Multiple myeloma is often associated with genetic aberrations. While the causes of such changes are not always clear, genetic predisposition is thought to play a role in many cases. Other risk factors include aging, radiation, and exposure to chemicals such as benzene. These aberrations usually affect genes coding for antibodies and include gene translocations from one chromosome to another or the gain of odd-numbered chromosomes. Patient survival is variable and usually dependent on the type of genetic aberration. The gain of odd-numbered chromosomes is usually associated with a better prognosis than the translocation of genes coding for antibodies.

In CAR-T therapies, T-cells are obtained from patient blood and infected with genetically modified viruses coding for a chimeric antigen receptor. The T-cell chimeric antigen receptor utilized in gene therapy against RRMM contains the intracellular 4-1BB and CD3-zeta molecules, a transmembrane linker region, and an extracellular region that recognizes the B-cell maturation antigen (BCMA). The 4-1BB and CD3-zeta molecules have co-stimulatory and signaling functions, respectively, promoting T-cell fitness, expansion, and activity against malignant plasma cells. The BCMA-recognizing region provides specificity against malignant plasma cells. Upon being returned to the patient, these modified T-cells are able to recognize malignant plasma cells through their BCMA. The interaction between the two cell types triggers the release of cytotoxic molecules that result in the destruction of the plasma cell.

There are two CAR-T cell therapies currently approved by the Food and Drug Administration (FDA) of the United States for the treatment of adult patients with RRMM: idecabtagene vicleucel and ciltacabtagene autoleucel. In both therapies, patient T-cells are genetically modified to produce a chimeric antigen receptor able to neutralize malignant plasma cells.