NEJM: CAR-T cell therapy in multiple myeloma

NEJM: CAR-T cell therapy in multiple myeloma. Interpretation of NEJM papers! Clinical trials show that CAR-T cell therapy produces deep and sustained remission in multiple myeloma.

An international clinical trial found that a major advancement in the treatment of multiple myeloma is that a CAR-T cell therapy has previously received multiple treatments Patients who relapsed later achieved deep and sustained remission. The relevant research results were published in the NEJM journal on February 25, 2021, with the title of the paper “Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma”.

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In this clinical study, researchers from the United States, Spain, France, Belgium, Italy, Germany, and Canada reported that nearly 75% of the participants called this idecabtagene vicleucel (ide-cel, also known as bb2121) The CAR-T cell therapy responded, and one-third of them had complete remission. These researchers said that the rate and duration of this remission response are significantly better than the remission response of current existing therapies to patients with multiple relapses.

Based on these findings, these researchers have submitted an application to the U.S. Food and Drug Administration (FDA) for approval of ide-cel as the standard therapy for patients with relapsed or treatment-resistant myeloma. The FDA is expected to make a decision on the application at the end of March 2021.

The corresponding author of the paper and Dr. Nikhil Munshi of the Dana-Farber Cancer Institute said, “Despite many advances in the treatment of multiple myeloma, recurrence is common. For patients whose disease continues to worsen after receiving standard treatment, In other words, there are relatively few treatment options that provide high response rates. The results of this trial represent a real turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other treatments for these patients. So effective.”

Multiple myeloma is a cancer of plasma cells, where plasma cells are a type of white blood cell responsible for making antibodies against invading bacteria. Approximately 35,000 people in the United States are diagnosed with this disease each year, making it the second most common blood cancer among adults. Among African Americans, it is the most common blood cancer.

The standard treatment for myeloma includes three main types of therapy: immunomodulatory drugs, proteasome inhibitors (which block the action of the proteasome in cells) and anti-CD38 antibodies. Patients who have exhausted these methods urgently need better treatments.

Like all CAR-T cell therapies, ide-cel collects the patient’s immune system T cells and genetically modifies them so that they express CAR receptors that recognize the surface proteins of cancer cells. After being injected into the same patient, CAR-T cells will target the tumor cells and destroy them.

The target of ide-cel is a protein called B-cell maturation antigen (BCMA) on the surface of myeloma cells. Munshi explained that BCMA has several advantages as a therapeutic target for myeloma: it is only expressed on the surface of plasma cells, especially on the surface of plasma cells transformed into myeloma cells; BCMA can transmit the growth and development of myeloma cells. An important signal for survival; and it is expressed in almost all myeloma patients.

In this phase 2 clinical study called KarMMa, 128 patients with active myeloma who had received at least 3 previous treatments received a single dose of ide-cel (different patients tested different doses). At a median follow-up of 13.3 months, 73% of patients (94 people) responded—their cancer was significantly reduced, and 33% of patients (42 people) had a complete or better remission. Among these 42 people, 79% of patients did not find myeloma. The median progression-free survival—the length of time the disease does not get worse after treatment—is 8-9 months. Some patients did not relapse more than two years after treatment.

These results exceed those achieved with standard treatment for multiple myeloma. Drugs such as selinexor, panobinostat, and isatuximab have a response rate of 25% to 30%, and a progression-free survival period of 3 to 4 months .

The most common side effects of ide-cel treatment are low blood cell count and cytokine release syndrome. Cytokine release syndrome is a sequelae that often occurs after CAR-T cell therapy: the immune system produces a high-intensity inflammatory response. Clinicians have developed effective treatments for this side effect.

The success of ide-cel in patients who had previously undergone several treatments prompted these researchers to carry out clinical trials of this CAR-T cell therapy in patients in the early stages of the disease.

(sourceinternet, reference only)

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