Aggressive Lymphomas

Lab mouse

Granulocyte colony-stimulating factor (G-CSF) could prevent infertility in male cancer patients, according to preclinical research published in Reproductive Biology and Endocrinology.

Researchers said they found that G-CSF protects spermatogenesis after alkylating chemotherapy by stimulating the proliferation of surviving spermatogonia.

The team also found evidence to suggest that G-CSF may be useful as a fertility-restoring treatment.

The researchers have been pursuing initiatives to restore fertility in men who have lost their ability to have children as a result of cancer treatments they received as children.

While working on methods to restart sperm production, the team discovered a link between G-CSF and the absence of normal damage to reproductive ability.

“We were using G-CSF to prevent infections in our research experiments,” said study author Brian Hermann, PhD, of The University of Texas at San Antonio.

“It turned out that the drug also had the unexpected impact of guarding against male infertility.”

To test the fertility-related impact of G-CSF, the researchers treated male mice with G-CSF before and/or after treatment with busulfan.

The team then evaluated effects on spermatogenesis in these mice and control mice that only received busulfan.

G-CSF had a protective effect on spermatogenesis that was stable for at least 19 weeks after chemotherapy.

And mice treated with G-CSF for 4 days after busulfan showed modestly enhanced spermatogenic recovery compared to controls.

The researchers said these results suggest G-CSF promotes spermatogonial proliferation, leading to enhanced spermatogenic regeneration from surviving spermatogonial stem cells.

Lab mouse

Granulocyte colony-stimulating factor (G-CSF) could prevent infertility in male cancer patients, according to preclinical research published in Reproductive Biology and Endocrinology.

Researchers said they found that G-CSF protects spermatogenesis after alkylating chemotherapy by stimulating the proliferation of surviving spermatogonia.

The team also found evidence to suggest that G-CSF may be useful as a fertility-restoring treatment.

The researchers have been pursuing initiatives to restore fertility in men who have lost their ability to have children as a result of cancer treatments they received as children.

While working on methods to restart sperm production, the team discovered a link between G-CSF and the absence of normal damage to reproductive ability.

“We were using G-CSF to prevent infections in our research experiments,” said study author Brian Hermann, PhD, of The University of Texas at San Antonio.

“It turned out that the drug also had the unexpected impact of guarding against male infertility.”

To test the fertility-related impact of G-CSF, the researchers treated male mice with G-CSF before and/or after treatment with busulfan.

The team then evaluated effects on spermatogenesis in these mice and control mice that only received busulfan.

G-CSF had a protective effect on spermatogenesis that was stable for at least 19 weeks after chemotherapy.

And mice treated with G-CSF for 4 days after busulfan showed modestly enhanced spermatogenic recovery compared to controls.

The researchers said these results suggest G-CSF promotes spermatogonial proliferation, leading to enhanced spermatogenic regeneration from surviving spermatogonial stem cells.

Lab mouse

Granulocyte colony-stimulating factor (G-CSF) could prevent infertility in male cancer patients, according to preclinical research published in Reproductive Biology and Endocrinology.

Researchers said they found that G-CSF protects spermatogenesis after alkylating chemotherapy by stimulating the proliferation of surviving spermatogonia.

The team also found evidence to suggest that G-CSF may be useful as a fertility-restoring treatment.

The researchers have been pursuing initiatives to restore fertility in men who have lost their ability to have children as a result of cancer treatments they received as children.

While working on methods to restart sperm production, the team discovered a link between G-CSF and the absence of normal damage to reproductive ability.

“We were using G-CSF to prevent infections in our research experiments,” said study author Brian Hermann, PhD, of The University of Texas at San Antonio.

“It turned out that the drug also had the unexpected impact of guarding against male infertility.”

To test the fertility-related impact of G-CSF, the researchers treated male mice with G-CSF before and/or after treatment with busulfan.

The team then evaluated effects on spermatogenesis in these mice and control mice that only received busulfan.

G-CSF had a protective effect on spermatogenesis that was stable for at least 19 weeks after chemotherapy.

And mice treated with G-CSF for 4 days after busulfan showed modestly enhanced spermatogenic recovery compared to controls.

The researchers said these results suggest G-CSF promotes spermatogonial proliferation, leading to enhanced spermatogenic regeneration from surviving spermatogonial stem cells.

DNA helix
Image by Spencer Phillips

Researchers have developed an online “knowledgebase” called CIViC, an open access resource for collecting and interpreting information from scientific publications on cancer genetics.

“CIViC” stands for Clinical Interpretations of Variants in Cancer, and the researchers liken it to a Wikipedia of cancer genetics.

Anyone can create an account and contribute information. That information is then curated by editors and moderators who are considered experts in the field.

The researchers described the resource in Nature Genetics.

“It’s relatively easy now to sequence the DNA of tumors—to gather the raw information—but there’s a big interpretation problem,” said study author Obi L. Griffith, PhD, of Washington University School of Medicine in St Louis, Missouri.

“What do these hundreds or thousands of mutations mean for this patient? There are a lot of studies being done to answer these questions. But oncologists trying to interpret the raw data are faced with an overwhelming task of plumbing the literature, reading papers, trying to understand what the latest studies tell them about these mutations and how they may or may not be important.”

The CIViC knowledgebase is an attempt to solve this problem. The researchers said this is one of many efforts to collect and interpret such information, but, to their knowledge, CIViC is the only one that is entirely open access. Anyone is free to contribute and use the content as well as the source code.

“We are committed to keeping this resource open and available to anyone who wants to contribute or make use of the information,” said Malachi Griffith, PhD, of Washington University School of Medicine.

“We would like it to be a community exercise and public resource. The information is in the public domain. There are no restrictions on its use, academic or commercial.”

Though anyone can submit a new piece of information or suggest edits to existing data, at least 2 independent contributors must agree that the new information should be incorporated, and 1 of those users must be an “expert editor.”

Expert editors are not permitted to approve their own submissions. Information on the CIViC website provides details about how new users may be promoted to expert editors and administrators.

To date, the site has seen over 17,500 users from academic institutions, governmental organizations, and commercial entities around the world.

Since CIViC’s launch, 59 users have volunteered their time to contribute their knowledge to CIViC, including descriptions of the clinical relevance of 732 mutations from 285 genes for 203 types of cancer, all gleaned from reviewing 1090 scientific and medical publications.

Despite the fact that there are many groups attempting to collect and interpret genomic variants in cancer, the researchers said the sheer volume of information has resulted in relatively little overlap in data gathered so far.

“While we believe this is the only such open access knowledgebase, there are other large research centers with similar resources,” Malachi Griffith said. “We did an analysis to compare the big ones.”

“Even though we all have access to the same published literature, if you look at the overlap of the information mined by each of these resources, it’s remarkably small. We’re all approaching the same problem, and, just by chance—and probably because of the amount of information out there—we haven’t duplicated our efforts very much yet.”

Obi and Malachi Griffith said finding a way to combine these resources is the primary goal of an international group they are helping lead called the Variant Interpretation for Cancer Consortium, which is a part of the Global Alliance for Genomics and Health (GA4GH).

“We’re just scratching the surface of the potential this holds for precision medicine,” Obi Griffith said. “There’s a lot of work to do.”

DNA helix
Image by Spencer Phillips

Researchers have developed an online “knowledgebase” called CIViC, an open access resource for collecting and interpreting information from scientific publications on cancer genetics.

“CIViC” stands for Clinical Interpretations of Variants in Cancer, and the researchers liken it to a Wikipedia of cancer genetics.

Anyone can create an account and contribute information. That information is then curated by editors and moderators who are considered experts in the field.

The researchers described the resource in Nature Genetics.

“It’s relatively easy now to sequence the DNA of tumors—to gather the raw information—but there’s a big interpretation problem,” said study author Obi L. Griffith, PhD, of Washington University School of Medicine in St Louis, Missouri.

“What do these hundreds or thousands of mutations mean for this patient? There are a lot of studies being done to answer these questions. But oncologists trying to interpret the raw data are faced with an overwhelming task of plumbing the literature, reading papers, trying to understand what the latest studies tell them about these mutations and how they may or may not be important.”

The CIViC knowledgebase is an attempt to solve this problem. The researchers said this is one of many efforts to collect and interpret such information, but, to their knowledge, CIViC is the only one that is entirely open access. Anyone is free to contribute and use the content as well as the source code.

“We are committed to keeping this resource open and available to anyone who wants to contribute or make use of the information,” said Malachi Griffith, PhD, of Washington University School of Medicine.

“We would like it to be a community exercise and public resource. The information is in the public domain. There are no restrictions on its use, academic or commercial.”

Though anyone can submit a new piece of information or suggest edits to existing data, at least 2 independent contributors must agree that the new information should be incorporated, and 1 of those users must be an “expert editor.”

Expert editors are not permitted to approve their own submissions. Information on the CIViC website provides details about how new users may be promoted to expert editors and administrators.

To date, the site has seen over 17,500 users from academic institutions, governmental organizations, and commercial entities around the world.

Since CIViC’s launch, 59 users have volunteered their time to contribute their knowledge to CIViC, including descriptions of the clinical relevance of 732 mutations from 285 genes for 203 types of cancer, all gleaned from reviewing 1090 scientific and medical publications.

Despite the fact that there are many groups attempting to collect and interpret genomic variants in cancer, the researchers said the sheer volume of information has resulted in relatively little overlap in data gathered so far.

“While we believe this is the only such open access knowledgebase, there are other large research centers with similar resources,” Malachi Griffith said. “We did an analysis to compare the big ones.”

“Even though we all have access to the same published literature, if you look at the overlap of the information mined by each of these resources, it’s remarkably small. We’re all approaching the same problem, and, just by chance—and probably because of the amount of information out there—we haven’t duplicated our efforts very much yet.”

Obi and Malachi Griffith said finding a way to combine these resources is the primary goal of an international group they are helping lead called the Variant Interpretation for Cancer Consortium, which is a part of the Global Alliance for Genomics and Health (GA4GH).

“We’re just scratching the surface of the potential this holds for precision medicine,” Obi Griffith said. “There’s a lot of work to do.”

DNA helix
Image by Spencer Phillips

Researchers have developed an online “knowledgebase” called CIViC, an open access resource for collecting and interpreting information from scientific publications on cancer genetics.

“CIViC” stands for Clinical Interpretations of Variants in Cancer, and the researchers liken it to a Wikipedia of cancer genetics.

Anyone can create an account and contribute information. That information is then curated by editors and moderators who are considered experts in the field.

The researchers described the resource in Nature Genetics.

“It’s relatively easy now to sequence the DNA of tumors—to gather the raw information—but there’s a big interpretation problem,” said study author Obi L. Griffith, PhD, of Washington University School of Medicine in St Louis, Missouri.

“What do these hundreds or thousands of mutations mean for this patient? There are a lot of studies being done to answer these questions. But oncologists trying to interpret the raw data are faced with an overwhelming task of plumbing the literature, reading papers, trying to understand what the latest studies tell them about these mutations and how they may or may not be important.”

The CIViC knowledgebase is an attempt to solve this problem. The researchers said this is one of many efforts to collect and interpret such information, but, to their knowledge, CIViC is the only one that is entirely open access. Anyone is free to contribute and use the content as well as the source code.

“We are committed to keeping this resource open and available to anyone who wants to contribute or make use of the information,” said Malachi Griffith, PhD, of Washington University School of Medicine.

“We would like it to be a community exercise and public resource. The information is in the public domain. There are no restrictions on its use, academic or commercial.”

Though anyone can submit a new piece of information or suggest edits to existing data, at least 2 independent contributors must agree that the new information should be incorporated, and 1 of those users must be an “expert editor.”

Expert editors are not permitted to approve their own submissions. Information on the CIViC website provides details about how new users may be promoted to expert editors and administrators.

To date, the site has seen over 17,500 users from academic institutions, governmental organizations, and commercial entities around the world.

Since CIViC’s launch, 59 users have volunteered their time to contribute their knowledge to CIViC, including descriptions of the clinical relevance of 732 mutations from 285 genes for 203 types of cancer, all gleaned from reviewing 1090 scientific and medical publications.

Despite the fact that there are many groups attempting to collect and interpret genomic variants in cancer, the researchers said the sheer volume of information has resulted in relatively little overlap in data gathered so far.

“While we believe this is the only such open access knowledgebase, there are other large research centers with similar resources,” Malachi Griffith said. “We did an analysis to compare the big ones.”

“Even though we all have access to the same published literature, if you look at the overlap of the information mined by each of these resources, it’s remarkably small. We’re all approaching the same problem, and, just by chance—and probably because of the amount of information out there—we haven’t duplicated our efforts very much yet.”

Obi and Malachi Griffith said finding a way to combine these resources is the primary goal of an international group they are helping lead called the Variant Interpretation for Cancer Consortium, which is a part of the Global Alliance for Genomics and Health (GA4GH).

“We’re just scratching the surface of the potential this holds for precision medicine,” Obi Griffith said. “There’s a lot of work to do.”

Micrograph showing CLL

Investigators say they have identified 9 new risk loci for chronic lymphocytic leukemia (CLL).

The team says the research, published in Nature Communications, provides additional evidence for genetic susceptibility to CLL and sheds new light on the biological basis of CLL development.

They also believe their findings could aid the development of new drugs for CLL or help in selecting existing therapies for CLL

patients.

“We knew people were more likely to develop chronic lymphocytic leukemia if someone in their family had suffered from the disease, but our new research takes a big step towards explaining the underlying genetics,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

“CLL is essentially a disease of the immune system, and it’s fascinating that so many of the new genetic variants we have uncovered seem to directly affect the behavior of white blood cells and their ability to fight disease. Understanding the genetics of CLL can point us towards new treatments for the disease and help us to use existing targeted drugs more effectively.”

For this study, Dr Houlston and his colleagues analyzed data from 8 studies involving a total of 6200 CLL patients and 17,598 controls.

From this, the team identified 9 CLL risk loci:

• 1p36.11 (rs34676223, P=5.04 × 10⁻¹³)
• 1q42.13 (rs41271473, P=1.06 × 10⁻¹⁰)
• 4q24 (rs71597109, P=1.37 × 10⁻¹⁰)
• 4q35.1 (rs57214277, P=3.69 × 10⁻⁸)
• 6p21.31 (rs3800461, P=1.97 × 10⁻⁸)
• 11q23.2 (rs61904987, P=2.64 × 10⁻¹¹)
• 18q21.1 (rs1036935, P=3.27 × 10⁻⁸)
• 19p13.3 (rs7254272, P=4.67 × 10⁻⁸)
• 22q13.33 (rs140522, P=2.70 × 10⁻⁹).

The investigators noted that the 4q24 association marked by rs71597109 maps to intron 1 of the gene encoding BANK1 (B-cell scaffold protein with ankyrin repeats 1). BANK1 is only ever activated in B cells and is linked to the autoimmune disease lupus.

The team also pointed out that the 19p13.3 association marked by rs7254272 maps 2.5 kb 5′ to ZBTB7A (zinc finger and BTB domain-containing protein 7a), which is a master regulator of B versus T lymphoid fate. So errors in ZBTB7A could lead to too many B cells in the bloodstream and bone marrow.

And rs140522 maps to 22q13.33, which has been linked to the development of multiple sclerosis. The investigators noted that this region of linkage disequilibrium contains 4 genes. One of them, NCAPH2 (non-SMC condensin II complex subunit H2), is differentially expressed in CLL and normal B cells.

“This fascinating study makes a link between genetic variants in the immune system and the development of leukemia and implicates regions of DNA which are also involved in autoimmune diseases,” said Paul Workman, PhD, chief executive and president of The Institute of Cancer Research, who was not involved in this research.

“The findings could point us towards new ways of treating leukemia or better ways of using existing treatments—potentially including immunotherapies.”

Micrograph showing CLL

Investigators say they have identified 9 new risk loci for chronic lymphocytic leukemia (CLL).

The team says the research, published in Nature Communications, provides additional evidence for genetic susceptibility to CLL and sheds new light on the biological basis of CLL development.

They also believe their findings could aid the development of new drugs for CLL or help in selecting existing therapies for CLL

patients.

“We knew people were more likely to develop chronic lymphocytic leukemia if someone in their family had suffered from the disease, but our new research takes a big step towards explaining the underlying genetics,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

“CLL is essentially a disease of the immune system, and it’s fascinating that so many of the new genetic variants we have uncovered seem to directly affect the behavior of white blood cells and their ability to fight disease. Understanding the genetics of CLL can point us towards new treatments for the disease and help us to use existing targeted drugs more effectively.”

For this study, Dr Houlston and his colleagues analyzed data from 8 studies involving a total of 6200 CLL patients and 17,598 controls.

From this, the team identified 9 CLL risk loci:

• 1p36.11 (rs34676223, P=5.04 × 10⁻¹³)
• 1q42.13 (rs41271473, P=1.06 × 10⁻¹⁰)
• 4q24 (rs71597109, P=1.37 × 10⁻¹⁰)
• 4q35.1 (rs57214277, P=3.69 × 10⁻⁸)
• 6p21.31 (rs3800461, P=1.97 × 10⁻⁸)
• 11q23.2 (rs61904987, P=2.64 × 10⁻¹¹)
• 18q21.1 (rs1036935, P=3.27 × 10⁻⁸)
• 19p13.3 (rs7254272, P=4.67 × 10⁻⁸)
• 22q13.33 (rs140522, P=2.70 × 10⁻⁹).

The investigators noted that the 4q24 association marked by rs71597109 maps to intron 1 of the gene encoding BANK1 (B-cell scaffold protein with ankyrin repeats 1). BANK1 is only ever activated in B cells and is linked to the autoimmune disease lupus.

The team also pointed out that the 19p13.3 association marked by rs7254272 maps 2.5 kb 5′ to ZBTB7A (zinc finger and BTB domain-containing protein 7a), which is a master regulator of B versus T lymphoid fate. So errors in ZBTB7A could lead to too many B cells in the bloodstream and bone marrow.

And rs140522 maps to 22q13.33, which has been linked to the development of multiple sclerosis. The investigators noted that this region of linkage disequilibrium contains 4 genes. One of them, NCAPH2 (non-SMC condensin II complex subunit H2), is differentially expressed in CLL and normal B cells.

“This fascinating study makes a link between genetic variants in the immune system and the development of leukemia and implicates regions of DNA which are also involved in autoimmune diseases,” said Paul Workman, PhD, chief executive and president of The Institute of Cancer Research, who was not involved in this research.

“The findings could point us towards new ways of treating leukemia or better ways of using existing treatments—potentially including immunotherapies.”

Micrograph showing CLL

Investigators say they have identified 9 new risk loci for chronic lymphocytic leukemia (CLL).

The team says the research, published in Nature Communications, provides additional evidence for genetic susceptibility to CLL and sheds new light on the biological basis of CLL development.

They also believe their findings could aid the development of new drugs for CLL or help in selecting existing therapies for CLL

patients.

“We knew people were more likely to develop chronic lymphocytic leukemia if someone in their family had suffered from the disease, but our new research takes a big step towards explaining the underlying genetics,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

“CLL is essentially a disease of the immune system, and it’s fascinating that so many of the new genetic variants we have uncovered seem to directly affect the behavior of white blood cells and their ability to fight disease. Understanding the genetics of CLL can point us towards new treatments for the disease and help us to use existing targeted drugs more effectively.”

For this study, Dr Houlston and his colleagues analyzed data from 8 studies involving a total of 6200 CLL patients and 17,598 controls.

From this, the team identified 9 CLL risk loci:

• 1p36.11 (rs34676223, P=5.04 × 10⁻¹³)
• 1q42.13 (rs41271473, P=1.06 × 10⁻¹⁰)
• 4q24 (rs71597109, P=1.37 × 10⁻¹⁰)
• 4q35.1 (rs57214277, P=3.69 × 10⁻⁸)
• 6p21.31 (rs3800461, P=1.97 × 10⁻⁸)
• 11q23.2 (rs61904987, P=2.64 × 10⁻¹¹)
• 18q21.1 (rs1036935, P=3.27 × 10⁻⁸)
• 19p13.3 (rs7254272, P=4.67 × 10⁻⁸)
• 22q13.33 (rs140522, P=2.70 × 10⁻⁹).

The investigators noted that the 4q24 association marked by rs71597109 maps to intron 1 of the gene encoding BANK1 (B-cell scaffold protein with ankyrin repeats 1). BANK1 is only ever activated in B cells and is linked to the autoimmune disease lupus.

The team also pointed out that the 19p13.3 association marked by rs7254272 maps 2.5 kb 5′ to ZBTB7A (zinc finger and BTB domain-containing protein 7a), which is a master regulator of B versus T lymphoid fate. So errors in ZBTB7A could lead to too many B cells in the bloodstream and bone marrow.

And rs140522 maps to 22q13.33, which has been linked to the development of multiple sclerosis. The investigators noted that this region of linkage disequilibrium contains 4 genes. One of them, NCAPH2 (non-SMC condensin II complex subunit H2), is differentially expressed in CLL and normal B cells.

“This fascinating study makes a link between genetic variants in the immune system and the development of leukemia and implicates regions of DNA which are also involved in autoimmune diseases,” said Paul Workman, PhD, chief executive and president of The Institute of Cancer Research, who was not involved in this research.

“The findings could point us towards new ways of treating leukemia or better ways of using existing treatments—potentially including immunotherapies.”

 

Obinutuzumab (Gazyva®)

 

Health Canada has approved the use of obinutuzumab (Gazyva®), an anti-CD20 monoclonal antibody, in patients with follicular lymphoma (FL).

The approval means obinutuzumab can be given, first in combination with bendamustine and then alone as maintenance therapy, to FL patients who relapsed after, or are refractory to, a rituximab-containing regimen.

Obinutuzumab is also approved in Canada for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.

Obinutuzumab is a product of Roche.

Health Canada’s approval of obinutuzumab in FL is based on results from the phase 3 GADOLIN trial.

The study included 413 patients with rituximab-refractory non-Hodgkin lymphoma, including 321 patients with FL, 46 with marginal zone lymphoma, and 28 with small lymphocytic lymphoma.

The patients were randomized to receive bendamustine alone (control arm) or a combination of bendamustine and obinutuzumab followed by obinutuzumab maintenance (every 2 months for 2 years or until progression). 

The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC). The secondary endpoints were PFS assessed by investigator review, best overall response, complete response (CR), partial response (PR), duration of response, overall survival, and safety profile.

Among patients with FL, the obinutuzumab regimen improved PFS compared to bendamustine alone, as assessed by the IRC (hazard ratio [HR]=0.48, P<0.0001). The median PFS was not reached in patients receiving the obinutuzumab regimen but was 13.8 months in those receiving bendamustine alone.

Investigator-assessed PFS was consistent with IRC-assessed PFS. Investigators said the median PFS with the obinutuzumab regimen was more than double that with bendamustine alone—29.2 months vs 13.7 months (HR=0.48, P<0.0001).

The best overall response for patients receiving the obinutuzumab regimen was 78.7% (15.5% CR, 63.2% PR), compared to 74.7% (18.7% CR, 56% PR) for those receiving bendamustine alone, as assessed by the IRC.

The median duration of response was not reached for patients receiving the obinutuzumab regimen and was 11.6 months for those receiving bendamustine alone.

At last follow-up, the median overall survival had not been reached in either study arm.
 
The most common grade 3/4 adverse events observed in patients receiving the obinutuzumab regimen were neutropenia (33%), infusion reactions (11%), and thrombocytopenia (10%).

The most common adverse events of any grade were infusion reactions (69%), neutropenia (35%), nausea (54%), fatigue (39%), cough (26%), diarrhea (27%), constipation (19%), fever (18%), thrombocytopenia (15%), vomiting (22%), upper respiratory tract infection (13%), decreased appetite (18%), joint or muscle pain (12%), sinusitis (12%), anemia (12%), general weakness (11%), and urinary tract infection (10%).

 

Obinutuzumab (Gazyva®)

 

Health Canada has approved the use of obinutuzumab (Gazyva®), an anti-CD20 monoclonal antibody, in patients with follicular lymphoma (FL).

The approval means obinutuzumab can be given, first in combination with bendamustine and then alone as maintenance therapy, to FL patients who relapsed after, or are refractory to, a rituximab-containing regimen.

Obinutuzumab is also approved in Canada for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.

Obinutuzumab is a product of Roche.

Health Canada’s approval of obinutuzumab in FL is based on results from the phase 3 GADOLIN trial.

The study included 413 patients with rituximab-refractory non-Hodgkin lymphoma, including 321 patients with FL, 46 with marginal zone lymphoma, and 28 with small lymphocytic lymphoma.

The patients were randomized to receive bendamustine alone (control arm) or a combination of bendamustine and obinutuzumab followed by obinutuzumab maintenance (every 2 months for 2 years or until progression). 

The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC). The secondary endpoints were PFS assessed by investigator review, best overall response, complete response (CR), partial response (PR), duration of response, overall survival, and safety profile.

Among patients with FL, the obinutuzumab regimen improved PFS compared to bendamustine alone, as assessed by the IRC (hazard ratio [HR]=0.48, P<0.0001). The median PFS was not reached in patients receiving the obinutuzumab regimen but was 13.8 months in those receiving bendamustine alone.

Investigator-assessed PFS was consistent with IRC-assessed PFS. Investigators said the median PFS with the obinutuzumab regimen was more than double that with bendamustine alone—29.2 months vs 13.7 months (HR=0.48, P<0.0001).

The best overall response for patients receiving the obinutuzumab regimen was 78.7% (15.5% CR, 63.2% PR), compared to 74.7% (18.7% CR, 56% PR) for those receiving bendamustine alone, as assessed by the IRC.

The median duration of response was not reached for patients receiving the obinutuzumab regimen and was 11.6 months for those receiving bendamustine alone.

At last follow-up, the median overall survival had not been reached in either study arm.
 
The most common grade 3/4 adverse events observed in patients receiving the obinutuzumab regimen were neutropenia (33%), infusion reactions (11%), and thrombocytopenia (10%).

The most common adverse events of any grade were infusion reactions (69%), neutropenia (35%), nausea (54%), fatigue (39%), cough (26%), diarrhea (27%), constipation (19%), fever (18%), thrombocytopenia (15%), vomiting (22%), upper respiratory tract infection (13%), decreased appetite (18%), joint or muscle pain (12%), sinusitis (12%), anemia (12%), general weakness (11%), and urinary tract infection (10%).

 

Obinutuzumab (Gazyva®)

 

Health Canada has approved the use of obinutuzumab (Gazyva®), an anti-CD20 monoclonal antibody, in patients with follicular lymphoma (FL).

The approval means obinutuzumab can be given, first in combination with bendamustine and then alone as maintenance therapy, to FL patients who relapsed after, or are refractory to, a rituximab-containing regimen.

Obinutuzumab is also approved in Canada for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.

Obinutuzumab is a product of Roche.

Health Canada’s approval of obinutuzumab in FL is based on results from the phase 3 GADOLIN trial.

The study included 413 patients with rituximab-refractory non-Hodgkin lymphoma, including 321 patients with FL, 46 with marginal zone lymphoma, and 28 with small lymphocytic lymphoma.

The patients were randomized to receive bendamustine alone (control arm) or a combination of bendamustine and obinutuzumab followed by obinutuzumab maintenance (every 2 months for 2 years or until progression). 

The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC). The secondary endpoints were PFS assessed by investigator review, best overall response, complete response (CR), partial response (PR), duration of response, overall survival, and safety profile.

Among patients with FL, the obinutuzumab regimen improved PFS compared to bendamustine alone, as assessed by the IRC (hazard ratio [HR]=0.48, P<0.0001). The median PFS was not reached in patients receiving the obinutuzumab regimen but was 13.8 months in those receiving bendamustine alone.

Investigator-assessed PFS was consistent with IRC-assessed PFS. Investigators said the median PFS with the obinutuzumab regimen was more than double that with bendamustine alone—29.2 months vs 13.7 months (HR=0.48, P<0.0001).

The best overall response for patients receiving the obinutuzumab regimen was 78.7% (15.5% CR, 63.2% PR), compared to 74.7% (18.7% CR, 56% PR) for those receiving bendamustine alone, as assessed by the IRC.

The median duration of response was not reached for patients receiving the obinutuzumab regimen and was 11.6 months for those receiving bendamustine alone.

At last follow-up, the median overall survival had not been reached in either study arm.
 
The most common grade 3/4 adverse events observed in patients receiving the obinutuzumab regimen were neutropenia (33%), infusion reactions (11%), and thrombocytopenia (10%).

The most common adverse events of any grade were infusion reactions (69%), neutropenia (35%), nausea (54%), fatigue (39%), cough (26%), diarrhea (27%), constipation (19%), fever (18%), thrombocytopenia (15%), vomiting (22%), upper respiratory tract infection (13%), decreased appetite (18%), joint or muscle pain (12%), sinusitis (12%), anemia (12%), general weakness (11%), and urinary tract infection (10%).

AMSTERDAM – Five years after a cancer diagnosis, patients who report having chronic neuropathic pain are twice as likely to be out of work as patients who report having no neuropathic pain, authors of a large longitudinal study said.

“For middle-term cancer survivors, suffering from chronic neuropathic pain unfortunately predicts labor-market exit,” said Marc-Karim Bendiane, from Aix-Marseille University in Marseille, France.

Pain is still frequently underdiagnosed, poorly managed, and undertreated among cancer survivors, and there is a need for alternatives to analgesics for control of chronic neuropathic pain (CNP), Mr. Bendiane said at an annual congress sponsored by the European Cancer Organisation.

Mr. Bendiane and colleagues used data from VICAN, a longitudinal survey of issues of concern to cancer survivors 2 years and 5 years after a diagnosis. The cohort consists of patients diagnosed with cancers who comprise 88% of all cancer diagnoses in France, including cancers of the breast; colon and rectum; lip, oral cavity, and pharynx; kidney; cervix; endometrium; non-Hodgkin lymphoma; melanoma; thyroid; bladder; and prostate.

[email protected]

AMSTERDAM – Five years after a cancer diagnosis, patients who report having chronic neuropathic pain are twice as likely to be out of work as patients who report having no neuropathic pain, authors of a large longitudinal study said.

“For middle-term cancer survivors, suffering from chronic neuropathic pain unfortunately predicts labor-market exit,” said Marc-Karim Bendiane, from Aix-Marseille University in Marseille, France.

Pain is still frequently underdiagnosed, poorly managed, and undertreated among cancer survivors, and there is a need for alternatives to analgesics for control of chronic neuropathic pain (CNP), Mr. Bendiane said at an annual congress sponsored by the European Cancer Organisation.

Mr. Bendiane and colleagues used data from VICAN, a longitudinal survey of issues of concern to cancer survivors 2 years and 5 years after a diagnosis. The cohort consists of patients diagnosed with cancers who comprise 88% of all cancer diagnoses in France, including cancers of the breast; colon and rectum; lip, oral cavity, and pharynx; kidney; cervix; endometrium; non-Hodgkin lymphoma; melanoma; thyroid; bladder; and prostate.

[email protected]

AMSTERDAM – Five years after a cancer diagnosis, patients who report having chronic neuropathic pain are twice as likely to be out of work as patients who report having no neuropathic pain, authors of a large longitudinal study said.

“For middle-term cancer survivors, suffering from chronic neuropathic pain unfortunately predicts labor-market exit,” said Marc-Karim Bendiane, from Aix-Marseille University in Marseille, France.

Pain is still frequently underdiagnosed, poorly managed, and undertreated among cancer survivors, and there is a need for alternatives to analgesics for control of chronic neuropathic pain (CNP), Mr. Bendiane said at an annual congress sponsored by the European Cancer Organisation.

Mr. Bendiane and colleagues used data from VICAN, a longitudinal survey of issues of concern to cancer survivors 2 years and 5 years after a diagnosis. The cohort consists of patients diagnosed with cancers who comprise 88% of all cancer diagnoses in France, including cancers of the breast; colon and rectum; lip, oral cavity, and pharynx; kidney; cervix; endometrium; non-Hodgkin lymphoma; melanoma; thyroid; bladder; and prostate.

[email protected]

Five-year survival for patients with non-Hodgkin lymphoma has more than doubled since the early 1950s, according to Ali H. Mokdad, PhD, and his associates.

Data from the Surveillance, Epidemiology, and End Results Program show that the 5-year relative survival rate for non-Hodgkin lymphoma in the United States went from 33% in 1950-1954 to 71.2% in 2008-2013, an increase of 116%, Dr. Mokdad and his associates reported (JAMA 2017;317[4]:388-406).

[email protected]

Five-year survival for patients with non-Hodgkin lymphoma has more than doubled since the early 1950s, according to Ali H. Mokdad, PhD, and his associates.

Data from the Surveillance, Epidemiology, and End Results Program show that the 5-year relative survival rate for non-Hodgkin lymphoma in the United States went from 33% in 1950-1954 to 71.2% in 2008-2013, an increase of 116%, Dr. Mokdad and his associates reported (JAMA 2017;317[4]:388-406).

[email protected]

Five-year survival for patients with non-Hodgkin lymphoma has more than doubled since the early 1950s, according to Ali H. Mokdad, PhD, and his associates.

Data from the Surveillance, Epidemiology, and End Results Program show that the 5-year relative survival rate for non-Hodgkin lymphoma in the United States went from 33% in 1950-1954 to 71.2% in 2008-2013, an increase of 116%, Dr. Mokdad and his associates reported (JAMA 2017;317[4]:388-406).

[email protected]

Five-year relative survival for Hodgkin lymphoma increased 189% over the approximately 60 years from the early 1950s to 2013, according to investigators looking at data from the Surveillance, Epidemiology, and End Results Program.

During 1950-1954, the 5-year relative survival rate for Hodgkin lymphoma was 30%, compared with 86.6% in 2008-2013, said Ali H. Mokdad, PhD, and his associates at the Institute for Health Metrics and Evaluation at the University of Washington, Seattle.

[email protected]

Five-year relative survival for Hodgkin lymphoma increased 189% over the approximately 60 years from the early 1950s to 2013, according to investigators looking at data from the Surveillance, Epidemiology, and End Results Program.

During 1950-1954, the 5-year relative survival rate for Hodgkin lymphoma was 30%, compared with 86.6% in 2008-2013, said Ali H. Mokdad, PhD, and his associates at the Institute for Health Metrics and Evaluation at the University of Washington, Seattle.

[email protected]

Five-year relative survival for Hodgkin lymphoma increased 189% over the approximately 60 years from the early 1950s to 2013, according to investigators looking at data from the Surveillance, Epidemiology, and End Results Program.

During 1950-1954, the 5-year relative survival rate for Hodgkin lymphoma was 30%, compared with 86.6% in 2008-2013, said Ali H. Mokdad, PhD, and his associates at the Institute for Health Metrics and Evaluation at the University of Washington, Seattle.

[email protected]

A newer technique aimed at detect circulating tumor DNA in the blood – cancer personalized profiling by deep sequencing (CAPP-Seq) – detected recurrence of diffuse large B cell lymphoma more than 6 months earlier than radiographic findings in a study at Stanford (Calif.) University, where the technique was invented.

The findings signal another win for “liquid biopsy,” the measurement of tumor DNA circulating in the blood, which is rapidly emerging as a quick and powerful tool for the diagnosis of a range of cancers and tumor subtypes, and prediction of tumor behavior and treatment response. Investigators at Stanford and elsewhere are studying liquid biopsy not only for lymphoma, but also for colorectal, thyroid, breast, prostate, and most other cancers. The Stanford team recently reported that its circulating DNA-detecting CAPP-Seq technique also helps in lung cancer.

In the new study, Stanford used CAPP-Seq (Cancer Personalized Profiling by deep Sequencing), which it called “an ultrasensitive capture-based targeted sequencing method” to analyze 166 plasma and 118 tissue samples from 92 patients with diffuse large B cell lymphoma (DLBCL) at diagnosis and various point afterward. The team compared the results to radiologic, and other standard diagnostic and monitoring techniques (Sci Transl Med. 2016 Nov 9;8[364]:364ra155).

At diagnosis, the amount of circulating DNA (ctDNA) correlated strongly with clinical indices and was independently predictive of patient outcomes; “whereas 100% of pretreatment samples had detectable ctDNA, only 37% of samples had abnormally high serum” lactate dehydrogenase, currently the most commonly used biomarker for DLBCL, said investigators, led by research fellow Florian Scherer, MD.

The group detected ctDNA in 73% of patients (8/11) who eventually relapsed a mean of 188 days before relapse was detected by standard-of-care radiologic techniques.

CAPP-Seq identified nine patients with a particular type of activated B cell-like tumor, for whom ibrutinib (Imbruvica) is particularly effective; ctDNA also predicted the transformation of indolent follicular lymphoma to DLBCL “with high sensitivity and specificity,” the group reported.

Stanford anticipates “ctDNA will have broad utility for dissecting tumor heterogeneity within and between patients with lymphomas and other cancer types, with applications for the identification of adverse risk groups, the discovery of resistance mechanisms to diverse therapies, and the development of risk-adapted therapeutics.”

The team said its approach “outperformed immunoglobulin sequencing and radiographic imaging for the detection of minimal residual disease and facilitated noninvasive identification of emergent resistance mutations to targeted therapies.” Meanwhile, while biomarkers hold “great promise for risk stratification and therapeutic targeting,” they are “currently difficult to measure in clinical settings,” the investigators said.

Roche bought the rights to CAPP-Seq from Stanford in 2015. Several authors are coinventors on patent applications for CAPP-Seq and also Roche consultants. Two are employees. Dr. Scherer had no disclosures. The work was funded by Stanford, the American Society of Hematology, the National Cancer Institute, and others.

[email protected]

A newer technique aimed at detect circulating tumor DNA in the blood – cancer personalized profiling by deep sequencing (CAPP-Seq) – detected recurrence of diffuse large B cell lymphoma more than 6 months earlier than radiographic findings in a study at Stanford (Calif.) University, where the technique was invented.

The findings signal another win for “liquid biopsy,” the measurement of tumor DNA circulating in the blood, which is rapidly emerging as a quick and powerful tool for the diagnosis of a range of cancers and tumor subtypes, and prediction of tumor behavior and treatment response. Investigators at Stanford and elsewhere are studying liquid biopsy not only for lymphoma, but also for colorectal, thyroid, breast, prostate, and most other cancers. The Stanford team recently reported that its circulating DNA-detecting CAPP-Seq technique also helps in lung cancer.

In the new study, Stanford used CAPP-Seq (Cancer Personalized Profiling by deep Sequencing), which it called “an ultrasensitive capture-based targeted sequencing method” to analyze 166 plasma and 118 tissue samples from 92 patients with diffuse large B cell lymphoma (DLBCL) at diagnosis and various point afterward. The team compared the results to radiologic, and other standard diagnostic and monitoring techniques (Sci Transl Med. 2016 Nov 9;8[364]:364ra155).

At diagnosis, the amount of circulating DNA (ctDNA) correlated strongly with clinical indices and was independently predictive of patient outcomes; “whereas 100% of pretreatment samples had detectable ctDNA, only 37% of samples had abnormally high serum” lactate dehydrogenase, currently the most commonly used biomarker for DLBCL, said investigators, led by research fellow Florian Scherer, MD.

The group detected ctDNA in 73% of patients (8/11) who eventually relapsed a mean of 188 days before relapse was detected by standard-of-care radiologic techniques.

CAPP-Seq identified nine patients with a particular type of activated B cell-like tumor, for whom ibrutinib (Imbruvica) is particularly effective; ctDNA also predicted the transformation of indolent follicular lymphoma to DLBCL “with high sensitivity and specificity,” the group reported.

Stanford anticipates “ctDNA will have broad utility for dissecting tumor heterogeneity within and between patients with lymphomas and other cancer types, with applications for the identification of adverse risk groups, the discovery of resistance mechanisms to diverse therapies, and the development of risk-adapted therapeutics.”

The team said its approach “outperformed immunoglobulin sequencing and radiographic imaging for the detection of minimal residual disease and facilitated noninvasive identification of emergent resistance mutations to targeted therapies.” Meanwhile, while biomarkers hold “great promise for risk stratification and therapeutic targeting,” they are “currently difficult to measure in clinical settings,” the investigators said.

Roche bought the rights to CAPP-Seq from Stanford in 2015. Several authors are coinventors on patent applications for CAPP-Seq and also Roche consultants. Two are employees. Dr. Scherer had no disclosures. The work was funded by Stanford, the American Society of Hematology, the National Cancer Institute, and others.

[email protected]

A newer technique aimed at detect circulating tumor DNA in the blood – cancer personalized profiling by deep sequencing (CAPP-Seq) – detected recurrence of diffuse large B cell lymphoma more than 6 months earlier than radiographic findings in a study at Stanford (Calif.) University, where the technique was invented.

The findings signal another win for “liquid biopsy,” the measurement of tumor DNA circulating in the blood, which is rapidly emerging as a quick and powerful tool for the diagnosis of a range of cancers and tumor subtypes, and prediction of tumor behavior and treatment response. Investigators at Stanford and elsewhere are studying liquid biopsy not only for lymphoma, but also for colorectal, thyroid, breast, prostate, and most other cancers. The Stanford team recently reported that its circulating DNA-detecting CAPP-Seq technique also helps in lung cancer.

In the new study, Stanford used CAPP-Seq (Cancer Personalized Profiling by deep Sequencing), which it called “an ultrasensitive capture-based targeted sequencing method” to analyze 166 plasma and 118 tissue samples from 92 patients with diffuse large B cell lymphoma (DLBCL) at diagnosis and various point afterward. The team compared the results to radiologic, and other standard diagnostic and monitoring techniques (Sci Transl Med. 2016 Nov 9;8[364]:364ra155).

At diagnosis, the amount of circulating DNA (ctDNA) correlated strongly with clinical indices and was independently predictive of patient outcomes; “whereas 100% of pretreatment samples had detectable ctDNA, only 37% of samples had abnormally high serum” lactate dehydrogenase, currently the most commonly used biomarker for DLBCL, said investigators, led by research fellow Florian Scherer, MD.

The group detected ctDNA in 73% of patients (8/11) who eventually relapsed a mean of 188 days before relapse was detected by standard-of-care radiologic techniques.

CAPP-Seq identified nine patients with a particular type of activated B cell-like tumor, for whom ibrutinib (Imbruvica) is particularly effective; ctDNA also predicted the transformation of indolent follicular lymphoma to DLBCL “with high sensitivity and specificity,” the group reported.

Stanford anticipates “ctDNA will have broad utility for dissecting tumor heterogeneity within and between patients with lymphomas and other cancer types, with applications for the identification of adverse risk groups, the discovery of resistance mechanisms to diverse therapies, and the development of risk-adapted therapeutics.”

The team said its approach “outperformed immunoglobulin sequencing and radiographic imaging for the detection of minimal residual disease and facilitated noninvasive identification of emergent resistance mutations to targeted therapies.” Meanwhile, while biomarkers hold “great promise for risk stratification and therapeutic targeting,” they are “currently difficult to measure in clinical settings,” the investigators said.

Roche bought the rights to CAPP-Seq from Stanford in 2015. Several authors are coinventors on patent applications for CAPP-Seq and also Roche consultants. Two are employees. Dr. Scherer had no disclosures. The work was funded by Stanford, the American Society of Hematology, the National Cancer Institute, and others.

[email protected]

 

Germinal center (rectangle) in
the spleen of a mouse, showing
inactivated GSK3 (magenta)
in B cells (blue) near follicular
dendritic cells (green).
Image from the lab of
Robert Rickert, PhD

 

Research published in Nature Immunology helps explain how B-cell metabolism adapts to different environments.

The study suggests the protein GSK3 acts as a metabolic checkpoint regulator in B cells, promoting the survival of circulating B cells while limiting the growth and proliferation of B cells in germinal centers.

“Our research shows that the protein GSK3 plays a crucial role in helping B cells meet the energy needs of their distinct states,” said study author Robert Rickert, PhD, of Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California.

“The findings are particularly relevant for certain B-cell pathologies, including lymphoma subtypes, where there is an increased demand for energy to support the hyperproliferation of cells in a microenvironment that may be limited in nutrients.”

Dr Rickert and his colleagues noted that B cells predominate in a quiescent state until they encounter an antigen, which prompts the cells to grow, proliferate, and differentiate.

The team’s new study showed that GSK3 adjusts B-cell metabolism to match the needs of these different cell states.

In circulating B cells, GSK3 limits overall metabolic activity. In proliferating B cells in germinal centers, GSK3 slows glycolysis and the production of mitochondria.

In fact, GSK3 function is essential for B-cell survival in germinal centers. To understand why, the researchers looked at how B cells in these regions generate energy.

The team found that because these B cells are so metabolically active, they consume nearly all available glucose. That switches on glycolysis.

High glycolytic activity leads to an accumulation of toxic reactive oxygen species, as does rapid manufacture of mitochondria, which tend to leak the same chemicals.

Thus, by restraining the metabolism in specific ways, GSK3 prevents cell death induced by reactive oxygen species.

“Our results were really surprising,” Dr Rickert said. “Until now, we would have thought that slowing metabolism would only be important for preventing B cells from becoming cancerous, which it indeed may be. These studies provide insight into the dynamic nature of B-cell metabolism that literally ‘fuels’ differentiation in the germinal center to produce an effective antibody response.”

“It’s not yet clear whether or how GSK3 might be a target for future therapies for B cell-related diseases, but this research opens a lot of doors for further studies. To start with, we plan to investigate how GSK3 is regulated in lymphoma and how that relates to changes in metabolism. That research could lead to new approaches to treating lymphoma.”

This research was performed in collaboration with scientists at Eli Lilly and the Lunenfeld-Tanenbaum Research Institute at the University of Toronto. Funding was provided by the National Institutes of Health, the Lilly Research Award Program, the Arthritis National Research Foundation, and the Canadian Institutes of Health Research.

 

Germinal center (rectangle) in
the spleen of a mouse, showing
inactivated GSK3 (magenta)
in B cells (blue) near follicular
dendritic cells (green).
Image from the lab of
Robert Rickert, PhD

 

Research published in Nature Immunology helps explain how B-cell metabolism adapts to different environments.

The study suggests the protein GSK3 acts as a metabolic checkpoint regulator in B cells, promoting the survival of circulating B cells while limiting the growth and proliferation of B cells in germinal centers.

“Our research shows that the protein GSK3 plays a crucial role in helping B cells meet the energy needs of their distinct states,” said study author Robert Rickert, PhD, of Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California.

“The findings are particularly relevant for certain B-cell pathologies, including lymphoma subtypes, where there is an increased demand for energy to support the hyperproliferation of cells in a microenvironment that may be limited in nutrients.”

Dr Rickert and his colleagues noted that B cells predominate in a quiescent state until they encounter an antigen, which prompts the cells to grow, proliferate, and differentiate.

The team’s new study showed that GSK3 adjusts B-cell metabolism to match the needs of these different cell states.

In circulating B cells, GSK3 limits overall metabolic activity. In proliferating B cells in germinal centers, GSK3 slows glycolysis and the production of mitochondria.

In fact, GSK3 function is essential for B-cell survival in germinal centers. To understand why, the researchers looked at how B cells in these regions generate energy.

The team found that because these B cells are so metabolically active, they consume nearly all available glucose. That switches on glycolysis.

High glycolytic activity leads to an accumulation of toxic reactive oxygen species, as does rapid manufacture of mitochondria, which tend to leak the same chemicals.

Thus, by restraining the metabolism in specific ways, GSK3 prevents cell death induced by reactive oxygen species.

“Our results were really surprising,” Dr Rickert said. “Until now, we would have thought that slowing metabolism would only be important for preventing B cells from becoming cancerous, which it indeed may be. These studies provide insight into the dynamic nature of B-cell metabolism that literally ‘fuels’ differentiation in the germinal center to produce an effective antibody response.”

“It’s not yet clear whether or how GSK3 might be a target for future therapies for B cell-related diseases, but this research opens a lot of doors for further studies. To start with, we plan to investigate how GSK3 is regulated in lymphoma and how that relates to changes in metabolism. That research could lead to new approaches to treating lymphoma.”

This research was performed in collaboration with scientists at Eli Lilly and the Lunenfeld-Tanenbaum Research Institute at the University of Toronto. Funding was provided by the National Institutes of Health, the Lilly Research Award Program, the Arthritis National Research Foundation, and the Canadian Institutes of Health Research.

 

Germinal center (rectangle) in
the spleen of a mouse, showing
inactivated GSK3 (magenta)
in B cells (blue) near follicular
dendritic cells (green).
Image from the lab of
Robert Rickert, PhD

 

Research published in Nature Immunology helps explain how B-cell metabolism adapts to different environments.

The study suggests the protein GSK3 acts as a metabolic checkpoint regulator in B cells, promoting the survival of circulating B cells while limiting the growth and proliferation of B cells in germinal centers.

“Our research shows that the protein GSK3 plays a crucial role in helping B cells meet the energy needs of their distinct states,” said study author Robert Rickert, PhD, of Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California.

“The findings are particularly relevant for certain B-cell pathologies, including lymphoma subtypes, where there is an increased demand for energy to support the hyperproliferation of cells in a microenvironment that may be limited in nutrients.”

Dr Rickert and his colleagues noted that B cells predominate in a quiescent state until they encounter an antigen, which prompts the cells to grow, proliferate, and differentiate.

The team’s new study showed that GSK3 adjusts B-cell metabolism to match the needs of these different cell states.

In circulating B cells, GSK3 limits overall metabolic activity. In proliferating B cells in germinal centers, GSK3 slows glycolysis and the production of mitochondria.

In fact, GSK3 function is essential for B-cell survival in germinal centers. To understand why, the researchers looked at how B cells in these regions generate energy.

The team found that because these B cells are so metabolically active, they consume nearly all available glucose. That switches on glycolysis.

High glycolytic activity leads to an accumulation of toxic reactive oxygen species, as does rapid manufacture of mitochondria, which tend to leak the same chemicals.

Thus, by restraining the metabolism in specific ways, GSK3 prevents cell death induced by reactive oxygen species.

“Our results were really surprising,” Dr Rickert said. “Until now, we would have thought that slowing metabolism would only be important for preventing B cells from becoming cancerous, which it indeed may be. These studies provide insight into the dynamic nature of B-cell metabolism that literally ‘fuels’ differentiation in the germinal center to produce an effective antibody response.”

“It’s not yet clear whether or how GSK3 might be a target for future therapies for B cell-related diseases, but this research opens a lot of doors for further studies. To start with, we plan to investigate how GSK3 is regulated in lymphoma and how that relates to changes in metabolism. That research could lead to new approaches to treating lymphoma.”

This research was performed in collaboration with scientists at Eli Lilly and the Lunenfeld-Tanenbaum Research Institute at the University of Toronto. Funding was provided by the National Institutes of Health, the Lilly Research Award Program, the Arthritis National Research Foundation, and the Canadian Institutes of Health Research.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

A new study shows that 5-year survival rates for US patients with hematologic malignancies have increased greatly since the 1950s, but there is still room for improvement, particularly for patients with acute myeloid leukemia (AML).

Researchers found the absolute difference in improvement for 5-year survival from 1950-1954 to 2008-2013 ranged from 38.2% for non-Hodgkin lymphoma (NHL) to 56.6% for Hodgkin lymphoma.

And although the 5-year survival rate for Hodgkin lymphoma patients reached 86.6% for 2008-2013, the 5-year survival rate for patients with AML only reached 27.4%.

This study also revealed large disparities in overall cancer mortality rates between different counties across the country.

Ali H. Mokdad, PhD, of the Institute for Health Metrics and Evaluation in Seattle, Washington, and his colleagues reported these findings in JAMA.

Overall cancer deaths

The researchers found there were 19,511,910 cancer deaths recorded in the US between 1980 and 2014. Cancer mortality decreased by 20.1% between 1980 and 2014, from 240.2 deaths per 100,000 people to 192.0 deaths per 100,000 people.

In 1980, cancer mortality ranged from 130.6 per 100,000 in Summit County, Colorado, to 386.9 per 100,000 in North Slope Borough, Alaska.

In 2014, cancer mortality ranged from 70.7 per 100,000 in Summit County, Colorado, to 503.1 per 100,000 in Union County, Florida.

“Such significant disparities among US counties is unacceptable,” Dr Mokdad said. “Every person should have access to early screenings for cancer, as well as adequate treatment.”

Mortality rates for hematologic malignancies

In 2014, the mortality rates, per 100,000 people, for hematologic malignancies were:

• 0.4 for Hodgkin lymphoma (rank out of all cancers, 27)
• 8.3 for NHL (rank, 7)
• 3.9 for multiple myeloma (rank, 16)
• 9.0 for all leukemias (rank, 6)
• 0.7 for acute lymphoid leukemia (ALL)
• 2.6 for chronic lymphoid leukemia (CLL)
• 5.1 for AML
• 0.6 for chronic myeloid leukemia (CML).

The leukemia subtypes were not assigned a rank.

5-year survival rates for hematologic malignancies

Hodgkin lymphoma

• 30% for 1950-54
• 68.6% for 1973-77
• 72.1% for 1978-82
• 86.6% for 2008-2013
• Absolute difference (between the first and latest year of data), 56.6%.

NHL

• 33% for 1950-54
• 45.3% for 1973-77
• 48.7% for 1978-82
• 71.2% for 2008-2013
• Absolute difference, 38.2%.

Multiple myeloma

• 6% for 1950-54
• 23.4% for 1973-77
• 26.6% for 1978-82
• 49.8% for 2008-2013
• Absolute difference, 43.8%.

Leukemia

• 10% for 1950-54
• 34% for 1973-77
• 36.3% for 1978-82
• 60.1% for 2008-2013
• Absolute difference, 50.1%.

ALL

• 39.2% for 1973-77
• 50.5% for 1978-82
• 68.1% for 2008-2013
• Absolute difference, 28.9%.

CLL

• 67% for 1973-77
• 66.3% for 1978-82
• 82.5% for 2008-2013
• Absolute difference, 15.5%.

AML

• 6.2% for 1973-77
• 7.9% for 1978-82
• 27.4% for 2008-2013
• Absolute difference, 21.2%.

CML

• 21.1% for 1973-77
• 25.8% for 1978-82
• 66.4% for 2008-2013
• Absolute difference, 45.3%.

For the leukemia subtypes, there was no data for 1950 to 1954.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

A new study shows that 5-year survival rates for US patients with hematologic malignancies have increased greatly since the 1950s, but there is still room for improvement, particularly for patients with acute myeloid leukemia (AML).

Researchers found the absolute difference in improvement for 5-year survival from 1950-1954 to 2008-2013 ranged from 38.2% for non-Hodgkin lymphoma (NHL) to 56.6% for Hodgkin lymphoma.

And although the 5-year survival rate for Hodgkin lymphoma patients reached 86.6% for 2008-2013, the 5-year survival rate for patients with AML only reached 27.4%.

This study also revealed large disparities in overall cancer mortality rates between different counties across the country.

Ali H. Mokdad, PhD, of the Institute for Health Metrics and Evaluation in Seattle, Washington, and his colleagues reported these findings in JAMA.

Overall cancer deaths

The researchers found there were 19,511,910 cancer deaths recorded in the US between 1980 and 2014. Cancer mortality decreased by 20.1% between 1980 and 2014, from 240.2 deaths per 100,000 people to 192.0 deaths per 100,000 people.

In 1980, cancer mortality ranged from 130.6 per 100,000 in Summit County, Colorado, to 386.9 per 100,000 in North Slope Borough, Alaska.

In 2014, cancer mortality ranged from 70.7 per 100,000 in Summit County, Colorado, to 503.1 per 100,000 in Union County, Florida.

“Such significant disparities among US counties is unacceptable,” Dr Mokdad said. “Every person should have access to early screenings for cancer, as well as adequate treatment.”

Mortality rates for hematologic malignancies

In 2014, the mortality rates, per 100,000 people, for hematologic malignancies were:

• 0.4 for Hodgkin lymphoma (rank out of all cancers, 27)
• 8.3 for NHL (rank, 7)
• 3.9 for multiple myeloma (rank, 16)
• 9.0 for all leukemias (rank, 6)
• 0.7 for acute lymphoid leukemia (ALL)
• 2.6 for chronic lymphoid leukemia (CLL)
• 5.1 for AML
• 0.6 for chronic myeloid leukemia (CML).

The leukemia subtypes were not assigned a rank.

5-year survival rates for hematologic malignancies

Hodgkin lymphoma

• 30% for 1950-54
• 68.6% for 1973-77
• 72.1% for 1978-82
• 86.6% for 2008-2013
• Absolute difference (between the first and latest year of data), 56.6%.

NHL

• 33% for 1950-54
• 45.3% for 1973-77
• 48.7% for 1978-82
• 71.2% for 2008-2013
• Absolute difference, 38.2%.

Multiple myeloma

• 6% for 1950-54
• 23.4% for 1973-77
• 26.6% for 1978-82
• 49.8% for 2008-2013
• Absolute difference, 43.8%.

Leukemia

• 10% for 1950-54
• 34% for 1973-77
• 36.3% for 1978-82
• 60.1% for 2008-2013
• Absolute difference, 50.1%.

ALL

• 39.2% for 1973-77
• 50.5% for 1978-82
• 68.1% for 2008-2013
• Absolute difference, 28.9%.

CLL

• 67% for 1973-77
• 66.3% for 1978-82
• 82.5% for 2008-2013
• Absolute difference, 15.5%.

AML

• 6.2% for 1973-77
• 7.9% for 1978-82
• 27.4% for 2008-2013
• Absolute difference, 21.2%.

CML

• 21.1% for 1973-77
• 25.8% for 1978-82
• 66.4% for 2008-2013
• Absolute difference, 45.3%.

For the leukemia subtypes, there was no data for 1950 to 1954.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

A new study shows that 5-year survival rates for US patients with hematologic malignancies have increased greatly since the 1950s, but there is still room for improvement, particularly for patients with acute myeloid leukemia (AML).

Researchers found the absolute difference in improvement for 5-year survival from 1950-1954 to 2008-2013 ranged from 38.2% for non-Hodgkin lymphoma (NHL) to 56.6% for Hodgkin lymphoma.

And although the 5-year survival rate for Hodgkin lymphoma patients reached 86.6% for 2008-2013, the 5-year survival rate for patients with AML only reached 27.4%.

This study also revealed large disparities in overall cancer mortality rates between different counties across the country.

Ali H. Mokdad, PhD, of the Institute for Health Metrics and Evaluation in Seattle, Washington, and his colleagues reported these findings in JAMA.

Overall cancer deaths

The researchers found there were 19,511,910 cancer deaths recorded in the US between 1980 and 2014. Cancer mortality decreased by 20.1% between 1980 and 2014, from 240.2 deaths per 100,000 people to 192.0 deaths per 100,000 people.

In 1980, cancer mortality ranged from 130.6 per 100,000 in Summit County, Colorado, to 386.9 per 100,000 in North Slope Borough, Alaska.

In 2014, cancer mortality ranged from 70.7 per 100,000 in Summit County, Colorado, to 503.1 per 100,000 in Union County, Florida.

“Such significant disparities among US counties is unacceptable,” Dr Mokdad said. “Every person should have access to early screenings for cancer, as well as adequate treatment.”

Mortality rates for hematologic malignancies

In 2014, the mortality rates, per 100,000 people, for hematologic malignancies were:

• 0.4 for Hodgkin lymphoma (rank out of all cancers, 27)
• 8.3 for NHL (rank, 7)
• 3.9 for multiple myeloma (rank, 16)
• 9.0 for all leukemias (rank, 6)
• 0.7 for acute lymphoid leukemia (ALL)
• 2.6 for chronic lymphoid leukemia (CLL)
• 5.1 for AML
• 0.6 for chronic myeloid leukemia (CML).

The leukemia subtypes were not assigned a rank.

5-year survival rates for hematologic malignancies

Hodgkin lymphoma

• 30% for 1950-54
• 68.6% for 1973-77
• 72.1% for 1978-82
• 86.6% for 2008-2013
• Absolute difference (between the first and latest year of data), 56.6%.

NHL

• 33% for 1950-54
• 45.3% for 1973-77
• 48.7% for 1978-82
• 71.2% for 2008-2013
• Absolute difference, 38.2%.

Multiple myeloma

• 6% for 1950-54
• 23.4% for 1973-77
• 26.6% for 1978-82
• 49.8% for 2008-2013
• Absolute difference, 43.8%.

Leukemia

• 10% for 1950-54
• 34% for 1973-77
• 36.3% for 1978-82
• 60.1% for 2008-2013
• Absolute difference, 50.1%.

ALL

• 39.2% for 1973-77
• 50.5% for 1978-82
• 68.1% for 2008-2013
• Absolute difference, 28.9%.

CLL

• 67% for 1973-77
• 66.3% for 1978-82
• 82.5% for 2008-2013
• Absolute difference, 15.5%.

AML

• 6.2% for 1973-77
• 7.9% for 1978-82
• 27.4% for 2008-2013
• Absolute difference, 21.2%.

CML

• 21.1% for 1973-77
• 25.8% for 1978-82
• 66.4% for 2008-2013
• Absolute difference, 45.3%.

For the leukemia subtypes, there was no data for 1950 to 1954.