Handling an Intricate Case of R/R MM With BCMA/GPRC5D Bispecific Antibodies

A multidisciplinary care team from the Huntsman Cancer Institute at the University of Utah in Salt Lake City considered the proper way to handle a complex case of relapsed/refractory multiple myeloma and ultimately decided to treat with talquetamab-tgvs (Talvey) during a Training Academy event hosted by CancerNetwork. Here are their takeaways.

Patient Case

A 76-year-old woman who was diagnosed with Revised International Staging System stage unknown oligosecretory IgG-κ light chain multiple myeloma in 2010 is on her eighth line of treatment and has been on single-agent talquetamab for over 1 year.

• The patient was previously treated with autologous hematopoietic stem cell transplant; bortezomib (Velcade), thalidomide (Thalomid), and dexamethasone; bortezomib, lenalidomide (Revlimid), and dexamethasone; daratumumab (Darzalex), bortezomib, and dexamethasone; and daratumumab, pomalidomide (Pomalyst), and dexamethasone, among others.
  • She handled treatment well despite neuropathy and recurrent infections.
  • On each line of treatment, she achieved the expected progression-free survival.
• The patient progressed after a clinical trial, and the care team opted to start her on talquetamab as she was determined to be B-cell maturation agent (BCMA) refractory.
  • The change was made because of the power of switching to a new target: GPRC5D
• The dosing process is as follows:
  • Day 1: 0.01 mg/kg subcutaneous injection
  • Day 3: 0.06 mg/kg
  • Day 5: 0.4 mg/kg
  • Patients are monitored in the hospital for 48 hours.
  • If the patient is released to the outpatient setting, then the dose is 0.8 mg/kg.
    • If the patient is still admitted, the care team will meet to discuss appropriate dosing strategies.
• The care team reduced dosing due to suspicion of a complete response.

• The patient was admitted for inpatient treatment after day 1 of talquetamab for cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome observation.
  • The patient elected not to undergo another bone marrow biopsy.
  • Adverse effects (AEs) forced dose holds, and data shows that reduced dose frequency of talquetamab should maintain responses while reducing AEs.
    • The patient experienced skin, nail, and oral toxicities.

Key Takeaways

• How do you prioritize treatment goals, given the patient’s age and comorbidities?
  • Through shared decision-making. Always discuss the pros and cons of treatment options with the patient.
• How do you assess the risks and benefits of continuing vs switching therapies?
  • By abiding by a low threshold for holding the drug and reducing the frequency of drug dosing once a patient achieves a response.
• What role does supportive care play in managing chronic symptoms?
  • Spaced out dosing of talquetamab gave her time to improve her other comorbidities by enrolling in a better exercise program and having closely managed nutrition to watch out for oral toxicities as well as weight loss.