Exploring GPRC5D as an Important Target for Multiple Myeloma

A recent Training Academy highlighted the use of GPRC5D therapy in patients with multiple myeloma. The most common and only approved option is talquetamab-tgvs (Talvey). The panel highlighted the treatment in the phase 1/2 MonumenTAL-1 trial (NCT03399799; NCT04634552).

Using, Treating, and Sequencing GPRC5D Therapy

• An important target because there needs to be a range of options developed to treat multiple myeloma.
  • This can be used prior to a B-cell maturation antigen (BCMA).
• Can be considered to be used as a bridge to a BCMA or chimeric antigen receptor T-cell therapy.
• GPRC5D is more commonly expressed in malignant plasma vs normal.
• Combination therapies may produce higher efficacy rates than these monotherapies.
• Talquetamab was assessed in the phase 1/2 MonumenTAL-3 trial (NCT05455320).
• The most common toxicities include oral and skin.
  • Not as severe as with bispecific antibodies.
  • Hypothesized, as this is given one treatment at a time vs continuous bispecific use.
• Dose de-escalation can be helpful to manage.
  • Monthly treatment may be an option to help lessen or avoid dysgeusia.

• Talquetamab has not shown adverse effects (AEs) related to cardiac issues, pulmonary issues, renal issues, or neuropathy.
• AEs typically happen at first onset and then lessen as the disease becomes better controlled.
• As a GPRC5D target, there is less infectious toxicity involved.
  • Intravenous immunoglobulin supplementation is not needed as much.