EMA Backs Talquetamab and Daratumumab Combination for Second-Line Multiple Myeloma

When multiple myeloma returns after an initial round of treatment, oncologists typically pivot to therapies targeting the BCMA protein, a well-worn path that eventually faces resistance. A new recommendation from European regulators shifts that paradigm by moving a completely different target, GPRC5D, directly into the second-line setting.[1]

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) formally backed the combination of talquetamab and daratumumab on October 16, 2026. The recommendation applies to adults with relapsed or refractory multiple myeloma who have undergone at least one prior line of therapy.[1][4][5]

Talquetamab, marketed as Talvey by Johnson & Johnson, is a bispecific antibody that was previously restricted to patients who had exhausted at least three prior treatments. This new regulatory step effectively pulls the therapy forward, offering it to patients immediately after their first relapse.[2][3]

"If approved, TALVEY plus daratumumab will be the only GPRC5D-targeting bispecific antibody combination therapy for relapsed or refractory multiple myeloma as early as second line," Johnson & Johnson stated following the committee's decision. The European Commission typically adopts CHMP recommendations within two months.[1][3]

Targeting a new protein

Multiple myeloma, a cancer of the plasma cells in the bone marrow, is notorious for mutating to evade therapies. By the time a patient relapses, the surviving cancer cells have often learned to hide the markers that earlier drugs used to find them.[1][5]

Daratumumab, an established monoclonal antibody, works by binding to the CD38 protein found on the surface of myeloma cells. Talquetamab takes a dual approach, simultaneously grabbing onto the GPRC5D protein on the cancer cell and the CD3 receptor on a patient's own T-cells.[2][3]

This mechanism physically drags the immune system's killer cells directly into contact with the cancer. Because GPRC5D is highly expressed on myeloma cells but rarely found on healthy tissue, the therapy can direct a potent immune response while sparing most normal cells.[3][4]

Moving this dual-action mechanism to the second line is a strategic shift in myeloma care. Rather than saving the most advanced immunotherapies for a last resort, oncologists are increasingly deploying them earlier, when a patient's immune system is less battered by years of chemotherapy.[1][5]

The clinical evidence

The CHMP's positive opinion rests heavily on data from the Phase 3 MonumenTAL-3 clinical trial. The study evaluated the safety and efficacy of combining talquetamab with daratumumab, both with and without the addition of the immunomodulatory drug pomalidomide.[4][5]

Researchers compared these combinations against standard-of-care regimens for patients who had received at least one prior line of therapy. The trial demonstrated a statistically significant improvement in progression-free survival for the patients receiving the talquetamab combinations.[1][4]

Progression-free survival measures the length of time a patient lives with the disease without it getting worse. For patients facing a first relapse, extending this window is the primary goal of second-line treatment, buying crucial time before the cancer adapts again.[2][5]

The trial also confirmed that the safety profile of the combination matched what researchers expected from the individual drugs. This predictability is vital for clinicians who must balance extending a patient's life with maintaining their quality of life during continuous treatment.[1][3]

What this means for patients

For a patient whose initial myeloma treatment has just stopped working, this recommendation translates into a fundamentally different conversation in the clinic. Instead of cycling through older drug classes, they may soon have access to a therapy that recruits their own T-cells.[4][5]

However, patients will need to navigate the specific side effects associated with GPRC5D-targeting drugs. Because the GPRC5D protein is also present in the skin and tissues of the mouth, talquetamab frequently causes skin peeling, nail changes, and altered taste.[1][3]

These side effects, while generally manageable, require proactive care and clear communication between the patient and their oncology team. Clinicians often use dose adjustments and supportive therapies, such as specialized mouthwashes and topical creams, to keep patients comfortable.[2][5]

The combination therapy is administered via subcutaneous injection, which reduces the time patients must spend in the infusion chair compared to older intravenous treatments. This logistical shift can significantly ease the weekly burden on patients and their caregivers.[3][4]

The regulatory horizon

The CHMP recommendation is the final scientific hurdle before the European Commission issues a formal marketing authorization. That authorization will apply across all 27 European Union member states, as well as Iceland, Norway, and Liechtenstein.[1][2]

Once the European Commission grants approval, individual countries will begin their own pricing and reimbursement negotiations. This means the actual availability of the talquetamab and daratumumab combination will roll out gradually across Europe throughout 2027.[4][5]

The European decision also sets a precedent that other global regulatory bodies frequently monitor. While the United States Food and Drug Administration operates independently, the MonumenTAL-3 data will likely support similar applications for earlier-line use in American clinics.[1][3]

For now, the CHMP backing signals a clear consensus among European regulators that bispecific antibodies belong closer to the front lines of myeloma care. It is a step that promises to reshape the treatment sequence for thousands of patients facing their first relapse.[2][5]