01 March 2021

A new CAR T-cell therapy has been hailed as a “turning point” for patients with relapsed multiple myeloma, with significantly increased response rates.

A global study called KarMMa, involving researchers from the USA, France, Italy, Germany, Canada and Spain, showed that almost 75% of the participants responded to idecabtagene vicleucel (ide-cel), with one third having a complete response.

The researchers say these response rates, and the duration of the responses, are significantly better than those produced by currently available therapies for patients with multiple relapses. The results have led to an application being submitted to the US Food and Drug Administration for the approval of ide-cel as a standard therapy for patients with relapsed or treatment-resistant myeloma.

Study leader Dr Nikhil Munshi, of Dana-Farber Cancer Institute, USA, said: “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.

“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.”

The results of the study are published online in the New England Journal of Medicine.

ide-cel is made by collecting a patient's T cells and genetically modifying them to express a chimeric antigen receptor (CAR) which binds to a protein on cancer cells. When they are infused back into the patient, the CAR-T cells lock onto tumour cells and destroy them.

The target of ide-cel is the B-cell maturation antigen (BCMA), which is expressed exclusively on plasma cells, and in particularly large quantities on transformed plasma cells. BCMA conducts signals that are important for myeloma cells' growth and survival, and it is expressed in virtually all patients with the disease.

In the KarMMa phase 2 study, 128 patients with active myeloma who had had at least three previous therapies were treated with a single dose of ide-cel.

At a median follow-up of 13.3 months, 73% of the patients had a measurable reduction in their cancer and 33% had a complete response or better. Within the latter group, 79% had no detectable myeloma.

The median progression-free survival was eight to nine months, with some of the patients remaining relapse-free more than two years after treatment.

The investigators say the results are far better than those achieved by standard treatments for multiply-relapsed myeloma. Drugs such as selinexor, panobinostat, and isatuximab have a response rate of 25% to 30% and a progression-free survival of three to four months.

The success of ide-cel in patients who had undergone several previous treatments has led the researchers to launch trials in patients in earlier stages of the disease.


Munshi NC, Anderson LD Jr, Shah N, Madduri D, Berdeja J, Lonial S, Raje N, Lin Y, Siegel D, Oriol A, Moreau P, Yakoub-Agha I, Delforge M, Cavo M, Einsele H, Goldschmidt H, Weisel K, Rambaldi A, Reece D, Petrocca F, Massaro M, Connarn JN, Kaiser S, Patel P, Huang L, Campbell TB, Hege K, San-Miguel J. (2021) “Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma.” New England Journal of Medicine, doi: 10.1056/NEJMoa2024850