The First Bispecific Antibody Is Now Available to Patients in the Clinical Setting.
On October 25, 2022, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the drug teclistamab (Tecvayli™) for patients with relapsed or refractory myeloma who have had at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Teclistamab is the first-in-line bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager.
The term “bispecific” means that the drug has two “arms.” One arm attaches to the myeloma cell through the BCMA on the surface of the myeloma cell. The other arm attaches to and activates a local T cell to destroy the myeloma cell. This is a remarkable method of employing a patient’s own immune system to fight against their myeloma. Teclistamab is a highly advanced form of immunotherapy.
Response rates
Most drugs that are used to treat myeloma – in a clinical setting and not in a clinical trial – have had response rates in heavily pretreated patients of approximately 25%–30%. Teclistamab, which was studied in patients with very advanced relapsed myeloma, had an overall response rate (ORR) of 61.8%. This impressive result will make it very attractive for our patients.
Teclistamab was evaluated in the MajesTEC-1 multi-center clinical trial. The efficacy population consisted of 110 patients with myeloma who had previously received at least 3 prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, but had not received prior BCMA-directed therapy. As noted above, the ORR was 61.8%. With a median follow-up of 7.4 months among responders, the estimated duration of response (DOR) rate was 90.6% at 6 months and 66.5% at 9 months.
Treatment with teclistamab
Teclistamab is an “off-the-shelf” drug. It can be given to a patient directly, as opposed to the process of CAR T-cell therapy that requires the harvesting of T cells from the patient in advance. The off-the-shelf availability of teclistamab may facilitate the use of this drug more widely, especially for patients who do not have access to a CAR T-cell therapy center.
However, like with every myeloma drug, there are some challenges and risks. To receive their first doses of teclistamab, most patients will initially have to be admitted to the hospital for approximately 2 weeks. This is necessary because the drug can cause a reaction called cytokine release syndrome (CRS), where the body responds to the process of activating the T cells. For most patients, CRS is mild, but some patients will require more intensive support in the hospital setting.
Other notable side effects can include neurological toxicities and low blood counts. It is also important to note that ongoing treatment with a bispecific antibody increases the risk of infections, and it is critical to monitor and rapidly treat infections. After the first few doses of teclistamab are administered, treatment can be continued on an outpatient basis. All treatment centers that provide teclistamab must adhere to a Risk Evaluation and Mitigation Strategy (REMS) program that monitors the risks of treatments.
Important new option in the clinic
Myeloma patients and their doctors now have a new and important treatment option. The very high response rate with teclistamab could benefit many patients in a unique and sustained way. And we are not done yet! More bispecific antibody myeloma therapies are in development – some have different targets on the myeloma cell – and each new drug brings with it the potential to further help in our goal to fight and cure myeloma. This is very exciting for the myeloma community!
(This article was published in the 2022 Fall Edition of the IMF's quarterly publication, Myeloma Today. Read the full publication here.)
