Gene Expression-Based Identifier Predicts Risk, Treatment Outcomes for DLBCL Subtype

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MHG indicates poor risk and treatment outcomes in patients with diffuse large B-cell lymphoma.
MHG indicates poor risk and treatment outcomes in patients with diffuse large B-cell lymphoma.

Heterogeneity inherent to diffuse large B-cell lymphoma (DLBCL) can pose a challenge to effective treatment. However, a team of researchers discovered a method for discerning patients with DLBCL who may benefit from nonstandard therapies, with the results presented in the Journal of Clinical Oncology.

The research team examined gene expression data from 928 patients with DLBCL who had participated in a clinical trial (Clinical Trials Identifier: NCT01324596) comparing outcomes with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) vs R-CHOP with bortezomib added (RB-CHOP).

During prior research in developing a gene expression-based classifier, the researchers had defined a molecular high-grade (MHG) designation of patterns associated with a poorer prognosis. After further validation, applying the classifier to this data set indicated the MHG designation fit for 83 (9% of total) patients in the study.

The MHG group showed significant differences in progression-free survival (PFS) and overall survival (OS) compared with other groups. Those patients in the MHG group treated with R-CHOP showed a 3-year PFS rate of 37% (95% CI, 24%-55%) vs 72% (95% CI, 68%-77%) in other patients. For those in the MHG group treated with RB-CHOP, the 3-year PFS rate was 58% (P = .08) — a nonsignificant difference from R-CHOP but suggestive of a potential benefit from including bortezomib.

The poor outcomes with R-CHOP experienced by patients with MHG DLBCL warrant treatment instead with either novel targeted agents or an intensification strategy akin to that of double-hit lymphomas, the researchers concluded. They also recommend further exploring the effects of bortezomib in this group, including any mechanism of action relevant to this subtype of DLBCL.

Reference

Sha C, Barrans S, Cucco F, et al. Molecular high-grade B-cell lymphoma: defining a poor-risk group that requires different approaches to therapy [published online December 3, 2018]. J Clin Oncol. doi: 10.1200/JCO.18.01314

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