Two SNPs linked to survival in R-CHOP–treated DLBCL

 

Two variations of the BCL2 gene are linked with the survival prospects of patients with diffuse large B-cell lymphoma (DLBCL) who are treated with the R-CHOP regimen, based on a study published in Haematologica.

In the population-based, case-control study of patients with non-Hodgkin’s lymphoma across the British Columbia province, Morteza Bashash, PhD, of the Dalla Lana School of Public Health, Toronto, and researchers at the British Columbia Cancer Agency analyzed 217 germline DLBCL samples, excluding those with primary mediastinal large B-cell lymphoma, specifically looking at nine single nucleotide polymorphisms (SNPs).

Nephron/Wikimedia Commons/CC BY-SA 3.0 ecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

They found interactions between two SNPs and overall survival that were seen only in those treated with primary R-CHOP, a regimen that includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and not in those treated with primary CHOP, without rituximab. The SNPs were rs7226979 and rs4456611 (P less than .01). Of these, a statistically significant association with progression-free survival (PFS) (P less than .05) was seen with rs7226979 but not with rs4456611 (Haematologica. 2017;102:e201).

Patients receiving R-CHOP who had the AA genotype at rs7226979 had a risk of death that was four times higher than that of those with a G allele, researchers said (P less than .01). The same pattern was seen for PFS, with AA carriers having twice the risk of an event, compared with the other genotypes (P less than .05).

For those with rs4456611, patients with the GG genotype had a risk of death that was 3 times greater than that of those with an A allele (P less than .01), but there was no association with PFS for that SNP.

In an analysis of an independent cohort, only the associations that were seen with rs7226979 – and not those with rs4456611 – were able to be replicated.

The researchers noted that, while most predictive markers that are used to guide clinical treatment are drawn from actual tumor material, host-related factors could also be important.

“Compared to genetic analysis of the tumor, the patient’s constitutional genetic profile is relatively easy to obtain and can be assessed before treatment is started,” they wrote. “Our result has the potential to be useful as a complementary tool to predict the outcome of patients treated with R-CHOP and enhance clinical decision-making after confirmation by further studies.”

 

Two variations of the BCL2 gene are linked with the survival prospects of patients with diffuse large B-cell lymphoma (DLBCL) who are treated with the R-CHOP regimen, based on a study published in Haematologica.

In the population-based, case-control study of patients with non-Hodgkin’s lymphoma across the British Columbia province, Morteza Bashash, PhD, of the Dalla Lana School of Public Health, Toronto, and researchers at the British Columbia Cancer Agency analyzed 217 germline DLBCL samples, excluding those with primary mediastinal large B-cell lymphoma, specifically looking at nine single nucleotide polymorphisms (SNPs).

Nephron/Wikimedia Commons/CC BY-SA 3.0 ecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

They found interactions between two SNPs and overall survival that were seen only in those treated with primary R-CHOP, a regimen that includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and not in those treated with primary CHOP, without rituximab. The SNPs were rs7226979 and rs4456611 (P less than .01). Of these, a statistically significant association with progression-free survival (PFS) (P less than .05) was seen with rs7226979 but not with rs4456611 (Haematologica. 2017;102:e201).

Patients receiving R-CHOP who had the AA genotype at rs7226979 had a risk of death that was four times higher than that of those with a G allele, researchers said (P less than .01). The same pattern was seen for PFS, with AA carriers having twice the risk of an event, compared with the other genotypes (P less than .05).

For those with rs4456611, patients with the GG genotype had a risk of death that was 3 times greater than that of those with an A allele (P less than .01), but there was no association with PFS for that SNP.

In an analysis of an independent cohort, only the associations that were seen with rs7226979 – and not those with rs4456611 – were able to be replicated.

The researchers noted that, while most predictive markers that are used to guide clinical treatment are drawn from actual tumor material, host-related factors could also be important.

“Compared to genetic analysis of the tumor, the patient’s constitutional genetic profile is relatively easy to obtain and can be assessed before treatment is started,” they wrote. “Our result has the potential to be useful as a complementary tool to predict the outcome of patients treated with R-CHOP and enhance clinical decision-making after confirmation by further studies.”

 

Two variations of the BCL2 gene are linked with the survival prospects of patients with diffuse large B-cell lymphoma (DLBCL) who are treated with the R-CHOP regimen, based on a study published in Haematologica.

In the population-based, case-control study of patients with non-Hodgkin’s lymphoma across the British Columbia province, Morteza Bashash, PhD, of the Dalla Lana School of Public Health, Toronto, and researchers at the British Columbia Cancer Agency analyzed 217 germline DLBCL samples, excluding those with primary mediastinal large B-cell lymphoma, specifically looking at nine single nucleotide polymorphisms (SNPs).

Nephron/Wikimedia Commons/CC BY-SA 3.0 ecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

They found interactions between two SNPs and overall survival that were seen only in those treated with primary R-CHOP, a regimen that includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and not in those treated with primary CHOP, without rituximab. The SNPs were rs7226979 and rs4456611 (P less than .01). Of these, a statistically significant association with progression-free survival (PFS) (P less than .05) was seen with rs7226979 but not with rs4456611 (Haematologica. 2017;102:e201).

Patients receiving R-CHOP who had the AA genotype at rs7226979 had a risk of death that was four times higher than that of those with a G allele, researchers said (P less than .01). The same pattern was seen for PFS, with AA carriers having twice the risk of an event, compared with the other genotypes (P less than .05).

For those with rs4456611, patients with the GG genotype had a risk of death that was 3 times greater than that of those with an A allele (P less than .01), but there was no association with PFS for that SNP.

In an analysis of an independent cohort, only the associations that were seen with rs7226979 – and not those with rs4456611 – were able to be replicated.

The researchers noted that, while most predictive markers that are used to guide clinical treatment are drawn from actual tumor material, host-related factors could also be important.

“Compared to genetic analysis of the tumor, the patient’s constitutional genetic profile is relatively easy to obtain and can be assessed before treatment is started,” they wrote. “Our result has the potential to be useful as a complementary tool to predict the outcome of patients treated with R-CHOP and enhance clinical decision-making after confirmation by further studies.”