Novel CAR-T Cell Therapy Produces Sustainable Response in Patients with Relapsed Multiple Myeloma

Treatment with the chimeric antigen receptor (CAR)-T cell therapy idecabtagene vicleucel (ide-cel) induced deep, sustained remissions in patients with relapsed multiple myeloma after they had failed on multiple prior therapies, according to study results published in the New England Journal of Medicine.

Based on these results, an application for approval from the Food and Drug Administration was submitted for ide-cel to become a standard therapy for patients with relapsed or treatment-resistant myeloma. The agency is expected to make its decision by March 27, 2021.

“Despite numerous advances in the treatment of multiple myeloma, relapses are common. Patients whose disease continues to worsen after receiving standard therapy have relatively few treatment options that provide high response rates,” lead investigator Dr. Nikhil Munshi, from the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute in Boston, said in a press release. “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

Currently, the standards of care for myeloma include treatment with immunomodulatory drugs, proteasome inhibitors and anti-CD38 antibodies. Despite advances made with these treatments, patients with myeloma often exhaust these approaches, highlighting a need for improved treatment options.

Ide-cel is a B-cell maturation antigen (BCMA)-directed CAR-T cell therapy that is made by collecting a patient’s T cells and genetically modifying them to express a protein receptor designed to destroy tumor cells. The cells are then infused back into the patient to treat their cancer.

“(BCMA) is expressed exclusively on plasma cells and in particularly large quantities on plasma-turned-myeloma cells; BCMA conducts signals important for myeloma cells’ growth and survival; and it is expressed in virtually all patients with the disease,” Munshi explained in the release.

Therefore, in the phase 2 KarMMa trial, Munshi and colleagues aimed to confirm the efficacy and safety of ide-cel in 128 patients who received at least three previous therapies.

Measuring overall response, which includes a partial response or better, served as the main goal of the study, while a complete response or better (disappearance of all signs of their cancer) was an additional goal.

After a median follow-up of 13.3 months, 73% of patients demonstrated a response to ide-cel therapy, including 33% who experienced a complete response or better. Among those with a complete response, 79% had no detectable myeloma. Moreover, the complete responses rates and duration of responses were significantly better than currently available therapies for relapsed disease, according to the researchers.

Median progression-free survival – or the time from treatment to disease progression or worsening – was eight to nine months, with some patients not experiencing a relapse for more than two years after treatment.

The most common side effects included low blood-cell counts and cytokine release syndrome, where the immune system generates an intensive inflammatory response. However, the researchers noted there are effective treatments currently developed to treat these side effects.

Because of the promising results reported from this study, the researchers aim to evaluate ide-cel in patients with earlier stages of multiple myeloma.

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