Research Seeks Other CAR T-Cell Targets in Multiple Myeloma

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of multiple myeloma, but the disease is still incurable, and many patients experience relapse or resistance to treatment.

“CAR T-cell therapy is one of the rapidly emerging and highly promising immunotherapeutic options that has shown unprecedented results in B-cell malignancies,” wrote the authors, led by Phaik Ju Teoh of the Yong Loo Lin School of Medicine at the National University of Singapore. “While B-cell maturation antigen (BCMA) is currently the most well-studied CAR T antigen target in this disease, many other antigens are also undergoing intensive investigations. Some studies have shown encouraging results, whereas some others have demonstrated unfavorable results due to reasons such as toxicity and lack of clinical efficacy.”

In an article published in Blood Cancer Journal, the authors reviewed the promising strides that have been made in CAR T-cell therapy for myeloma. However, they also pointed out the treatment is still very new in myeloma, as compared to lymphoma and acute lymphoblastic leukemia, and therefore faces several challenges.

Much of the research to date has focused on BCMA, “an ideal antigenic target due to its preferential expression on the plasma cells but not on hematopoietic stem cells.” Targeting BCMA (such as CD19) promotes growth and proliferation of plasma cells in the bone marrow, and BCMA is present in all multiple myeloma cells. However, anti-BCMA CAR T-cell therapies often come with toxicities such as cytokine release syndrome (CRS) and neurotoxicity. And some cases display treatment resistance.

Therefore, the authors wrote, researchers are exploring other non-BCMA target molecules, such as:

  • SLAMF7/CS1
  • CD38
  • TACI
  • CD138

In addition, studies are exploring the utility of combining CAR T-cell therapy with other treatments, such as lenalidomide.

“In our constant pursuit to develop personalized medicine, CAR T-cell therapy is perhaps the ultimate, as nothing can be more personalized than a treatment that harnesses the patient’s own immune system for tumor destruction,” the authors concluded. “We have every single reason to remain hopeful and optimistic that CAR T-cell therapies may one day render multiple myeloma a chronic but highly manageable and curable disease.”