New York, NY (December 10, 2022) — A new therapy that causes the immune system to kill bone marrow cancer cells was successful in 73 percent of patients in two clinical trials, according to researchers from the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.
The therapy, known as a bispecific antibody, binds to both T cells and multiple myeloma cells and directs the T cells—white blood cells that can be used to fight disease—to kill the multiple myeloma cells. The researchers described this strategy as “bringing your army directly to the enemy.”
An off-the-shelf immunotherapy called talquetamab has shown success even in patients whose cancer is resistant to all approved multiple myeloma treatments. It uses a different target than other approved treatments: a receptor expressed on the surface of cancer cells known as GPRC5D.
Talquetamab has been tested in phase 1 and phase 2 trials. A phase 1 trial has been reported New England Journal of Medicine (NEJM), Two recommended doses were tested in a phase 2 trial. The results of the Phase 2 trials were reported on Saturday, December 10 at the annual meeting of the American Society of Hematology. All of the study participants had previously been treated with at least three different treatments without achieving sustained remission, suggesting that talquetamab could offer new hope for patients. With multiple myeloma, which is difficult to treat.
“This means that almost three-quarters of these patients are looking at a new lease on life,” said Ajai Chari, Director of Clinical Research in Tisch Cancer Institute’s Multiple Myeloma Program and lead author of both studies. “Talquetamab produced a significant response in patients with heavily treated, relapsed or refractory multiple myeloma, the second most common blood cancer. It is the first bispecific agent targeting the GPRC5d protein in multiple myeloma patients.
Almost all patients with myeloma who receive standard treatment consistently relapse. Patients who relapse or are resistant to all approved multiple myeloma therapies have a poor prognosis, so additional treatment is urgently needed. Although this study is an early-stage trial designed to detect tolerability and find a safe dose, it is an important step in addressing this need.
This Phase 1 clinical trial enrolled 232 patients from January 2018 to November 2021 at several cancer centers around the world. Patients received different doses of therapy either intravenously or subcutaneously; future studies will focus only on weekly or weekly subcutaneous doses
The efficacy and safety findings in the phase 1 study were confirmed in the phase 2 trial presented at ASH. The phase 2 trial included 143 patients treated with a weekly dose and 145 patients treated with a higher dose every two weeks.
The overall response rate in these two groups was about 73 percent, Dr. Chari said. Response rates were maintained in the various subgroups studied, except for patients with the rare form of multiple myeloma that also spreads to organs and soft tissues. More than 30 percent of patients in both groups had a complete response (no myeloma-specific markers were detected) or better, and about 60 percent had a “very good partial response” or better (indicating that the cancer had shrunk significantly, but not necessarily to zero). .
The median time to measurable response was approximately 1.2 months in both dosage groups, and the median duration of response to date is 9.3 months with weekly dosing. The researchers are continuing to collect data on the duration of response for patients who had a complete or better response in the 0.8 mg/kg weekly group and in both dose groups.
Side effects were relatively common but usually mild. About three-quarters of patients experienced cytokine release syndrome, a cluster of symptoms, including fever, common with immunotherapies. About 60 percent experienced skin-related side effects, such as rash, about half taste changes, and about half nail disorders. Very few patients (5 to 6 percent) discontinued talquetamab treatment because of side effects, the researchers said.
Dr. The response rate observed in the study, Chari explained, suggests that talquetamab is superior to currently available treatments, offering a chance to extend life and benefits for patients whose myeloma stops responding to most current treatments. from other new and future treatments as they develop.
These trials were funded by Janssen.
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New England Journal of Medicine
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