New Standard of Multiple Myeloma Care? FDA Approves Tecvayli Combination

When she was diagnosed with multiple myeloma at age 60, former elementary school cafeteria manager Vickie M.’s life hit a standstill. After an initial bone marrow transplant failed to keep her cancer at bay, the uncertainty of relapsed disease forced her into early retirement.

"When someone tells you in a doctor's office, they bring up the 'C' word ... most people automatically think they're doomed," Vickie told CURE. "But I am just screaming glad I made that choice [to join a trial]."

The choice she made was to participate in the MajesTEC-3 clinical trial. Her success story is now a reality for thousands of others, as the U.S. Food and Drug Administration (FDA) recently approved the combination of Tecvayli (teclistamab) and Darzalex Faspro (daratumumab and hyaluronidase-fihj) for adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy.

A Powerful "One-Two Punch"

The approval is a landmark shift for patients who have already tried proteasome inhibitors and immunomodulatory agents. Tecvayli is a bispecific T-cell engager that physically pulls the body’s own immune cells toward the cancer cells to destroy them. Darzalex Faspro is a monoclonal antibody that targets the CD38 protein on myeloma cells.

"In general, when we're using targets, we want targets to be specific to the cancer, but not the rest of the body," explained Dr. Ajai Chari, Director of the Multiple Myeloma Program at University of California, San Francisco. "When you combine these two, you have this amazing response ... there's a flattening of the curve, which suggests that this combination is quite efficacious, and many people are not relapsing once they've achieved a remission."

The data from MajesTEC-3 showed an 83% reduction in the risk of disease progression or death compared to standard-of-care triplets.

Breaking the Steroid Cycle

For decades, the cornerstone of myeloma treatment has been dexamethasone — a steroid known for side effects like irritability, weight gain and insomnia. One key aspect of this new approval is its steroid-sparing approach.

While steroids are used during the initial "step-up" doses to prevent reactions, they are largely phased out afterward. "It's the family member who notices that the patient is irritable and eating a lot and not sleeping," Chari noted. "You really don’t need the dexamethasone indefinitely ... that speaks to tremendous improvement in quality of life."

Dr. Luciano Costa, Professor of Multiple Myeloma and Director of the Multiple Myeloma Research and Treatment Program at the University of Alabama at Birmingham, and Primary Investigator of MajesTEC-3, agrees that the goalposts have shifted.

"I think the first step is to show that we have therapies that can lead the majority of patients to achieve deep responses... so that the majority of them will not have to ever start a new line of therapy and live a near-normal lifespan," Dr. Costa said. "I believe we are there with Tec-Dara."

Safety and Accessibility

Despite a Boxed Warning for cytokine release syndrome (CRS) and neurologic toxicity (ICANS), Costa emphasized that the safety profile is highly manageable. In the trial, no patients experienced fatal CRS or ICANS.

"There is nothing to limit this treatment to academic centers," Dr. Costa said, noting that the subcutaneous (under the skin) delivery makes it easier to administer than hours-long intravenous (IV) infusions. "This is the dataset that teaches us that T-cell engagers are no longer a specialized niche therapy ... it needs to be offered to all patients as early as second line of therapy."

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.