Talquetamab Still Works Well in Myeloma Patients, Even With Immune Response

The recent study featured in the 2025 EHA Congress found that the talquetamab, a multiple myeloma drug, continues to be effective, despite patients developing an immune response against it. These are the results of the MonumenTAL-1 trial, in which this novel treatment is being tested in patients with relapsed or difficult-to-treat multiple myeloma.

Talquetamab is a bispecific antibody that aids the immune system to locate and destroy cancer cells by binding to two proteins- CD3 and GPRC5D. It is administered as an under-the-skin shot and has demonstrated robust findings in earlier trials, also in patients who have undergone numerous other procedures.

The study aimed to provide further insight into the frequency of patients forming antidrug antibodies (ADAs) proteins that the body might make in response to a treatment and determine whether the antibodies decrease the efficacy or safety of talquetamab. Investigators also examined a form of ADA known as neutralizing antibodies (NAbs), which can inhibit the mechanism of action of the drug in the body.

This study involved 363 patients with RRMM treating talquetamab at two dosing regimens, 0.4 mg/kg once weekly (QW) or 0.8 mg/kg every other week (Q2W). Patients had all received at least three previous lines of treatment, with a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. Some also had prior history of other T-cell redirecting therapies.

By September 2024, ADAs were observed in 36 percent of patients and NAbs in 18 percent. These percentages might look high, but the treatment effectiveness did not seem to be reduced by the presence of these antibodies. The response rates were equivalent or even greater in patients who developed ADAs or NAbs than in those who did not.

Ninety-two percent of the ADA- positive patients were sensitive to therapy in patients receiving weekly therapy as compared to 69 percent of the ADA- negative patients. In patients treated every other week response rates were 90 percent in ADA positive patients and 60 percent in ADA negative patients. Likewise, the rates of response in NAb-positive patients were 96 percent and 100 percent in the QW and Q2W arm, compared to 72 percent and 64 percent in NAb-negative patients.

The initial response time was about 5 weeks, and the antibodies were apparently produced 4-5 months later. This means that immune response did not interfere with early or overall treatment success.

In terms of safety, the principal variations in side effects were not identified between patients with and without antibodies development. This means that talquetamab was tolerated well regardless of immune response.

In conclusion, this study shows that talquetamab can be further administered in RRMM, even when a patient acquires antidrug or neutralizing antibodies. The outcomes are promising both to the physicians and the patients, since they demonstrate that the therapy is efficient and safe despite such immune reactions.