By Danai Dima, MD, as told to Denise Mann
Danai Dima, MD is a hematologist-oncologist and clinician-researcher who specializes in multiple myeloma at the Fred Hutch Cancer Center and is an assistant professor in the Division of Hematology and Oncology at the University of Washington School of Medicine, both in Seattle. The information here represents her research and knowledge as a medical professional.
Who typically benefits from Tecvayli?
Danai Dima, MD: "Tecvayli (teclistamab) is a first-in-class bispecific antibody for people whose myeloma has come back (relapsed) or did not respond to previous treatment (refractory). It was approved by the U.S. Food and Drug Administration (FDA) in 2022 for adults who have received at least four prior lines of myeloma treatment. Bispecifics harness your immune system to target and destroy myeloma cells. More recently, the FDA approved a combination of Tecvayli plus daratumumab (Darzalex Faspro), also known as Tec-Dara, that can be used even earlier – after one previous treatment."
How do the new drugs work separately and in combination?
Dima: "Tecvayli targets the B-cell maturation antigen (BCMA) on myeloma cells to help your immune system destroy these cells. Darzalex aims at a special protein called CD38 on myeloma cells, which helps your immune system seek out and destroy abnormal blood cells. The combination packs a one-two punch against myeloma cells.
"Tecvayli, on its own, has a pretty high overall response rate of up to 63%. This refers to the percentage of patients whose cancer shrinks or disappears. [In studies,] it also had a progression-free survival of almost a year, meaning that the disease did not get worse during this time.
"In myeloma, single therapies tend to be less effective than combinations. When these two drugs are combined, they enhance each other's efficacy to work better. They attack multiple myeloma in different but complementary ways, making the immune system better at finding and killing myeloma cells. Daratumumab helps prepare and strengthen the immune environment, while teclistamab guides T cells directly to the myeloma cells. The combination can also be used earlier in the disease than Tecvayli alone."
How do the new drugs compare to chimeric antigen receptor (CAR) T-cell therapy?
Dima: "The combination is off the shelf and ready to use, meaning it can be given in any physician's office or community practice. However, Tecvayli requires step-up dosing at the start of treatment. This means beginning with a small dose of the drug and gradually increasing it until the full dose is reached. The process can sometimes cause immune-related side effects. That's why patients may need to be admitted to the hospital for monitoring during the first doses. This requirement can sometimes limit the ability of smaller community centers to administer Tecvayli.
By contrast, chimeric antigen receptor (CAR) T-cell therapy — another type of cancer immunotherapy that can be used if myeloma comes back or does not respond to earlier treatment — is not as widely available and can only be given at accredited centers. You must stay close to the CAR T center for almost a month after treatment and have a 24/7 caregiver during that time.
"The new combination therapy does not carry the risk of delayed neurotoxicity or risk of secondary cancers associated with CAR T-cell therapy. Delayed neurotoxicity may include nerve palsies or even Parkinson-like symptoms, such as tremor, difficulty walking, slowed movements, changes in speech, memory problems, and/or behavior changes, which are often irreversible. In addition, CRS and ICANS can occur with CAR T at higher rates and with greater severity compared with Tecvayli. An older or frailer patient might not want CAR T-cell therapy due to these risks, so now there is this novel combination that they can use."
What sort of side effects can people expect with Tecvayli or the new combination, and are there ways to handle them?
Dima: "Tecvayli and daratumumab increase your risk for infections. We now have a lot of experience with preventative strategies for infections. We can give intravenous immunoglobulin (IVIg) treatment to help you fight off infection and prescribe prophylactic antibiotics to mitigate severe infections.
"Most of the time, patients get infections at the beginning of treatment. As they go through their treatment, this rate actually drops. If you do have a fever, call your doctor right away and let them know because you'll need to come in and be assessed. We take fevers pretty seriously as they indicate infection. If a patient on a bispecific develops an infection, we can just stop the treatment and give them a break until the infection is resolved. With CAR T therapy, once you get the infusion, we can't stop it.
"A lot of people might have low blood counts, including low neutrophils, which are infection-fighting cells, or other blood cells, such as low platelets, or develop anemia. We can support them with transfusions or the use of erythropoiesis-stimulating agents to spur blood cell production.
"The short-term risk with all bispecific antibodies is CRS and ICANS, which can cause temporary confusion, language disturbance, tremors, and handwriting changes. The combination doesn't really increase these risks. Nowadays, we can prescribe the biologic drug tocilizumab to prevent CRS, and we see less and less CRS as a result."
How is the combination administered, and how are patients monitored?
Dima: "Patients come in weekly for their injections at first. The injection itself takes about five minutes, so it's super-duper easy. Before treatment, they have routine lab tests, such as a complete blood count and a complete metabolic panel. If these are OK, they get the injections. Patients are typically seen by a physician or an advanced practitioner every month, and we check myeloma labs monthly to monitor the abnormal proteins and see how they are responding to treatment. Once we see a deep response, usually after the first six months of therapy, we can space the dosing of Tecvayli to every other week or even once a month. Daratumumab is given weekly for the first two cycles, then every two weeks for cycles three through six, followed by every four weeks."
How much does this treatment cost? Will insurance cover it?
Dima: "The cost of most drugs used in multiple myeloma is approximately $100,000 per year. I don't really have a lot of trouble getting approval for insurance to pay for bispecifics because the indications are pretty clear. We submit a request for prior authorization, and if the patient has received four or more lines of therapy, approval is generally straightforward. Now, we can get approval of the combination after one line of therapy. I don't anticipate a lot of insurance pushback. Getting approval for the prophylactic tocilizumab and prophylactic IVIg can be trickier."
What were the results that led to the new approval?
Dima: "The MajesTEC-3 phase 3 trial, which was published in The New England Journal of Medicine and presented at the 2025 American Society of Hematology Annual Meeting and Exposition, led to the new approval for the combination treatment. The trial is ongoing and not expected to end until 2030. The hope is that it will become the new standard of care for the appropriate group of myeloma patients.
"We saw excellent results compared to standard-of-care regimens. The complete response rate (or the percentage of patients whose treatment led to the disappearance of all detectable signs of myeloma) was above 80%, which is great. This combination also led to high rates of minimal residual disease (MRD) negativity, meaning that there were no cancer cells detected in the bone marrow, and significant improvements in progression-free survival and overall survival, which is very promising.
"The approval was granted under a new FDA Priority Review Voucher (CNPV) pilot program that aims to speed the review and approval of novel drugs."
How will you know if this treatment is right for you?
Dima: "Every patient with multiple myeloma is so unique. Their disease is unique, and their personal situation is unique, so you just have to talk to patients about their available options and basically make an informed, shared decision. This involves talking to your doctor and carefully weighing the risks and benefits of each option along with personal factors that may affect your choice."
