Evaluating combination CAR-T cell therapy for recurrent or treatment-resistant multiple myeloma

This study evaluated the safety and effectiveness of combining two T-cell therapies for multiple myeloma (MM) that has come back or stopped responding to treatment. This study concluded that this treatment showed promising effectiveness for these patients.

Treatment for patients with MM that has come back (relapsed) or become refractory (stopped responding to treatment) can be challenging. Chimeric antigen receptor (CAR) T-cell therapy is one option for these patients. CAR T-cell therapy uses genetically modified T-cells (immune cells) to help the immune system attack cancer cells.

The modified T-cells make a protein called CAR, which helps them recognize molecules on cancer cells called antigens. Cancer cells can have different kinds of antigens, such as BMCA. CD19 is another antigen found on aggressive myeloma cells. Whether combining T-cells that recognize these antigens into one cell therapy is effective for MM is unclear.

This study included 21 patients with relapsed or refractory MM. Patients had an average of 6 lines of prior therapy. In this study, patients were given chemotherapy followed by infusions of two types of CAR-T cells. The average follow-up was 179 days.

Overall, 95% of patients responded to treatment. 43% of patients had a complete response (no signs of cancer after treatment). 24% of patients had a very good partial response (significant tumor shrinkage). 14% of patients had some tumor shrinkage.

Patients who had tumor shrinkage survived for an average of 243 days without disease progression. 43% of patients who had no signs of cancer after treatment continued to be cancer-free for more than 6 months. 19% of patients remained cancer-free for more than 1 year.

Overall, 95% of patients had serious side effects. The most common one was seriously low white blood cell count (86%). 62% of patients also had seriously low red blood cell or platelet counts (cells involved in blood clotting).

90% of patients developed cytokine release syndrome (CRS). In this syndrome, the immune system is overactive, causing symptoms such as fever and fatigue. Most cases were mild (80%).

This study concluded that combining T-cell therapies for two different antigens (BMCA and CD19) showed promise in treating relapsed or refractory MM. The authors suggest that this CAR-T cell combination warrants further investigation.

This was a Phase 2 study with a small number of patients. This study also did not have a control group as a source of comparison. Larger studies with a longer follow-up are needed to confirm these results and show the long-term effects of combined T-cell therapy.