Using Real-World Data to Form GPRC5D Therapy Strategies in R/R Multiple Myeloma

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ONCOLOGY® CompanionONCOLOGY® Companion, Volume 38, Supplement 11
Volume 38
Issue 11
Pages: 26-27

Experts in multiple myeloma discussed real-world efficacy and safety data associated with the use of GPRC5D-targeting bispecific agents to treat patients with R/R multiple myeloma.

Meet the experts

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
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