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Talquetamab is the first drug against GPRC5D, a second myeloma target used after BCMA therapies stop working; taste and skin side effects are its signature.
Talquetamab is a humanised IgG4 GPRC5DxCD3 bispecific antibody and the first drug against GPRC5D, a receptor expressed on plasma cells and on keratinised tissue. In MonumenTAL-1 the ORR was about 73% at both the weekly and biweekly doses, including about 65% in patients after prior T-cell redirection, showing that a second target works after BCMA therapy stops. Accelerated approval followed in August 2023 after at least 4 prior lines. Dysgeusia (72%), skin toxicity (67%) and nail disorders (54%) are frequent, cytokine release syndrome was grade 3 or higher in only 2%, and infection rates are lower than with BCMA agents. Combinations with teclistamab (RedirecTT-1, ORR about 80% with extramedullary disease) and daratumumab (TRIMM-2) are in phase 3 (MonumenTAL-3, -5 and -6). It opened a second target after BCMA in myeloma, at the cost of taste and skin effects.
Backbone ribbon from PDB 9IMA. RCSB PDB 9IMA. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
Humanised IgG4 GPRC5D×CD3 bispecific; GPRC5D is expressed on plasma cells and keratinised tissue. Connects to GPRC5D and CD3.
1.One arm of Talquetamab binds GPRC5D on the cancer cell.
Given by infusion or injection in a clinic or hospital outpatient department, so it is a Part B drug: Medicare pays 80% after the Part B deductible and the patient owes 20% coinsurance, uncapped in Original Medicare unless a Medigap policy applies. Step-up dosing is often started in hospital (Part A) because of cytokine release syndrome monitoring, then continued in the outpatient setting.
Covered under the medical benefit with prior authorisation confirming diagnosis, biomarker status and line of therapy; site-of-care policies may steer infusions away from hospital outpatient departments.
20% Part B coinsurance on a high-cost infusion adds up quickly: Medigap Plan G or N, Medicare Advantage maximum out-of-pocket, Medicaid dual eligibility, or a charity fund are the usual buffers.
Sources: Medicare.gov: Chemotherapy · Medicare.gov: Prescription drugs (outpatient, Part B). Not medical or financial advice; verify with your plan.
Sources: NICE TA1114. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
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Adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody
Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 3.1 years later, when the FDA's table was read. source
| Region | Year | Indication |
|---|---|---|
| US | 2023 | Relapsed/refractory myeloma after ≥4 lines (accelerated) |
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Dysgeusia | 72% | - |
| Skin toxicity | 67% | - |
| Nail disorders | 54% | - |
| Cytokine release syndrome | 77% | 2% |
MonumenTAL-1. Events listed without rates were not read from a primary source; see the label. Blank cells mean the figure was not sourced, not that it is zero.
Read for the class this product belongs to (bispecific t-cell engagers) unless the answer names the product. Population figures from the cohorts named, not a prediction for one person. Blank where no source gives a recovery figure.
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Elranatamab confirmed that BCMA bispecifics are a class, not a one-off, and its protocol-built dose reduction after response set a precedent for lowering the immunosuppressive burden of T-cell engagers. Patients now have two approved BCMA bispecifics and one against GPRC5D (talquetamab). Choosing between them, and sequencing them with CAR-T, remains guided by availability and toxicity profile rather than head-to-head data.
Teclistamab showed that an off-the-shelf bispecific can approach CAR-T-like response rates in late myeloma, giving patients who cannot wait for or access cell therapy a real option. It also exposed the price: prolonged T-cell engagement causes profound immunosuppression, so infection prophylaxis and immunoglobulin replacement are now routine. Less frequent dosing after response is being adopted to reduce this burden.
A second bispecific target beyond BCMA gives patients an option after BCMA-directed CAR-T or bispecifics have failed; it was approved in 2023.
Query for this drug: (TITLE:"Talquetamab" OR ABSTRACT:"Talquetamab" OR TITLE:"Talvey" OR ABSTRACT:"Talvey") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Talquetamab, not a curated reading list.
Shares A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma, BCMA-directed therapy → GPRC5D-directed therapy, ISB 2001, A Study Comparing Talquetamab Plus Pomalidomide, Talquetamab Plus Teclistamab, and Elotuzumab, Pomalidomide, and Dexamethasone or Pomalidomide, Bortez.
Shares MonumenTAL-1, GPRC5D, CD3, T-cell engagers (bispecific).
Shares MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma, Relapsed or refractory multiple myeloma, Johnson & Johnson, T-cell engagers (bispecific).
Shares MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma, Relapsed or refractory multiple myeloma, Johnson & Johnson, T-cell engagers (bispecific).
Shares MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response, MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma, Relapsed or refractory multiple myeloma, Multiple myeloma.
Shares MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response, MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma, CD3, Relapsed or refractory multiple myeloma.
Shares MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response, Relapsed or refractory multiple myeloma, T-cell engagers (bispecific), Multiple myeloma.
Shares MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response, Relapsed or refractory multiple myeloma, T-cell engagers (bispecific), Multiple myeloma.