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PD-1/PD-L1 inhibitors in multiple myeloma: The present and the future
1Faculty of Science, University of Ostrava, Czech Republic; Department of Haematooncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Czech Republic; Centro de Investigacion Medica Aplicada (CIMA), Clinica Universidad de Navarra, IDISNA, Pamplona, Spain.
Abstract:
The introduction of PD-1/PD-L1 pathway inhibitors has marked a significant milestone in the treatment of various types of solid tumors. The current situation in multiple myeloma (MM) is rather unclear, as distinct research groups have reported discordant results. This discrepancy dominantly concerns the expression of PD-1/PD-L1 molecules as well as the identification of the responsible immune effector cell population. The results of monotherapy with PD-1/PD-L1 inhibitors have been unsatisfactory in MM, suggesting that a combination approach is needed. The most logical partners are immunomodulatory agents as they possess many synergistic effects. We are also proposing other rational and promising combinations (e.g., daratumumab, ibrutinib, anti-CD137) that warrant further investigation.
Insights
Programmed cell death protein 1 (PD-1)/PD-L1 inhibitors show promise in solid tumors but are unclear in multiple myeloma (MM). Combination therapies, particularly with immunomodulatory agents, are suggested for better MM treatment outcomes.
Area of Science:
- Oncology
- Immunology
- Hematology
Background:
- PD-1/PD-L1 inhibitors are effective in solid tumors.
- Their role in multiple myeloma (MM) remains unclear due to conflicting research.
- Discrepancies exist regarding PD-1/PD-L1 expression and immune cell involvement in MM.
Purpose of the Study:
- To clarify the role of PD-1/PD-L1 pathway inhibitors in multiple myeloma.
- To investigate the reasons for discordant results in current research.
- To propose effective combination strategies for MM treatment.
Main Methods:
- Review of existing research on PD-1/PD-L1 inhibitors in multiple myeloma.
- Analysis of discrepancies in PD-1/PD-L1 expression and immune effector cell identification.
- Evaluation of potential synergistic combinations for MM therapy.
Main Results:
- Monotherapy with PD-1/PD-L1 inhibitors has yielded unsatisfactory results in MM.
- Immunomodulatory agents show potential synergistic effects with PD-1/PD-L1 inhibitors.
- Other combinations like daratumumab, ibrutinib, and anti-CD137 warrant investigation.
Conclusions:
- PD-1/PD-L1 inhibitors alone are insufficient for MM treatment.
- Combination therapies are necessary to improve outcomes in MM.
- Further research into novel combinations is crucial for advancing MM therapy.
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