What is the role of managing monocytes in the treatment of multiple myeloma (MM)?

Role of Monocytes in Multiple Myeloma Treatment

There is no established role for specifically managing monocytes in the treatment of multiple myeloma (MM), as current treatment guidelines focus on targeting plasma cells through immunotherapies, proteasome inhibitors, and other novel agents rather than monocyte-directed therapies.

Current Treatment Approaches in MM

The management of MM has evolved significantly over the past decade with the introduction of novel therapeutic agents. Current guidelines focus on:

Risk-Stratified Treatment Approach

• Mayo Clinic's mSMART guidelines recommend risk stratification based on cytogenetic features to guide therapy 1:

  • High-risk patients: More aggressive and continuous therapies
  • Standard-risk patients: Less intense therapy with similar efficacy
  • Intermediate-risk patients (with t(4;14)): More responsive to bortezomib-based therapy

• Treatment decisions are primarily based on:

  • Patient age and comorbidities
  • Cytogenetic risk profile
  • Disease burden
  • Prior treatments

First-Line Treatment Options

• For transplant-eligible patients: Induction with bortezomib-containing regimens followed by autologous stem cell transplantation 1
• For transplant-ineligible patients: Oral melphalan and prednisone or other appropriate combinations 1

Emerging Understanding of Monocytes in MM

While not part of standard treatment guidelines, recent research has begun to explore the role of monocytes in MM:

Monocyte Involvement in Immunotherapy Response

• CD14+ CD16+ monocytes have been identified as important mediators in daratumumab-mediated killing of myeloma cells 2
• The ratio between monocytes (CD14+) and MM cells (CD138+) may influence response to daratumumab therapy 2
• Formation of CD138+ CD14+ double-positive populations correlates with anti-MM killing effects 2

Tumor Microenvironment Considerations

• The bone marrow microenvironment plays a fundamental role in MM development and progression 3
• Cellular components of the microenvironment, including monocytes and monocyte-derived cells, affect myeloma cell survival and drug resistance 3

Potential Future Directions

Based on emerging research, potential approaches involving monocytes might include:

• Combination strategies targeting CD47/SIRPα axis alongside anti-CD38 monoclonal antibodies like daratumumab 2
• Dendritic cell-based immunotherapies, which are derived from monocytes, though clinical responses have been limited 4
• Targeting immunosuppressive cytokines (TGF-β, IL-10, IL-6, VEGF) that modulate monocyte and dendritic cell function 4

Current Consensus on Treatment Sequencing

The NCI Multiple Myeloma Steering Committee recommends:

• Consideration of targeted approaches for specific genetic subsets of MM 1
• Optimizing the role of immunotherapies and combinations 1
• Exploring sequencing and retreatment strategies based on prior drug exposure 1

Clinical Implications

• At present, there are no specific recommendations to target or manage monocytes as part of standard MM treatment
• The focus remains on plasma cell-directed therapies and immunomodulation
• Monitoring of immune cell populations, including monocytes, may become more important as immunotherapies continue to evolve

Conclusion

While emerging research suggests monocytes may play a role in MM treatment response, particularly with immunotherapies like daratumumab, current treatment guidelines do not include specific strategies for managing monocytes. Future research may lead to monocyte-directed approaches or consideration of monocyte populations when selecting immunotherapeutic strategies.