CAR T-Cell Therapy: A New Treatment for Myeloma?

Chimeric antigen receptor (CAR) T-cell therapy could soon be approved as a new treatment for patients with relapsed or refractory multiple myeloma, according to results from a clinical trial called CARTITUDE-1.

CAR T-cell therapy is a type of cancer treatment in which a patient’s T-cells (a type of immune system cell) are taken from a patient’s blood, changed in a laboratory to become cancer-attacking cells, and then re-injected into the patient’s body.

The term “relapsed” refers to patients whose cancer reappeared or grew again after a period of remission. “Refractory” is used to describe a person whose cancer did not respond to treatment (meaning that their cancer cells continued to grow) or whose response to treatment did not last very long.

Clinical trials are designed to test the safety and effectiveness of new drugs. Phase 1b trials (like CARTITUDE-1) usually involve a small number of patients who did not respond to other standard therapies. The people who participate in these trials are the first to receive a new treatment, and in this study, patients were treated with a new CAR T-cell therapy called JNJ-4528.

Recent progress has led to longer survival in patients with multiple myeloma, but CAR T-cell therapy is not yet approved for the treatment of this particular type of cancer, and patients with relapsed or refractory multiple myeloma who have failed on all approved treatments typically survive for about another year.

“Every single patient responded to treatment”

But in this study, 100% of patients responded to the new treatment. Sixty-nine percent of patients were in complete response, meaning they had no evidence of myeloma cells in their bone marrow or blood, and 86% of patients had a very good partial response or better (this means they responded well to therapy, but still have a small number of remaining myeloma cells).

“Every single patient on the study responded to therapy, for an overall response rate of 100%, with 66% showing stringent complete responses,” said Dr. Deepu Madduri, one of the study’s lead investigators. “Considering these patients have all received multiple prior therapies, these results are extremely encouraging.” (Stringent complete response is the highest classification of treatment response, and is better than complete response, very good partial response, partial response, or stable disease.)

Patients whose cancer was getting worse and who had received at least 3 previous treatments, including at least 1 proteasome inhibitor, 1 immunomodulatory drug and 1 CD38 therapy were allowed in the trial. These patients were very heavily pretreated, and had received anywhere from 3 to 18 lines of treatment before participating in the study.

After enrolling in the trial, T-cells were collected from patients and were genetically altered. Then, patients received lymphodepletion chemotherapy, which wiped out their T-cells to make room for the newly engineered cells to move in and do their job. Finally, a total of 29 patients were injected with the new JNJ-4528 cells. These new CAR T-cells were specially engineered to attack the B-cell maturation antibody (BCMA) protein that is found on myeloma cells.

Most patients responded quickly to the treatment, and their responses were long lasting. When the researchers collected the data from this part of the study, 27 of 29 patients still had not progressed, meaning their cancer did not get any worse.

The most common side effects were neutropenia (in 93% of patients), anemia (in 86%), and thrombocytopenia (in 86%). Side effects not related to the blood or bone marrow were very uncommon. All but 2 patients experienced cytokine release syndrome (CRS), but most were mild, and symptoms of CRS typically showed up in about a week.

“It was thought initially that CAR T-therapy was going to cure these patients,” said Dr. Madduri. “Maybe ‘cure’ isn’t the right word yet, but perhaps we can give a one-time treatment for these patients who usually come once or twice a week for infusions.”

In early December, JNJ-4528 received breakthrough designation from the US Food and Drug Administration. This is a process that gets the drug approved more quickly, so doctors can treat patients with it sooner.