Meet the experts

In a recent Training Academy segment hosted by CancerNetwork, a panel of experts in multiple myeloma discussed real-world efficacy and safety data associated with the use of GPRC5D-targeting bispecific agents to treat patients with relapsed/refractory multiple myeloma. They highlighted how findings from real-world settings may compare with prior reports from clinical trials and addressed logistical barriers associated with administering anti-GPRC5D therapies in a community setting. Here are their key takeaways:

Real-World Efficacy of GPRC5D Bispecific Therapies

• Talquetamab-tgvs (Talvey) has elicited real-world responses comparable to those in clinical trials.
  • Responses have even occurred among those with severe renal insufficiency; these patients are typically excluded from clinical trials.
• Real-world responses with talquetamab have occurred among patients who have received prior lines of anti– B-cell maturation antigen (BCMA) agents or antibody-drug conjugates.
  • Talquetamab has yielded responses among those with poor cytogenetics or extramedullary disease.
• Regarding clinical features, patients with weight issues may not be suitable candidates to undergo GPRC5D-targeted therapy compared with anti-BCMA agents.
  • However, GPRC5D-targeted treatment may confer a lower risk of infections vs BCMA therapy.
    • Patients who are older and have frailty may be candidates to receive GPRC5D therapy before considering anti-BCMA agents.
• Those with preexisting psoriasis or skin lesions may not be eligible to receive talquetamab.

Community Setting Considerations and Challenges

• Working with community partners to administer GPRC5D-targeted therapy requires FDA Risk Evaluation and Mitigation Strategies certification.
  • Physicians and nurses becoming more experienced with using these agents in an outpatient setting may benefit a community.
  • Access disparities may exist for patients who live in rural areas or locations far from a treatment center.
  • Social workers and case managers can assist patients and their loved ones with transportation.
• Finding the most effective talquetamab-based combination therapy is an ongoing initiative.
  • Data from the phase 1b MonumenTAL-2 trial (NCT05050097) showed high response rates with talquetamab plus pomalidomide (Pomalyst), even among those who previously received pomalidomide or had triple-class refractory disease.¹
• As bispecific agents move into earlier lines of treatment, sequencing them with other standard multiple myeloma therapies may be a challenge.
  • Considering patient factors such as their ability to tolerate different treatments, organ function, and frailty may support the selection of one agent over another.
  • It may be important to identify molecular patterns that can help predict which patients are most likely to respond to this therapy.

Real-World Toxicity Associated With GPRC5D Therapy

• Following cytokine release syndrome in the short term, continuous use of GPRC5D therapy may result in a risk of infections due to profound immune suppression.
• Oral toxicities and weight changes may be difficult to manage in patients.
  • GPRC5D receptors in the tongue may correlate with oral toxicities such as taste changes.
  • Assistance from a nutritionist and supplementary protein shakes may help mitigate weight changes.
• Patients may require intravenous immunoglobulin prophylaxis regularly when receiving continuous GPRC5D-targeted therapy.
  • It may be possible to delay dosing from once every 2 weeks to once every 4 or 6 weeks if a patient’s disease appears to be under control.

Reference

1. Matous J, Biran N, Perrot A, et al. Talquetamab +pomalidomide in patients with relapsed/refractory multiple myeloma: safety and preliminary efficacy results from the phase 1b MonumenTAL-2 study. Blood. 2023;142(suppl 1):1014. doi:10.1182/blood-2023-187706