- The Food and Drug Administration on Friday approved the first CAR-T cell therapy for multiple myeloma, expanding use of the powerful but complex-to-manufacture treatments beyond leukemia and lymphoma, two other blood cancers for which several other cell-based drugs are already cleared.
- Called Abecma, the newly approved therapy is for patients who have received at least four previous multiple myeloma medicines, including standard drugs like Revlimid and Darzalex. Clinical testing showed three-quarters of participants responded to treatment with Abecma, about a third of whom went into remission.
- Abecma was developed by Bluebird bio and Bristol Myers Squibb, which acquired rights through its buyout of Celgene in 2019. The therapy is now Bristol Myers' second FDA-approved CAR-T treatment following last month's clearance of Breyanzi for lymphoma.
Abecma is at the front of a wave of new multiple myeloma therapies emerging from clinical testing that could greatly expand the number of options available for people with the persistent and deadly blood cancer. They'll join an already wide array of drugs approved since the early 2010s that have extended patient survival and given doctors more weapons to drive multiple myeloma into remission.
Even with more options, though, patients commonly relapse. Nearly all of the many drugs brought to market since the landmark approval of Revlimid in 2005 work in one of three different ways, meaning resistance to one type of therapy can make it unlikely others of the same group will be effective.
Abecma and the new crop of treatments of which it's a part work differently. Their development has been fueled by research on a tell-tale protein called BCMA that's commonly found on cancerous B cells, but not on healthy cells. One such BCMA-targeting drug, GlaxoSmithKline's Blenrep, won U.S. approval last year, and others from Johnson & Johnson, Amgen, Regeneron, AbbVie and AstraZeneca are in testing.
Many of those companies' drugs are antibodies that bind to both BCMA and immune cells. Abecma, by contrast, is a CAR-T cell therapy, consisting of a patient's own immune cells that are extracted and genetically engineered in a laboratory to seek out BCMA.
CAR-T therapies are complex and particularly laborious to construct and administer. Abecma, for instance, takes a little more than three weeks to produce and administer, from when the patient cells are extracted to when they're reinfused back into the body.
CAR-T treatment can also trigger dangerous neurological side effects and an immune overreaction known as cytokine release syndrome.
But the therapies can be exceptionally powerful for some patients. In the Phase 2 trial that supported Abecma's approval, a third of all 128 treated patients went into remission after treatment. For about a quarter of patients, researchers could not find any signs of multiple myeloma — a more stringent standard known as minimal residual disease.
Overall, 73% of patients in the study had some response to treatment. Median duration of response, a measure of how long a patient's cancer is held in check, was about 11 months. Among patients from whom treatment worked particularly well, the median duration of response was much longer, approximately 19 months.
As with other CAR-T therapies, Abecma's label carries a black box warning for cytokine release syndrome and neurological side effects. The prescribing information also cautions that treatment can in rare cases lead to a potentially life-threatening condition called hemophagocytic lymphohistiocytosis, or HLH. In Bristol Myers' study, five patients had HLH, two of whom died.
Because of the safety concerns, Abecma is approved with a risk management plan that requires treatment to be administered through certified healthcare facilities.
Approval of Abecma was a long time coming for Bristol Myers and Bluebird, which had submitted the treatment to the FDA last May only for the agency to reject their application over manufacturing issues. Bristol Myers also ran into delays with its other CAR-T therapy Breyanzi.
Despite approval coming months later than the companies had initially hoped for, Bristol Myers and Bluebird are still a step ahead of Johnson & Johnson, which has a rival CAR-T therapy for multiple myeloma in development. The pharma, which licensed the program from Legend Biotech, began submitting its application to the FDA for approval last December.
Bristol Myers and Bluebird, which are jointly commercializing Abecma, set the list price of the therapy at $419,500, roughly in the same range as other approved CAR-T therapies. While patients can be re-dosed with Abecma and other CAR-Ts, the therapies are generally still thought of as a one-time treatment.