Revised International Prognostic Index and Genetic Alterations Are Associated with Early Failure to R-CHOP in Patients with DLBCL

By Robert Dillard - Last Updated: November 2, 2021

A study assessed clinical biological features in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients to discern variables associated with early to failure (EF) to treatment. The findings were published in the British Journal of Haematology.

Researchers assessed 373 patients with DLBCL who were homogeneously treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). In this analysis, EF was defined as primary refractoriness or relapse within 12 months from diagnosis. In addition to clinical features, the researchers analyzed mutational status of 106 genes via targeted next generation sequencing in 111 cases, copy number alterations in 87, and gene expression profile (GEP) in 39.

The results showed 26% of patients were identified as EF and showed significantly shorter overall survival (OS). Patients with B symptoms, advanced stage, high levels of serum lactate dehydrogenase (LDH) or ?2-microglobulin, low lymphocyte/monocyte ratio and higher Revised International Prognostic Index (R-IPI) scores, as well as those with BCL2 rearrangements more frequently showed EF, with R-IPI being the most important in logistic regression, the researchers noted. They observed that mutations in NOTCH2 and gains in 5p15·33 (TERT), 12q13 (CDK2), 12q14·1 (CDK4) and 12q15 (MDM2) were predictive for EF independently from R-IPI.

“GEP studies showed that EF cases were significantly enriched in sets related to cell cycle regulation and inflammatory response, while cases in response showed over-representation of gene sets related to extra-cellular matrix and tumor microenvironment,” the researchers concluded.

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