Key Takeaways and Future Directions in Later Relapsed/Refractory MM
Panelists discuss how talquetamab’s unique targeting mechanism offers significant advantages for patients with prior T-cell therapy exposure, whereas future research should focus on combination strategies and understanding primary resistance mechanisms.
EP: 1.Later R/R MM Treatment Landscape and Unmet Needs
EP: 2.ASCO 2025: MonumenTAL-1 Extended Follow-Up for Talquetamab in R/R MM
EP: 3.Insights From MonumenTAL-1: Impressions of Updated Efficacy Outcomes
EP: 4.MonumenTAL-1: Implications of Talquetamab, Prior TCR, and Sequencing for R/R MM
EP: 5.Safety Updates and Concluding Thoughts From Extended Follow-Up of MonumenTAL-1
EP: 6.Talquetamab in R/R MM: Managing GPRC5D-direced AEs, Prophylaxis, and New Safety Signals
EP: 7.A Review of Outpatient Step-Up Dosing for Talquetamab in R/R MM
EP: 8.Real-World Use, Outpatient Dosing and Transitions of Care in Academic and Community Settings
EP: 9.Key Takeaways and Future Directions in Later Relapsed/Refractory MM
Despite significant advances in multiple myeloma treatment, substantial unmet needs remain in achieving durable remissions and potential cures for patients. Talquetamab represents a major advancement due to its unique GPRC5D targeting, which provides comparable response rates around 70% with unprecedented 3-year survival rates of 45% in T-cell redirecting therapy-exposed patients. The lower infection risk profile compared to BCMA-directed therapies makes talquetamab particularly valuable for frail patients with comorbidities and those requiring sequential bispecific therapy approaches.
Current research priorities focus on combination therapy strategies to enhance response durability and overcome resistance mechanisms. Areas of particular interest include patients with extramedullary disease, adverse cytogenetics including 17p deletion, and stage III disease, who typically show lower response rates to bispecific monotherapy. The development of rational combination approaches, optimal sequencing strategies, and methods to preserve T-cell fitness between successive T-cell engaging therapies represent critical research directions for improving long-term outcomes.
The most significant remaining challenge involves understanding and addressing primary refractory disease, where approximately 30% of patients fail to respond to bispecific antibodies, including talquetamab. Research efforts are focusing on identifying both tumor-intrinsic and T-cell–related mechanisms contributing to treatment resistance, with the goal of developing strategies to overcome these barriers. Future therapeutic development must address the need for new targets and agents and the optimization of existing highly effective therapies through improved combination strategies and sequencing approaches to maximize patient benefit and move closer to curative outcomes in multiple myeloma.
