Approved drug cuts risk of cancer worsening in smoldering myeloma
In small trial, injection therapy shown to prevent progression for over 90%
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Treatment with Tecvayli (teclistamab), an approved cancer drug, can reduce the risk of disease progression in people with high-risk smoldering multiple myeloma, an early disease stage in which cancerous cells are present but not yet causing organ damage.
That’s according to new, early results from a small mid-stage clinical trial that’s testing Tecvayli — approved for certain people with hard-to-treat multiple myeloma — versus another treatment for potential use in smoldering myeloma. Among the trial participants, nearly two-thirds were deemed to be at high risk of having their cancer progress.
The data show that most patients given Tecvayli did not have detectable cancer following treatment. Further, over a median follow-up period longer than two years, more than 90% of participants receiving Tecvayli were free from disease progression, the researchers noted.
“Overall, [treatment] response rates, duration of response and time to [disease] progression (TTP) were significantly improved [better with Tecvayli] compared” with the other treatment — a combination therapy including a steroid — being tested, the team noted. Still, the scientists stressed that this data comes early on and no conclusions can yet be drawn.
Results from the trial were detailed in a paper titled “Teclistamab versus lenalidomide-dexamethasone in high-risk smoldering multiple myeloma: a randomized phase 2 trial,” published in the journal Nature Medicine. The work was funded by Johnson & Johnson, which markets Tecvayli.
Multiple myeloma is a blood cancer marked by the uncontrolled growth of plasma cells — a type of immune cell — in the bone marrow, the soft, spongy tissue found in the center of most bones. Smoldering multiple myeloma, or SMM, is an asymptomatic early stage in which cancer cells have started to accumulate, but not to the point where they’re causing organ damage.
Some people with SMM will never progress to overt myeloma, the cancer’s active, symptomatic form, but many will.
First treatment for smoldering myeloma approved last year
Historically, SMM was managed mainly by careful monitoring. Last year, however, the U.S. Food and Drug Administration (FDA) approved an injection therapy called Darzalex Faspro (daratumumab and hyaluronidase) as the first treatment formally authorized for high-risk SMM. That approval was based on clinical trial data showing the therapy could reduce the risk of conversion from SMM to active myeloma.
Scientists are now examining a combination therapy using an approved drug for overt myeloma, Revlimid (lenalidomide), for possible use in SMM. That combo treatment, comprised of Revlimid and the corticosteroid dexamethasone, has also shown promise for SMM in clinical testing.
Tecvayli, meanwhile, is a bispecific antibody that’s also approved for overt myeloma. It works by simultaneously sticking to a plasma cell protein on myeloma cells called BCMA, and to a protein on cancer-killing immune cells called T-cells. By binding both targets, the therapy effectively prompts T-cells to attack and destroy cancerous myeloma cells.
As of now, Tecvayli is FDA-approved as part of multiple regimens for myeloma that has failed to respond to prior treatments.
Tecvayli being tested against another myeloma treatment
This ongoing Phase 2 clinical trial (NCT05469893) — slated to run through 2030 — is testing Tecvayli’s potential as a treatment for high-risk SMM. At a data cutoff point this May, 59 patients had completed at least one cycle of assigned treatment at one of the trial’s three study locations. Data from these patients were analyzed. Among them, 45 received Tecvayli while the other 14 were given treatment with Revlimid and dexamethasone (a regimen abbreviated Rd).
The study’s main goal is to assess complete response rates, that is, the number of patients with no detectable cancer after treatment. These early results showed that 78% of patients on Tecvayli achieved a complete response, and 82% achieved minimal residual disease negativity at some point, meaning they had no detectable cancer cells. By contrast, none of the patients on Rd achieved either a complete response or minimal residual disease negativity.
“In this randomized phase 2 study, [Tecvayli] produced frequent deep responses, including high rates of [minimal residual disease] negativity, in patients with [high risk]-SMM,” the researchers wrote.
Slightly more than half of patients on the Rd regimen experienced disease progression within two years of entering the trial. By contrast, 92% of patients on Tecvayli were progression-free at two years.
“Longer follow-up will be required to determine whether these deep responses and the observed improvement in [progression-free survival] translate into durable prevention of progression to symptomatic myeloma, and no conclusions regarding overall survival benefit or disease eradication can be drawn from the current follow-up period,” the scientists wrote.
Safety data from this study were consistent with the known profile of Tecvayli. The therapy, which is given by injection under the skin, can cause side effects such as immune reactions, digestive issues, fatigue, and infections.
“These results suggest that early [treatment with Tecvayli] can achieve substantial molecular disease clearance in a precursor-disease state, with a manageable safety profile and without the added treatment burden of combination therapy,” the researchers concluded.
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