It directs the patient’s immune system to kill multiple myeloma cells.
Experimental immunotherapy shows benefits in over 70% of cancer patients.
A new therapy that prompts the immune system to kill bone marrow cancer cells has been successful in as many as 73 percent of patients in two clinical trials, according to researchers at the Tisch Cancer Institute at Mount Sinai’s Icahn School of Medicine. The therapy is based on the bispecific monoclonal antibody, an artificial protein that is composed of fragments of two different monoclonal antibodies; this allows it to bind to two different types of antigens at the same time. Specifically to this research, it binds to T lymphocytes as well as myeloma cells multiple and directs T lymphocytes – white blood cells that can be recruited to fight disease – to kill myeloma cells. The researchers have described this strategy as “taking the army straight to the enemy.”
The success of this immunotherapy, called talquetamab, has also been seen in patients whose cancer was resistant to all approved therapies for multiple myeloma. The drug uses a different target than other approved therapies: a receptor expressed on the surface of cancer cells known as GPRC5D .
Talquetamab has been tested in Phase 1 and Phase 2 studies. The Phase 1 study, reported in the New England Journal of Medicine (NEJM), established two recommended doses that were tested in the Phase 2 study. The results of the phase 2 study were presented at the American Society of Hematology annual meeting on Dec. 10. All study participants had previously been treated with at least three different therapies without achieving durable remission, suggesting that talquetamab could offer new hope to patients with difficult-to-treat multiple myeloma.
“This means that nearly three-quarters of these patients have a new lease on life ahead of them,” said Ajai Chari, director of clinical research for the Tisch Cancer Institute’s Multiple Myeloma Program and lead author of both studies. “Talquetamab induced a substantial response in patients with heavily pretreated, relapsed or refractory multiple myeloma, the second most common blood cancer. It is the first bispecific agent that targets the GPRC5d protein in patients with multiple myeloma.”
Almost all myeloma patients who receive standard therapies always relapse. Patients who relapse or become resistant to all approved multiple myeloma therapies have a poor prognosis, requiring further treatment urgently. This study, while an early stage designed to detect tolerability and find a safe dose , is an important step in meeting this need.
The efficacy and safety results from the phase 1 study were validated in the phase 2 study presented at the meeting. The Phase 2 study included 143 patients treated with a weekly dose and 145 patients treated with a higher twice-weekly dose. More than 30% of patients in both groups had a complete response (no detection of specific myeloma markers) or better, and nearly 60% had a “very good partial response” or better (indicating that the tumor is been substantially reduced, but not necessarily eliminated).
Side effects were relatively frequent, but usually mild. About three-quarters of patients experienced cytokine release syndrome, a constellation of symptoms that includes fever , common with immunotherapies. About 60% experienced skin-related side effects, such as rashes , about half reported taste changes, and about half reported nail complaints. The researchers said that very few patients (5 to 6%) discontinued treatment with talquetamab due to side effects.
The response rate observed in the study suggests that talquetamab could be a viable option for patients whose myeloma has ceased to respond to most available therapies, offering the potential to prolong life and benefit from other new and future therapies as they are developed.
- Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma (nejm.org)
