On August 9, 2023, the United States Food and Drug Administration (FDA) granted accelerated approval to talquetamab-tgvs (Talvey, Janssen Biotech, Inc.). According to the FDA, talquetamab is indicated for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor (such as bortezomib, carfilzomib or ixazomib), an immunomodulatory agent (such as lenalidomide, pomalidomide or thalidomide), and an anti-CD38 monoclonal antibody (such as daratumumab or isatuximab).

Talquetamab is a bispecific antibody which targets GPRC5D on myeloma cells and CD3 at the surface of T-cells. CD3 (cluster of differentiation 3) is a protein complex involved in T-cell-mediated immunoresponse and GPRC5D (human G-protein coupled receptor family C group 5 member D) is a tumor-associated antigen primarily found on myeloma cells. Through this bispecific interaction, talquetamab facilitates tumor cell elimination through T-cells by bringing both cell types into close contact.

Bispecific antibodies are promising immunotherapies under investigation for the treatment of multiple myeloma. Different products targeting different antigens are being studied, many with preliminary results showing high response rates. Among those, teclistamab (TECVAYLI^TM) targets BCMA on myeloma cells and CD3 on T-cells and has already been approved by the FDA in October 2022 and received conditional marketing authorisation in European Union in August 2022.

As for the European Union, on July 20, 2023, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion on talquetamab, recommending the granting of conditional marketing authorisation. The CHMP is the European Medicines Agency’s (EMA) committee responsible for human medicines. The European Commission will then take a legally binding decision based on the EMA’s recommendation. The full indication is the following: talquetamab monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.

“These approvals are good news as the response rates are promising and will provide myeloma patients with more treatment options. We also hope these new off-the-shelf therapies will overcome some of the current access challenges of CAR-T therapies,” said Solène Clavreul, Head of Medical Education and Scientific Engagement at Myeloma Patients Europe (MPE).

Talquetamab approval is based on efficacy results from the MonumenTAL-1 clinical trial, which included 187 patients who had previously received at least four prior lines of therapies. Patients received talquetamab subcutaneously every week or every two weeks at higher doses, following two or three step-up doses, until their disease progressed or intolerable side effects were experienced. Step-up doses in the first week of therapy are meant to incrementally increase the dose administered before reaching the target dose level to prime the immune system gradually and reduce side effects.

The MonumenTAL-1 clinical trial assessed response rates to talquetamab and duration of response. 73% of patients responded to the treatment and 85% of the responders maintained their response for nine months or more. The study also included patients with prior exposure to bispecific antibody or CAR-T cell therapy (94% had B-cell maturation antigen (BCMA)-directed therapy) who received a weekly dose of talquetamab. 72% of these patients responded to the treatment and 59% of the responders maintained their response for nine months or more.

The most common adverse reactions observed with talquetamab treatment include cytokine release syndrome (CRS); taste, nail and skin disorders; musculoskeletal pain; fatigue; weight loss; dry mouth; fever; dry skin; rashes; swallowing difficulties; upper respiratory tract infection; and diarrhoea.

Talquetamab is currently under investigation for treating myeloma in combination with other compounds.