High-grade B-cell lymphomas: high difficulties to diagnose and treat?

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• High-grade B-cell lymphomas (HGBLs) are a heterogeneous group of mature B-cell malignancies.
• Recent molecular and genomic studies are clarifying their shared oncogenic mechanisms and leading to classification changes.
• These tumors often exhibit aggressive behavior and may resist standard treatments like R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone).

Purpose of the Study:

• To review the current understanding of HGBLs, focusing on their evolving classification based on molecular diagnostics.
• To discuss the distinct biological features of different HGBL subtypes, such as double-hit lymphomas.
• To highlight the challenges in clinical management and explore emerging therapeutic strategies.

Main Methods:

• Review of current literature on HGBL pathology, molecular genetics, and clinical outcomes.
• Analysis of genomic studies identifying key oncogenic aberrations in HGBL subtypes.
• Synthesis of data on treatment responses and novel therapeutic approaches.

Main Results:

• Double-hit HGBLs with MYC and BCL2 translocations show a homogeneous germinal center B-cell phenotype and biology.
• HGBLs with MYC and BCL6 translocations lack a unifying biological profile.
• HGBLs not otherwise specified remain poorly characterized by distinct genetic aberrations.
• Aggressive features and poor response to R-CHOP are common in HGBLs, necessitating intensified regimens.
• Chimeric antigen receptor T-cell therapy shows significant efficacy in relapsed/refractory settings.

Conclusions:

• Understanding the molecular biology of HGBLs is crucial for accurate classification and improved patient outcomes.
• Prospective studies are needed to optimize treatment strategies for these aggressive lymphomas.
• Novel therapies, including CAR T-cell therapy and bispecific antibodies, offer promising avenues for managing relapsed and refractory HGBLs.