Multiple Myeloma Relapse: How Cells Adapt to Immunotherapy

Research led by the University of Calgary has explored why some patients with multiple myeloma relapse after receiving a specific form of immunotherapy. The study focused on patients who had undergone treatment with bispecific T-cell engagers, finding that multiple myeloma cells can adapt to these therapies, which helps explain the recurrence of the cancer.

Multiple myeloma is identified as the second most common blood cancer in adults. The disease originates in the white blood cells responsible for producing antibodies that fight infections.

Understanding Immunotherapy and Relapse

The international study examined tumor cells from patients who experienced a relapse following the use of bispecific T-cell engagers. This type of immunotherapy is designed to help the immune system target and eliminate cancer cells, but the findings suggest that the cancer cells possess the ability to adapt to the treatment.

This adaptive capability allows the cancer cells to survive despite the presence of immunotherapy, eventually leading to the relapse of the disease in many patients.

The Landscape of Multiple Myeloma Treatments

Medical advancements have significantly extended progression-free survival for patients with multiple myeloma, with some reaching 17 years due to the use of contemporary quadruplet induction therapies. However, there is a continuing need for new treatment options, particularly for high-risk patients.

Current cellular immunotherapy efforts focus on several primary chimeric antigen receptor T (CAR-T) cell target molecules, including:

• BCMA (B-cell maturation antigen)
• GPRC5D
• FcRH5
• SLAMF7
• TACI

To improve treatment efficacy, researchers are developing dual-target treatments. For example, bispecific CS1-BCMA CAR-T cells have shown clinical activity in patients with relapsed or refractory multiple myeloma.

Specific CAR-T cell therapies, such as ide-cel and cilta-cel, which target BCMA, have received approval from the U.S. Food and Drug Administration for the treatment of relapsed/refractory multiple myeloma. These approvals were based on the results of the KarMMa and CARTITUDE phase 2 trials.

Future Directions in Research

While current CAR-T therapies are used for relapsed or refractory cases, research is ongoing to determine if these products can be administered to newly diagnosed patients or used as a form of maintenance therapy.

The synthesis of recent advances emphasizes the transformative impact of bispecific antibodies and BCMA-targeted CAR-T cells in managing relapsed/refractory multiple myeloma. By understanding how cells adapt and cause relapse, researchers aim to develop more resilient therapies that can prevent the cancer from evolving past the immune system’s defenses.