Bispecific Antibodies Now an Option for Myeloma Treatment

Patients with multiple myeloma will soon have a new treatment option. On Oct. 25, 2022, the U.S. Food and Drug Administration (FDA) granted accelerated approval to teclistamab (Tecvayli) for the treatment of myeloma patients who have already been treated with at least four other therapies.

This decision was based on a study that found 62% of 110 patients saw their cancers shrink after receiving the treatment.

The decision translates into hope for those with multiple myeloma, according to Alfred L. Garfall, MD, an oncologist at Penn Medicine’s Abramson Cancer Center in Philadelphia and an investigator in the ongoing clinical trial.

“I think many, if not most, of these patients would have passed away if it weren’t for this drug. And now with FDA approval, many more will have the opportunity to take advantage of the medication,” Dr. Garfall told Patient Power, referring to the patients who were treated as part of the study.

What Is Teclistamab?

Teclistamab is a bispecific antibody – a newer class of antibody therapy. While classic monoclonal antibodies bind to a single target, bispecific antibodies bind to two different targets at once. In the case of teclistamab, the drug binds to the BCMA protein on myeloma cells, as well as the CD3 protein on T cells, a type of immune cell. Together the two targets bring the T cell near the cancer cell, recruiting the T cells to kill cancer cells. While bispecific antibodies have been approved to treat other cancer types, such as lung cancer and uveal melanoma, teclistamab is the first such therapy approved to treat multiple myeloma.

Who Is Eligible for Treatment?

Teclistamab has received an accelerated approval, which means the FDA has tentatively approved the treatment based on preliminary data. It is approved for patients whose myeloma has returned and who have received multiple treatments, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

“Those are the other therapies that really have been proven in big phase 3 trials to be effective,” Dr. Garfall said. To receive a full approval for teclistamab, the company that makes it will need to submit more data confirming that patients really benefit from its use.

What Does Treatment Look Like?

Patients are admitted to the hospital for the first week of treatment, to ensure swift medical attention in the event of any severe adverse reactions. Over the course of that week, the patient will receive three injections, with increasing doses of the drug.

After waiting 48 hours following the third dose, the patient can be discharged and will receive all subsequent doses as an outpatient. FDA instructions stipulate weekly doses until disease progression or unacceptable toxicity.

What Are the Side Effects?

The most common adverse reactions among patients who participated in the study included fever, cytokine release syndrome (CRS), neurologic toxicity, musculoskeletal pain, injection site reactions, fatigue, nausea, headache, and diarrhea. These side effects each occurred in 20% or more of patients.

The FDA highlighted CRS and neurologic toxicity as reactions that could even be life-threatening or fatal. In the study, 72% of patients who received the recommended dose of teclistamab experienced CRS, and 57% experienced neurologic toxicity. However, just 0.6% of patients had severe CRS, and 2.4% of patients had severe or life-threatening neurologic toxicity.

As teclistamab is an immunosuppressant, it also leaves patients more susceptible to infectious disease, such as pneumonia, COVID-19, and shingles. Upper respiratory tract infections and pneumonia were among the most common side effects in the study. Some of the trial’s patients received prophylactic antibiotics against Pneumocystis pneumonia, a fungal infection, and the FDA recommends that patients consider prophylactic antiviral medication to prevent shingles.

While any of these infections are potentially life-threatening, according to Dr. Garfall, “these preventative measures are largely effective, and we believe that when measured against the remarkable efficacy of the drug, the benefits far outweigh the risks.”

What Other Treatments Are Available?

Other treatments available for this group of patients with multiple myeloma include the antibody-drug conjugate belantamab mafodotin (Blenrep) and the XPO1 inhibitor selinexor (Xpovio).

Another option is CAR T-cell therapy. This treatment involves collecting T cells from a patient and shipping them to a lab, where technicians add a gene to help the cells attach to a specific cancer cell antigen, thus boosting their ability to fight the disease. After the cells are modified, they are expanded and reinfused into the patient.

Both teclistamab and CAR T-cell therapy work by activating the patient’s T cells, and both have similar potential toxicities. CAR T-cell therapy, however, is not widely available, as it requires an expert who can collect the T cells and is a bespoke medication that must be tailored for each individual. These complexities often result in a backlog and considerable waiting period. Teclistamab, on the other hand, is an off-the-shelf medicine, bought from a pharmacist and administered by a physician through injection.

According to Dr. Garfall, the key is to try all the medications at some point, as any effectiveness will help to prolong the ability to keep the disease under control. One thing that has impressed him about teclistamab, however, has been patient feedback.

“The patients on the clinical trial generally have been through a lot of multiple myeloma therapy over years,” Dr. Garfall said, “and they say that their quality of life when they’re on teclistamab is better than it was with any of the prior myeloma therapies they received before.”

It will take a few months before the drug becomes widely available, as centers wishing to carry it will first have to undergo a Risk Evaluation and Mitigation Strategy program, to certify the site and its relevant physicians in administering the medication and handling its potential toxicity.