IN OCTOBER 2022, the Food and Drug Administration (FDA) granted accelerated approval for Tecvayli (teclistamab) to treat relapsed or refractory multiple myeloma. Known as a bispecific antibody, this type of immunotherapy provides a new option for patients with myeloma who have received at least four prior lines of therapy.
In MajesTEC-1, the phase I/II clinical trial on which the approval is based, the overall response rate, defined as the percentage of participants who had a partial response or better to the drug, was 63%. Additionally, study participants lived a median of 11.3 months without their cancer progressing. “Getting an accelerated approval with this high of a response rate is kind of unprecedented,” says Saad Usmani, a hematologist-oncologist at Memorial Sloan Kettering Cancer Center in New York City and the principal investigator on the trial. Other drugs approved to treat relapsed or refractory multiple myeloma have had overall response rates of 20% to 30%, according to Usmani. “The treatment is efficacious, and it’s going to help prolong our patients’ lives,” he says.
Tecvayli also stands out as the first bispecific antibody approved for use in multiple myeloma. A bispecific antibody is a drug that binds to two different cell surface markers and can thus bring together immune cells—specifically T cells—and cancer cells so that the former can more easily kill the latter.
The first bispecific antibody was approved for acute lymphoblastic leukemia in 2014, and others were approved for hemophilia A and some lung cancers in subsequent years. But several new developments for bispecific antibodies in blood cancers made the news in 2022. In addition to the Tecvayli approval in October, the FDA approved Lunsumio (mosunetuzumab) for follicular lymphoma in late December. Additionally, bispecific antibodies, given alone or in combination with other treatments, were studied in several prominent clinical trials featured in December at the American Society of Hematology Annual Meeting and Exposition in New Orleans.
Cancer Today spoke with Usmani about Tecvayli and the future for bispecific antibodies as cancer treatments.
CT: Why use a mediator, such as bispecific antibodies, to bring together cancer cells and T cells? Is this an alternative to creating CAR T cells, which are engineered to bind to cancer cells directly?
USMANI: The terminology utilized for bispecific antibodies is T-cell redirection. The advantage of bispecific antibodies is that they attempt to do something similar to what the CAR T cells are doing, but they are an off-the-shelf option and don’t require reengineering of the patient’s T cells. Right now, that process is labor-intensive for both patients and the companies.
CT: Tecvayli and other bispecific antibodies for cancer treatment often have a side effect called cytokine release syndrome [CRS], which can involve fever, rash, rapid heartbeat, low blood pressure and difficulty breathing. Although most cases of CRS are mild, it can be life-threatening. Do you feel that the benefits of these drugs outweigh the risks?
USMANI: We don’t have any alternative therapies in that space. In the absence of an option like [Tecvayli], death is inevitable. The cytokine release syndrome side effect is actually not something new or surprising. Almost all patients who get CAR T-cell therapies develop cytokine release syndrome, and we know how to manage those side effects. With bispecific antibodies, cytokine release syndrome happens in fewer patients than what one would expect with CAR T cells.
The side effects of cytokine release syndrome are very manageable. It only happens with the first two step-up doses, when patients are gradually increasing their dose of the drug during the first week of treatment. When we didn’t know how to manage CRS a decade ago, things were a bit more challenging, but now we know what CRS is. You recognize it early, you treat it, and patients do fine. With any new drug, there is going to be a learning curve for us as physicians. That’s how new advances happen. These are lifesaving drugs.
CT: Why are bispecific antibodies such a hot topic in blood cancer treatment right now?
USMANI: If you look at most of cellular therapy, or T-cell-directing treatment advances, they actually started from blood cancers and then went towards other malignancies. We already have known targets that have been utilized by monoclonal antibodies in different hematologic malignancies, so it’s a low-hanging fruit in trying to develop therapies there.
CT: What do you see as the future of bispecific antibodies?
USMANI: The future I see is using these antibodies to get patients to a very deep response and defining the duration for which we are giving treatment. Currently, the model in myeloma has been to keep patients on treatment until relapse or progression. But I think we might move away from that model to a fixed duration of treatment. Something we are just learning about bispecific antibodies is that as we keep patients longer on treatment, they have a higher chance of getting infections. While we learn more about that potential risk, the thought has also emerged: If patients get a great response, do we really need to keep them on bispecifics? Can we just limit it so that they don’t get those opportunistic infections? So that’s where the future is headed. I think bispecific antibodies may have a role in early relapse and even in frontline treatment in the future.
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