What Is the Impact of the Talquetamab Accelerated Approval in Multiple Myeloma?

By Ajai Chari, MD - Last Updated: September 25, 2023

Ajai Chari, MD, of the University of California, San Francisco, discusses the MonumenTAL-1 study, the accelerated approval of talquetamab, and real-world considerations for using the therapy in patients with relapsed or refractory multiple myeloma (MM).

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The US Food and Drug Administration granted accelerated approval to talquetamab, a bispecific T-cell-engaging antibody that binds to CD3 and GPRC5D, in August 2023.

“Even though we don’t have full approval yet, this accelerated approval is really exciting, and it gives us options for our patients,” Dr. Chari said.

The approval, which is based upon data from the MonumenTAL-1 trial, is for adults with relapsed or refractory MM who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. Talquetamab is approved as a weekly or biweekly subcutaneous injection after an initial step-up phase.

The MonumenTAL-1 study included patients who received at least four prior lines of therapy and who were not exposed to prior T-cell redirection therapy. The study also included 32 patients who were exposed to prior bispecific antibody or chimeric antigen receptor T-cell therapy and had received at least four prior lines of therapy.

The study showed a response rate of around 70% in patients who were heavily pretreated but had not previously received T-cell redirection therapy, Dr. Chari said.

“Even in those who were had prior exposure to these drugs—which is the new unmet need—the response rate was 63%,” he said. Dr. Chari highlighted the progression-free survival (PFS) outcomes that were observed in patients receiving a dose of talquetamab 0.8 mg/kg every two weeks.

The PFS was a “very impressive 14 months” in these patients, he said, noting this outcome is “actually the best of any bispecific that we have to date.”

He also outlined the safety profile of talquetamab, noting that it has the “typical bispecific characteristics” of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The CRS rate was 70% to 80% he said, while “primarily low-grade” ICANS occurred in around 10% of patients. “

Some of that is in the setting of CRS, and interestingly, unlike the BCMA compounds, we don’t see a lot of deaths due to infection, or infection complications in general,” Dr. Chari said.

He also discussed how talquetamab fits into the treatment landscape for relapsed or refractory MM.

“The fact that this is the only product targeting this [GPRC5D] antigen shows its unique place in the armamentarium,” Dr. Chari said. “There’s a dire need for all of these assets because although our patients are living longer and longer, our patients still relapse.”

Dr. Chari explained the practical steps and education that will be needed to expand the use of the treatment.

“We’re in this learning curve now … the first thing is to do the [Risk Evaluation and Mitigation Strategies] program, not only [for] the physicians but also the pharmacists, and anyone who’s touching the drug,” he said. “Second is to educate the whole hospital system on CRS.”

This will be critical to increase access, Dr. Chari emphasized.

“There are so many patients that need this drug and they’re not going to all be able to come to academic centers, and the sooner we can make this safe for everybody to give at a center near you, the better it is for patients,” he said.

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