Researchers from Mount Sinai have shown that a therapy using talquetamab, an off-the-shelf drug known as a bispecific antibody, can be enlisted to kill multiple myeloma cells (a type of white blood cell) that can build up in the bone marrow and form tumors in bones. The therapy destroys cancerous cells in 3 out of 4 patients, and side effects, while common, are not severe.
The drug was tested in both phase 1 and phase 2 trials — the phase 1 trial established the safety and established a recommendation of two doses, whereas the phase 2 trials tested the effectiveness on 143 patients treated on a weekly dose and 145 patients treated at a higher biweekly dose.
The overall response rate was 73%, said Ajai Chari, study author. Around a third of the patients in both groups had a complete response — there was no detection of any myeloma-specific markers after the treatment. Almost 60% had a “very good partial response”, which means that the cancer was substantially reduced but not to zero.
“This means that almost three-quarters of these patients are looking at a new lease on life,” said Chari. “Talquetamab induced a substantial response among patients with heavily pretreated, relapsed, or refractory multiple myeloma, the second-most-common blood cancer. It is the first bispecific agent targeting the protein GPRC5d in multiple myeloma patients.”
The results are particularly exciting because patients who receive standard therapy for myeloma have a very high rate of relapse — and the more they relapse, the worse the prognosis becomes. But the success of talquematab was even seen in participants who were resistant to all other approved therapies, which makes this approach particularly promising. The researchers described this strategy as “bringing your army right to the enemy.”
The median time to a measurable response was just 1.2 months, in both dosing groups, and the median duration of the total response to date was 9.3 months, but researchers are still closely following the patients to collect data. Also, the researchers note that effects were relatively frequent but typically mild. About three-quarters of patients experienced something called cytokine release syndrome, which manifests through symptoms like fever. Also, 60% of patients experienced skin-related side effects like rashes, but overall, just 5-6% of patients had to stop taking the treatment because of the side effects.
Ultimately, it’s still a small-scale study and the patients still need to be followed for a longer term to see if the success rate continues, but the results are encouraging. Chari says the success rate is higher than most existing therapies, and it could offer a viable option for patients whose treatment stops responding to other treatments, offering a chance to incorporate new treatments into the oncologist’s arsenal — for such a dangerous disease, this is very much needed.
Journal Reference: Ajai Chari et al, New England Journal of Medicine (2022). dx.doi.org/10.1056/NEJMoa2204591