New Immunotherapy Treatment Looks Promising in Relapsed/Refractory Multiple Myeloma

Patients with relapsed or refractory multiple myeloma responded well to a treatment called chimeric antigen receptor (CAR) T-cell therapy, according to data from a phase 1 clinical trial called LEGEND-2.

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 re-appeared 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, and phase 1 trials (like LEGEND-2) usually involve a small number of patients who didn’t respond to other standard therapies. The people who participate in these trials are usually the first to receive a new treatment, and, in this particular study, patients were treated with a new CAR T-cell therapy called LCAR-B38M.

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 other approved treatments typically only survive for about another year.

This study involved 74 patients with relapsed or refractory multiple myeloma who were enrolled at 4 different hospitals in China. As of the July 31, 2019, cutoff date, 57 patients had been infused with LCAR-B38M at one of those 4 sites. At the 2019 ASH Annual Meeting, Bai-Yan Wang, MD, PhD, one of the study’s lead investigators, presented the long-term follow-up data from those 57 patients.

After leukapheresis (a laboratory procedure in which white blood cells are separated from a sample of the patient’s blood), patients received the chemotherapy drug cyclophosphamide, followed by an infusion of CAR T-cells.

The overall response rate was an impressive 88%, with complete responses seen in 42 patients (74%), 68% of whom became minimal residual disease (MRD)-negative, which is a sign of an effective treatment. MRD is a term used to describe the small number of cancer cells in the body after cancer treatment, so an MRD-negative result means that no disease was detected after treatment. Doctors use MRD to measure the effectiveness of treatment and to predict which patients are at risk of relapse.

Response rates are another way to tell how effective a new treatment is, and the overall response rate refers to the number of patients who had a partial response (a decrease in the amount of cancer in the body), a very good partial response (they responded well to therapy, but still have a small number of remaining myeloma cells), or a complete response (they had no evidence of myeloma cells left in their bone marrow or blood).

Very good partial responses were seen in 2 patients (4%) in the group, and partial responses were seen in 6 patients (11%).

Median progression-free survival was 19.9 months in all treated patients, and it rose to 28.2 months in MRD-negative complete responders. In patients without complete response, progression-free survival was a little over 3 months. Progression-free survival is the length of time that a person lives with their cancer without it getting any worse, and measuring it is yet another way for doctors to determine how well a treatment works.

“Patients who reached complete response in this study had a long survival benefit,” Dr. Wang pointed out.

There was one particularly remarkable patient in the study, with a progression-free survival of 39 months. This man had received 5 previous lines of treatment and didn’t respond well to any of them, but as of September 2019, he remains cancer-free.

“No maintenance treatment was given after his LCAR-B38M infusion,” she added. “This patient is now tumor-free and treatment-free.”

Almost all patients experienced some side effects, including pyrexia in 91%, cytokine release syndrome in 90%, thrombocytopenia in 49%, and leukopenia in 47% of patients.

Grade 3 or worse side effects were seen in 65% of patients, including leukopenia in 30%, thrombocytopenia in 23%, and increased aspartate aminotransferase in 21% of patients. Only 4 patients developed grade 3 cytokine release syndrome (grade 3 side effects are severe or medically significant, but not immediately life-threatening).

“This study provides evidence that LCAR-B38M is a highly effective therapy for relapsed/refractory myeloma,” said Dr. Wang. “LCAR-B38M displayed a manageable safety profile…and with a median follow-up of 25 months, demonstrated a high overall response rate and deep and durable responses.”