FDA Approves First CAR T-Cell Therapy for Multiple Myeloma

CAR T-Cell Therapy Now Available for Multiple Myeloma Patients

The FDA has approved the first chimeric antigen receptor (CAR) T-cell therapy for adult patients with multiple myeloma who have not responded to or have relapsed after at least four different types of therapy, including lenalidomide (Revlimid) and daratumumab (Darzalex).

Abecma (idecabtagene vicleucel), which was developed by bluebird bio and Bristol Myers Squibb, targets the B-cell maturation antigen (BCMA), a protein expressed by multiple myeloma cells. It is a one-time infusion created by using a patient’s own T cells, which are collected and genetically modified to kill BCMA-expressing cells. Once the T cells are modified, they are infused back into the patient. 

This is Bristol Myers Squibb’s second FDA-approved CAR T-cell treatment following February’s approval of Breyanzi (lisocabtagene maraleucel or liso-cel) for large B-cell lymphoma, and the first CAR T-cell therapy approved for use outside of leukemia and lymphoma.

“CAR T-cell therapies have shown transformational potential for the treatment of hematologic malignancies…” said Dr. Samit Hirawat, chief medical officer of Bristol Myers Squibb, in a March 26 press release. “As our second FDA-approved CAR T-cell therapy, Abecma underscores our commitment to deliver on the promise of cell therapies for patients who are battling aggressive and advanced blood cancers with limited effective treatment options.” 

How Effective is Abecma?

Abecma was studied in patients with relapsed/refractory myeloma, who had received at least three prior therapies (triple-exposed), including an immunomodulatory agent (such as lenalidomide), a proteasome inhibitor (like bortezomib) and an anti-CD38 antibody (such as daratumumab). About 88% of the participants had received four or more therapies.

Of the 100 evaluable participants 72% responded to the treatment; 28% had a complete response or better — the disappearance of all signs of multiple myeloma — and 65% of this group remained in complete response to the treatment for at least 12 months. The responses were fast — a median time of 30 days — and durable, lasting a median of 11 months. 

“As a treating physician, I often work with patients with relapsed or refractory multiple myeloma who are in critical need of new therapies,” Dr. Nikhil C. Munshi, associate director of the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston, said in the release. “Now, with the approval of ide-cel … we are excited to finally be able to offer patients a new, effective personalized treatment option that is delivered through a single infusion.”

What Are the Side Effects of Abecma?

Abecma carries boxed warnings for cytokine release syndrome, a systemic inflammatory response associated with CAR T therapy (symptoms include fever, nausea, headache, rash, rapid heartbeat, low blood pressure and trouble breathing) and neurologic toxicities, such as aphasia (speech issues), tremors, confusion and seizures.

Because of this, it is being approved with a risk evaluation and mitigation strategy. The FDA is requiring that hospitals and their associated clinics that dispense Abecma be specially certified, and that staff who are involved in the prescribing, dispensing or administering of Abecma be trained to recognize and manage the drug’s side effects.

“On rare occasions, (CRS) can be severe and patients need to go to the intensive-care unit,” said Dr. Sergio Giralt, of Memorial Sloan Kettering Cancer Center in New York City, in a recent Patient Power interview. “But generally speaking, with early recognition and rapid treatment, these complications are reversible, and the chances of serious life-threatening complications are relatively low when this is done in a specialized center that has a lot of experience doing this.”

Are We Any Closer to a Cure for Multiple Myeloma?

While there is still no cure for multiple myeloma, there has been significant progress in the treatment of this blood cancer.

Last week, the FDA approved Sarclisa (isatuximab-irfc) in combination with carfilzomib and dexamethasone (Kd) for adult patients with relapsed/refractory multiple myeloma who have received one to three prior lines of therapy. Earlier in March, the agency approved Pepaxto (melphalan flufenamide) in combination with dexamethasone for adult patients with relapsed/refractory multiple myeloma who have received at least four prior lines of therapy.

Last year saw the approval of Blenrep (belantamab mafodotin-blmf); Darzalex Faspro (daratumumab and hyaluronidase-fihj); and Sarclisa, in combination with pomalidomide (Pomalyst) and dexamethasone.

"What I tell patients when I first started in this, I would always start off the diagnosis saying, ‘We don't have a cure for this,’” said Dr. Joshua Richter, assistant professor of medicine in The Tisch Cancer Institute at Mount Sinai in New York City, in a Patient Power Myeloma Answers Now program.

“And what I say now is, ‘My goal is to keep you alive until there's a cure.’ And in fact, that we may have a cure today for some patients if we use the right drugs, the right technologies, and the right combinations. To me, that's been the biggest change over the last couple of years — is at least how I conceptualize even curing myeloma.”