Teclistamab Approved for Myeloma

The FDA has approved teclistamab (Tecvayli; Janssen Biotech) for patients with relapsed or refractory multiple myeloma (MM) who have already received at least four treatment regimens. Oncologists say the drug is a welcome option for patients who no longer respond to several other therapies.

Teclistamab is a bispecific T-cell engager (BiTE), which consists of two fused antibody fragments that coax T cells to attack cancer cells. One antibody fragment latches onto the T-cell receptor component CD3 and the other onto BCMA on myeloma cells. By tethering the two cells, teclistamab spurs the T cell to destroy its partner. The only other FDA-approved BiTE is blinatumomab (Blincyto; Amgen), a treatment for acute lymphoblastic leukemia that targets CD19.

The evidence for teclistamab's approval comes from the phase I/II MajesTEC-1 trial. All 165 patients in the trial had stopped responding to at least three classes of drugs, and 70.3% of patients had received drugs from five classes. The latest results show an overall response rate (ORR) of 63% and a median duration of response of 18.4 months (N Engl J Med 2022;387:495–505). Median progression-free survival was 11.3 months; overall survival data were not mature.

As for safety, 72.1% of patients developed cytokine release syndrome and 14.5% suffered neurotoxic side effects, most commonly headache. Infections were also frequent, occurring in 76.4% of patients. Twelve patients died from COVID-19.

Because many people with relapsed or refractory MM no longer respond to multiple classes of treatment, having another option “is a very important advance,” says Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston, MA. Chimeric antigen receptor (CAR) T-cell therapy can yield an ORR greater than 90%, but teclistamab has an advantage because of its “availability and practicality,” he says.

Over the last decade, the initial single-agent approvals in later-line myeloma, such as the CD38-targeted mAb daratumumab (Darzalex; Janssen Biotech), have yielded ORRs in the range of 22% to 30%. “Teclistamab has a much higher response rate in an even more heavily pretreated population,” says Joshua Richter, MD, of the Icahn School of Medicine at Mount Sinai in New York, NY.

The drug could have yet another benefit—expanding the pool of patients who can receive treatment. CAR T cells are available only in academic centers, whereas teclistamab can be given in community hospitals, where most patients with MM are treated, Richter says.

Other physicians are enthusiastic about teclistamab's approval as well. “We all have patients waiting for it,” says Douglas Sborov, MD, of the University of Utah School of Medicine in Salt Lake City. Patients whose disease has progressed after CAR T-cell therapy or who are ineligible for the treatment “may be ideal candidates” for teclistamab.

Richardson notes that the drug is expensive—$400,000 for a full course. And given the results reported so far, including the mortality from COVID-19, oncologists may need to be cautious when prescribing teclistamab, he says.

The approval limits teclistamab's use to people who have received four or more classes of therapy, adds Sarah Holstein, MD, PhD, of the University of Nebraska Medical Center in Omaha. But the “fourth-line treatment is when we would want to be able to use BCMA-directed therapy,” she says. “Whether insurance companies will count lines of therapy or look at whether patients are triple-class refractory and allow use of teclistamab as fourth-line therapy remains to be determined.” However, patient eligibility could expand as trials test teclistamab earlier in the course of the disease. –Mitch Leslie