Mitigating Adverse Effects Following GPRC5DTargeted Therapy in Multiple Myeloma

In a recent Training Academy segment hosted by CancerNetwork®, a panel of experts in multiple myeloma discussed strategies for monitoring and mitigating adverse effects (AEs) associated with GPRC5D-targeting bispecific agents for patients with relapsed/refractory disease. They shared strategies for managing cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), and other toxicities in patients who receive this class of bispecific antibodies. Here are their key takeaways.

The expert panel.

The expert panel

B-Cell Maturation Antigen Therapy–Related Toxicity

• Short-term AEs associated with agents such as elranatamab-bcmm (Elrexfio) and teclistamab-cqyv (Tecvayli) include CRS and ICANS.
  • Tocilizumab (Actemra) plus dexamethasone may effectively lessen the severity of
    these events.
• Long-term toxicities include an increased risk of infection and hypogammaglobulinemia.
  • These events may require management with intravenous immunoglobulin or antibiotic and antiviral prophylaxis.

AEs Following GPRC5D-Directed Therapy

• In addition to cytopenia, infection, CRS, and ICANS, treatment with talquetamab-tgvs (Talvey) may result in skin-, nail-, and oral-related AEs.
  • Events may include rash, dry skin, itchiness, nail loss, taste changes, dry mouth, and swelling.
    • Nail hardeners may protect nails; steroid cream and ammonium lactate can help with rashes and dry skin, respectively.
  • Depending on the dose level, skin-related AEs occurred in 67% to 70% of patients who received talquetamab in the phase 1/2 MonumenTAL-1 trial (NCT03399799; NCT04634552).
• Dysgeusia may negatively impact the quality of life.
  • It may become undesirable or painful for patients to eat, which can result in weight loss.
    • Weight loss may lead to weakness and fatigue.
  • Delayed dosing, soft foods from squeeze pouches, artificial saliva, and dentist visits may help mitigate symptoms associated with taste changes and dry mouth.

CRS and ICANS Prophylaxis After Anti-GPRC5D Treatment

• Prophylactic tocilizumab plus pretreatment steroids may mitigate CRS or ICANS in patients who receive talquetamab.
  • Those who receive outpatient treatment may be instructed to come to a hospital to undergo CRS monitoring and complete step-up dosing.
• Collaboration with nurses and advanced practitioners can help determine the extent of CRS or ICANS, thereby establishing an appropriate course of prophylaxis.
  • Patients with grade 2 or higher CRS may be eligible to receive tocilizumab.
    • This treatment is also suitable for those with grade 1 events plus persistent fever for more than 3 days.
  • It may be appropriate to add anakinra (Kineret) for patients with higher-
    grade CRS who do not respond to tocilizumab/steroids.

AE Education and Mandates

• The FDA Risk Evaluation and Mitigation Strategies (REMS) program requires institutions to have formal plans for managing CRS and ICANS risks following bispecific therapy.
  • Drug developers can educate health care providers, nurses, and pharmacists on managing and reporting serious AEs in
    this population.
  • Patients receive education on the risks of CRS and ICANS and must have REMS numbers associated with each day of dosing.
• Regarding coordinating care, a center becoming REMS certified may allow referred patients to receive a bispecific antibody upon returning to a community center.
  • Various methods of communication, including phone calls, written medical records, and slips of paper, can help educate patients on notable toxicities and the safety of administering dexamethasone during bispecific antibody therapy.

Reference

Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-cell–redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med. 2022;387(24):2232-2244. doi:10.1056/ NEJMoa2204591