627. Aggressive Lymphoma (Diffuse Large B-Cell & Other Aggressive B-Cell NHL)-Results from Retrospective/Observational Studies: Molecular Characterization of Diffuse Large B Cell Lymphoma


Impact of Immunohistochemistry-Defined Cell of Origin and MYC Rearrangements on Outcomes in Patients with PET-Defined Stage I/II Diffuse Large B-Cell Lymphoma Treated with R-CHOP ± Radiotherapy: An International Multi-Center Retrospective Study

Allison Barraclough, et al.

The authors of the study conclude:

In patients with PET-CT-defined stage I/II DLBCL treated with R-CHOP ± radiation, COO, DE and DH status did not adversely affect PFS or OS. The SM-IPI continues to have prognostic relevance in R-CHOP treated patients. Escalated induction therapy (e.g. dose adjusted EPOCH-R) may not be necessary in patients with stage I/II DH lymphoma. Updated results for the IHC and FISH analyses will be presented at the meeting.



A New Immunohistochemical Algorithm Using Four Antibodies Has a High Concordance with Gene Expression Profiling Defined ABC and GCB  Diffuse Large B-Cell Lymphoma

Henry Theophraste, Resident et al.

The authors of the study conclude:

Our new algorithm shows excellent performance compared to the Gold Standard GEP classification, using only 4 immunostains, and allows for more accurate risk stratification both for PFS and OS than Hans'algorithm. Therefore, it can be used as a useful tool in addition to molecular signatures.



Comprehensive Genomic Profiling (CGP) Identifies Novel BCL6 Rearrangements in Diverse Subtypes of Non-Hodgkin Lymphoma (NHL) As Well As Known Rearrangements Not Detected Using Standard of Care (SOC) Assays

Jo-Anne Vergilio, et al.

The authors of the study conclude:

In this study, novel BCL6 rearrangements were identified in 22% of cases examined; notably, these novel partners comprised >50% of all partners detected. In the most recent WHO classification (2016), BCL6 rearrangement has known diagnostic and possible prognostic utility in high-grade BCLs, whereas previously Ig-BCL6 was considered secondary to other immunoglobulin gene partners (e.g. BCL2, MYC). Additionally, the presence of BCL6 rearrangements can distinguish t(14;18)-negative FL, a unique clinicopathologic entity with a worse prognosis. Non-Ig rearrangements may also portend a worse prognosis in other lymphoma subtypes; therefore, both the identification of novel partners and an understanding of their frequency has clinical utility and may lead to improved management for patients. Furthermore, the presence of false-negative results for known partners, using FISH, suggests an opportunity for alternative diagnostic testing via CGP.



BCL2 Expression Identifies a Population with Unmet Medical Need in Previously Untreated (1L) Patients with DLBCL

Edith Szafer-Glusman et al.

The authors of the study conclude:

Using a newly developed BCL2 IHC scoring algorithm, we demonstrate that DLBCL patients positive for BCL2 have a consistently inferior prognosis compared with patients negative for BCL2. The prognostic value of BCL2 IHC is independent of IPI and COO in GOYA and BCCA. The Ventana assay is currently being used in a Phase 2 study of venetoclax in combination with R-CHOP to evaluate the correlation (if any) of BCL2 expression with venetoclax + R-CHOP treatment (CAVALLI – NCT02055820).



A Simulation Analysis to Evaluate the Effect of Prospective Biomarker Testing on Progression-Free Survival (PFS) in DLBCL

Edith Szafer-Glusman, et al.

The authors of the study conclude:

In GOYA, short PFS was associated with <15 days from diagnosis to randomization and <8 days from diagnosis to screening, possibly attributable to high-risk biology, such as high expression of BCL2 and DH. Despite seemingly expedited work-up, these high-risk patients do poorly, highlighting the need for targeted therapies and innovative trial designs. In this example, additional screening time similar to the time required for prospective testing did not adversely affect PFS. Our results may have implications for designing precision medicine trials in DLBCL.



The Prognostic Significance of the Complete IgH Rearrangement Pattern Using the BIOMED-2 Protocol in Diffuse Large B-Cell Lymphoma

Tomohiro Yabushita, et al.

The authors of the study conclude:

Complete IgH rearrangement detected by all three primer sets in the BIOMED-2 PCR protocol was associated with poor prognosis in patients with DLBCL. Combined with the additional sequencing analysis, this suggests that the lower levels of VH SHMs may be associated with unfavorable prognosis in DLBCL