talquetamab — Drug Monograph

Talquetamab (Talvey) — GPRC5D Bispecific for Multiple Myeloma

Talquetamab (Talvey) is a GPRC5D-directed, CD3-engaging bispecific antibody for relapsed or refractory multiple myeloma. It targets GPRC5D on myeloma plasma cells and CD3 on T cells to drive T-cell-mediated killing. GPRC5D is also expressed in taste receptor cells, keratinocytes, and hair follicles, producing the characteristic non-hematologic toxicities of this class (dysgeusia, nail and skin changes). Because T-cell activation can trigger cytokine release syndrome (CRS), talquetamab uses a subcutaneous step-up schedule. This monograph covers talquetamab indications across multiple myeloma treatment lines, the GPRC5D targeting mechanism, step-up dosing, and specialized management of its unique skin, nail, and oral/taste toxicities.

Indications (FDA / NCCN)

• Relapsed or refractory multiple myeloma after ≥4 prior lines (including a PI, an IMiD, and an anti-CD38 antibody)
• GPRC5D-directed bispecific — distinct target from BCMA agents
• Two approved regimens: 0.4 mg/kg Q2W or 0.8 mg/kg weekly

Dosing

• Subcutaneous step-up: 0.01 mg/kg (Wk1 D1) → 0.06 mg/kg (Wk1 D4)
• Then 0.4 mg/kg SC every 2 weeks OR 0.8 mg/kg SC weekly
• Rotate injection sites (abdomen and thigh preferred)
• Premedicate (antipyretic, antihistamine, corticosteroid) before each step-up dose

Monitoring

• Hospitalize ≥48 h after each step-up dose for CRS
• Dysgeusia / taste changes (~69%) — nutritional counseling, taste-neutral foods
• Nail dystrophy and onycholysis (~66%); skin toxicity — emollients, topical steroids
• Weight loss and xerostomia; CBC and neurologic assessment for ICANS

Brand names: Talvey

Drug class: Other

Mechanism of Action

IgG4 bispecific antibody that simultaneously targets GPRC5D (G protein-coupled receptor class C group 5 member D) on myeloma cells and CD3ε on T cells, directing T-cell-mediated cytotoxic killing of GPRC5D-expressing multiple myeloma cells. GPRC5D is an orphan receptor highly expressed on myeloma plasma cells and, importantly, also expressed in taste receptor cells (taste buds), keratinocytes, and hair follicles, accounting for the characteristic off-target toxicities of this drug class.

FDA Indications

• Relapsed or refractory multiple myeloma after ≥4 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody (FDA accelerated approval August 2023, MonumenTAL-1: 73% ORR at 0.8 mg/kg weekly; 64% ORR at 0.4 mg/kg biweekly dosing)

Common Side Effects

• Dysgeusia/taste changes (69%) — class effect from GPRC5D on taste buds
• Nail toxicity: nail dystrophy, onycholysis (66%) — class effect from GPRC5D on keratinocytes
• Skin toxicity: rash, skin exfoliation, dry skin (65%)
• CRS (77%)
• Weight loss and decreased appetite
• Xerostomia (dry mouth)
• Fatigue
• Musculoskeletal pain
• Infections

Clinical Pearl

GPRC5D-related toxicities (dysgeusia, nail changes, skin toxicity, weight loss, xerostomia) are unique class effects not seen with anti-BCMA bispecifics (teclistamab, elranatamab) and reflect GPRC5D expression in normal oral, skin, and nail tissues. Supportive care for these toxicities includes taste-neutral foods, nail emollients, topical corticosteroids for skin, and nutritional counseling. These toxicities are generally manageable with dose modifications.

Related Therapies & Mechanisms

• Ciltacabtagene autoleucel (Carvykti) — Other · Myeloma
• Idecabtagene vicleucel (Abecma) — Other · Myeloma
• Panobinostat (Farydak) — Other · Myeloma
• Selinexor (Xpovio) — Other · Myeloma