The Lymphoma Research Foundation's 2024 Marginal Zone Lymphoma (MZL) Virtual Scientific Workshop convened leading researchers to evaluate progress and chart the future direction of MZL research. The meeting highlighted both significant advances and persistent challenges in understanding and treating this rare form of non-Hodgkin lymphoma.
Current Understanding and Challenges
MZL comprises three key subtypes - extranodal, nodal, and splenic MZL - that arise from B cells in the marginal zones of lymphoid tissues. While generally indolent, MZL presents significant clinical challenges due to its heterogeneous nature and limited treatment options. Current five-year survival rates are highest for extranodal MZL at 96%, followed by splenic and nodal at 85%.
Researchers identified several critical knowledge gaps, including:
- Inconsistent diagnostic criteria across MZL subtypes
- Limited understanding of transformation mechanisms
- Lack of MZL-specific clinical trials
- Need for improved prognostic markers
- Absence of standardized treatment approaches
Research Priorities and Future Directions
The workshop established key research priorities across multiple domains:
Biology and Pathology
Short-term goals include better definition of disease subtypes and exploration of the tumor microenvironment. Long-term objectives focus on establishing MZL-specific biological correlates and identifying disease precursors.
Clinical Assessment
Immediate priorities include developing:
- New response criteria specific to MZL subtypes
- Better understanding of minimal residual disease monitoring
- Role of PET imaging in staging and assessment
- Validated surrogate endpoints for clinical trials
Treatment Approaches
The workshop emphasized the need for:
- Standardized treatment protocols for each MZL subtype
- MZL-specific clinical trials rather than combined indolent lymphoma studies
- Development of novel targeted therapies
- Strategies to overcome treatment resistance
Emerging Therapeutic Approaches
Several promising therapeutic strategies are under investigation:
- BTK inhibitors with and without anti-IL16 agents
- PI3K inhibitors combined with STAT inhibitors
- CAR T-cell therapy for resistant disease
- Novel antibody-drug conjugates
- Immune checkpoint modulators
Path Forward
The workshop concluded by emphasizing the importance of international collaboration and the need for dedicated research funding to address these priorities. Experts stressed that improving outcomes for MZL patients will require both better understanding of basic disease biology and development of more effective, targeted treatments.
The meeting's comprehensive review and strategic planning provide a roadmap for advancing MZL research over the next decade, with the ultimate goal of developing more effective, personalized treatments for patients with this challenging disease.
