Diffuse Large B-cell Lymphoma

Chemo Length May Not Affect Survival in Some B-cell Lymphomas

CHICAGO – It doesn’t seem to matter whether patients with newly diagnosed, diffuse large B-cell lymphoma receive a standard chemotherapy regimen in a dose-dense fashion every 14 days for six cycles, or every 21 days for eight cycles, said investigators in a multinational trial that was presented at the annual meeting of the American Society of Clinical Oncology.

There were no significant differences in the primary outcome of overall survival or the secondary outcome of failure-free survival among 1,080 patients who were randomly assigned to the two R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens, reported Dr. David Cunningham of the Royal Marsden Hospital in London, on behalf of colleagues in the U.K. National Cancer Research Institute’s lymphoma clinical study group.

Half the population received R-CHOP every 3 weeks for eight cycles (R-CHOP-21), and the other half was assigned to R-CHOP every 2 weeks for six cycles, followed by two additional rituximab infusions (R-CHOP-14).

Dr. Cunningham highlighted the following findings:

• The 2-year overall survival rates were 81% in the R-CHOP-21 arm, and 83% in the R-CHOP-14 arm (log rank P = .70).

• Overall response rates (a combination of complete responses [CR], complete unconfirmed responses [CRu], and partial responses [PR]) were 88% in R-CHOP-21 and 90% in R-CHOP-14 ( P = .11).

• Rates of combined CR/CRu were 63% and 58%, respectively ( P = .15).

• The 2-year failure-free survival rates were identical, at 75% in each group.

Toxicities were also generally similar between the treatment groups, except for a lower incidence of neutropenia in the R-CHOP-14 arm, which reflected primary prophylaxis with granulocyte-colony-stimulating factor (G-CSF) in that group.

There were no differences in failure-free survival between the treatment arms when patients were stratified by age, sex, disease stage, bulky disease, B symptoms, prognostic score, IPI (International Prognostic Index) score, cell proliferation (as measured by the MIB-1 monoclonal antibody), or diffuse large B-cell lymphoma (DLBCL) phenotype.

"We couldn’t actually identify any of the subsets or subgroups that benefited from one or the other treatment," Dr. Cunningham said.

MicroRNA expression in diffuse large B-cell lymphoma treated with ...

Abstract

DLBCL prognostication requires additional biological markers. MicroRNAs (miRNAs) may constitute markers for cancer diagnosis, outcome or therapy response. Here we have analyzed the miRNA expression profile in a retrospective multicenter series of DLBCL patients (258 cases) uniformly treated with chemoimmunotherapy. Findings were correlated with OS and PFS. miRNA and gene expression profiles were studied using microarrays in an initial set of 36 cases. A selection of miRNAs associated with either DLBCL molecular subtypes (GCB/ABC) or clinical outcome were studied by multiplex RT-PCR in a test group of 240 cases with available FFPE diagnostic sample, divided into a training set (123 patients), which was used to derive miRNA-based and combined (with IPI score) Cox regression models, and an independent validation series (117 patients). A model based on miRNA expression predicts OS and PFS. This model improves the prediction based on clinical variables. Combined models with IPI score identify a high-risk group of patients with a 2-year OS and PFS probability of less than 50%. In summary, a precise miRNA signature is associated with poor clinical outcome in chemoimmunotherapy-treated DLBCL patients. This information improves IPI-based prediction and identifies a subgroup of candidate patients for alternative therapeutic regimens to those of standard therapies.

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