New York, NY (December 10, 2022) — A new therapy that forces the immune system to kill bone marrow cancer cells has been successful in up to 73% 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 T cells – white blood cells that can be recruited to fight disease – to kill myeloma cells multiple. Researchers have described this strategy as “bringing your army straight to the enemy.”
The success of off-the-shelf immunotherapy, called talquetamab, has even been seen in patients whose cancer was resistant to all approved multiple myeloma therapies. It uses a different target than other approved therapies: a receptor expressed on the surface of cancer cells called GPRC5D.
Talquetamab has been tested in phase 1 and phase 2 trials. The phase 1 trial, which was reported in The New England Journal of Medicine (NEJM), established two recommended doses that were tested in the phase 2 trial. The results of the phase 2 trial were reported at the annual meeting of the American Society of Hematology on Saturday, December 10. The study participants had all previously been treated with at least three different therapies without achieving lasting remission, suggesting that talquetamab may offer new hope to patients. with difficult-to-treat multiple myeloma.
“That means nearly three-quarters of these patients are planning a new life,” said Ajai Chari, MD, director of clinical research for the multiple myeloma program at the Tisch Cancer Institute 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 targeting the GPRC5d protein in patients with multiple myeloma.
Almost all myeloma patients who receive standard therapies continually relapse. Patients who relapse or become resistant to all approved multiple myeloma therapies have a poor prognosis, so additional treatments are urgently needed. This study, although an early phase trial designed to detect tolerance and find a safe dose, is an important step in addressing this need.
This Phase 1 clinical trial enrolled 232 patients at multiple cancer centers around the world between January 2018 and November 2021. Patients received various doses of the therapy intravenously or injected under the skin; future studies will focus on doses administered only under the skin, either once a week or every two weeks
The efficacy and safety results of the phase 1 study have been validated 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 twice-weekly dose.
The overall response rate in these two groups was about 73%, Dr. Chari said. The response rate was maintained in the different subgroups examined, with the exception of patients with a rare form of multiple myeloma that also spreads to organs and soft tissues. More than 30% of patients in both groups had a complete response (no detection of myeloma-specific markers) or better, and nearly 60% had a “very good partial response” or better (indicating that the cancer was significantly reduced but not necessarily down to zero).
The median time to a measurable response was approximately 1.2 months in both dosing groups and the median duration of response to date is 9.3 months with weekly dosing. Researchers are continuing to collect data on the duration of response in the group receiving 0.8 mg/kg every other week and for patients in both dosage groups who had a complete response or better.
Side effects were relatively common, but generally mild. About three-quarters of the patients experienced cytokine release syndrome, which is a constellation of symptoms, including fever, common with immunotherapies. About 60% experienced skin side effects such as rashes, about half reported taste changes, and about half reported nail disorders. The researchers said that very few patients (5-6%) discontinued talquetamab treatment due to side effects.
The response rate seen in the study, which Dr. Chari says is higher than most currently available therapies, suggests that talquetamab may offer a viable option for patients whose myeloma has stopped responding to most available therapies, offering a chance to prolong life and benefit from other new and future therapies as they are developed.
These trials were sponsored and funded by Janssen.
About Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metropolitan area, with more than 43,000 employees working in eight hospitals, more than 400 outpatient practices, nearly 300 laboratories, a nursing school and a large school of medicine and higher education. Mount Sinai advances health for everyone, everywhere, by addressing the most complex health challenges of our time – discovering and applying new knowledge and scientific knowledge; developing safer and more effective treatments; train the next generation of medical leaders and innovators; and supporting local communities by providing high quality care to all who need it.
Through the integration of its hospitals, laboratories and schools, Mount Sinai offers comprehensive healthcare solutions from birth to geriatrics, leveraging innovative approaches such as artificial intelligence and IT while keeping patients’ medical and emotional needs at the center of all treatments. The health system includes approximately 7,300 primary and specialty care physicians; 13 joint venture day surgery centers in the five boroughs of New York, Westchester, Long Island and Florida; and over 30 affiliated community health centers. We are regularly ranked by US News and World Report‘s Best Hospitals, receiving a high “Honor Roll” status, and are highly ranked: #1 in Geriatrics and top 20 in Cardiology/Cardiac Surgery, Diabetes/Endocrinology, Gastroenterology/Gastrointestinal Surgery, Neurology/Neurosurgery, orthopaedics, pulmonology/lung Surgery, rehabilitation and urology. New York Eye and Ear Infirmary of Mount Sinai is ranked #12 in ophthalmology. US News and World ReportMount Sinai Kravis Children’s Hospital’s “Best Hospitals for Children” ranking is one of the best in the country in several pediatric specialties. The Icahn School of Medicine at Mount Sinai is one of three medical schools that has distinguished itself by several indicators: it is consistently ranked in the top 20 by US News and World Report“Best Medical Schools”, aligned with a US News and World Report “Honor Roll” Hospital, and among the top 20 in the nation for funding from the National Institutes of Health and among the top 5 in the nation for many areas of basic and clinical research. NewsweekThe “World’s Best Smart Hospitals” ranks Mount Sinai Hospital number one in New York and among the top five in the world, and Mount Sinai Morningside in the top 20 globally.
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New England Journal of Medicine
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