Recurrent Mutations Linked with Chemo-Immunotherapy Relapse in Lymphoma

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There are various recurrent mutations associated with chemo-immunotherapy relapse in patients with diffuse large B-cell lymphoma.
There are various recurrent mutations associated with chemo-immunotherapy relapse in patients with diffuse large B-cell lymphoma.

ORLANDO ­– There are various recurrent mutations associated with chemo-immunotherapy relapse in patients with diffuse large B-cell lymphoma (DLBCL), a study presented at the American Society of Hematology (ASH) 57th Annual Meeting & Exposition has shown.1

DLBCL is the most common form of adult lymphoma with the standard of care being a combination chemo-immunotherapy RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). However, relapses typically occur within 2 to 3 years. Therefore, researchers sought to analyze the mutational heterogeneity of DLBCL in order to identify novel biomarkers to improve stratification of patients with DLBCL for clinical management.

Because the rate of relapse is higher in Nordic populations, “we wanted to focus on relapsed/refractory DLBCL,” Jillian Frances Wise, PhD, post-doctoral fellow at Oslo University Hospital in Oslo, Norway, said during her presentation

For the study, researchers analyzed DLBCL samples from 37 cases. “All cases came from Norway or Finland,” Dr Wise noted.

Seventeen cases never relapsed while 20 cases relapsed from RCHOP or related therapy. Whole exome sequencing was performed on 15 biopsies taken at diagnosis and 13 taken at relapse.

Researchers identified 102 potential driver mutations, of which many had been previously discovered genes associated with DLBCL, including MLL2, B2M, CD58, MEF2B, FOXO1, TP53, PIM1, SOCS1, MYC, GNA13, SGK1, TNFAIP3, MYD88, PRDM1, CDKN2A, EZH2 and CIITA. “The majority of our genes were missense mutations," Dr Wise said.

However, there was minimal overlap between the gene list identified in this study and gene lists from earlier DLBCL exome sequencing analyses.

“We then looked at how these potential driver mutations correlated with overall survival,” Dr Wise said. “Fourteen potential driver genes correlated to survival by Cox Regression analysis.”

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The findings ultimately provide a novel view of the DLBCL mutational landscape with respect to relapse and chemo-immunotherapy resistance.

“Standardizing sequencing, bioinformatics pipelines, and selection tools should help further define the mutational burden of DLBCL,” she said.

Reference

  1. Wise JF, Nakken S, Vodak S, et al. Discovery of recurrent mutations associated with chemo-immunotherapy relapse in diffuse large B-cell lymphoma. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.

ORLANDO ­– There are various recurrent mutations associated with chemo-immunotherapy relapse in patients with diffuse large B-cell lymphoma (DLBCL), a study presented at the American Society of Hematology (ASH) 57th Annual Meeting & Exposition has shown.1

DLBCL is the most common form of adult lymphoma with the standard of care being a combination chemo-immunotherapy RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). However, relapses typically occur within 2 to 3 years. Therefore, researchers sought to analyze the mutational heterogeneity of DLBCL in order to identify novel biomarkers to improve stratification of patients with DLBCL for clinical management.

Because the rate of relapse is higher in Nordic populations, “we wanted to focus on relapsed/refractory DLBCL,” Jillian Frances Wise, PhD, post-doctoral fellow at Oslo University Hospital in Oslo, Norway, said during her presentation

For the study, researchers analyzed DLBCL samples from 37 cases. “All cases came from Norway or Finland,” Dr Wise noted.

Seventeen cases never relapsed while 20 cases relapsed from RCHOP or related therapy. Whole exome sequencing was performed on 15 biopsies taken at diagnosis and 13 taken at relapse.

Researchers identified 102 potential driver mutations, of which many had been previously discovered genes associated with DLBCL, including MLL2, B2M, CD58, MEF2B, FOXO1, TP53, PIM1, SOCS1, MYC, GNA13, SGK1, TNFAIP3, MYD88, PRDM1, CDKN2A, EZH2 and CIITA. “The majority of our genes were missense mutations," Dr Wise said.

However, there was minimal overlap between the gene list identified in this study and gene lists from earlier DLBCL exome sequencing analyses.

“We then looked at how these potential driver mutations correlated with overall survival,” Dr Wise said. “Fourteen potential driver genes correlated to survival by Cox Regression analysis.”

The findings ultimately provide a novel view of the DLBCL mutational landscape with respect to relapse and chemo-immunotherapy resistance.

“Standardizing sequencing, bioinformatics pipelines, and selection tools should help further define the mutational burden of DLBCL,” she said.

Reference

1.     Wise JF, Nakken S, Vodak S, et al. Discovery of recurrent mutations associated with chemo-immunotherapy relapse in diffuse large B-cell lymphoma. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.

 

 

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