FDA Approves BCMA-Targeted CAR T-Cell Therapy for Multiple Myeloma

April 14, 2021, by Nadia Jaber

A type of immunotherapy called CAR T-cell therapy is now an option for some people with multiple myeloma. On March 26, the Food and Drug Administration (FDA) approved idecabtagene vicleucel (Abecma) for people with multiple myeloma that has not responded to or has returned after at least four different prior cancer treatments.

Multiple myeloma is a type of cancer that occurs when abnormal white blood cells build up and form tumors in the bones and other locations. Although there are many treatments for multiple myeloma, they typically work for only a few months and can cause many side effects.

The new approval is based, in part, on the results of a small study in which idecabtagene vicleucel (ide-cel) partially or completely shrank tumors in 72% of patients. These effects lasted for a median of 11 months.

“I’m very excited about this [approval]. This work builds on earlier work conducted by my group at NCI that showed CAR T cells could be an effective treatment for multiple myeloma,” said James Kochenderfer, M.D., a senior investigator in NCI’s Center for Cancer Research.

“However, we still have a long way to go because very few patients, if any, are cured [by ide-cel]. So we need to continue research to improve the treatment to try to permanently cure patients of multiple myeloma,” Dr. Kochenderfer added.

To make CAR T-cell therapies, a patient’s own T cells are collected, genetically engineered so they are better able to “see” and kill cancer cells, and then given back to the patient. With ide-cel, genetic engineering lets the CAR T cells “see” BCMA, a protein that’s present at high amounts in multiple myeloma cells. BCMA is found in a small subset of healthy white blood cells but not in other healthy cells.

Like other CAR T-cell therapies, ide-cel can have serious side effects, including overactive immune responses that can be life threatening. CAR T-cell therapy is also custom made for each patient, which takes a few weeks to a month. For that reason, these therapies are typically only available at bigger hospitals. In addition, they can be expensive. The list price for ide-cel, which consists of a single infusion, is $419,500. However, the cost to an individual will vary depending on their insurance plan.

Effects of Ide-cel on Multiple Myeloma

In the study that led to the approval, 100 participants received a single infusion of ide-cel. More than half of the patients (60%) were men and 78% were white. They had previously received between 3 and 16 different cancer treatments. Bristol Myers Squibb and bluebird bio, the manufacturers of ide-cel, funded the study.

For people with multiple myeloma who have already received several different treatments, additional therapies typically work for 3 to 4 months and rarely eliminate the cancer completely.

Overall, 72 participants (72%) responded to ide-cel, including 44 whose tumors partially shrunk and 28 whose tumors disappeared completely. People whose tumors disappeared completely stayed in remission for a median of 19 months. For all participants who responded to the treatment, the remission lasted a median of 11 months.

“During these remissions, patients do not need to take any other multiple myeloma therapy, which allows them to avoid [certain] side effects and to have a high quality of life,” Dr. Kochenderfer noted. That’s a big difference from standard multiple myeloma treatments, which patients often take even if they are in remission, he explained.

“Patients are usually very happy after they get the CAR T-cell therapy because, for the first time in a long time, they have a lot of energy,” he said.

Additional results from the study were published February 25 in New England Journal of Medicine.

What Are the Side Effects of Ide-cel?

Nearly all trial participants (99%) experienced a serious side effect. The most common side effects were fatigue, infections, and cytokine release syndrome.

The approval comes with a boxed warning (a notification of serious or life-threatening risks) for four treatment-related side effects:

• cytokine release syndrome
• hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)
• brain-related side effects (neurotoxicity)
• lower-than-normal number of blood cells (prolonged cytopenia)

Because CAR T-cell therapies boost the immune system, they can sometimes go too far, causing a dangerous overreaction like cytokine release syndrome or HLH/MAS. Although serious and potentially life threatening, these complications can usually be treated if the symptoms are recognized early. Symptoms of both reactions include high fever, low blood pressure, and flu-like symptoms.

Like other CAR T-cell therapies, ide-cel also caused brain-related side effects such as confusion, seizure, tremor, loss of speech, and delirium. Three patients in the trial had brain-related side effects that didn’t go away.

Side effects	Any reaction (mild to deadly)	Serious reaction	Deaths
Cytokine release syndrome	85%	9%	1
HLH/MAS	4%	4%	2
Brain-related side effects	28%	4%	0
Prolonged thrombocytopenia	-	49%	0
Prolonged neutropenia	-	41%	0

FDA requires staff who prescribe, dispense, or administer ide-cel to be trained to recognize and manage these serious side effects. FDA also advises staff to monitor patients for these side effects for at least 4 weeks and to have counteractive treatments readily available.

Ide-cel’s Origins at NCI

Dr. Kochenderfer and his NCI colleagues designed and created the first BCMA-targeted CAR T cells for multiple myeloma in 2013. Two years later, the technology was licensed by bluebird bio and developed under a cooperative research agreement between NCI, bluebird bio, and Bristol Myers Squibb.

“The first five patients to receive Abecma, which was then called bb2121, were treated at NCI,” said Dr. Kochenderfer, who led the first clinical study of the treatment.

He recalled one patient with very advanced multiple myeloma that hadn’t responded to any standard therapies. After treatment with ide-cel, the patient went into remission for 39 months.

“That’s what [the treatment] can do when it works at its best,” he said.

Dr. Kochenderfer and his team continue to develop and test CAR T-cell therapies for multiple myeloma, including CAR T cells that target a protein called SLAMF7. Several other CAR T-cell therapies are also in development for multiple myeloma, including another BCMA-targeted CAR T-cell therapy known as ciltacabtagene autoleucel (cilta-cel).