Hodgkin Lymphoma

Micrograph showing HL

LONDON—Results of a small, phase 1 trial suggest CD30-directed chimeric antigen receptor (CAR) T-cell therapy is feasible in patients with aggressive Hodgkin lymphoma (HL).

The trial included 7 patients with relapsed or refractory HL.

Five of the patients achieved stable disease or better after infusions of CAR T cells, and the researchers said treatment-related adverse events were manageable.

William (Wei) Cao, PhD, of Cellular Biomedicine Group, presented these results at the 10th Annual World Stem Cells & Regenerative Medicine Congress.

The research was funded by Cellular Biomedicine Group, the company developing the CAR T-cell therapy (known as CBM-C30.1), as well as by grants from the National Natural Science Foundation of China and the National Basic Science and Development Program of China.

The trial included 7 patients with progressive HL. Two patients had stage III disease, and 5 had stage IV. The patients had a median of 16 prior treatments (range, 8-24) and limited prognosis (several months to less than 2-year survival) with currently available therapies.

The patients received escalating doses of autologous T cells transduced with a CD30-directed CAR moiety for 3 to 5 days, following a conditioning regimen. The researchers measured the level of CAR transgenes in peripheral blood and biopsied tumor tissues by quantitative PCR.

Two patients achieved a partial response to CAR T-cell therapy, and 3 attained stable disease. So the therapy resulted in an overall disease control rate of 71.4% (5/7) and an objective response rate of 28.6% (2/7).

Stable disease lasted 2 months in 2 of the patients and more than 3.5 months in the third patient. Partial response lasted more than 2 months in 1 patient and more than 3.5 months in the other.

Dr Cao said adverse events consisted largely of fever and were manageable with medical intervention. One patient experienced 5-day self-limiting arthralgia, myalgia, and dual knee swelling 2 weeks after cell infusion. There were no delayed or severe adverse events.

“We are very encouraged by the efficacy and toxicity profile of our CAR-T CD30 technology,” Dr Cao said, “given that the [patients] were diagnosed with stage III and IV Hodgkin’s lymphoma.”

Micrograph showing HL

LONDON—Results of a small, phase 1 trial suggest CD30-directed chimeric antigen receptor (CAR) T-cell therapy is feasible in patients with aggressive Hodgkin lymphoma (HL).

The trial included 7 patients with relapsed or refractory HL.

Five of the patients achieved stable disease or better after infusions of CAR T cells, and the researchers said treatment-related adverse events were manageable.

William (Wei) Cao, PhD, of Cellular Biomedicine Group, presented these results at the 10th Annual World Stem Cells & Regenerative Medicine Congress.

The research was funded by Cellular Biomedicine Group, the company developing the CAR T-cell therapy (known as CBM-C30.1), as well as by grants from the National Natural Science Foundation of China and the National Basic Science and Development Program of China.

The trial included 7 patients with progressive HL. Two patients had stage III disease, and 5 had stage IV. The patients had a median of 16 prior treatments (range, 8-24) and limited prognosis (several months to less than 2-year survival) with currently available therapies.

The patients received escalating doses of autologous T cells transduced with a CD30-directed CAR moiety for 3 to 5 days, following a conditioning regimen. The researchers measured the level of CAR transgenes in peripheral blood and biopsied tumor tissues by quantitative PCR.

Two patients achieved a partial response to CAR T-cell therapy, and 3 attained stable disease. So the therapy resulted in an overall disease control rate of 71.4% (5/7) and an objective response rate of 28.6% (2/7).

Stable disease lasted 2 months in 2 of the patients and more than 3.5 months in the third patient. Partial response lasted more than 2 months in 1 patient and more than 3.5 months in the other.

Dr Cao said adverse events consisted largely of fever and were manageable with medical intervention. One patient experienced 5-day self-limiting arthralgia, myalgia, and dual knee swelling 2 weeks after cell infusion. There were no delayed or severe adverse events.

“We are very encouraged by the efficacy and toxicity profile of our CAR-T CD30 technology,” Dr Cao said, “given that the [patients] were diagnosed with stage III and IV Hodgkin’s lymphoma.”

Micrograph showing HL

LONDON—Results of a small, phase 1 trial suggest CD30-directed chimeric antigen receptor (CAR) T-cell therapy is feasible in patients with aggressive Hodgkin lymphoma (HL).

The trial included 7 patients with relapsed or refractory HL.

Five of the patients achieved stable disease or better after infusions of CAR T cells, and the researchers said treatment-related adverse events were manageable.

William (Wei) Cao, PhD, of Cellular Biomedicine Group, presented these results at the 10th Annual World Stem Cells & Regenerative Medicine Congress.

The research was funded by Cellular Biomedicine Group, the company developing the CAR T-cell therapy (known as CBM-C30.1), as well as by grants from the National Natural Science Foundation of China and the National Basic Science and Development Program of China.

The trial included 7 patients with progressive HL. Two patients had stage III disease, and 5 had stage IV. The patients had a median of 16 prior treatments (range, 8-24) and limited prognosis (several months to less than 2-year survival) with currently available therapies.

The patients received escalating doses of autologous T cells transduced with a CD30-directed CAR moiety for 3 to 5 days, following a conditioning regimen. The researchers measured the level of CAR transgenes in peripheral blood and biopsied tumor tissues by quantitative PCR.

Two patients achieved a partial response to CAR T-cell therapy, and 3 attained stable disease. So the therapy resulted in an overall disease control rate of 71.4% (5/7) and an objective response rate of 28.6% (2/7).

Stable disease lasted 2 months in 2 of the patients and more than 3.5 months in the third patient. Partial response lasted more than 2 months in 1 patient and more than 3.5 months in the other.

Dr Cao said adverse events consisted largely of fever and were manageable with medical intervention. One patient experienced 5-day self-limiting arthralgia, myalgia, and dual knee swelling 2 weeks after cell infusion. There were no delayed or severe adverse events.

“We are very encouraged by the efficacy and toxicity profile of our CAR-T CD30 technology,” Dr Cao said, “given that the [patients] were diagnosed with stage III and IV Hodgkin’s lymphoma.”

Doctor examines patient

Results from two new studies indicate that lymphadenopathy and head and neck masses are associated with a higher risk of lymphoma than we thought.

These two factors proved to be the strongest predictors of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

So unless these symptoms can be explained, general practitioners should refer affected patients to specialists as quickly as possible, study investigators said.

Both studies were published in the British Journal of General Practice.

“Cancer guidelines are based on the most robust evidence, and, up to now, this has been missing,” said Willie Hamilton, MD, of the University of Exeter Medical School in the UK.

“Our research has revealed the importance of persistent, swollen lymph glands, particularly in the neck, as part of cancer. Of course, swollen glands are common with throat infections, but in cancer, they are usually larger and painless. It’s been known for a long time that this could represent cancer. This study shows that the risk is higher than previously thought.”

The first study was a large-scale assessment of symptoms that are markers of NHL. Researchers assessed 4362 NHL patients (≥ 40 years of age) and 19,468 controls.

The 5 symptoms associated with the highest risk of developing NHL were lymphadenopathy (odds ratio [OR]=263), head and neck mass not described as lymphadenopathy (OR=49), other mass (OR=12), weight loss (OR=3.2), and abdominal pain (OR=2.5).

In the second study, investigators assessed 283 HL patients (≥ 40 years of age) and 1237 control subjects.

The team found that 6 features were independently associated with HL—lymphadenopathy (OR=280), head and neck mass not described as lymphadenopathy (OR=260), other mass (OR=12), thrombocytosis (OR=6.0), raised inflammatory markers (OR=5.2), and low full blood count (OR=2.8).

Combining the results of both studies, the investigators found that, for subjects older than 60 years of age, lymphadenopathy had a positive-predictive value of 18.6% for either NHL or HL. The positive-predictive value was 4.6% for head and neck mass and 1.1% for a mass elsewhere.

Therefore, the team said patients in this age group who present with lymphadenopathy or a head and neck mass should be referred to a specialist, unless there is a clear alternative explanation.

Referral is particularly urgent if either symptom has been present for 6 weeks or more, according to the investigators. They said that no blood test or other symptoms change that.

“Early diagnosis is vital to reducing cancer deaths,” said Liz Shephard, PhD, of the University of Exeter Medical School. “We now hope that this research will feed into guidelines to help GPs refer earlier and potentially to save lives.”

Doctor examines patient

Results from two new studies indicate that lymphadenopathy and head and neck masses are associated with a higher risk of lymphoma than we thought.

These two factors proved to be the strongest predictors of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

So unless these symptoms can be explained, general practitioners should refer affected patients to specialists as quickly as possible, study investigators said.

Both studies were published in the British Journal of General Practice.

“Cancer guidelines are based on the most robust evidence, and, up to now, this has been missing,” said Willie Hamilton, MD, of the University of Exeter Medical School in the UK.

“Our research has revealed the importance of persistent, swollen lymph glands, particularly in the neck, as part of cancer. Of course, swollen glands are common with throat infections, but in cancer, they are usually larger and painless. It’s been known for a long time that this could represent cancer. This study shows that the risk is higher than previously thought.”

The first study was a large-scale assessment of symptoms that are markers of NHL. Researchers assessed 4362 NHL patients (≥ 40 years of age) and 19,468 controls.

The 5 symptoms associated with the highest risk of developing NHL were lymphadenopathy (odds ratio [OR]=263), head and neck mass not described as lymphadenopathy (OR=49), other mass (OR=12), weight loss (OR=3.2), and abdominal pain (OR=2.5).

In the second study, investigators assessed 283 HL patients (≥ 40 years of age) and 1237 control subjects.

The team found that 6 features were independently associated with HL—lymphadenopathy (OR=280), head and neck mass not described as lymphadenopathy (OR=260), other mass (OR=12), thrombocytosis (OR=6.0), raised inflammatory markers (OR=5.2), and low full blood count (OR=2.8).

Combining the results of both studies, the investigators found that, for subjects older than 60 years of age, lymphadenopathy had a positive-predictive value of 18.6% for either NHL or HL. The positive-predictive value was 4.6% for head and neck mass and 1.1% for a mass elsewhere.

Therefore, the team said patients in this age group who present with lymphadenopathy or a head and neck mass should be referred to a specialist, unless there is a clear alternative explanation.

Referral is particularly urgent if either symptom has been present for 6 weeks or more, according to the investigators. They said that no blood test or other symptoms change that.

“Early diagnosis is vital to reducing cancer deaths,” said Liz Shephard, PhD, of the University of Exeter Medical School. “We now hope that this research will feed into guidelines to help GPs refer earlier and potentially to save lives.”

Doctor examines patient

Results from two new studies indicate that lymphadenopathy and head and neck masses are associated with a higher risk of lymphoma than we thought.

These two factors proved to be the strongest predictors of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

So unless these symptoms can be explained, general practitioners should refer affected patients to specialists as quickly as possible, study investigators said.

Both studies were published in the British Journal of General Practice.

“Cancer guidelines are based on the most robust evidence, and, up to now, this has been missing,” said Willie Hamilton, MD, of the University of Exeter Medical School in the UK.

“Our research has revealed the importance of persistent, swollen lymph glands, particularly in the neck, as part of cancer. Of course, swollen glands are common with throat infections, but in cancer, they are usually larger and painless. It’s been known for a long time that this could represent cancer. This study shows that the risk is higher than previously thought.”

The first study was a large-scale assessment of symptoms that are markers of NHL. Researchers assessed 4362 NHL patients (≥ 40 years of age) and 19,468 controls.

The 5 symptoms associated with the highest risk of developing NHL were lymphadenopathy (odds ratio [OR]=263), head and neck mass not described as lymphadenopathy (OR=49), other mass (OR=12), weight loss (OR=3.2), and abdominal pain (OR=2.5).

In the second study, investigators assessed 283 HL patients (≥ 40 years of age) and 1237 control subjects.

The team found that 6 features were independently associated with HL—lymphadenopathy (OR=280), head and neck mass not described as lymphadenopathy (OR=260), other mass (OR=12), thrombocytosis (OR=6.0), raised inflammatory markers (OR=5.2), and low full blood count (OR=2.8).

Combining the results of both studies, the investigators found that, for subjects older than 60 years of age, lymphadenopathy had a positive-predictive value of 18.6% for either NHL or HL. The positive-predictive value was 4.6% for head and neck mass and 1.1% for a mass elsewhere.

Therefore, the team said patients in this age group who present with lymphadenopathy or a head and neck mass should be referred to a specialist, unless there is a clear alternative explanation.

Referral is particularly urgent if either symptom has been present for 6 weeks or more, according to the investigators. They said that no blood test or other symptoms change that.

“Early diagnosis is vital to reducing cancer deaths,” said Liz Shephard, PhD, of the University of Exeter Medical School. “We now hope that this research will feed into guidelines to help GPs refer earlier and potentially to save lives.”

 

 

AACR Annual Meeting 2015

 

PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.

Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.

The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.

The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.

Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).

The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).

Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.

“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”

Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).

This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).

Hematologic malignancies

WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.

Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.

“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”

The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).

“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”

She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.

In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.

Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).

Solid tumors

WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.

The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).

“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.

She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.

“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”

Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.

Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.

 

 

AACR Annual Meeting 2015

 

PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.

Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.

The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.

The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.

Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).

The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).

Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.

“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”

Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).

This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).

Hematologic malignancies

WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.

Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.

“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”

The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).

“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”

She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.

In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.

Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).

Solid tumors

WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.

The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).

“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.

She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.

“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”

Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.

Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.

 

 

AACR Annual Meeting 2015

 

PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.

Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.

The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.

The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.

Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).

The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).

Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.

“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”

Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).

This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).

Hematologic malignancies

WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.

Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.

“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”

The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).

“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”

She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.

In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.

Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).

Solid tumors

WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.

The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).

“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.

She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.

“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”

Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.

Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.

Patient receives chemotherapy

Photo by Rhoda Baer

Survivors of Hodgkin lymphoma (HL) have an increased risk of developing cardiovascular diseases throughout their lives, according to a study published in JAMA Internal Medicine.

Previous research suggested that HL treatment is associated with an increased risk of cardiovascular diseases.

However, those studies did not determine how long the increased risk persists or pinpoint the risk factors for various cardiovascular diseases.

So Flora E. van Leeuwen, PhD, of the Netherlands Cancer Institute in Amsterdam, and her colleagues decided to investigate.

The team examined the risk for cardiovascular disease in HL survivors up to 40 years after they received treatment and compared that with the risk for cardiovascular disease in the general population. The researchers also studied treatment-related risk factors.

The study included 2524 Dutch patients who were diagnosed with HL when they were younger than 51 years of age. The patients’ median age was 27.3 years.

The patients were treated from 1965 through 1995 and had survived for at least 5 years after diagnosis. In all, 2052 patients (81.3%) had received mediastinal radiotherapy, and 773 (30.6%) had received chemotherapy containing an anthracycline.

At a median of 20.3 years of follow-up, there were 1713 cardiovascular events in 797 patients (31.6%), and 410 of those patients (51.4%) had experienced 2 events or more.

The most frequently occurring cardiovascular disease was coronary heart disease (CHD), with 401 patients developing it as their first event. This was followed by valvular heart disease (VHD, 374 events) and heart failure (HF, 140 events).

HL survivors had a 3.2-fold increased risk of developing CHD and a 6.8-fold increased risk of developing HF compared to the general population.

HL survivors who had been treated before age 25 had a 4.6-fold to 7.5-fold increased risk of CHD and a 10.9-fold to 40.5-fold increased risk of HF, depending on the age they ultimately attained.

HL survivors treated at 35 to 50 years of age had a 2.0-fold to 2.3-fold increased risk of CHD and a 3.1-fold to 5.2-fold increased risk of HF, depending on their attained age.

The risks of CHD and HF remained significantly increased beyond 35 years after HL treatment. The standardized incidence ratios were 3.9 and 5.8, respectively.

The median times between HL treatment and first cardiovascular disease events were 18 years for CHD, 24 years for VHD, and 19 years for HF.

The cumulative risk of any type of cardiovascular disease was 50% at 40 years after HL diagnosis. For patients who were treated for HL before they were 25, the cumulative risk of developing a cardiovascular disease at 60 years of age or older was 20% for CHD, 31% for VHD, and 11% for HF.

The study also suggested that mediastinal radiotherapy increased the risk of CHD, VHD, and HF. But anthracycline-containing chemotherapy only increased the risk of VHD and HF.

Dr van Leeuwen and her colleagues concluded that both physicians and patients should be aware that HL survivors have a persistently increased risk of developing cardiovascular diseases throughout their lives. The team also believes the results of their study may direct guidelines for follow-up in HL survivors.

A commentary related to this research is available in JAMA Internal Medicine as well.

Patient receives chemotherapy

Photo by Rhoda Baer

Survivors of Hodgkin lymphoma (HL) have an increased risk of developing cardiovascular diseases throughout their lives, according to a study published in JAMA Internal Medicine.

Previous research suggested that HL treatment is associated with an increased risk of cardiovascular diseases.

However, those studies did not determine how long the increased risk persists or pinpoint the risk factors for various cardiovascular diseases.

So Flora E. van Leeuwen, PhD, of the Netherlands Cancer Institute in Amsterdam, and her colleagues decided to investigate.

The team examined the risk for cardiovascular disease in HL survivors up to 40 years after they received treatment and compared that with the risk for cardiovascular disease in the general population. The researchers also studied treatment-related risk factors.

The study included 2524 Dutch patients who were diagnosed with HL when they were younger than 51 years of age. The patients’ median age was 27.3 years.

The patients were treated from 1965 through 1995 and had survived for at least 5 years after diagnosis. In all, 2052 patients (81.3%) had received mediastinal radiotherapy, and 773 (30.6%) had received chemotherapy containing an anthracycline.

At a median of 20.3 years of follow-up, there were 1713 cardiovascular events in 797 patients (31.6%), and 410 of those patients (51.4%) had experienced 2 events or more.

The most frequently occurring cardiovascular disease was coronary heart disease (CHD), with 401 patients developing it as their first event. This was followed by valvular heart disease (VHD, 374 events) and heart failure (HF, 140 events).

HL survivors had a 3.2-fold increased risk of developing CHD and a 6.8-fold increased risk of developing HF compared to the general population.

HL survivors who had been treated before age 25 had a 4.6-fold to 7.5-fold increased risk of CHD and a 10.9-fold to 40.5-fold increased risk of HF, depending on the age they ultimately attained.

HL survivors treated at 35 to 50 years of age had a 2.0-fold to 2.3-fold increased risk of CHD and a 3.1-fold to 5.2-fold increased risk of HF, depending on their attained age.

The risks of CHD and HF remained significantly increased beyond 35 years after HL treatment. The standardized incidence ratios were 3.9 and 5.8, respectively.

The median times between HL treatment and first cardiovascular disease events were 18 years for CHD, 24 years for VHD, and 19 years for HF.

The cumulative risk of any type of cardiovascular disease was 50% at 40 years after HL diagnosis. For patients who were treated for HL before they were 25, the cumulative risk of developing a cardiovascular disease at 60 years of age or older was 20% for CHD, 31% for VHD, and 11% for HF.

The study also suggested that mediastinal radiotherapy increased the risk of CHD, VHD, and HF. But anthracycline-containing chemotherapy only increased the risk of VHD and HF.

Dr van Leeuwen and her colleagues concluded that both physicians and patients should be aware that HL survivors have a persistently increased risk of developing cardiovascular diseases throughout their lives. The team also believes the results of their study may direct guidelines for follow-up in HL survivors.

A commentary related to this research is available in JAMA Internal Medicine as well.

Patient receives chemotherapy

Photo by Rhoda Baer

Survivors of Hodgkin lymphoma (HL) have an increased risk of developing cardiovascular diseases throughout their lives, according to a study published in JAMA Internal Medicine.

Previous research suggested that HL treatment is associated with an increased risk of cardiovascular diseases.

However, those studies did not determine how long the increased risk persists or pinpoint the risk factors for various cardiovascular diseases.

So Flora E. van Leeuwen, PhD, of the Netherlands Cancer Institute in Amsterdam, and her colleagues decided to investigate.

The team examined the risk for cardiovascular disease in HL survivors up to 40 years after they received treatment and compared that with the risk for cardiovascular disease in the general population. The researchers also studied treatment-related risk factors.

The study included 2524 Dutch patients who were diagnosed with HL when they were younger than 51 years of age. The patients’ median age was 27.3 years.

The patients were treated from 1965 through 1995 and had survived for at least 5 years after diagnosis. In all, 2052 patients (81.3%) had received mediastinal radiotherapy, and 773 (30.6%) had received chemotherapy containing an anthracycline.

At a median of 20.3 years of follow-up, there were 1713 cardiovascular events in 797 patients (31.6%), and 410 of those patients (51.4%) had experienced 2 events or more.

The most frequently occurring cardiovascular disease was coronary heart disease (CHD), with 401 patients developing it as their first event. This was followed by valvular heart disease (VHD, 374 events) and heart failure (HF, 140 events).

HL survivors had a 3.2-fold increased risk of developing CHD and a 6.8-fold increased risk of developing HF compared to the general population.

HL survivors who had been treated before age 25 had a 4.6-fold to 7.5-fold increased risk of CHD and a 10.9-fold to 40.5-fold increased risk of HF, depending on the age they ultimately attained.

HL survivors treated at 35 to 50 years of age had a 2.0-fold to 2.3-fold increased risk of CHD and a 3.1-fold to 5.2-fold increased risk of HF, depending on their attained age.

The risks of CHD and HF remained significantly increased beyond 35 years after HL treatment. The standardized incidence ratios were 3.9 and 5.8, respectively.

The median times between HL treatment and first cardiovascular disease events were 18 years for CHD, 24 years for VHD, and 19 years for HF.

The cumulative risk of any type of cardiovascular disease was 50% at 40 years after HL diagnosis. For patients who were treated for HL before they were 25, the cumulative risk of developing a cardiovascular disease at 60 years of age or older was 20% for CHD, 31% for VHD, and 11% for HF.

The study also suggested that mediastinal radiotherapy increased the risk of CHD, VHD, and HF. But anthracycline-containing chemotherapy only increased the risk of VHD and HF.

Dr van Leeuwen and her colleagues concluded that both physicians and patients should be aware that HL survivors have a persistently increased risk of developing cardiovascular diseases throughout their lives. The team also believes the results of their study may direct guidelines for follow-up in HL survivors.

A commentary related to this research is available in JAMA Internal Medicine as well.

PET scan of the body

Image by Jens Langner

Performing PET scans immediately after chemotherapy may reveal which Hodgkin lymphoma (HL) patients need radiotherapy (RT).

A study published in NEJM showed similar rates of progression-free survival in HL patients who werePET-negative after chemotherapy, whether they received subsequent RT or not.

However, the investigators said longer follow-up is needed to determine if eliminating RT in PET-negative patients will lead to fewer late effects and improved overall survival.

The 602 patients who agreed to take part in this trial, known as RAPID, had a PET scan performed after chemotherapy. Patients who tested positive received RT.

Those who tested negative were divided into 2 groups. One group of 211 patients received no further treatment, and the other group of 209 patients had the standard RT.

At a median of 60 months of follow-up, the proportion of patients who were alive and disease-free was 94.6% in the RT group and 90.8% in the group that hadn’t received further treatment.

Eight patients in the RT group progressed, and 8 died (3 with disease progression, 1 of whom died from HL). Five of the deaths occurred in patients who did not ultimately receive RT.

In the untreated group, 20 patients progressed, and 4 patients died (2 with disease progression and none from HL).

“This research is an important step forward,” said study author John Radford, of The University of Manchester and The Christie NHS Foundation Trust in the UK.

“The results of RAPID show that, in early stage Hodgkin lymphoma, radiotherapy after initial chemotherapy marginally reduces the recurrence rate, but this is bought at the expense of exposing to radiation all patients with negative PET findings, most of whom are already cured.”

PET scan of the body

Image by Jens Langner

Performing PET scans immediately after chemotherapy may reveal which Hodgkin lymphoma (HL) patients need radiotherapy (RT).

A study published in NEJM showed similar rates of progression-free survival in HL patients who werePET-negative after chemotherapy, whether they received subsequent RT or not.

However, the investigators said longer follow-up is needed to determine if eliminating RT in PET-negative patients will lead to fewer late effects and improved overall survival.

The 602 patients who agreed to take part in this trial, known as RAPID, had a PET scan performed after chemotherapy. Patients who tested positive received RT.

Those who tested negative were divided into 2 groups. One group of 211 patients received no further treatment, and the other group of 209 patients had the standard RT.

At a median of 60 months of follow-up, the proportion of patients who were alive and disease-free was 94.6% in the RT group and 90.8% in the group that hadn’t received further treatment.

Eight patients in the RT group progressed, and 8 died (3 with disease progression, 1 of whom died from HL). Five of the deaths occurred in patients who did not ultimately receive RT.

In the untreated group, 20 patients progressed, and 4 patients died (2 with disease progression and none from HL).

“This research is an important step forward,” said study author John Radford, of The University of Manchester and The Christie NHS Foundation Trust in the UK.

“The results of RAPID show that, in early stage Hodgkin lymphoma, radiotherapy after initial chemotherapy marginally reduces the recurrence rate, but this is bought at the expense of exposing to radiation all patients with negative PET findings, most of whom are already cured.”

PET scan of the body

Image by Jens Langner

Performing PET scans immediately after chemotherapy may reveal which Hodgkin lymphoma (HL) patients need radiotherapy (RT).

A study published in NEJM showed similar rates of progression-free survival in HL patients who werePET-negative after chemotherapy, whether they received subsequent RT or not.

However, the investigators said longer follow-up is needed to determine if eliminating RT in PET-negative patients will lead to fewer late effects and improved overall survival.

The 602 patients who agreed to take part in this trial, known as RAPID, had a PET scan performed after chemotherapy. Patients who tested positive received RT.

Those who tested negative were divided into 2 groups. One group of 211 patients received no further treatment, and the other group of 209 patients had the standard RT.

At a median of 60 months of follow-up, the proportion of patients who were alive and disease-free was 94.6% in the RT group and 90.8% in the group that hadn’t received further treatment.

Eight patients in the RT group progressed, and 8 died (3 with disease progression, 1 of whom died from HL). Five of the deaths occurred in patients who did not ultimately receive RT.

In the untreated group, 20 patients progressed, and 4 patients died (2 with disease progression and none from HL).

“This research is an important step forward,” said study author John Radford, of The University of Manchester and The Christie NHS Foundation Trust in the UK.

“The results of RAPID show that, in early stage Hodgkin lymphoma, radiotherapy after initial chemotherapy marginally reduces the recurrence rate, but this is bought at the expense of exposing to radiation all patients with negative PET findings, most of whom are already cured.”

Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.

The results were published online April 20 in the Journal of Clinical Oncology.

The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).

Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.

At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.

Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).

“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.

“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.

Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.

Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.

Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.

The results were published online April 20 in the Journal of Clinical Oncology.

The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).

Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.

At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.

Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).

“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.

“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.

Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.

Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.

Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.

The results were published online April 20 in the Journal of Clinical Oncology.

The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).

Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.

At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.

Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).

“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.

“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.

Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.

Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.

Micrograph showing HL

The anti-CD30 antibody-drug conjugate brentuximab vedotin can prolong progression-free survival (PFS) in Hodgkin lymphoma (HL) patients who have undergone autologous stem cell transplant (ASCT), results of the phase 3 AETHERA trial have shown.

The median PFS for patients who received brentuximab vedotin immediately after ASCT was nearly twice that of patients who received placebo—42.9 months and 24.1 months, respectively.

“No medication available today has had such dramatic results in patients with hard-to-treat Hodgkin lymphoma,” said Craig Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.

Dr Moskowitz and his colleagues detailed these results in The Lancet. The results were previously presented at the 2014 ASH Annual Meeting. The research was funded by Seattle Genetics, Inc., and Takeda Pharmaceutical Company Limited, the companies developing brentuximab vedotin.

The AETHERA study included 329 HL patients age 18 or older who were thought to be at high risk of relapse or progression after ASCT. Patients were randomized to receive placebo or 16 cycles of brentuximab vedotin once every 3 weeks.

After a median observation time of 30 months (range, 0-50 months), the rate of PFS was significantly higher in the brentuximab vedotin arm than the placebo arm. The hazard ratio was 0.57 (P=0.0013), according to an independent review group.

The estimated 2-year PFS was 63% in the brentuximab vedotin arm and 51% in the placebo arm, according to the independent review group. But according to investigators, the estimated 2-year PFS was 65% in the brentuximab vedotin arm and 45% in the placebo arm.

“Nearly all of these patients who are progression-free at 2 years are likely to be cured, since relapse 2 years after a transplant is unlikely,” Dr Moskowitz noted.

An interim analysis revealed no significant difference between the treatment arms with regard to overall survival.

The researchers said brentuximab vedotin was generally well-tolerated. The most common adverse events were peripheral neuropathy—occurring in 67% of brentuximab vedotin-treated patients and 13% of placebo-treated patients—and neutropenia—occurring in 35% and 12%, respectively.

In all, 53 patients died, 17% of those in the brentuximab vedotin arm and 16% of those in the placebo arm. The proportion of patients who died from disease-related illness was the same in both arms—11%.

“The bottom line is that brentuximab vedotin is a very effective drug in poor-risk Hodgkin lymphoma, and it spares patients from the harmful effects of further traditional chemotherapy by breaking down inside the cell, resulting in less toxicity,” Dr Moskowitz said.

Writing in a linked comment article, Andreas Engert, MD, of the University Hospital of Cologne in Germany, discussed how best to define which patients are at high risk of relapse and should receive brentuximab vedotin.

“AETHERA is a positive study establishing a promising new treatment approach for patients with Hodgkin’s lymphoma at high risk for relapse,” he wrote. “However, with a progression-free survival of about 50% at 24 months in the placebo group, whether this patient population is indeed high-risk could be debated.”

“An international consortium is currently reassessing the effect of risk factors in patients with relapsed Hodgkin’s lymphoma to define a high-risk patient population in need of consolidation treatment. We look forward to a better definition of patients with relapsed Hodgkin’s lymphoma who should receive consolidation treatment with brentuximab vedotin.”

Micrograph showing HL

The anti-CD30 antibody-drug conjugate brentuximab vedotin can prolong progression-free survival (PFS) in Hodgkin lymphoma (HL) patients who have undergone autologous stem cell transplant (ASCT), results of the phase 3 AETHERA trial have shown.

The median PFS for patients who received brentuximab vedotin immediately after ASCT was nearly twice that of patients who received placebo—42.9 months and 24.1 months, respectively.

“No medication available today has had such dramatic results in patients with hard-to-treat Hodgkin lymphoma,” said Craig Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.

Dr Moskowitz and his colleagues detailed these results in The Lancet. The results were previously presented at the 2014 ASH Annual Meeting. The research was funded by Seattle Genetics, Inc., and Takeda Pharmaceutical Company Limited, the companies developing brentuximab vedotin.

The AETHERA study included 329 HL patients age 18 or older who were thought to be at high risk of relapse or progression after ASCT. Patients were randomized to receive placebo or 16 cycles of brentuximab vedotin once every 3 weeks.

After a median observation time of 30 months (range, 0-50 months), the rate of PFS was significantly higher in the brentuximab vedotin arm than the placebo arm. The hazard ratio was 0.57 (P=0.0013), according to an independent review group.

The estimated 2-year PFS was 63% in the brentuximab vedotin arm and 51% in the placebo arm, according to the independent review group. But according to investigators, the estimated 2-year PFS was 65% in the brentuximab vedotin arm and 45% in the placebo arm.

“Nearly all of these patients who are progression-free at 2 years are likely to be cured, since relapse 2 years after a transplant is unlikely,” Dr Moskowitz noted.

An interim analysis revealed no significant difference between the treatment arms with regard to overall survival.

The researchers said brentuximab vedotin was generally well-tolerated. The most common adverse events were peripheral neuropathy—occurring in 67% of brentuximab vedotin-treated patients and 13% of placebo-treated patients—and neutropenia—occurring in 35% and 12%, respectively.

In all, 53 patients died, 17% of those in the brentuximab vedotin arm and 16% of those in the placebo arm. The proportion of patients who died from disease-related illness was the same in both arms—11%.

“The bottom line is that brentuximab vedotin is a very effective drug in poor-risk Hodgkin lymphoma, and it spares patients from the harmful effects of further traditional chemotherapy by breaking down inside the cell, resulting in less toxicity,” Dr Moskowitz said.

Writing in a linked comment article, Andreas Engert, MD, of the University Hospital of Cologne in Germany, discussed how best to define which patients are at high risk of relapse and should receive brentuximab vedotin.

“AETHERA is a positive study establishing a promising new treatment approach for patients with Hodgkin’s lymphoma at high risk for relapse,” he wrote. “However, with a progression-free survival of about 50% at 24 months in the placebo group, whether this patient population is indeed high-risk could be debated.”

“An international consortium is currently reassessing the effect of risk factors in patients with relapsed Hodgkin’s lymphoma to define a high-risk patient population in need of consolidation treatment. We look forward to a better definition of patients with relapsed Hodgkin’s lymphoma who should receive consolidation treatment with brentuximab vedotin.”

Micrograph showing HL

The anti-CD30 antibody-drug conjugate brentuximab vedotin can prolong progression-free survival (PFS) in Hodgkin lymphoma (HL) patients who have undergone autologous stem cell transplant (ASCT), results of the phase 3 AETHERA trial have shown.

The median PFS for patients who received brentuximab vedotin immediately after ASCT was nearly twice that of patients who received placebo—42.9 months and 24.1 months, respectively.

“No medication available today has had such dramatic results in patients with hard-to-treat Hodgkin lymphoma,” said Craig Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.

Dr Moskowitz and his colleagues detailed these results in The Lancet. The results were previously presented at the 2014 ASH Annual Meeting. The research was funded by Seattle Genetics, Inc., and Takeda Pharmaceutical Company Limited, the companies developing brentuximab vedotin.

The AETHERA study included 329 HL patients age 18 or older who were thought to be at high risk of relapse or progression after ASCT. Patients were randomized to receive placebo or 16 cycles of brentuximab vedotin once every 3 weeks.

After a median observation time of 30 months (range, 0-50 months), the rate of PFS was significantly higher in the brentuximab vedotin arm than the placebo arm. The hazard ratio was 0.57 (P=0.0013), according to an independent review group.

The estimated 2-year PFS was 63% in the brentuximab vedotin arm and 51% in the placebo arm, according to the independent review group. But according to investigators, the estimated 2-year PFS was 65% in the brentuximab vedotin arm and 45% in the placebo arm.

“Nearly all of these patients who are progression-free at 2 years are likely to be cured, since relapse 2 years after a transplant is unlikely,” Dr Moskowitz noted.

An interim analysis revealed no significant difference between the treatment arms with regard to overall survival.

The researchers said brentuximab vedotin was generally well-tolerated. The most common adverse events were peripheral neuropathy—occurring in 67% of brentuximab vedotin-treated patients and 13% of placebo-treated patients—and neutropenia—occurring in 35% and 12%, respectively.

In all, 53 patients died, 17% of those in the brentuximab vedotin arm and 16% of those in the placebo arm. The proportion of patients who died from disease-related illness was the same in both arms—11%.

“The bottom line is that brentuximab vedotin is a very effective drug in poor-risk Hodgkin lymphoma, and it spares patients from the harmful effects of further traditional chemotherapy by breaking down inside the cell, resulting in less toxicity,” Dr Moskowitz said.

Writing in a linked comment article, Andreas Engert, MD, of the University Hospital of Cologne in Germany, discussed how best to define which patients are at high risk of relapse and should receive brentuximab vedotin.

“AETHERA is a positive study establishing a promising new treatment approach for patients with Hodgkin’s lymphoma at high risk for relapse,” he wrote. “However, with a progression-free survival of about 50% at 24 months in the placebo group, whether this patient population is indeed high-risk could be debated.”

“An international consortium is currently reassessing the effect of risk factors in patients with relapsed Hodgkin’s lymphoma to define a high-risk patient population in need of consolidation treatment. We look forward to a better definition of patients with relapsed Hodgkin’s lymphoma who should receive consolidation treatment with brentuximab vedotin.”

Brentuximab vedotin (Adcetris) increased progression-free survival to 43 months when given to adults with hard-to-treat Hodgkin’s lymphoma immediately after stem cell transplant, compared to 24 months for placebo, according to research published online March 18 in The Lancet.

As part of the AETHERA phase III trial, 329 patients with Hodgkin’s lymphoma who were at high risk of relapse or progression after autologous stem cell transplant were given brentuximab vedotin infusions or placebo every 3 weeks for up to 16 cycles. After a 2-year follow-up, the cancer had not progressed in 65% of the patients in the treatment group, compared with 45% in the placebo group.

The most common side effects were peripheral neuropathy (67% vs. 13% placebo) and neutropenia (35% vs. 12% placebo), noted Dr. Craig Moskowitz of Memorial Sloan Kettering Cancer Center, New York, and his associates.

Read the full article here.

Brentuximab vedotin (Adcetris) increased progression-free survival to 43 months when given to adults with hard-to-treat Hodgkin’s lymphoma immediately after stem cell transplant, compared to 24 months for placebo, according to research published online March 18 in The Lancet.

As part of the AETHERA phase III trial, 329 patients with Hodgkin’s lymphoma who were at high risk of relapse or progression after autologous stem cell transplant were given brentuximab vedotin infusions or placebo every 3 weeks for up to 16 cycles. After a 2-year follow-up, the cancer had not progressed in 65% of the patients in the treatment group, compared with 45% in the placebo group.

The most common side effects were peripheral neuropathy (67% vs. 13% placebo) and neutropenia (35% vs. 12% placebo), noted Dr. Craig Moskowitz of Memorial Sloan Kettering Cancer Center, New York, and his associates.

Read the full article here.

Brentuximab vedotin (Adcetris) increased progression-free survival to 43 months when given to adults with hard-to-treat Hodgkin’s lymphoma immediately after stem cell transplant, compared to 24 months for placebo, according to research published online March 18 in The Lancet.

As part of the AETHERA phase III trial, 329 patients with Hodgkin’s lymphoma who were at high risk of relapse or progression after autologous stem cell transplant were given brentuximab vedotin infusions or placebo every 3 weeks for up to 16 cycles. After a 2-year follow-up, the cancer had not progressed in 65% of the patients in the treatment group, compared with 45% in the placebo group.

The most common side effects were peripheral neuropathy (67% vs. 13% placebo) and neutropenia (35% vs. 12% placebo), noted Dr. Craig Moskowitz of Memorial Sloan Kettering Cancer Center, New York, and his associates.

Read the full article here.

PET/CT scanner

New guidelines on radiation therapy aim to help physicians more effectively treat pediatric Hodgkin lymphoma (HL) while reducing the radiation dose to normal tissue.

Previous guidelines for pediatric HL have focused on 2D imaging and bony landmarks to define dose volumes for radiation therapy, and they’ve recommended treating large volumes of normal tissue, in part, because of uncertainty about which lymph node areas were involved.

The new guidelines, published in Practical Radiation Oncology, describe how to use modern imaging and advances in radiation therapy planning technology to treat patients with pediatric HL while decreasing the risk of late side effects, including second cancers and heart disease.

The authors describe methods for identifying target volumes for radiation therapy and how to implement the concept of involved-site radiation to define radiation target volumes and limit the dose to normal organs at risk.

According to the guidelines, accurate assessment of the extent and location of disease requires both contrast-enhanced CT as well as FDG-PET.

The document describes how the evaluation of response to chemotherapy influences the targeting of the lymphoma and the volume of normal tissue treated, by fusing CT and FDG-PET images taken before and after chemotherapy to CT imaging taken for radiation therapy planning.

“The emergence of new imaging technologies, more accurate ways of delivering radiation therapy, and more detailed patient selection criteria have made a significant change in our ability to customize treatment for many cancer patients,” said lead guideline author David C. Hodgson, MD, of the University of Toronto in Ontario, Canada.

“This guideline has the potential to reduce the radiation therapy breast dose by about 80% and the heart dose by about 65% for an adolescent girl with Hodgkin lymphoma. This shift in more personalized treatment planning tailored to the individual patient’s disease will optimize risk-benefit considerations for our patients and reduce the likelihood that they will suffer late effects from radiation therapy.”

PET/CT scanner

New guidelines on radiation therapy aim to help physicians more effectively treat pediatric Hodgkin lymphoma (HL) while reducing the radiation dose to normal tissue.

Previous guidelines for pediatric HL have focused on 2D imaging and bony landmarks to define dose volumes for radiation therapy, and they’ve recommended treating large volumes of normal tissue, in part, because of uncertainty about which lymph node areas were involved.

The new guidelines, published in Practical Radiation Oncology, describe how to use modern imaging and advances in radiation therapy planning technology to treat patients with pediatric HL while decreasing the risk of late side effects, including second cancers and heart disease.

The authors describe methods for identifying target volumes for radiation therapy and how to implement the concept of involved-site radiation to define radiation target volumes and limit the dose to normal organs at risk.

According to the guidelines, accurate assessment of the extent and location of disease requires both contrast-enhanced CT as well as FDG-PET.

The document describes how the evaluation of response to chemotherapy influences the targeting of the lymphoma and the volume of normal tissue treated, by fusing CT and FDG-PET images taken before and after chemotherapy to CT imaging taken for radiation therapy planning.

“The emergence of new imaging technologies, more accurate ways of delivering radiation therapy, and more detailed patient selection criteria have made a significant change in our ability to customize treatment for many cancer patients,” said lead guideline author David C. Hodgson, MD, of the University of Toronto in Ontario, Canada.

“This guideline has the potential to reduce the radiation therapy breast dose by about 80% and the heart dose by about 65% for an adolescent girl with Hodgkin lymphoma. This shift in more personalized treatment planning tailored to the individual patient’s disease will optimize risk-benefit considerations for our patients and reduce the likelihood that they will suffer late effects from radiation therapy.”

PET/CT scanner

New guidelines on radiation therapy aim to help physicians more effectively treat pediatric Hodgkin lymphoma (HL) while reducing the radiation dose to normal tissue.

Previous guidelines for pediatric HL have focused on 2D imaging and bony landmarks to define dose volumes for radiation therapy, and they’ve recommended treating large volumes of normal tissue, in part, because of uncertainty about which lymph node areas were involved.

The new guidelines, published in Practical Radiation Oncology, describe how to use modern imaging and advances in radiation therapy planning technology to treat patients with pediatric HL while decreasing the risk of late side effects, including second cancers and heart disease.

The authors describe methods for identifying target volumes for radiation therapy and how to implement the concept of involved-site radiation to define radiation target volumes and limit the dose to normal organs at risk.

According to the guidelines, accurate assessment of the extent and location of disease requires both contrast-enhanced CT as well as FDG-PET.

The document describes how the evaluation of response to chemotherapy influences the targeting of the lymphoma and the volume of normal tissue treated, by fusing CT and FDG-PET images taken before and after chemotherapy to CT imaging taken for radiation therapy planning.

“The emergence of new imaging technologies, more accurate ways of delivering radiation therapy, and more detailed patient selection criteria have made a significant change in our ability to customize treatment for many cancer patients,” said lead guideline author David C. Hodgson, MD, of the University of Toronto in Ontario, Canada.

“This guideline has the potential to reduce the radiation therapy breast dose by about 80% and the heart dose by about 65% for an adolescent girl with Hodgkin lymphoma. This shift in more personalized treatment planning tailored to the individual patient’s disease will optimize risk-benefit considerations for our patients and reduce the likelihood that they will suffer late effects from radiation therapy.”

Team treats cancer patient

Photo by Rhoda Baer

A new analysis suggests that although US spending on cancer treatment has increased greatly in recent years, cancer mortality rates have decreased only modestly.

The study showed that care in the US often failed to prevent cancer-related deaths as well as care in Western Europe.

And when deaths were averted in the US, there was a substantial cost attached, said study author Samir Soneji, PhD, of the Norris Cotton Cancer Center in Lebanon, New Hampshire.

He and JaeWon Yang, a former undergraduate at Dartmouth College in Hanover, New Hampshire, reported these findings in Health Affairs.

The researchers compared cancer deaths and money spent on cancer care in the US and Western Europe between 1982 and 2010. They found that costs were higher in the US than in Europe for all cancers analyzed.

And compared to Western Europe, the US had 64,560 excess leukemia deaths; 164,429 excess non-Hodgkin lymphoma (NHL) deaths; 1,119,599 excess lung cancer deaths; and 39,144 excess melanoma deaths.

On the other hand, the US averted 4859 Hodgkin lymphoma deaths; 66,797 breast cancer deaths; 4354 cervical/uterine cancer deaths; 264,632 colorectal cancer deaths; 59,882 prostate cancer deaths; 621,820 stomach cancer deaths; 3372 testicular cancer deaths; and 18,320 thyroid cancer deaths.

“The greatest number of deaths averted occurred in cancers for which decreasing mortality rates were more likely to be the result of successful prevention and screening rather than advancements in treatment,” Dr Soneji noted.

He and Yang also found that the ratio of incremental cost to quality-adjusted life years (QALYs) saved in the US was $156,045 for Hodgkin lymphoma; $402,369 for breast cancer; $110,009 for colorectal cancer; $1,978,542 for prostate cancer; $4635 for stomach cancer; $222,839 for testicular cancer; and $139,681 for thyroid cancer.

But the US lost QALYs despite additional spending for leukemia, NHL, and a few other cancers. The incremental cost divided by QALYs saved was -$30,790 for leukemia; -$41,362 for NHL; -$855,019 for cervical/uterine cancer; -$18,815 for lung cancer, and -$136,592 for melanoma.

Dr Soneji described these results as, “substantially contrary to previous findings, especially for breast and prostate cancer, despite using the same data” as a previous study published in Health Affairs.

Non-replicability is a serious problem throughout academia, Dr Soneji noted. So to promote open discussion, he makes his data and procedures available to all scholars on an open-access repository called Dataverse.

Team treats cancer patient

Photo by Rhoda Baer

A new analysis suggests that although US spending on cancer treatment has increased greatly in recent years, cancer mortality rates have decreased only modestly.

The study showed that care in the US often failed to prevent cancer-related deaths as well as care in Western Europe.

And when deaths were averted in the US, there was a substantial cost attached, said study author Samir Soneji, PhD, of the Norris Cotton Cancer Center in Lebanon, New Hampshire.

He and JaeWon Yang, a former undergraduate at Dartmouth College in Hanover, New Hampshire, reported these findings in Health Affairs.

The researchers compared cancer deaths and money spent on cancer care in the US and Western Europe between 1982 and 2010. They found that costs were higher in the US than in Europe for all cancers analyzed.

And compared to Western Europe, the US had 64,560 excess leukemia deaths; 164,429 excess non-Hodgkin lymphoma (NHL) deaths; 1,119,599 excess lung cancer deaths; and 39,144 excess melanoma deaths.

On the other hand, the US averted 4859 Hodgkin lymphoma deaths; 66,797 breast cancer deaths; 4354 cervical/uterine cancer deaths; 264,632 colorectal cancer deaths; 59,882 prostate cancer deaths; 621,820 stomach cancer deaths; 3372 testicular cancer deaths; and 18,320 thyroid cancer deaths.

“The greatest number of deaths averted occurred in cancers for which decreasing mortality rates were more likely to be the result of successful prevention and screening rather than advancements in treatment,” Dr Soneji noted.

He and Yang also found that the ratio of incremental cost to quality-adjusted life years (QALYs) saved in the US was $156,045 for Hodgkin lymphoma; $402,369 for breast cancer; $110,009 for colorectal cancer; $1,978,542 for prostate cancer; $4635 for stomach cancer; $222,839 for testicular cancer; and $139,681 for thyroid cancer.

But the US lost QALYs despite additional spending for leukemia, NHL, and a few other cancers. The incremental cost divided by QALYs saved was -$30,790 for leukemia; -$41,362 for NHL; -$855,019 for cervical/uterine cancer; -$18,815 for lung cancer, and -$136,592 for melanoma.

Dr Soneji described these results as, “substantially contrary to previous findings, especially for breast and prostate cancer, despite using the same data” as a previous study published in Health Affairs.

Non-replicability is a serious problem throughout academia, Dr Soneji noted. So to promote open discussion, he makes his data and procedures available to all scholars on an open-access repository called Dataverse.

Team treats cancer patient

Photo by Rhoda Baer

A new analysis suggests that although US spending on cancer treatment has increased greatly in recent years, cancer mortality rates have decreased only modestly.

The study showed that care in the US often failed to prevent cancer-related deaths as well as care in Western Europe.

And when deaths were averted in the US, there was a substantial cost attached, said study author Samir Soneji, PhD, of the Norris Cotton Cancer Center in Lebanon, New Hampshire.

He and JaeWon Yang, a former undergraduate at Dartmouth College in Hanover, New Hampshire, reported these findings in Health Affairs.

The researchers compared cancer deaths and money spent on cancer care in the US and Western Europe between 1982 and 2010. They found that costs were higher in the US than in Europe for all cancers analyzed.

And compared to Western Europe, the US had 64,560 excess leukemia deaths; 164,429 excess non-Hodgkin lymphoma (NHL) deaths; 1,119,599 excess lung cancer deaths; and 39,144 excess melanoma deaths.

On the other hand, the US averted 4859 Hodgkin lymphoma deaths; 66,797 breast cancer deaths; 4354 cervical/uterine cancer deaths; 264,632 colorectal cancer deaths; 59,882 prostate cancer deaths; 621,820 stomach cancer deaths; 3372 testicular cancer deaths; and 18,320 thyroid cancer deaths.

“The greatest number of deaths averted occurred in cancers for which decreasing mortality rates were more likely to be the result of successful prevention and screening rather than advancements in treatment,” Dr Soneji noted.

He and Yang also found that the ratio of incremental cost to quality-adjusted life years (QALYs) saved in the US was $156,045 for Hodgkin lymphoma; $402,369 for breast cancer; $110,009 for colorectal cancer; $1,978,542 for prostate cancer; $4635 for stomach cancer; $222,839 for testicular cancer; and $139,681 for thyroid cancer.

But the US lost QALYs despite additional spending for leukemia, NHL, and a few other cancers. The incremental cost divided by QALYs saved was -$30,790 for leukemia; -$41,362 for NHL; -$855,019 for cervical/uterine cancer; -$18,815 for lung cancer, and -$136,592 for melanoma.

Dr Soneji described these results as, “substantially contrary to previous findings, especially for breast and prostate cancer, despite using the same data” as a previous study published in Health Affairs.

Non-replicability is a serious problem throughout academia, Dr Soneji noted. So to promote open discussion, he makes his data and procedures available to all scholars on an open-access repository called Dataverse.