User login
miR expression may predict long-term prognosis in DLBCL
Photo courtesy of NIH
MicroRNA (miR) expression may help us predict long-term prognosis in diffuse large B-cell lymphoma (DLBCL), according to a study published in
Investigators identified 8 miRs that were differently expressed in DLBCL patients with poor prognosis and patients with favorable prognosis.
However, many of the miRs that have been linked to DLBCL prognosis in previous studies were not associated with prognosis in this study.
“Our data are in agreement with previous findings showing that miR signature is predictive of prognosis for patients with DLBCL, although with different miRs achieving statistical significance,” said study author Meir Lahav, MD, of Tel Aviv University in Israel.
Dr Lahav and his colleagues analyzed miR signatures from tissue biopsies taken from 83 patients with DLBCL who were treated between 1995 and 2003.
Patients who relapsed within 9 months from the start of treatment were defined as poor prognosis (n=43), and patients with disease-free survival of at least 5 years were defined as good prognosis (n=40).
The investigators analyzed RNA using microarrays developed by Rosetta Genomics. To validate the microarray results, the team used quantitative real-time polymerase chain reaction (qRT-PCR) and an independent set of 13 samples.
They found that 4 miRs were upregulated in the poor-prognosis group compared to the good-prognosis group: hsa-miR-17-5p, hsa-miR-19b-3p, hsa-miR-20a-5p, and hsa-miR-106a-5p.
And 4 miRs were downregulated in the poor-prognosis group compared to the good-prognosis group: hsa-miR-150-5p, hsa-miR-342-3p, hsa-miR-181a-5p, and hsa-miR-140-3p.
The investigators said the strongest and most consistent correlation was for miR-342-3p and miR-150-5p, which discriminated between the 2 prognostic groups in the microarray analysis, qRT-PCR, and the independent validation set.
Several miRs that were found to have prognostic value in previous studies did not differentiate the prognostic groups in this study. These were miR-155-5p, miR-21-5p, miR-18a-5p, miR-221-3p, and miR-222-3p. However, one miR—miR-181a-5p—had prognostic value in a previous study and the current study.
The investigators said the differences in miRs might be explained by the fact that this study had a larger sample size and longer follow-up than previous studies.
The differences might also reflect prognostic changes with rituximab treatment, as the patients in this study did not receive rituximab (only CHOP).
Either way, the investigators said these results suggest that analyzing miR expression can potentially improve our ability to predict prognosis in DLBCL and may therefore have a significant clinical impact. 
Photo courtesy of NIH
MicroRNA (miR) expression may help us predict long-term prognosis in diffuse large B-cell lymphoma (DLBCL), according to a study published in
Investigators identified 8 miRs that were differently expressed in DLBCL patients with poor prognosis and patients with favorable prognosis.
However, many of the miRs that have been linked to DLBCL prognosis in previous studies were not associated with prognosis in this study.
“Our data are in agreement with previous findings showing that miR signature is predictive of prognosis for patients with DLBCL, although with different miRs achieving statistical significance,” said study author Meir Lahav, MD, of Tel Aviv University in Israel.
Dr Lahav and his colleagues analyzed miR signatures from tissue biopsies taken from 83 patients with DLBCL who were treated between 1995 and 2003.
Patients who relapsed within 9 months from the start of treatment were defined as poor prognosis (n=43), and patients with disease-free survival of at least 5 years were defined as good prognosis (n=40).
The investigators analyzed RNA using microarrays developed by Rosetta Genomics. To validate the microarray results, the team used quantitative real-time polymerase chain reaction (qRT-PCR) and an independent set of 13 samples.
They found that 4 miRs were upregulated in the poor-prognosis group compared to the good-prognosis group: hsa-miR-17-5p, hsa-miR-19b-3p, hsa-miR-20a-5p, and hsa-miR-106a-5p.
And 4 miRs were downregulated in the poor-prognosis group compared to the good-prognosis group: hsa-miR-150-5p, hsa-miR-342-3p, hsa-miR-181a-5p, and hsa-miR-140-3p.
The investigators said the strongest and most consistent correlation was for miR-342-3p and miR-150-5p, which discriminated between the 2 prognostic groups in the microarray analysis, qRT-PCR, and the independent validation set.
Several miRs that were found to have prognostic value in previous studies did not differentiate the prognostic groups in this study. These were miR-155-5p, miR-21-5p, miR-18a-5p, miR-221-3p, and miR-222-3p. However, one miR—miR-181a-5p—had prognostic value in a previous study and the current study.
The investigators said the differences in miRs might be explained by the fact that this study had a larger sample size and longer follow-up than previous studies.
The differences might also reflect prognostic changes with rituximab treatment, as the patients in this study did not receive rituximab (only CHOP).
Either way, the investigators said these results suggest that analyzing miR expression can potentially improve our ability to predict prognosis in DLBCL and may therefore have a significant clinical impact.
Photo courtesy of NIH
MicroRNA (miR) expression may help us predict long-term prognosis in diffuse large B-cell lymphoma (DLBCL), according to a study published in
Investigators identified 8 miRs that were differently expressed in DLBCL patients with poor prognosis and patients with favorable prognosis.
However, many of the miRs that have been linked to DLBCL prognosis in previous studies were not associated with prognosis in this study.
“Our data are in agreement with previous findings showing that miR signature is predictive of prognosis for patients with DLBCL, although with different miRs achieving statistical significance,” said study author Meir Lahav, MD, of Tel Aviv University in Israel.
Dr Lahav and his colleagues analyzed miR signatures from tissue biopsies taken from 83 patients with DLBCL who were treated between 1995 and 2003.
Patients who relapsed within 9 months from the start of treatment were defined as poor prognosis (n=43), and patients with disease-free survival of at least 5 years were defined as good prognosis (n=40).
The investigators analyzed RNA using microarrays developed by Rosetta Genomics. To validate the microarray results, the team used quantitative real-time polymerase chain reaction (qRT-PCR) and an independent set of 13 samples.
They found that 4 miRs were upregulated in the poor-prognosis group compared to the good-prognosis group: hsa-miR-17-5p, hsa-miR-19b-3p, hsa-miR-20a-5p, and hsa-miR-106a-5p.
And 4 miRs were downregulated in the poor-prognosis group compared to the good-prognosis group: hsa-miR-150-5p, hsa-miR-342-3p, hsa-miR-181a-5p, and hsa-miR-140-3p.
The investigators said the strongest and most consistent correlation was for miR-342-3p and miR-150-5p, which discriminated between the 2 prognostic groups in the microarray analysis, qRT-PCR, and the independent validation set.
Several miRs that were found to have prognostic value in previous studies did not differentiate the prognostic groups in this study. These were miR-155-5p, miR-21-5p, miR-18a-5p, miR-221-3p, and miR-222-3p. However, one miR—miR-181a-5p—had prognostic value in a previous study and the current study.
The investigators said the differences in miRs might be explained by the fact that this study had a larger sample size and longer follow-up than previous studies.
The differences might also reflect prognostic changes with rituximab treatment, as the patients in this study did not receive rituximab (only CHOP).
Either way, the investigators said these results suggest that analyzing miR expression can potentially improve our ability to predict prognosis in DLBCL and may therefore have a significant clinical impact.
Epigenomic findings may help predict relapse in DLBCL
Photo by Rhoda Baer
Epigenomic heterogeneity at diagnosis may predict relapse in diffuse large B-cell lymphoma (DLBCL), according to research published in Nature Communications.
Investigators made this connection by reviewing biopsies taken from DLBCL patients before and after treatment.
The epigenome in these patients’ cancer cells changed greatly after treatment, and the global epigenome of pretreatment biopsies was substantially different in patients who relapsed and those who did not. There was more cell-to-cell heterogeneity in patients who relapsed.
“This is the first study I know of in cancer that looks at changes in the epigenome before and after treatment, and what we found could ultimately make traditional treatments much more effective,” said study author Olivier Elemento, PhD, of Weill Cornell Medical College in New York, New York.
To uncover the role of epigenetic involvement in DLBCL, Dr Elemento and his colleagues analyzed banked biopsies from patients. In each sample set, the investigators looked at sites in the epigenome where a methyl group was added or removed after DLBCL recurred.
They found a change in methylation that occurred between 39,808 and 1,035,960 specific methylation sites, depending on the sample. In addition, they identified between 78 and 13,162 differently methylated regions in the epigenome in relapsed disease.
“These are massive changes, given that the epigenome has 20 million methylation sites,” Dr Elemento said. “Our study shows that, in some cases, up to one-twentieth of the entire epigenome is changed after treatment. There are many more epigenetic changes than there are altered genes in DLBCL.”
“Once you have changes in methylation, the end result is an imbalanced expression of proteins,” added Giorgio Inghirami, MD, also of Weill Cornell.
“The tumor after chemotherapy is not the same as the tumor before treatment. This why it is so critical to have biopsies before any treatment of [primary or relapsed] lesions.”
The investigators hope this work will ultimately allow clinicians and researchers to predict treatment resistance in individual patients.
Photo by Rhoda Baer
Epigenomic heterogeneity at diagnosis may predict relapse in diffuse large B-cell lymphoma (DLBCL), according to research published in Nature Communications.
Investigators made this connection by reviewing biopsies taken from DLBCL patients before and after treatment.
The epigenome in these patients’ cancer cells changed greatly after treatment, and the global epigenome of pretreatment biopsies was substantially different in patients who relapsed and those who did not. There was more cell-to-cell heterogeneity in patients who relapsed.
“This is the first study I know of in cancer that looks at changes in the epigenome before and after treatment, and what we found could ultimately make traditional treatments much more effective,” said study author Olivier Elemento, PhD, of Weill Cornell Medical College in New York, New York.
To uncover the role of epigenetic involvement in DLBCL, Dr Elemento and his colleagues analyzed banked biopsies from patients. In each sample set, the investigators looked at sites in the epigenome where a methyl group was added or removed after DLBCL recurred.
They found a change in methylation that occurred between 39,808 and 1,035,960 specific methylation sites, depending on the sample. In addition, they identified between 78 and 13,162 differently methylated regions in the epigenome in relapsed disease.
“These are massive changes, given that the epigenome has 20 million methylation sites,” Dr Elemento said. “Our study shows that, in some cases, up to one-twentieth of the entire epigenome is changed after treatment. There are many more epigenetic changes than there are altered genes in DLBCL.”
“Once you have changes in methylation, the end result is an imbalanced expression of proteins,” added Giorgio Inghirami, MD, also of Weill Cornell.
“The tumor after chemotherapy is not the same as the tumor before treatment. This why it is so critical to have biopsies before any treatment of [primary or relapsed] lesions.”
The investigators hope this work will ultimately allow clinicians and researchers to predict treatment resistance in individual patients.
Photo by Rhoda Baer
Epigenomic heterogeneity at diagnosis may predict relapse in diffuse large B-cell lymphoma (DLBCL), according to research published in Nature Communications.
Investigators made this connection by reviewing biopsies taken from DLBCL patients before and after treatment.
The epigenome in these patients’ cancer cells changed greatly after treatment, and the global epigenome of pretreatment biopsies was substantially different in patients who relapsed and those who did not. There was more cell-to-cell heterogeneity in patients who relapsed.
“This is the first study I know of in cancer that looks at changes in the epigenome before and after treatment, and what we found could ultimately make traditional treatments much more effective,” said study author Olivier Elemento, PhD, of Weill Cornell Medical College in New York, New York.
To uncover the role of epigenetic involvement in DLBCL, Dr Elemento and his colleagues analyzed banked biopsies from patients. In each sample set, the investigators looked at sites in the epigenome where a methyl group was added or removed after DLBCL recurred.
They found a change in methylation that occurred between 39,808 and 1,035,960 specific methylation sites, depending on the sample. In addition, they identified between 78 and 13,162 differently methylated regions in the epigenome in relapsed disease.
“These are massive changes, given that the epigenome has 20 million methylation sites,” Dr Elemento said. “Our study shows that, in some cases, up to one-twentieth of the entire epigenome is changed after treatment. There are many more epigenetic changes than there are altered genes in DLBCL.”
“Once you have changes in methylation, the end result is an imbalanced expression of proteins,” added Giorgio Inghirami, MD, also of Weill Cornell.
“The tumor after chemotherapy is not the same as the tumor before treatment. This why it is so critical to have biopsies before any treatment of [primary or relapsed] lesions.”
The investigators hope this work will ultimately allow clinicians and researchers to predict treatment resistance in individual patients.
New mAb can overcome resistance to other mAbs
Photo courtesy of the
University of Southampton
A newly developed monoclonal antibody (mAb) can reverse resistance to other mAbs in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), according to research published in Cancer Cell.
Investigators found that some cancer cells draw mAbs inside themselves, making them invisible to immune cells.
But a mAb called BI-1206 can prevent this process and enhance cancer killing by binding to a molecule called FcγRIIB.
In preclinical experiments, BI-1206 was able to overcome resistance to mAbs such as rituximab.
“With more monoclonal antibody treatments being developed, there is an urgent need to understand how tumors become resistant to them and develop ways to overcome it,” said study author Mark Cragg, PhD, of the University of Southampton in the UK.
“Not only does BI-1206 appear to be able to reverse resistance to a range of monoclonal antibodies, it is also effective at directly killing cancer cells itself.”
In the Cancer Cell paper, BI-1206 is referred to as 6G11. The investigators found that 6G11 can block rituximab internalization and has “potent antitumor activity” in vitro. 6G11 was also well-tolerated and did not prompt cytokine storm.
In a mouse model of CLL, 6G11 enhanced rituximab-mediated depletion of primary CLL cells and improved responses when compared to rituximab alone.
In mice engrafted with cells from patients with CLL that was refractory to rituximab, ofatumumab, and/or alemtuzumab, 6G11 alone depleted CLL cells but did not improve overall response rates compared to rituximab alone. However, 6G11 in combination with rituximab did improve overall response rates compared to rituximab alone.
In a mouse model of MCL, neither 6G11 nor rituximab alone improved long-term survival. However, 30% of mice treated with both drugs survived tumor-free out to 100 days.
Combining 6G11 with obinutuzumab significantly improved splenic tumor cell depletion in mice with CLL. And more than 90% of mice that received 6G11 and alemtuzumab had a complete response to the treatment.
The investigators said these data suggest 6G11 can overcome mAb resistance for multiple targets. They said the drug will be tested in patients with CLL and non-Hodgkin lymphoma in an early stage clinical trial.
Photo courtesy of the
University of Southampton
A newly developed monoclonal antibody (mAb) can reverse resistance to other mAbs in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), according to research published in Cancer Cell.
Investigators found that some cancer cells draw mAbs inside themselves, making them invisible to immune cells.
But a mAb called BI-1206 can prevent this process and enhance cancer killing by binding to a molecule called FcγRIIB.
In preclinical experiments, BI-1206 was able to overcome resistance to mAbs such as rituximab.
“With more monoclonal antibody treatments being developed, there is an urgent need to understand how tumors become resistant to them and develop ways to overcome it,” said study author Mark Cragg, PhD, of the University of Southampton in the UK.
“Not only does BI-1206 appear to be able to reverse resistance to a range of monoclonal antibodies, it is also effective at directly killing cancer cells itself.”
In the Cancer Cell paper, BI-1206 is referred to as 6G11. The investigators found that 6G11 can block rituximab internalization and has “potent antitumor activity” in vitro. 6G11 was also well-tolerated and did not prompt cytokine storm.
In a mouse model of CLL, 6G11 enhanced rituximab-mediated depletion of primary CLL cells and improved responses when compared to rituximab alone.
In mice engrafted with cells from patients with CLL that was refractory to rituximab, ofatumumab, and/or alemtuzumab, 6G11 alone depleted CLL cells but did not improve overall response rates compared to rituximab alone. However, 6G11 in combination with rituximab did improve overall response rates compared to rituximab alone.
In a mouse model of MCL, neither 6G11 nor rituximab alone improved long-term survival. However, 30% of mice treated with both drugs survived tumor-free out to 100 days.
Combining 6G11 with obinutuzumab significantly improved splenic tumor cell depletion in mice with CLL. And more than 90% of mice that received 6G11 and alemtuzumab had a complete response to the treatment.
The investigators said these data suggest 6G11 can overcome mAb resistance for multiple targets. They said the drug will be tested in patients with CLL and non-Hodgkin lymphoma in an early stage clinical trial.
Photo courtesy of the
University of Southampton
A newly developed monoclonal antibody (mAb) can reverse resistance to other mAbs in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), according to research published in Cancer Cell.
Investigators found that some cancer cells draw mAbs inside themselves, making them invisible to immune cells.
But a mAb called BI-1206 can prevent this process and enhance cancer killing by binding to a molecule called FcγRIIB.
In preclinical experiments, BI-1206 was able to overcome resistance to mAbs such as rituximab.
“With more monoclonal antibody treatments being developed, there is an urgent need to understand how tumors become resistant to them and develop ways to overcome it,” said study author Mark Cragg, PhD, of the University of Southampton in the UK.
“Not only does BI-1206 appear to be able to reverse resistance to a range of monoclonal antibodies, it is also effective at directly killing cancer cells itself.”
In the Cancer Cell paper, BI-1206 is referred to as 6G11. The investigators found that 6G11 can block rituximab internalization and has “potent antitumor activity” in vitro. 6G11 was also well-tolerated and did not prompt cytokine storm.
In a mouse model of CLL, 6G11 enhanced rituximab-mediated depletion of primary CLL cells and improved responses when compared to rituximab alone.
In mice engrafted with cells from patients with CLL that was refractory to rituximab, ofatumumab, and/or alemtuzumab, 6G11 alone depleted CLL cells but did not improve overall response rates compared to rituximab alone. However, 6G11 in combination with rituximab did improve overall response rates compared to rituximab alone.
In a mouse model of MCL, neither 6G11 nor rituximab alone improved long-term survival. However, 30% of mice treated with both drugs survived tumor-free out to 100 days.
Combining 6G11 with obinutuzumab significantly improved splenic tumor cell depletion in mice with CLL. And more than 90% of mice that received 6G11 and alemtuzumab had a complete response to the treatment.
The investigators said these data suggest 6G11 can overcome mAb resistance for multiple targets. They said the drug will be tested in patients with CLL and non-Hodgkin lymphoma in an early stage clinical trial.
Technique helps determine DLBCL subtypes
Photo by Darren Baker
A new technique can quickly and easily differentiate the two major subtypes of diffuse large B-cell lymphoma (DLBCL), researchers have reported in The Journal of Molecular Diagnostics.
The method is based on a reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) assay and 14 gene signatures.
It proved as accurate as the gold standard technology for identifying germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL.
So the researchers believe this RT-MLPA-based assay could help clinicians evaluate a patient’s prognosis and choose the optimal therapy for a person with DLBCL.
“Differences in the progression of the disease and clinical outcomes can, at least in part, be explained by the heterogeneity of lymphoma, which can be classified into two major subtypes with different outcomes,” said study author Philippe Ruminy, PhD, of the University of Rouen in France.
“Unfortunately, these lymphomas are morphologically undistinguishable in routine diagnosis, which is a major problem for the development of targeted therapies. Furthermore, array-based gene expression profiling (GEP), which is considered the gold standard for discriminating these tumors, remains poorly transposable to routine diagnosis, and the surrogate immunohistochemical (IHC) algorithms that have been proposed are often considered poorly reliable.”
With this in mind, Dr Ruminy and his colleagues tested the RT-MLPA-based assay alongside GEP techniques in samples from 259 patients with de novo DLBCL.
The team used a series of 195 patients from a single institution to train and validate the new technique. Of these patients, 115 had a classification determined with a Veracode DASL assay, 100 had an IHC classification, and 135 had survival data. A second series of 64 patients that were previously analyzed by Affymetrix U133+2 GEP arrays served as an external validation cohort.
When the researchers looked at 50 patients randomly selected from the training cohort, they found that the RT-MLPA-based assay classified 90% of the cases within the expected subtypes (20 GCB and 25 ABC). The remaining 10% (1 GCB and 4 ABC) were considered unclassified.
In the external validation cohort, the RT-MLPA-based assay classified 80% of cases within the expected subtypes (24 ABC and 28 GCB). However, 13.8% were considered unclassified (3 GCB and 6 ABC), and 4 were misclassified.
The researchers also found the RT-MLPA-based assay was sensitive for analyzing archived formalin-fixed, paraffin-embedded (FFPE) tissue samples. A comparison of samples from paired frozen and FFPE biopsies showed that the technique correctly classified 89.3% of 28 cases.
“Because RT-MLPA requires only short cDNA fragments for the correct binding and ligation of the gene-specific oligonucleotide probes, it is less affected by the use of low RNA concentrations and RNA degradation,” Dr Ruminy said.
“It could thus be used for the retrospective analysis of archival collections and for the inclusion of patients in prospective clinical trials, because only a few institutions routinely collect frozen biopsy material.”
To evaluate the prognostic value of the assay, the researchers looked at survival in 135 treated DLBCL patients who were diagnosed between 2001 and 2011.
Patients determined to have the ABC subtype by the RT-MLPA-based assay had significantly worse progression-free survival and overall survival than patients with the GCB subtype. And the expression of several individual genes within the MLPA signature was significantly associated with prognosis (ie, high LMO2, high BCL6, and low TNFRSF13B expression).
“The robust and cost-effective RT-MLPA assay can yield results within one day and requires reagents costing less than $5 per sample,” Dr Ruminy said. “Since RT-MLPA utilizes materials and equipment that are standard in many laboratories, the process can easily be implemented for routine use.”
Photo by Darren Baker
A new technique can quickly and easily differentiate the two major subtypes of diffuse large B-cell lymphoma (DLBCL), researchers have reported in The Journal of Molecular Diagnostics.
The method is based on a reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) assay and 14 gene signatures.
It proved as accurate as the gold standard technology for identifying germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL.
So the researchers believe this RT-MLPA-based assay could help clinicians evaluate a patient’s prognosis and choose the optimal therapy for a person with DLBCL.
“Differences in the progression of the disease and clinical outcomes can, at least in part, be explained by the heterogeneity of lymphoma, which can be classified into two major subtypes with different outcomes,” said study author Philippe Ruminy, PhD, of the University of Rouen in France.
“Unfortunately, these lymphomas are morphologically undistinguishable in routine diagnosis, which is a major problem for the development of targeted therapies. Furthermore, array-based gene expression profiling (GEP), which is considered the gold standard for discriminating these tumors, remains poorly transposable to routine diagnosis, and the surrogate immunohistochemical (IHC) algorithms that have been proposed are often considered poorly reliable.”
With this in mind, Dr Ruminy and his colleagues tested the RT-MLPA-based assay alongside GEP techniques in samples from 259 patients with de novo DLBCL.
The team used a series of 195 patients from a single institution to train and validate the new technique. Of these patients, 115 had a classification determined with a Veracode DASL assay, 100 had an IHC classification, and 135 had survival data. A second series of 64 patients that were previously analyzed by Affymetrix U133+2 GEP arrays served as an external validation cohort.
When the researchers looked at 50 patients randomly selected from the training cohort, they found that the RT-MLPA-based assay classified 90% of the cases within the expected subtypes (20 GCB and 25 ABC). The remaining 10% (1 GCB and 4 ABC) were considered unclassified.
In the external validation cohort, the RT-MLPA-based assay classified 80% of cases within the expected subtypes (24 ABC and 28 GCB). However, 13.8% were considered unclassified (3 GCB and 6 ABC), and 4 were misclassified.
The researchers also found the RT-MLPA-based assay was sensitive for analyzing archived formalin-fixed, paraffin-embedded (FFPE) tissue samples. A comparison of samples from paired frozen and FFPE biopsies showed that the technique correctly classified 89.3% of 28 cases.
“Because RT-MLPA requires only short cDNA fragments for the correct binding and ligation of the gene-specific oligonucleotide probes, it is less affected by the use of low RNA concentrations and RNA degradation,” Dr Ruminy said.
“It could thus be used for the retrospective analysis of archival collections and for the inclusion of patients in prospective clinical trials, because only a few institutions routinely collect frozen biopsy material.”
To evaluate the prognostic value of the assay, the researchers looked at survival in 135 treated DLBCL patients who were diagnosed between 2001 and 2011.
Patients determined to have the ABC subtype by the RT-MLPA-based assay had significantly worse progression-free survival and overall survival than patients with the GCB subtype. And the expression of several individual genes within the MLPA signature was significantly associated with prognosis (ie, high LMO2, high BCL6, and low TNFRSF13B expression).
“The robust and cost-effective RT-MLPA assay can yield results within one day and requires reagents costing less than $5 per sample,” Dr Ruminy said. “Since RT-MLPA utilizes materials and equipment that are standard in many laboratories, the process can easily be implemented for routine use.”
Photo by Darren Baker
A new technique can quickly and easily differentiate the two major subtypes of diffuse large B-cell lymphoma (DLBCL), researchers have reported in The Journal of Molecular Diagnostics.
The method is based on a reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) assay and 14 gene signatures.
It proved as accurate as the gold standard technology for identifying germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL.
So the researchers believe this RT-MLPA-based assay could help clinicians evaluate a patient’s prognosis and choose the optimal therapy for a person with DLBCL.
“Differences in the progression of the disease and clinical outcomes can, at least in part, be explained by the heterogeneity of lymphoma, which can be classified into two major subtypes with different outcomes,” said study author Philippe Ruminy, PhD, of the University of Rouen in France.
“Unfortunately, these lymphomas are morphologically undistinguishable in routine diagnosis, which is a major problem for the development of targeted therapies. Furthermore, array-based gene expression profiling (GEP), which is considered the gold standard for discriminating these tumors, remains poorly transposable to routine diagnosis, and the surrogate immunohistochemical (IHC) algorithms that have been proposed are often considered poorly reliable.”
With this in mind, Dr Ruminy and his colleagues tested the RT-MLPA-based assay alongside GEP techniques in samples from 259 patients with de novo DLBCL.
The team used a series of 195 patients from a single institution to train and validate the new technique. Of these patients, 115 had a classification determined with a Veracode DASL assay, 100 had an IHC classification, and 135 had survival data. A second series of 64 patients that were previously analyzed by Affymetrix U133+2 GEP arrays served as an external validation cohort.
When the researchers looked at 50 patients randomly selected from the training cohort, they found that the RT-MLPA-based assay classified 90% of the cases within the expected subtypes (20 GCB and 25 ABC). The remaining 10% (1 GCB and 4 ABC) were considered unclassified.
In the external validation cohort, the RT-MLPA-based assay classified 80% of cases within the expected subtypes (24 ABC and 28 GCB). However, 13.8% were considered unclassified (3 GCB and 6 ABC), and 4 were misclassified.
The researchers also found the RT-MLPA-based assay was sensitive for analyzing archived formalin-fixed, paraffin-embedded (FFPE) tissue samples. A comparison of samples from paired frozen and FFPE biopsies showed that the technique correctly classified 89.3% of 28 cases.
“Because RT-MLPA requires only short cDNA fragments for the correct binding and ligation of the gene-specific oligonucleotide probes, it is less affected by the use of low RNA concentrations and RNA degradation,” Dr Ruminy said.
“It could thus be used for the retrospective analysis of archival collections and for the inclusion of patients in prospective clinical trials, because only a few institutions routinely collect frozen biopsy material.”
To evaluate the prognostic value of the assay, the researchers looked at survival in 135 treated DLBCL patients who were diagnosed between 2001 and 2011.
Patients determined to have the ABC subtype by the RT-MLPA-based assay had significantly worse progression-free survival and overall survival than patients with the GCB subtype. And the expression of several individual genes within the MLPA signature was significantly associated with prognosis (ie, high LMO2, high BCL6, and low TNFRSF13B expression).
“The robust and cost-effective RT-MLPA assay can yield results within one day and requires reagents costing less than $5 per sample,” Dr Ruminy said. “Since RT-MLPA utilizes materials and equipment that are standard in many laboratories, the process can easily be implemented for routine use.”
Combo improves PFS in untreated CLL
Results of a phase 3 study suggest that adding ofatumumab to chlorambucil can improve progression-free survival (PFS) in treatment-naïve patients with chronic lymphocytic leukemia (CLL).
Ofatumumab plus chlorambucil improved the median PFS by 71% compared to chlorambucil alone.
The combination also improved the overall response rate, duration of response, and time to next treatment.
However, patients in the combination arm had a higher rate of grade 3 or greater adverse events (AEs).
Researchers reported these results in The Lancet. The study, known as COMPLEMENT 1, was funded by GlaxoSmithKline and Genmab A/S.
The study included 447 patients with previously untreated CLL for whom fludarabine-based therapy was considered inappropriate. Patients were randomized to treatment with up to 12 cycles of ofatumumab in combination with chlorambucil (n=221) or up to 12 cycles of chlorambucil alone (n=226).
The study’s primary endpoint was the median PFS, which was 22.4 months in the combination arm and 13.1 months in the chlorambucil arm (hazard ratio [HR]=0.57, P<0.0001). This improvement in PFS was observed in most subgroups, irrespective of age, gender, disease stage, and prognostic factors.
As for secondary endpoints, patients in the combination arm had a higher overall response rate than patients in the chlorambucil arm—82% and 69%, respectively (odds ratio=2.16, P=0.001).
And combination treatment increased the duration of response compared to chlorambucil alone—22.1 months and 13.2 months, respectively (HR=0.56, P<0.001).
Patients in the combination arm also experienced a significantly longer time to next therapy compared to the chlorambucil arm—39.8 months and 24.7 months, respectively (HR=0.49, P<0.0001).
Safety data
The most common AEs (occurring in at least 2% of patients) were neutropenia, thrombocytopenia, anemia, infections, and infusion-related reactions.
Neutropenia occurred more frequently in the combination arm (27% vs 18%), as did infusion-related reactions (67% vs 0%) and infections (46% vs 42%). But thrombocytopenia and anemia were more frequent in the chlorambucil arm (26% vs 14% and 13% vs 9%, respectively).
The incidence of grade 3 or greater AEs was higher in the combination arm than the chlorambucil arm—50% and 43%, respectively.
Grade 3/4 infusion-related reactions occurred in 10% of patients in the combination arm, leading to drug withdrawal in 3% of patients and hospitalization in 2% of patients. No fatal infusion-related reactions were reported.
The most common infections were respiratory tract infections, with an incidence of 27% in the combination arm and 31% in the chlorambucil arm. There were similar frequencies of sepsis (3% and 2%, respectively) and opportunistic infections between the arms (4% and 5%, respectively).
The incidence of AEs leading to treatment withdrawal was 13% in both arms. And the incidence of death during treatment or within 60 days after the last dose was 3% in both arms.
These data formed the basis for regulatory approvals of ofatumumab (Arzerra) in the US and European Union, as well as the recent inclusion of ofatumumab plus chlorambucil in the National Comprehensive Cancer Network treatment guidelines.
Results of a phase 3 study suggest that adding ofatumumab to chlorambucil can improve progression-free survival (PFS) in treatment-naïve patients with chronic lymphocytic leukemia (CLL).
Ofatumumab plus chlorambucil improved the median PFS by 71% compared to chlorambucil alone.
The combination also improved the overall response rate, duration of response, and time to next treatment.
However, patients in the combination arm had a higher rate of grade 3 or greater adverse events (AEs).
Researchers reported these results in The Lancet. The study, known as COMPLEMENT 1, was funded by GlaxoSmithKline and Genmab A/S.
The study included 447 patients with previously untreated CLL for whom fludarabine-based therapy was considered inappropriate. Patients were randomized to treatment with up to 12 cycles of ofatumumab in combination with chlorambucil (n=221) or up to 12 cycles of chlorambucil alone (n=226).
The study’s primary endpoint was the median PFS, which was 22.4 months in the combination arm and 13.1 months in the chlorambucil arm (hazard ratio [HR]=0.57, P<0.0001). This improvement in PFS was observed in most subgroups, irrespective of age, gender, disease stage, and prognostic factors.
As for secondary endpoints, patients in the combination arm had a higher overall response rate than patients in the chlorambucil arm—82% and 69%, respectively (odds ratio=2.16, P=0.001).
And combination treatment increased the duration of response compared to chlorambucil alone—22.1 months and 13.2 months, respectively (HR=0.56, P<0.001).
Patients in the combination arm also experienced a significantly longer time to next therapy compared to the chlorambucil arm—39.8 months and 24.7 months, respectively (HR=0.49, P<0.0001).
Safety data
The most common AEs (occurring in at least 2% of patients) were neutropenia, thrombocytopenia, anemia, infections, and infusion-related reactions.
Neutropenia occurred more frequently in the combination arm (27% vs 18%), as did infusion-related reactions (67% vs 0%) and infections (46% vs 42%). But thrombocytopenia and anemia were more frequent in the chlorambucil arm (26% vs 14% and 13% vs 9%, respectively).
The incidence of grade 3 or greater AEs was higher in the combination arm than the chlorambucil arm—50% and 43%, respectively.
Grade 3/4 infusion-related reactions occurred in 10% of patients in the combination arm, leading to drug withdrawal in 3% of patients and hospitalization in 2% of patients. No fatal infusion-related reactions were reported.
The most common infections were respiratory tract infections, with an incidence of 27% in the combination arm and 31% in the chlorambucil arm. There were similar frequencies of sepsis (3% and 2%, respectively) and opportunistic infections between the arms (4% and 5%, respectively).
The incidence of AEs leading to treatment withdrawal was 13% in both arms. And the incidence of death during treatment or within 60 days after the last dose was 3% in both arms.
These data formed the basis for regulatory approvals of ofatumumab (Arzerra) in the US and European Union, as well as the recent inclusion of ofatumumab plus chlorambucil in the National Comprehensive Cancer Network treatment guidelines.
Results of a phase 3 study suggest that adding ofatumumab to chlorambucil can improve progression-free survival (PFS) in treatment-naïve patients with chronic lymphocytic leukemia (CLL).
Ofatumumab plus chlorambucil improved the median PFS by 71% compared to chlorambucil alone.
The combination also improved the overall response rate, duration of response, and time to next treatment.
However, patients in the combination arm had a higher rate of grade 3 or greater adverse events (AEs).
Researchers reported these results in The Lancet. The study, known as COMPLEMENT 1, was funded by GlaxoSmithKline and Genmab A/S.
The study included 447 patients with previously untreated CLL for whom fludarabine-based therapy was considered inappropriate. Patients were randomized to treatment with up to 12 cycles of ofatumumab in combination with chlorambucil (n=221) or up to 12 cycles of chlorambucil alone (n=226).
The study’s primary endpoint was the median PFS, which was 22.4 months in the combination arm and 13.1 months in the chlorambucil arm (hazard ratio [HR]=0.57, P<0.0001). This improvement in PFS was observed in most subgroups, irrespective of age, gender, disease stage, and prognostic factors.
As for secondary endpoints, patients in the combination arm had a higher overall response rate than patients in the chlorambucil arm—82% and 69%, respectively (odds ratio=2.16, P=0.001).
And combination treatment increased the duration of response compared to chlorambucil alone—22.1 months and 13.2 months, respectively (HR=0.56, P<0.001).
Patients in the combination arm also experienced a significantly longer time to next therapy compared to the chlorambucil arm—39.8 months and 24.7 months, respectively (HR=0.49, P<0.0001).
Safety data
The most common AEs (occurring in at least 2% of patients) were neutropenia, thrombocytopenia, anemia, infections, and infusion-related reactions.
Neutropenia occurred more frequently in the combination arm (27% vs 18%), as did infusion-related reactions (67% vs 0%) and infections (46% vs 42%). But thrombocytopenia and anemia were more frequent in the chlorambucil arm (26% vs 14% and 13% vs 9%, respectively).
The incidence of grade 3 or greater AEs was higher in the combination arm than the chlorambucil arm—50% and 43%, respectively.
Grade 3/4 infusion-related reactions occurred in 10% of patients in the combination arm, leading to drug withdrawal in 3% of patients and hospitalization in 2% of patients. No fatal infusion-related reactions were reported.
The most common infections were respiratory tract infections, with an incidence of 27% in the combination arm and 31% in the chlorambucil arm. There were similar frequencies of sepsis (3% and 2%, respectively) and opportunistic infections between the arms (4% and 5%, respectively).
The incidence of AEs leading to treatment withdrawal was 13% in both arms. And the incidence of death during treatment or within 60 days after the last dose was 3% in both arms.
These data formed the basis for regulatory approvals of ofatumumab (Arzerra) in the US and European Union, as well as the recent inclusion of ofatumumab plus chlorambucil in the National Comprehensive Cancer Network treatment guidelines.
Inhibitor controls WM long-term
Photo by Sam Odgen
Updated results of a phase 2 trial suggest the Bruton’s tyrosine kinase inhibitor ibrutinib can control Waldenstrom’s macroglobulinemia (WM) long-term.
In previously treated WM patients, ibrutinib produced an overall response rate of 91%.
The 2-year overall survival rate was 95%, and 69% of patients had not progressed at 2 years.
Researchers reported these results in NEJM. The research was supported by Pharmacyclics, Janssen Pharmaceuticals, and several foundations.
An earlier analysis of data from this trial supported the US Food and Drug Administration’s approval of ibrutinib as the first treatment for WM.
“These findings herald a new era for the treatment of Waldenstrom’s macroglobulinemia and show how genome sequencing can lead to the discovery of cancer mutations that can be specifically targeted by new therapies,” said study author Steven Treon, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.
Dr Treon and his colleagues enrolled 63 WM patients on this trial. The patients had received a median of 2 prior therapies (range, 1-9), 56 patients (89%) had the MYD88L265P mutation, and 21 (34%) had the CXCR4WHIM mutation.
Patients received ibrutinib at 420 mg once daily until disease progression or unacceptable toxicity. After a median treatment duration of 19.1 months (range, 0.5-29.7 months), the overall response rate was 91%. The median time to response was 4 weeks.
Investigator-determined responses were impacted by the MYD88 and CXCR4 mutations. Patients carrying MYD88L265P and CXCR4WT achieved the highest responses, with a 100% overall response rate and 91% major response rate.
For all patients, the estimated progression-free and overall survival rates at 24 months were 69% and 95%, respectively.
“The results are remarkable when you consider that patients had received an average of 2 prior therapies, and 40% showed no response to the previous treatments,” Dr Treon said. “The findings herald a new era for the treatment of Waldenstrom’s macroglobulinemia.”
Dr Treon and his colleagues also said ibrutinib was well-tolerated. At the time of analysis, 68% of patients remained on therapy.
The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Grade 3 or higher neutropenia and thrombocytopenia occurred in 9 (14%) and 8 (13%) patients, respectively.
Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.
Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.
Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.
Photo by Sam Odgen
Updated results of a phase 2 trial suggest the Bruton’s tyrosine kinase inhibitor ibrutinib can control Waldenstrom’s macroglobulinemia (WM) long-term.
In previously treated WM patients, ibrutinib produced an overall response rate of 91%.
The 2-year overall survival rate was 95%, and 69% of patients had not progressed at 2 years.
Researchers reported these results in NEJM. The research was supported by Pharmacyclics, Janssen Pharmaceuticals, and several foundations.
An earlier analysis of data from this trial supported the US Food and Drug Administration’s approval of ibrutinib as the first treatment for WM.
“These findings herald a new era for the treatment of Waldenstrom’s macroglobulinemia and show how genome sequencing can lead to the discovery of cancer mutations that can be specifically targeted by new therapies,” said study author Steven Treon, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.
Dr Treon and his colleagues enrolled 63 WM patients on this trial. The patients had received a median of 2 prior therapies (range, 1-9), 56 patients (89%) had the MYD88L265P mutation, and 21 (34%) had the CXCR4WHIM mutation.
Patients received ibrutinib at 420 mg once daily until disease progression or unacceptable toxicity. After a median treatment duration of 19.1 months (range, 0.5-29.7 months), the overall response rate was 91%. The median time to response was 4 weeks.
Investigator-determined responses were impacted by the MYD88 and CXCR4 mutations. Patients carrying MYD88L265P and CXCR4WT achieved the highest responses, with a 100% overall response rate and 91% major response rate.
For all patients, the estimated progression-free and overall survival rates at 24 months were 69% and 95%, respectively.
“The results are remarkable when you consider that patients had received an average of 2 prior therapies, and 40% showed no response to the previous treatments,” Dr Treon said. “The findings herald a new era for the treatment of Waldenstrom’s macroglobulinemia.”
Dr Treon and his colleagues also said ibrutinib was well-tolerated. At the time of analysis, 68% of patients remained on therapy.
The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Grade 3 or higher neutropenia and thrombocytopenia occurred in 9 (14%) and 8 (13%) patients, respectively.
Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.
Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.
Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.
Photo by Sam Odgen
Updated results of a phase 2 trial suggest the Bruton’s tyrosine kinase inhibitor ibrutinib can control Waldenstrom’s macroglobulinemia (WM) long-term.
In previously treated WM patients, ibrutinib produced an overall response rate of 91%.
The 2-year overall survival rate was 95%, and 69% of patients had not progressed at 2 years.
Researchers reported these results in NEJM. The research was supported by Pharmacyclics, Janssen Pharmaceuticals, and several foundations.
An earlier analysis of data from this trial supported the US Food and Drug Administration’s approval of ibrutinib as the first treatment for WM.
“These findings herald a new era for the treatment of Waldenstrom’s macroglobulinemia and show how genome sequencing can lead to the discovery of cancer mutations that can be specifically targeted by new therapies,” said study author Steven Treon, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.
Dr Treon and his colleagues enrolled 63 WM patients on this trial. The patients had received a median of 2 prior therapies (range, 1-9), 56 patients (89%) had the MYD88L265P mutation, and 21 (34%) had the CXCR4WHIM mutation.
Patients received ibrutinib at 420 mg once daily until disease progression or unacceptable toxicity. After a median treatment duration of 19.1 months (range, 0.5-29.7 months), the overall response rate was 91%. The median time to response was 4 weeks.
Investigator-determined responses were impacted by the MYD88 and CXCR4 mutations. Patients carrying MYD88L265P and CXCR4WT achieved the highest responses, with a 100% overall response rate and 91% major response rate.
For all patients, the estimated progression-free and overall survival rates at 24 months were 69% and 95%, respectively.
“The results are remarkable when you consider that patients had received an average of 2 prior therapies, and 40% showed no response to the previous treatments,” Dr Treon said. “The findings herald a new era for the treatment of Waldenstrom’s macroglobulinemia.”
Dr Treon and his colleagues also said ibrutinib was well-tolerated. At the time of analysis, 68% of patients remained on therapy.
The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Grade 3 or higher neutropenia and thrombocytopenia occurred in 9 (14%) and 8 (13%) patients, respectively.
Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.
Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.
Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.
Inhibitor gets orphan designation for DLBCL
The US Food and Drug Administration (FDA) has granted orphan drug designation to CUDC-907 for the treatment of diffuse large B-cell lymphoma (DLBCL).
CUDC-907 is an oral, dual inhibitor of histone deacetylase and phosphoinositide 3-kinase enzymes. It is currently under investigation in phase 1 trials in patients with relapsed or refractory lymphomas, multiple myeloma, and advanced/relapsed solid tumors.
The FDA grants orphan status to products intended for treating diseases that affect fewer than 200,000 people in the US. Orphan designation qualifies the drug’s developer—in this case, Curis, Inc.—with incentives such as tax credits for qualified trials, the ability to apply for annual grant funding, and 7 years of market exclusivity once the drug is approved.
Phase 1 data
At the 2013 ASH Annual Meeting, researchers presented interim data from a phase 1, dose-escalation trial of CUDC-907 in patients with advanced lymphoma or multiple myeloma.
Thirteen patients had received CUDC-907 on either once-daily (QD) or twice-weekly (BIW) schedules at doses of 30 mg QD (n=7), 60 mg QD (n=3), or 60 mg BIW (n=3).
Dose-limiting toxicities (DLTs) of grade 3 diarrhea and grade 4 hyperglycemia were reported in 1 patient at the 60 mg QD dose. The most frequent grade 3 or 4 adverse events reported in 2 or more patients included thrombocytopenia, diarrhea, and neutropenia. Tolerability limited the ability to further dose escalate using the QD schedule.
No DLTs or dose interruptions were reported for patients enrolled on the BIW schedule. So dose escalation is ongoing with the BIW schedule as well as a separate, thrice-weekly treatment schedule.
Of the 13 patients treated, 11 were evaluable for response. One patient with mixed follicular lymphoma/DLBCL achieved a partial response, with a 70% reduction in a single target lesion observed at the 30 mg QD dose level.
Seven other patients met criteria for stable disease, including 4 with stable disease lasting at least 4 cycles of treatment.
Following the ASH presentation, Curis reported additional data from a subset of patients that suggest CUDC-907 has antitumor activity in patients with DLBCL.
For the November 10, 2014, data cutoff period, 8 patients with DLBCL were evaluable. One of these patients had a complete response, 2 had a partial response (tumor shrinkage greater than 50%), and 4 had tumor shrinkage ranging from 5% to 46%.
The dose-escalation stage of the trial is nearing completion, and Curis expects to present full data this year. Curis has also initiated an expansion cohort to further evaluate CUDC-907 in patients with DLBCL or multiple myeloma at the recommended phase 2 dose.
The US Food and Drug Administration (FDA) has granted orphan drug designation to CUDC-907 for the treatment of diffuse large B-cell lymphoma (DLBCL).
CUDC-907 is an oral, dual inhibitor of histone deacetylase and phosphoinositide 3-kinase enzymes. It is currently under investigation in phase 1 trials in patients with relapsed or refractory lymphomas, multiple myeloma, and advanced/relapsed solid tumors.
The FDA grants orphan status to products intended for treating diseases that affect fewer than 200,000 people in the US. Orphan designation qualifies the drug’s developer—in this case, Curis, Inc.—with incentives such as tax credits for qualified trials, the ability to apply for annual grant funding, and 7 years of market exclusivity once the drug is approved.
Phase 1 data
At the 2013 ASH Annual Meeting, researchers presented interim data from a phase 1, dose-escalation trial of CUDC-907 in patients with advanced lymphoma or multiple myeloma.
Thirteen patients had received CUDC-907 on either once-daily (QD) or twice-weekly (BIW) schedules at doses of 30 mg QD (n=7), 60 mg QD (n=3), or 60 mg BIW (n=3).
Dose-limiting toxicities (DLTs) of grade 3 diarrhea and grade 4 hyperglycemia were reported in 1 patient at the 60 mg QD dose. The most frequent grade 3 or 4 adverse events reported in 2 or more patients included thrombocytopenia, diarrhea, and neutropenia. Tolerability limited the ability to further dose escalate using the QD schedule.
No DLTs or dose interruptions were reported for patients enrolled on the BIW schedule. So dose escalation is ongoing with the BIW schedule as well as a separate, thrice-weekly treatment schedule.
Of the 13 patients treated, 11 were evaluable for response. One patient with mixed follicular lymphoma/DLBCL achieved a partial response, with a 70% reduction in a single target lesion observed at the 30 mg QD dose level.
Seven other patients met criteria for stable disease, including 4 with stable disease lasting at least 4 cycles of treatment.
Following the ASH presentation, Curis reported additional data from a subset of patients that suggest CUDC-907 has antitumor activity in patients with DLBCL.
For the November 10, 2014, data cutoff period, 8 patients with DLBCL were evaluable. One of these patients had a complete response, 2 had a partial response (tumor shrinkage greater than 50%), and 4 had tumor shrinkage ranging from 5% to 46%.
The dose-escalation stage of the trial is nearing completion, and Curis expects to present full data this year. Curis has also initiated an expansion cohort to further evaluate CUDC-907 in patients with DLBCL or multiple myeloma at the recommended phase 2 dose.
The US Food and Drug Administration (FDA) has granted orphan drug designation to CUDC-907 for the treatment of diffuse large B-cell lymphoma (DLBCL).
CUDC-907 is an oral, dual inhibitor of histone deacetylase and phosphoinositide 3-kinase enzymes. It is currently under investigation in phase 1 trials in patients with relapsed or refractory lymphomas, multiple myeloma, and advanced/relapsed solid tumors.
The FDA grants orphan status to products intended for treating diseases that affect fewer than 200,000 people in the US. Orphan designation qualifies the drug’s developer—in this case, Curis, Inc.—with incentives such as tax credits for qualified trials, the ability to apply for annual grant funding, and 7 years of market exclusivity once the drug is approved.
Phase 1 data
At the 2013 ASH Annual Meeting, researchers presented interim data from a phase 1, dose-escalation trial of CUDC-907 in patients with advanced lymphoma or multiple myeloma.
Thirteen patients had received CUDC-907 on either once-daily (QD) or twice-weekly (BIW) schedules at doses of 30 mg QD (n=7), 60 mg QD (n=3), or 60 mg BIW (n=3).
Dose-limiting toxicities (DLTs) of grade 3 diarrhea and grade 4 hyperglycemia were reported in 1 patient at the 60 mg QD dose. The most frequent grade 3 or 4 adverse events reported in 2 or more patients included thrombocytopenia, diarrhea, and neutropenia. Tolerability limited the ability to further dose escalate using the QD schedule.
No DLTs or dose interruptions were reported for patients enrolled on the BIW schedule. So dose escalation is ongoing with the BIW schedule as well as a separate, thrice-weekly treatment schedule.
Of the 13 patients treated, 11 were evaluable for response. One patient with mixed follicular lymphoma/DLBCL achieved a partial response, with a 70% reduction in a single target lesion observed at the 30 mg QD dose level.
Seven other patients met criteria for stable disease, including 4 with stable disease lasting at least 4 cycles of treatment.
Following the ASH presentation, Curis reported additional data from a subset of patients that suggest CUDC-907 has antitumor activity in patients with DLBCL.
For the November 10, 2014, data cutoff period, 8 patients with DLBCL were evaluable. One of these patients had a complete response, 2 had a partial response (tumor shrinkage greater than 50%), and 4 had tumor shrinkage ranging from 5% to 46%.
The dose-escalation stage of the trial is nearing completion, and Curis expects to present full data this year. Curis has also initiated an expansion cohort to further evaluate CUDC-907 in patients with DLBCL or multiple myeloma at the recommended phase 2 dose.
Test predicts DLBCL relapse better than CT, team says
Photo by Larry Young
Surveillance of circulating tumor DNA (ctDNA) can help predict relapse in most patients with diffuse large B-cell lymphoma before there is clinical evidence of the disease, according to a study published in The Lancet Oncology.
Investigators analyzed ctDNA using the clonoSEQ minimal residual disease (MRD) test and found they could predict relapse with a positive predictive value (PPV) of 88% and a negative predictive value (NPV) of 98%.
The test detected relapse a median of 3.5 months quicker than computed tomography (CT) scans.
“Patients with DLBCL with low amounts of disease at relapse have better survival than those with more disease, which is the rationale for surveillance CT scans,” said study author Wyndham Wilson, MD, PhD, of the National Cancer Institute in Bethesda, Maryland.
“Because the ctDNA test detects disease at a molecular level, it detects microscopic disease, which cannot be detected by CT scans, and may improve patient survival. Furthermore, ctDNA is non-invasive and can be employed as frequently needed, unlike surveillance CT scans, which expose patients to radiation and intravenous contrast.”
For this study, Dr Wilson and his colleagues evaluated 126 DLBCL patients who had participated in clinical trials from May 1993 to June 2013 and were followed for a median of 11 years post-treatment.
Surveillance monitoring
To investigate whether ctDNA monitoring could overcome the limitations of standard imaging techniques, the researchers compared serial ctDNA samples to CT scans taken at the same time post-treatment in patients who had achieved complete remission. This was known as “surveillance monitoring.”
The investigators performed surveillance monitoring of ctDNA in 107 patients who achieved complete remission.
The hazard ratio for clinical disease progression was 228 for patients who had detectable ctDNA during surveillance, when compared to patients with undetectable ctDNA (P<0.0001).
Surveillance ctDNA had a PPV of 88.2% and an NPV of 97.8%. And it revealed the risk of recurrence at a median of 3.5 months (range, 0-200 months) before there was evidence of clinical disease.
Interim monitoring
The researchers also analyzed whether the presence of ctDNA at the beginning of the third cycle of treatment predicted relapse, regardless of whether patients achieved complete remission by the end of treatment. This was known as “interim monitoring.”
Of the 108 patients included in the interim monitoring analysis, ctDNA was detected in 24 patients, 15 of whom eventually relapsed. Only 17 of the 84 patients with undetectable interim ctDNA relapsed.
Five years after the interim serum samples were taken, 80.2% of the patients who were negative for ctDNA were relapse-free, as were 41.7% of patients who were positive for ctDNA (P<0.0001).
Detectable interim ctDNA had a PPV of 62.5% and an NPV of 79.8%.
Fourteen of the 15 patients with detectable ctDNA who relapsed did so within 6 months of the end of treatment, as did 7 of the 17 patients without interim ctDNA.
Based on these results, the investigators concluded that surveillance monitoring of ctDNA identifies DLBCL patients at risk of disease recurrence before clinical evidence of disease in most patients, and interim monitoring of ctDNA is a promising biomarker to identify patients at high risk of treatment failure.
This research was funded by Adaptive Biotechnologies, the company developing the clonoSEQ MRD test, as well as the National Cancer Institute.
Photo by Larry Young
Surveillance of circulating tumor DNA (ctDNA) can help predict relapse in most patients with diffuse large B-cell lymphoma before there is clinical evidence of the disease, according to a study published in The Lancet Oncology.
Investigators analyzed ctDNA using the clonoSEQ minimal residual disease (MRD) test and found they could predict relapse with a positive predictive value (PPV) of 88% and a negative predictive value (NPV) of 98%.
The test detected relapse a median of 3.5 months quicker than computed tomography (CT) scans.
“Patients with DLBCL with low amounts of disease at relapse have better survival than those with more disease, which is the rationale for surveillance CT scans,” said study author Wyndham Wilson, MD, PhD, of the National Cancer Institute in Bethesda, Maryland.
“Because the ctDNA test detects disease at a molecular level, it detects microscopic disease, which cannot be detected by CT scans, and may improve patient survival. Furthermore, ctDNA is non-invasive and can be employed as frequently needed, unlike surveillance CT scans, which expose patients to radiation and intravenous contrast.”
For this study, Dr Wilson and his colleagues evaluated 126 DLBCL patients who had participated in clinical trials from May 1993 to June 2013 and were followed for a median of 11 years post-treatment.
Surveillance monitoring
To investigate whether ctDNA monitoring could overcome the limitations of standard imaging techniques, the researchers compared serial ctDNA samples to CT scans taken at the same time post-treatment in patients who had achieved complete remission. This was known as “surveillance monitoring.”
The investigators performed surveillance monitoring of ctDNA in 107 patients who achieved complete remission.
The hazard ratio for clinical disease progression was 228 for patients who had detectable ctDNA during surveillance, when compared to patients with undetectable ctDNA (P<0.0001).
Surveillance ctDNA had a PPV of 88.2% and an NPV of 97.8%. And it revealed the risk of recurrence at a median of 3.5 months (range, 0-200 months) before there was evidence of clinical disease.
Interim monitoring
The researchers also analyzed whether the presence of ctDNA at the beginning of the third cycle of treatment predicted relapse, regardless of whether patients achieved complete remission by the end of treatment. This was known as “interim monitoring.”
Of the 108 patients included in the interim monitoring analysis, ctDNA was detected in 24 patients, 15 of whom eventually relapsed. Only 17 of the 84 patients with undetectable interim ctDNA relapsed.
Five years after the interim serum samples were taken, 80.2% of the patients who were negative for ctDNA were relapse-free, as were 41.7% of patients who were positive for ctDNA (P<0.0001).
Detectable interim ctDNA had a PPV of 62.5% and an NPV of 79.8%.
Fourteen of the 15 patients with detectable ctDNA who relapsed did so within 6 months of the end of treatment, as did 7 of the 17 patients without interim ctDNA.
Based on these results, the investigators concluded that surveillance monitoring of ctDNA identifies DLBCL patients at risk of disease recurrence before clinical evidence of disease in most patients, and interim monitoring of ctDNA is a promising biomarker to identify patients at high risk of treatment failure.
This research was funded by Adaptive Biotechnologies, the company developing the clonoSEQ MRD test, as well as the National Cancer Institute.
Photo by Larry Young
Surveillance of circulating tumor DNA (ctDNA) can help predict relapse in most patients with diffuse large B-cell lymphoma before there is clinical evidence of the disease, according to a study published in The Lancet Oncology.
Investigators analyzed ctDNA using the clonoSEQ minimal residual disease (MRD) test and found they could predict relapse with a positive predictive value (PPV) of 88% and a negative predictive value (NPV) of 98%.
The test detected relapse a median of 3.5 months quicker than computed tomography (CT) scans.
“Patients with DLBCL with low amounts of disease at relapse have better survival than those with more disease, which is the rationale for surveillance CT scans,” said study author Wyndham Wilson, MD, PhD, of the National Cancer Institute in Bethesda, Maryland.
“Because the ctDNA test detects disease at a molecular level, it detects microscopic disease, which cannot be detected by CT scans, and may improve patient survival. Furthermore, ctDNA is non-invasive and can be employed as frequently needed, unlike surveillance CT scans, which expose patients to radiation and intravenous contrast.”
For this study, Dr Wilson and his colleagues evaluated 126 DLBCL patients who had participated in clinical trials from May 1993 to June 2013 and were followed for a median of 11 years post-treatment.
Surveillance monitoring
To investigate whether ctDNA monitoring could overcome the limitations of standard imaging techniques, the researchers compared serial ctDNA samples to CT scans taken at the same time post-treatment in patients who had achieved complete remission. This was known as “surveillance monitoring.”
The investigators performed surveillance monitoring of ctDNA in 107 patients who achieved complete remission.
The hazard ratio for clinical disease progression was 228 for patients who had detectable ctDNA during surveillance, when compared to patients with undetectable ctDNA (P<0.0001).
Surveillance ctDNA had a PPV of 88.2% and an NPV of 97.8%. And it revealed the risk of recurrence at a median of 3.5 months (range, 0-200 months) before there was evidence of clinical disease.
Interim monitoring
The researchers also analyzed whether the presence of ctDNA at the beginning of the third cycle of treatment predicted relapse, regardless of whether patients achieved complete remission by the end of treatment. This was known as “interim monitoring.”
Of the 108 patients included in the interim monitoring analysis, ctDNA was detected in 24 patients, 15 of whom eventually relapsed. Only 17 of the 84 patients with undetectable interim ctDNA relapsed.
Five years after the interim serum samples were taken, 80.2% of the patients who were negative for ctDNA were relapse-free, as were 41.7% of patients who were positive for ctDNA (P<0.0001).
Detectable interim ctDNA had a PPV of 62.5% and an NPV of 79.8%.
Fourteen of the 15 patients with detectable ctDNA who relapsed did so within 6 months of the end of treatment, as did 7 of the 17 patients without interim ctDNA.
Based on these results, the investigators concluded that surveillance monitoring of ctDNA identifies DLBCL patients at risk of disease recurrence before clinical evidence of disease in most patients, and interim monitoring of ctDNA is a promising biomarker to identify patients at high risk of treatment failure.
This research was funded by Adaptive Biotechnologies, the company developing the clonoSEQ MRD test, as well as the National Cancer Institute.
FDA grants drug orphan designation for DLBCL
The US Food and Drug Administration (FDA) has granted orphan drug designation for IMO-8400, an antagonist of the endosomal toll-like receptors (TLRs) 7, 8, and 9, for the treatment of diffuse large B-cell lymphoma (DLBCL).
The FDA grants orphan designation to drugs intended to treat conditions that affect fewer than 200,000 people in the US.
The designation will provide Idera Pharmaceuticals, the company developing IMO-8400, with certain incentives. These include eligibility for federal grants, research and development tax credits, and a 7-year period of marketing exclusivity if the product is approved.
Relevant research
Preclinical research published in Leukemia showed that the MYD88 L265P oncogenic mutation is an independent prognostic factor in DLBCL. In DLBCL patients with this mutation, TLR signaling is over-activated, which enables tumor cell survival and proliferation.
Data presented at the 2014 AACR Annual Meeting showed that IMO-8400 inhibited the survival and proliferation of DLBCL cells and Waldenstrom’s macroglobulinemia (WM) cells harboring the MYD88 L265P mutation.
A phase 1 trial of IMO-8400 presented at the 2013 FOCIS Annual Meeting showed the drug was active and well-tolerated in 42 healthy subjects. IMO-8400 was given at single and multiple escalating doses up to 0.6 mg/kg for 4 weeks. The drug inhibited immune responses mediated by TLRs 7, 8, and 9.
Idera Pharmaceuticals is currently conducting a phase 1/2 trial of IMO-8400 in patients with relapsed or refractory DLBCL who harbor the MYD88 L265P mutation. The protocol includes 3 dose-escalation cohorts in which IMO-8400 is administered subcutaneously.
Idera is also pursuing clinical development of IMO-8400 in WM. The FDA recently granted the drug orphan designation to treat WM.
The US Food and Drug Administration (FDA) has granted orphan drug designation for IMO-8400, an antagonist of the endosomal toll-like receptors (TLRs) 7, 8, and 9, for the treatment of diffuse large B-cell lymphoma (DLBCL).
The FDA grants orphan designation to drugs intended to treat conditions that affect fewer than 200,000 people in the US.
The designation will provide Idera Pharmaceuticals, the company developing IMO-8400, with certain incentives. These include eligibility for federal grants, research and development tax credits, and a 7-year period of marketing exclusivity if the product is approved.
Relevant research
Preclinical research published in Leukemia showed that the MYD88 L265P oncogenic mutation is an independent prognostic factor in DLBCL. In DLBCL patients with this mutation, TLR signaling is over-activated, which enables tumor cell survival and proliferation.
Data presented at the 2014 AACR Annual Meeting showed that IMO-8400 inhibited the survival and proliferation of DLBCL cells and Waldenstrom’s macroglobulinemia (WM) cells harboring the MYD88 L265P mutation.
A phase 1 trial of IMO-8400 presented at the 2013 FOCIS Annual Meeting showed the drug was active and well-tolerated in 42 healthy subjects. IMO-8400 was given at single and multiple escalating doses up to 0.6 mg/kg for 4 weeks. The drug inhibited immune responses mediated by TLRs 7, 8, and 9.
Idera Pharmaceuticals is currently conducting a phase 1/2 trial of IMO-8400 in patients with relapsed or refractory DLBCL who harbor the MYD88 L265P mutation. The protocol includes 3 dose-escalation cohorts in which IMO-8400 is administered subcutaneously.
Idera is also pursuing clinical development of IMO-8400 in WM. The FDA recently granted the drug orphan designation to treat WM.
The US Food and Drug Administration (FDA) has granted orphan drug designation for IMO-8400, an antagonist of the endosomal toll-like receptors (TLRs) 7, 8, and 9, for the treatment of diffuse large B-cell lymphoma (DLBCL).
The FDA grants orphan designation to drugs intended to treat conditions that affect fewer than 200,000 people in the US.
The designation will provide Idera Pharmaceuticals, the company developing IMO-8400, with certain incentives. These include eligibility for federal grants, research and development tax credits, and a 7-year period of marketing exclusivity if the product is approved.
Relevant research
Preclinical research published in Leukemia showed that the MYD88 L265P oncogenic mutation is an independent prognostic factor in DLBCL. In DLBCL patients with this mutation, TLR signaling is over-activated, which enables tumor cell survival and proliferation.
Data presented at the 2014 AACR Annual Meeting showed that IMO-8400 inhibited the survival and proliferation of DLBCL cells and Waldenstrom’s macroglobulinemia (WM) cells harboring the MYD88 L265P mutation.
A phase 1 trial of IMO-8400 presented at the 2013 FOCIS Annual Meeting showed the drug was active and well-tolerated in 42 healthy subjects. IMO-8400 was given at single and multiple escalating doses up to 0.6 mg/kg for 4 weeks. The drug inhibited immune responses mediated by TLRs 7, 8, and 9.
Idera Pharmaceuticals is currently conducting a phase 1/2 trial of IMO-8400 in patients with relapsed or refractory DLBCL who harbor the MYD88 L265P mutation. The protocol includes 3 dose-escalation cohorts in which IMO-8400 is administered subcutaneously.
Idera is also pursuing clinical development of IMO-8400 in WM. The FDA recently granted the drug orphan designation to treat WM.
Vitamin D levels linked to outcomes in FL
Vitamin D deficiency may negatively impact outcomes in patients with follicular lymphoma (FL), according to research published in the Journal of Clinical Oncology.
The study showed that FL patients with vitamin D deficiency had inferior progression-free survival (PFS) and overall survival (OS) compared to patients with higher vitamin D levels.
According to researchers, this suggests serum vitamin D might be the first potentially modifiable factor to be associated with survival in FL.
However, additional research is needed to determine the effects of vitamin D supplementation in these patients.
Jonathan W. Friedberg, MD, of the Wilmot Cancer Institute at the University of Rochester in New York, and his colleagues conducted this research, analyzing data from 2 cohorts of FL patients.
One cohort consisted of patients derived from 3 SWOG trials (S9800, S9911, and S0016), and the other consisted of patients from a Lymphoma Study Association (LYSA) trial known as PRIMA.
SWOG patients had received CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab), and LYSA patients had received rituximab plus chemotherapy (and were randomized to rituximab maintenance or observation).
SWOG cohort
After a median follow-up of 5.4 years, patients with vitamin D deficiency (defined as <20 ng/mL) had significantly inferior PFS (hazard ratio [HR]=2.00; P=0.011) and OS (HR=3.57; P=0.003) compared to patients with higher vitamin D levels.
Results were similar when the researchers adjusted for other variables, such as prognostic index (IPI), body mass index, and latitude (≥ vs <35°N). For PFS, the adjusted HR was 1.97 (P=0.023). And for OS, the adjusted HR was 4.16 (P=0.002).
Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but neither result was significant.
LYSA cohort
After a median follow-up of 6.6 years, patients with vitamin D deficiency (defined as <10 ng/mL) had significantly inferior PFS (HR=1.66; P=0.013) but not OS (HR=1.84; P=0.14) compared to patients with higher vitamin D levels.
Results were similar when the researchers adjusted for other variables, such as prognostic index (FLIPI), body mass index, latitude (Europe vs Australia), and hemoglobin. For PFS, the adjusted HR was 1.50 (P=0.095). For OS, the adjusted HR was 1.92 (P=0.192).
Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but only the association with OS reached statistical significance (HR=5.32; P=0.037).
Dr Friedberg said that, taken together, these results suggest vitamin D levels may be a modifiable factor associated with prognosis in patients with FL.
“Our data, replicated internationally, supports other published observations linking vitamin D deficiency with inferior cancer outcomes,” he said. “However, the mechanisms of this link are likely complex and require further study.”
Vitamin D deficiency may negatively impact outcomes in patients with follicular lymphoma (FL), according to research published in the Journal of Clinical Oncology.
The study showed that FL patients with vitamin D deficiency had inferior progression-free survival (PFS) and overall survival (OS) compared to patients with higher vitamin D levels.
According to researchers, this suggests serum vitamin D might be the first potentially modifiable factor to be associated with survival in FL.
However, additional research is needed to determine the effects of vitamin D supplementation in these patients.
Jonathan W. Friedberg, MD, of the Wilmot Cancer Institute at the University of Rochester in New York, and his colleagues conducted this research, analyzing data from 2 cohorts of FL patients.
One cohort consisted of patients derived from 3 SWOG trials (S9800, S9911, and S0016), and the other consisted of patients from a Lymphoma Study Association (LYSA) trial known as PRIMA.
SWOG patients had received CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab), and LYSA patients had received rituximab plus chemotherapy (and were randomized to rituximab maintenance or observation).
SWOG cohort
After a median follow-up of 5.4 years, patients with vitamin D deficiency (defined as <20 ng/mL) had significantly inferior PFS (hazard ratio [HR]=2.00; P=0.011) and OS (HR=3.57; P=0.003) compared to patients with higher vitamin D levels.
Results were similar when the researchers adjusted for other variables, such as prognostic index (IPI), body mass index, and latitude (≥ vs <35°N). For PFS, the adjusted HR was 1.97 (P=0.023). And for OS, the adjusted HR was 4.16 (P=0.002).
Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but neither result was significant.
LYSA cohort
After a median follow-up of 6.6 years, patients with vitamin D deficiency (defined as <10 ng/mL) had significantly inferior PFS (HR=1.66; P=0.013) but not OS (HR=1.84; P=0.14) compared to patients with higher vitamin D levels.
Results were similar when the researchers adjusted for other variables, such as prognostic index (FLIPI), body mass index, latitude (Europe vs Australia), and hemoglobin. For PFS, the adjusted HR was 1.50 (P=0.095). For OS, the adjusted HR was 1.92 (P=0.192).
Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but only the association with OS reached statistical significance (HR=5.32; P=0.037).
Dr Friedberg said that, taken together, these results suggest vitamin D levels may be a modifiable factor associated with prognosis in patients with FL.
“Our data, replicated internationally, supports other published observations linking vitamin D deficiency with inferior cancer outcomes,” he said. “However, the mechanisms of this link are likely complex and require further study.”
Vitamin D deficiency may negatively impact outcomes in patients with follicular lymphoma (FL), according to research published in the Journal of Clinical Oncology.
The study showed that FL patients with vitamin D deficiency had inferior progression-free survival (PFS) and overall survival (OS) compared to patients with higher vitamin D levels.
According to researchers, this suggests serum vitamin D might be the first potentially modifiable factor to be associated with survival in FL.
However, additional research is needed to determine the effects of vitamin D supplementation in these patients.
Jonathan W. Friedberg, MD, of the Wilmot Cancer Institute at the University of Rochester in New York, and his colleagues conducted this research, analyzing data from 2 cohorts of FL patients.
One cohort consisted of patients derived from 3 SWOG trials (S9800, S9911, and S0016), and the other consisted of patients from a Lymphoma Study Association (LYSA) trial known as PRIMA.
SWOG patients had received CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab), and LYSA patients had received rituximab plus chemotherapy (and were randomized to rituximab maintenance or observation).
SWOG cohort
After a median follow-up of 5.4 years, patients with vitamin D deficiency (defined as <20 ng/mL) had significantly inferior PFS (hazard ratio [HR]=2.00; P=0.011) and OS (HR=3.57; P=0.003) compared to patients with higher vitamin D levels.
Results were similar when the researchers adjusted for other variables, such as prognostic index (IPI), body mass index, and latitude (≥ vs <35°N). For PFS, the adjusted HR was 1.97 (P=0.023). And for OS, the adjusted HR was 4.16 (P=0.002).
Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but neither result was significant.
LYSA cohort
After a median follow-up of 6.6 years, patients with vitamin D deficiency (defined as <10 ng/mL) had significantly inferior PFS (HR=1.66; P=0.013) but not OS (HR=1.84; P=0.14) compared to patients with higher vitamin D levels.
Results were similar when the researchers adjusted for other variables, such as prognostic index (FLIPI), body mass index, latitude (Europe vs Australia), and hemoglobin. For PFS, the adjusted HR was 1.50 (P=0.095). For OS, the adjusted HR was 1.92 (P=0.192).
Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but only the association with OS reached statistical significance (HR=5.32; P=0.037).
Dr Friedberg said that, taken together, these results suggest vitamin D levels may be a modifiable factor associated with prognosis in patients with FL.
“Our data, replicated internationally, supports other published observations linking vitamin D deficiency with inferior cancer outcomes,” he said. “However, the mechanisms of this link are likely complex and require further study.”