it has become popular for oncology clinics around the country to offer patients a survivorship care plan—a one- or two-page document that outlines the patient’s history with cancer, any potential long-term problems they might experience, and recommendations for follow-up care or screening tests.

PRIMARY CARE PHYSICIAN JENNIFER KIM IS HELPING PATIENTS BRIDGE THE GAP BETWEEN CANCER TREATMENT AND THE REST OF THEIR LIVES.

Every cancer patient hopes for a clean scan or blood test showing that all signs of cancer have disappeared. But it doesn’t always mean the end of the cancer story. Compared with the rest of the population, cancer survivors are at an increased risk of recurrence and second tumors. They also can have a host of complex physical, emotional, and psychosocial concerns related to their disease.

Many survivors are plagued by a fear of their cancer returning, and the anxiety can manifest itself in many ways. Treatments can also leave patients with ongoing nerve pain, lung and heart problems, or fertility issues.

Finding a health care provider to address those issues can be tricky. While oncologists can’t keep seeing patients indefinitely after signs of their cancer have disappeared, primary care physicians can be wary of answering patients’ questions that might relate to an oncology diagnosis. It leaves patients in an awkward position.

“People often feel a little bit lost when their oncologist, who they’ve been seeing regularly for months or years, says they’re doing great and don’t need to come back,” says Jennifer Kim, MD, a clinical assistant professor of medicine who is piloting a cancer survivorship clinic at Stanford.

Through her new clinic, Kim is helping bridge the gap between oncology and primary care, ushering both patients and health care providers through this transition.

A Growing Population
As of 2019, the population of cancer survivors in the United States has grown to 17 million people. Improved treatments and earlier detection methods mean that people live longer after a cancer diagnosis than ever before—many decades, in some cases. That growing population has led to the emergence of cancer survivorship as a niche field within medicine.

In recent years, it has become popular for oncology clinics around the country to offer patients a survivorship care plan—a one- or two-page document that outlines the patient’s history with cancer, any potential long-term problems they might experience, and recommendations for follow-up care or screening tests.

“Even when this is done, the information in the document isn’t always being fully communicated to primary care doctors,” says Kim.

Oncology programs have also started looking for other ways to ease patients through the transition from cancer treatment to more routine medical care, including integrating primary care doctors into their practices more closely.

Launching a Clinic
Two years ago, breast oncologist Lidia Schapira, MD, approached Kim about starting a survivorship clinic. First, Kim had to read up on what Schapira meant.

“In all my training, I hadn’t even heard of the word survivorship,” says Kim.

But the more she read—and the more meetings and seminars on survivorship she attended—the more intrigued she became. She agreed to start a pilot program; she spent time shadowing oncologists at Stanford so she’d better understand the ins and outs of cancer treatment. Then she set aside two half-days a week to see patients with breast and gynecologic cancers from the Stanford Women’s Cancer Center.

She helped address specific problems each patient might be having, whether or not the issues were related to a tumor, and set up a long-term plan for cancer screening and primary care needs. The model was immediately successful, with positive feedback from patients and oncologists alike, and Kim’s schedule filled. Since then, she’s expanded to see people who are survivors of lung, colon, and childhood cancers.

For some people, one appointment with Kim is enough to send them on their way with a plan. For others, it may require months of follow-up before they feel ready to move to another primary care provider. In either case, Kim gives them information to pass along to their doctor—or, if they’re continuing to receive care at Stanford, she might call or message the primary care provider directly.

“The advantage of me doing this instead of an oncologist is that I know what most primary care doctors can understand,” says Kim. “I try to hand off recommendations that are manageable and not full of the kind of detail and inside jargon that oncologists might use.”

Survivorship Education for Doctors
Kim can see only so many patients, but her hope is that as more primary care doctors become aware of the unique needs of cancer survivors, others will step up. To that end, Kim and Schapira designed an online continuing education course for primary care doctors to learn key points about survivorship—common long-term and delayed effects of chemotherapy and radiation, for instance.

“You don’t need to be a survivorship expert to integrate these things into your everyday practice,” says Kim. For instance, if someone who once had prostate cancer treatment complains of frequent urination to their primary care doctor, they might normally test for diabetes or pelvic floor issues. But simply being aware that this can be a delayed complication of prostate cancer treatment can help them treat it more appropriately.

She thinks that with a little extra education, primary care doctors can become more comfortable treating cancer survivors. Rather than referring these patients back to oncologists, primary care physicians armed with the right knowledge can handle many of the long-term effects of cancer and cancer treatment on their own.

“Survivorship is a chronic disease, just like diabetes and high blood pressure,” says Kim. “So it’s appropriate for primary care doctors to manage these patients who need a little extra care; it’s just that some training is needed for us to get there.”

“Even when this is done, the information in the document isn’t always being fully communicated to primary care doctors,” says Kim.

Oncology programs have also started looking for other ways to ease patients through the transition from cancer treatment to more routine medical care, including integrating primary care doctors into their practices more closely.

Launching a Clinic
Two years ago, breast oncologist Lidia Schapira, MD, approached Kim about starting a survivorship clinic. First, Kim had to read up on what Schapira meant.

“In all my training, I hadn’t even heard of the word survivorship,” says Kim.

But the more she read—and the more meetings and seminars on survivorship she attended—the more intrigued she became. She agreed to start a pilot program; she spent time shadowing oncologists at Stanford so she’d better understand the ins and outs of cancer treatment. Then she set aside two half-days a week to see patients with breast and gynecologic cancers from the Stanford Women’s Cancer Center.

She helped address specific problems each patient might be having, whether or not the issues were related to a tumor, and set up a long-term plan for cancer screening and primary care needs. The model was immediately successful, with positive feedback from patients and oncologists alike, and Kim’s schedule filled. Since then, she’s expanded to see people who are survivors of lung, colon, and childhood cancers.

For some people, one appointment with Kim is enough to send them on their way with a plan. For others, it may require months of follow-up before they feel ready to move to another primary care provider. In either case, Kim gives them information to pass along to their doctor—or, if they’re continuing to receive care at Stanford, she might call or message the primary care provider directly.

“The advantage of me doing this instead of an oncologist is that I know what most primary care doctors can understand,” says Kim. “I try to hand off recommendations that are manageable and not full of the kind of detail and inside jargon that oncologists might use.”

Survivorship Education for Doctors
Kim can see only so many patients, but her hope is that as more primary care doctors become aware of the unique needs of cancer survivors, others will step up. To that end, Kim and Schapira designed an online continuing education course for primary care doctors to learn key points about survivorship—common long-term and delayed effects of chemotherapy and radiation, for instance.

“You don’t need to be a survivorship expert to integrate these things into your everyday practice,” says Kim. For instance, if someone who once had prostate cancer treatment complains of frequent urination to their primary care doctor, they might normally test for diabetes or pelvic floor issues. But simply being aware that this can be a delayed complication of prostate cancer treatment can help them treat it more appropriately.

She thinks that with a little extra education, primary care doctors can become more comfortable treating cancer survivors. Rather than referring these patients back to oncologists, primary care physicians armed with the right knowledge can handle many of the long-term effects of cancer and cancer treatment on their own.

“Survivorship is a chronic disease, just like diabetes and high blood pressure,” says Kim. “So it’s appropriate for primary care doctors to manage these patients who need a little extra care; it’s just that some training is needed for us to get there.”