AVAHO

SAN DIEGO – Daily hydroxyurea treatment for sickle cell disease is feasible, safe, and effective for children in sub-Saharan Africa, according to the results of a large open-label, phase 1-2, international trial.

Andrew Bowser/MDedge News

Hydroxyurea was associated with reduced rates of malaria and other infections, resulting in improved survival, according to Léon Tshilolo, MD, PhD, of Centre Hospitalier Monkole in Kinshasa, the Democratic Republic of the Congo.

“Based on that data, we believe that wider access to hydroxyurea for sickle cell anemia has the potential to save millions of lives in Africa,” Dr. Tshilolo said in a press conference at the annual meeting of the American Society of Hematology.

Use of hydroxyurea has been limited in Africa because of cost, access issues, and challenges associated with laboratory monitoring, according to the researchers.

Moreover, most of the data on the efficacy of hydroxyurea come from studies conducted in the United States, Europe, and other high-income settings, said the study’s senior author Russell E. Ware, MD, PhD, of Cincinnati Children’s Hospital Center.

“Now that there’s data in an African setting, I think this will go a long way to advancing [hydroxyurea therapy] and encouraging governments, organizations, and pharmaceutical companies to bring it in,” Dr. Ware said in an interview.

In the study by Dr. Ware, Dr. Tshilolo, and their colleagues, 606 children in four sub-Saharan African countries completed a 2-month pretreatment screening phase designed to capture baseline clinical and laboratory data. The children, who were aged 1-10 years, were started at 15-20 mg/kg of hydroxyurea for 6 months, followed by escalation to the maximum tolerated dose.

With a median of 2.5 years of treatment, treated children experienced less pain and anemia, fewer cases of malaria and other infections, and lower rates of transfusions and death versus rates observed in the pretreatment screening phase of the trial.

The rate of vasoocclusive pain during hydroxyurea treatment was 44.6 events per 100 patient-years, compared with 98.3 events per 100 patient-years in the pretreatment period (incidence rate ratio, 0.45; 95% confidence interval, 0.37-0.56), according to data simultaneously published in the New England Journal of Medicine.

Malaria infection rates were 22.9 events per 100 patient-years in the hydroxyurea treatment period versus 46.9 events in the pretreatment period (IRR, 0.49; 95% CI, 0.37-0.66). Rates of nonmalaria infections were 90.0 events per 100 patient-years in the hydroxyurea treatment period versus 142.5 events per 100 patient-years in the pretreatment period (IRR, 0.62; 95% CI, 0.53-0.72).

Dr. Tshilolo said investigators were “encouraged” by the reduced infection rates, particularly in light of previous concerns that hydroxyurea could suppress the immune system and put children at risk for malaria.

Death rates were 1.1 per 100 patient-years in the hydroxyurea group and 3.6 per 100 patient-years in the pretreatment period (IR, 0.30; 95% CI, 0.10-0.88). Dose-limiting toxic events occurred in 5.1% of the children, which was below the protocol-specified threshold for safety, Dr. Tshilolo added.

Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the NIH/NHLBI and Bristol-Myers Squibb.

SOURCE: Tshilolo L et al. ASH 2018, Abstract 3.

SAN DIEGO – Daily hydroxyurea treatment for sickle cell disease is feasible, safe, and effective for children in sub-Saharan Africa, according to the results of a large open-label, phase 1-2, international trial.

Andrew Bowser/MDedge News

Hydroxyurea was associated with reduced rates of malaria and other infections, resulting in improved survival, according to Léon Tshilolo, MD, PhD, of Centre Hospitalier Monkole in Kinshasa, the Democratic Republic of the Congo.

“Based on that data, we believe that wider access to hydroxyurea for sickle cell anemia has the potential to save millions of lives in Africa,” Dr. Tshilolo said in a press conference at the annual meeting of the American Society of Hematology.

Use of hydroxyurea has been limited in Africa because of cost, access issues, and challenges associated with laboratory monitoring, according to the researchers.

Moreover, most of the data on the efficacy of hydroxyurea come from studies conducted in the United States, Europe, and other high-income settings, said the study’s senior author Russell E. Ware, MD, PhD, of Cincinnati Children’s Hospital Center.

“Now that there’s data in an African setting, I think this will go a long way to advancing [hydroxyurea therapy] and encouraging governments, organizations, and pharmaceutical companies to bring it in,” Dr. Ware said in an interview.

In the study by Dr. Ware, Dr. Tshilolo, and their colleagues, 606 children in four sub-Saharan African countries completed a 2-month pretreatment screening phase designed to capture baseline clinical and laboratory data. The children, who were aged 1-10 years, were started at 15-20 mg/kg of hydroxyurea for 6 months, followed by escalation to the maximum tolerated dose.

With a median of 2.5 years of treatment, treated children experienced less pain and anemia, fewer cases of malaria and other infections, and lower rates of transfusions and death versus rates observed in the pretreatment screening phase of the trial.

The rate of vasoocclusive pain during hydroxyurea treatment was 44.6 events per 100 patient-years, compared with 98.3 events per 100 patient-years in the pretreatment period (incidence rate ratio, 0.45; 95% confidence interval, 0.37-0.56), according to data simultaneously published in the New England Journal of Medicine.

Malaria infection rates were 22.9 events per 100 patient-years in the hydroxyurea treatment period versus 46.9 events in the pretreatment period (IRR, 0.49; 95% CI, 0.37-0.66). Rates of nonmalaria infections were 90.0 events per 100 patient-years in the hydroxyurea treatment period versus 142.5 events per 100 patient-years in the pretreatment period (IRR, 0.62; 95% CI, 0.53-0.72).

Dr. Tshilolo said investigators were “encouraged” by the reduced infection rates, particularly in light of previous concerns that hydroxyurea could suppress the immune system and put children at risk for malaria.

Death rates were 1.1 per 100 patient-years in the hydroxyurea group and 3.6 per 100 patient-years in the pretreatment period (IR, 0.30; 95% CI, 0.10-0.88). Dose-limiting toxic events occurred in 5.1% of the children, which was below the protocol-specified threshold for safety, Dr. Tshilolo added.

Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the NIH/NHLBI and Bristol-Myers Squibb.

SOURCE: Tshilolo L et al. ASH 2018, Abstract 3.

SAN DIEGO – Daily hydroxyurea treatment for sickle cell disease is feasible, safe, and effective for children in sub-Saharan Africa, according to the results of a large open-label, phase 1-2, international trial.

Andrew Bowser/MDedge News

Hydroxyurea was associated with reduced rates of malaria and other infections, resulting in improved survival, according to Léon Tshilolo, MD, PhD, of Centre Hospitalier Monkole in Kinshasa, the Democratic Republic of the Congo.

“Based on that data, we believe that wider access to hydroxyurea for sickle cell anemia has the potential to save millions of lives in Africa,” Dr. Tshilolo said in a press conference at the annual meeting of the American Society of Hematology.

Use of hydroxyurea has been limited in Africa because of cost, access issues, and challenges associated with laboratory monitoring, according to the researchers.

Moreover, most of the data on the efficacy of hydroxyurea come from studies conducted in the United States, Europe, and other high-income settings, said the study’s senior author Russell E. Ware, MD, PhD, of Cincinnati Children’s Hospital Center.

“Now that there’s data in an African setting, I think this will go a long way to advancing [hydroxyurea therapy] and encouraging governments, organizations, and pharmaceutical companies to bring it in,” Dr. Ware said in an interview.

In the study by Dr. Ware, Dr. Tshilolo, and their colleagues, 606 children in four sub-Saharan African countries completed a 2-month pretreatment screening phase designed to capture baseline clinical and laboratory data. The children, who were aged 1-10 years, were started at 15-20 mg/kg of hydroxyurea for 6 months, followed by escalation to the maximum tolerated dose.

With a median of 2.5 years of treatment, treated children experienced less pain and anemia, fewer cases of malaria and other infections, and lower rates of transfusions and death versus rates observed in the pretreatment screening phase of the trial.

The rate of vasoocclusive pain during hydroxyurea treatment was 44.6 events per 100 patient-years, compared with 98.3 events per 100 patient-years in the pretreatment period (incidence rate ratio, 0.45; 95% confidence interval, 0.37-0.56), according to data simultaneously published in the New England Journal of Medicine.

Malaria infection rates were 22.9 events per 100 patient-years in the hydroxyurea treatment period versus 46.9 events in the pretreatment period (IRR, 0.49; 95% CI, 0.37-0.66). Rates of nonmalaria infections were 90.0 events per 100 patient-years in the hydroxyurea treatment period versus 142.5 events per 100 patient-years in the pretreatment period (IRR, 0.62; 95% CI, 0.53-0.72).

Dr. Tshilolo said investigators were “encouraged” by the reduced infection rates, particularly in light of previous concerns that hydroxyurea could suppress the immune system and put children at risk for malaria.

Death rates were 1.1 per 100 patient-years in the hydroxyurea group and 3.6 per 100 patient-years in the pretreatment period (IR, 0.30; 95% CI, 0.10-0.88). Dose-limiting toxic events occurred in 5.1% of the children, which was below the protocol-specified threshold for safety, Dr. Tshilolo added.

Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the NIH/NHLBI and Bristol-Myers Squibb.

SOURCE: Tshilolo L et al. ASH 2018, Abstract 3.

SAN DIEGO – Researchers were able to “flip the switch” from the adult to fetal form of hemoglobin using autologous stem cells genetically modified to simultaneously induce the fetal form of hemoglobin and decrease sickle hemoglobin.

The advance was announced by investigators at the Dana-Farber Cancer Institute and Boston Children’s Hospital at the annual meeting of the American Society of Hematology. At 6 months of follow-up, one adult patient in the proof-of-concept study has experienced a reversal of the sickle cell phenotype, with no pain episodes or respiratory or neurologic events.

The fetal form of hemoglobin is known to be protective against the signs and symptoms of sickle cell disease, but apart from a few rare exceptions, people with the disorder begin to experience debilitating symptoms as levels of the fetal form begin to decline in early childhood and levels of the adult form of hemoglobin steadily rise.

In this video interview, Erica B. Esrick, MD, from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, describes the novel approach of using RNA interference to knock down a repressor that suppresses expression of gamma globin in sickle cell disease.

SAN DIEGO – Researchers were able to “flip the switch” from the adult to fetal form of hemoglobin using autologous stem cells genetically modified to simultaneously induce the fetal form of hemoglobin and decrease sickle hemoglobin.

The advance was announced by investigators at the Dana-Farber Cancer Institute and Boston Children’s Hospital at the annual meeting of the American Society of Hematology. At 6 months of follow-up, one adult patient in the proof-of-concept study has experienced a reversal of the sickle cell phenotype, with no pain episodes or respiratory or neurologic events.

The fetal form of hemoglobin is known to be protective against the signs and symptoms of sickle cell disease, but apart from a few rare exceptions, people with the disorder begin to experience debilitating symptoms as levels of the fetal form begin to decline in early childhood and levels of the adult form of hemoglobin steadily rise.

In this video interview, Erica B. Esrick, MD, from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, describes the novel approach of using RNA interference to knock down a repressor that suppresses expression of gamma globin in sickle cell disease.

SAN DIEGO – Researchers were able to “flip the switch” from the adult to fetal form of hemoglobin using autologous stem cells genetically modified to simultaneously induce the fetal form of hemoglobin and decrease sickle hemoglobin.

The advance was announced by investigators at the Dana-Farber Cancer Institute and Boston Children’s Hospital at the annual meeting of the American Society of Hematology. At 6 months of follow-up, one adult patient in the proof-of-concept study has experienced a reversal of the sickle cell phenotype, with no pain episodes or respiratory or neurologic events.

The fetal form of hemoglobin is known to be protective against the signs and symptoms of sickle cell disease, but apart from a few rare exceptions, people with the disorder begin to experience debilitating symptoms as levels of the fetal form begin to decline in early childhood and levels of the adult form of hemoglobin steadily rise.

In this video interview, Erica B. Esrick, MD, from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, describes the novel approach of using RNA interference to knock down a repressor that suppresses expression of gamma globin in sickle cell disease.

The Food and Drug Administration has approved a biosimilar rituximab product for the treatment of non-Hodgkin lymphoma (NHL).

Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan (rituximab) and the first biosimilar approved in the United States to treat NHL.

Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy. Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL. Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.

Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy. Truxima also is approved as a single agent to treat nonprogressing, low-grade, CD20-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.

The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”

Findings from a phase 3 trial suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma (Lancet Haematol. 2018 Nov;5[11]:e543-53).

jensmith@mdedge.com

The Food and Drug Administration has approved a biosimilar rituximab product for the treatment of non-Hodgkin lymphoma (NHL).

Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan (rituximab) and the first biosimilar approved in the United States to treat NHL.

Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy. Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL. Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.

Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy. Truxima also is approved as a single agent to treat nonprogressing, low-grade, CD20-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.

The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”

Findings from a phase 3 trial suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma (Lancet Haematol. 2018 Nov;5[11]:e543-53).

jensmith@mdedge.com

The Food and Drug Administration has approved a biosimilar rituximab product for the treatment of non-Hodgkin lymphoma (NHL).

Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan (rituximab) and the first biosimilar approved in the United States to treat NHL.

Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy. Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL. Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.

Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy. Truxima also is approved as a single agent to treat nonprogressing, low-grade, CD20-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.

The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”

Findings from a phase 3 trial suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma (Lancet Haematol. 2018 Nov;5[11]:e543-53).

jensmith@mdedge.com

Cancer survivors have a higher risk of depression within 2 years after the diagnosis, according to a meta-analysis. But is that true of survivors of all types of cancer? In fact, risk is multifactorial because patients, cancers, comorbidities, and impacts of treatments are all different, say researchers who conducted a study to compare the risk of mood disorders longitudinally.

They matched 190,748 survivors with controls from the Taiwan National Health Insurance Research Database. The median follow-up times were 8.13 and 8.49 years, respectively. The 3 most common cancers were breast, colorectal, and head and neck. Surgery alone was the main treatment, followed by combinations of surgery, chemotherapy, and radiation.

Survivors had a significantly higher risk of mood disorders: 8.38 per 1,000 person-years, compared with 7.21 in the control patients. Major depression and depression disorder were the most common subtypes.

However, the risk of mood disorders (1.13-fold) peaked during the year after the index date and declined thereafter. Moreover, 2 and 5 years later, the risk was similar between the 2 groups. And after 5 years, the risk was even lower in the survivor group than in the control group.

The researchers found patients fell into 3 main categories: persistently increasing risk, higher risk in the first few years and after 5 years of follow-up, and higher risk in the first few years but no difference thereafter. Patients with head and neck cancer, nasopharyngeal cancer, and esophageal cancer were in the first group, with distinct longitudinal patterns. Their risk at 5 years was greater than that of the general population.

Being female, aged 40-59 years, having > 2 primary cancers, having ≥ 2 treatment modalities, Charlson comorbidity index scores > 3, higher urbanization level, and lower income levels were independent risk factors for mood disorders.

The researchers say their findings highlight the importance of taking follow-up time, cancer types, and cancer-related treatment into consideration when evaluating mood disorders in cancer survivors. They also emphasize the need for better psychological management not only in the early postdiagnosis years, but in late follow-up for patients with a “persistent” risk.

Source:
Huang WK, Juang YY, Chung CC, et al. J Affect Disord. 2018;236:80-87.

Cancer survivors have a higher risk of depression within 2 years after the diagnosis, according to a meta-analysis. But is that true of survivors of all types of cancer? In fact, risk is multifactorial because patients, cancers, comorbidities, and impacts of treatments are all different, say researchers who conducted a study to compare the risk of mood disorders longitudinally.

They matched 190,748 survivors with controls from the Taiwan National Health Insurance Research Database. The median follow-up times were 8.13 and 8.49 years, respectively. The 3 most common cancers were breast, colorectal, and head and neck. Surgery alone was the main treatment, followed by combinations of surgery, chemotherapy, and radiation.

Survivors had a significantly higher risk of mood disorders: 8.38 per 1,000 person-years, compared with 7.21 in the control patients. Major depression and depression disorder were the most common subtypes.

However, the risk of mood disorders (1.13-fold) peaked during the year after the index date and declined thereafter. Moreover, 2 and 5 years later, the risk was similar between the 2 groups. And after 5 years, the risk was even lower in the survivor group than in the control group.

The researchers found patients fell into 3 main categories: persistently increasing risk, higher risk in the first few years and after 5 years of follow-up, and higher risk in the first few years but no difference thereafter. Patients with head and neck cancer, nasopharyngeal cancer, and esophageal cancer were in the first group, with distinct longitudinal patterns. Their risk at 5 years was greater than that of the general population.

Being female, aged 40-59 years, having > 2 primary cancers, having ≥ 2 treatment modalities, Charlson comorbidity index scores > 3, higher urbanization level, and lower income levels were independent risk factors for mood disorders.

The researchers say their findings highlight the importance of taking follow-up time, cancer types, and cancer-related treatment into consideration when evaluating mood disorders in cancer survivors. They also emphasize the need for better psychological management not only in the early postdiagnosis years, but in late follow-up for patients with a “persistent” risk.

Source:
Huang WK, Juang YY, Chung CC, et al. J Affect Disord. 2018;236:80-87.

Cancer survivors have a higher risk of depression within 2 years after the diagnosis, according to a meta-analysis. But is that true of survivors of all types of cancer? In fact, risk is multifactorial because patients, cancers, comorbidities, and impacts of treatments are all different, say researchers who conducted a study to compare the risk of mood disorders longitudinally.

They matched 190,748 survivors with controls from the Taiwan National Health Insurance Research Database. The median follow-up times were 8.13 and 8.49 years, respectively. The 3 most common cancers were breast, colorectal, and head and neck. Surgery alone was the main treatment, followed by combinations of surgery, chemotherapy, and radiation.

Survivors had a significantly higher risk of mood disorders: 8.38 per 1,000 person-years, compared with 7.21 in the control patients. Major depression and depression disorder were the most common subtypes.

However, the risk of mood disorders (1.13-fold) peaked during the year after the index date and declined thereafter. Moreover, 2 and 5 years later, the risk was similar between the 2 groups. And after 5 years, the risk was even lower in the survivor group than in the control group.

The researchers found patients fell into 3 main categories: persistently increasing risk, higher risk in the first few years and after 5 years of follow-up, and higher risk in the first few years but no difference thereafter. Patients with head and neck cancer, nasopharyngeal cancer, and esophageal cancer were in the first group, with distinct longitudinal patterns. Their risk at 5 years was greater than that of the general population.

Being female, aged 40-59 years, having > 2 primary cancers, having ≥ 2 treatment modalities, Charlson comorbidity index scores > 3, higher urbanization level, and lower income levels were independent risk factors for mood disorders.

The researchers say their findings highlight the importance of taking follow-up time, cancer types, and cancer-related treatment into consideration when evaluating mood disorders in cancer survivors. They also emphasize the need for better psychological management not only in the early postdiagnosis years, but in late follow-up for patients with a “persistent” risk.

Source:
Huang WK, Juang YY, Chung CC, et al. J Affect Disord. 2018;236:80-87.

The use of bortezomib may help overcome treatment resistance in patients with Waldenström macroglobulinemia (WM) with CXCR4 mutations, according to new research.

Romanos Sklavenitis-Pistofidis, MD, of the Dana-Farber Cancer Institute in Boston, and his colleagues compared the effects of treatment with bortezomib/rituximab in patients with WM based on their CXCR4 mutation status. They found no significant difference in progression-free survival (Log-rank, P = .994) or overall survival (Log-rank, P = .407) when comparing patients who have CXCR4 mutations with those who have CXCR4 wild type.

“We report for the first time that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote in Blood. “Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”

The researchers noted, however, that the mechanism at work may be different than that seen with bortezomib in other cancers.

“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma. However, despite the complicated association in those cancer types, in WM there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data,” they wrote.

The researchers recommended that the theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations. Another question to be investigated, they pointed out, is the role of rituximab in the survival results seen in the current analysis.

The study included 63 patients with WM who were treated with bortezomib/rituximab either as upfront treatment or in the relapsed/refractory setting as part of a phase 2 trial.

Bortezomib was given by IV weekly at 1.6 mg/m² for six cycles and rituximab was given at 375 mg/m² during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.

The researchers excluded 20 patients from the study because of a lack of material for genotyping. However, they noted that their clinical characteristics were not different from those patients who were included.

Out of 43 patients who were genotyped for CXCR4, 17 patients had a mutation. All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations. The median follow-up of the analysis was 90.7 months.

The researchers repeated the analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.

The study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.

mschneider@mdedge.com

SOURCE: Sklavenitis-Pistofidis R et al. Blood. 2018 Oct 26. doi: 10.1182/blood-2018-07-863241.

The use of bortezomib may help overcome treatment resistance in patients with Waldenström macroglobulinemia (WM) with CXCR4 mutations, according to new research.

Romanos Sklavenitis-Pistofidis, MD, of the Dana-Farber Cancer Institute in Boston, and his colleagues compared the effects of treatment with bortezomib/rituximab in patients with WM based on their CXCR4 mutation status. They found no significant difference in progression-free survival (Log-rank, P = .994) or overall survival (Log-rank, P = .407) when comparing patients who have CXCR4 mutations with those who have CXCR4 wild type.

“We report for the first time that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote in Blood. “Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”

The researchers noted, however, that the mechanism at work may be different than that seen with bortezomib in other cancers.

“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma. However, despite the complicated association in those cancer types, in WM there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data,” they wrote.

The researchers recommended that the theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations. Another question to be investigated, they pointed out, is the role of rituximab in the survival results seen in the current analysis.

The study included 63 patients with WM who were treated with bortezomib/rituximab either as upfront treatment or in the relapsed/refractory setting as part of a phase 2 trial.

Bortezomib was given by IV weekly at 1.6 mg/m² for six cycles and rituximab was given at 375 mg/m² during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.

The researchers excluded 20 patients from the study because of a lack of material for genotyping. However, they noted that their clinical characteristics were not different from those patients who were included.

Out of 43 patients who were genotyped for CXCR4, 17 patients had a mutation. All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations. The median follow-up of the analysis was 90.7 months.

The researchers repeated the analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.

The study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.

mschneider@mdedge.com

SOURCE: Sklavenitis-Pistofidis R et al. Blood. 2018 Oct 26. doi: 10.1182/blood-2018-07-863241.

The use of bortezomib may help overcome treatment resistance in patients with Waldenström macroglobulinemia (WM) with CXCR4 mutations, according to new research.

Romanos Sklavenitis-Pistofidis, MD, of the Dana-Farber Cancer Institute in Boston, and his colleagues compared the effects of treatment with bortezomib/rituximab in patients with WM based on their CXCR4 mutation status. They found no significant difference in progression-free survival (Log-rank, P = .994) or overall survival (Log-rank, P = .407) when comparing patients who have CXCR4 mutations with those who have CXCR4 wild type.

“We report for the first time that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote in Blood. “Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”

The researchers noted, however, that the mechanism at work may be different than that seen with bortezomib in other cancers.

“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma. However, despite the complicated association in those cancer types, in WM there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data,” they wrote.

The researchers recommended that the theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations. Another question to be investigated, they pointed out, is the role of rituximab in the survival results seen in the current analysis.

The study included 63 patients with WM who were treated with bortezomib/rituximab either as upfront treatment or in the relapsed/refractory setting as part of a phase 2 trial.

Bortezomib was given by IV weekly at 1.6 mg/m² for six cycles and rituximab was given at 375 mg/m² during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.

The researchers excluded 20 patients from the study because of a lack of material for genotyping. However, they noted that their clinical characteristics were not different from those patients who were included.

Out of 43 patients who were genotyped for CXCR4, 17 patients had a mutation. All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations. The median follow-up of the analysis was 90.7 months.

The researchers repeated the analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.

The study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.

mschneider@mdedge.com

SOURCE: Sklavenitis-Pistofidis R et al. Blood. 2018 Oct 26. doi: 10.1182/blood-2018-07-863241.

The combination of azacitidine and nivolumab produced “encouraging” results in a phase 2 trial of patients with relapsed or refractory acute myeloid leukemia (AML), according to researchers.

The overall response rate was 33%, and the median overall survival (OS) was 6.3 months. However, the researchers identified factors associated with improved response and survival that could be used to select patients for this treatment.

A quarter of patients on this trial had immune-related adverse events (AEs) that were considered related to treatment, and two patients died of AEs that may have been treatment related.

Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his colleagues reported these results in Cancer Discovery.

The trial included 70 patients with a median age of 70 years. More than half of the patients (56%) had de novo AML, and 44% had secondary AML. The median number of prior therapies was two; 64% of patients had received hypomethylating agents, 47% had received targeted therapies, and 19% had received allogeneic stem cell transplant (SCT).

For this trial, patients received azacitidine at 75 mg/m² on days 1 to 7 and nivolumab at 3 mg/kg on days 1 and 14 of each cycle. The median number of cycles was three. Patients had a median time on study of 3.5 months and reasons for discontinuation included primary refractory disease, relapse after initial response, proceeding to SCT, patient preference, and death.

The most common treatment-related, nonhematologic AEs were constipation, diarrhea, pneumonitis, nausea, and lung infection. The rate of immune-related AEs was 25% (n = 18), with grade 2-4 immune-related AEs occurring in 16 patients (8 with grade 3-4); 14 responded to steroids and were safely rechallenged with nivolumab, according to the researchers.

Nine patients (13%) discontinued nivolumab (but continued with azacitidine) because of AEs. Two patients died of AEs that were considered possibly related to treatment. One death was caused by progressive pneumonia/pneumonitis, and one was caused by hemophagocytic lymphohistiocytosis.

The overall response rate was 33% (n = 23), with 4 patients achieving a complete response (CR) and 11 achieving a CR with incomplete count recovery (CRi). One patient had a partial response, and seven had hematologic improvement in one or more parameter maintained for more than 6 months. Six patients had stable disease lasting more than 6 months.

The researchers noted that the response rate was higher among patients who had not received prior treatment with hypomethylating agents. Additionally, a higher frequency of pretherapy CD3 and CD8 cells in the bone marrow or peripheral blood appeared to predict response.

“In particular, CD3 appeared to have a high sensitivity and specificity rate for predicting response, indicating it might serve as a reliable biomarker for selecting patients for this combination therapy,” Dr. Daver said in a statement.

At a median follow-up of 21.4 months, 81% of patients (n = 57) had died; 16 died on study treatment and 41 died after discontinuation. The median OS overall was 6.3 months, and the median event-free survival was 4.5 months.

The median OS was 16.1 months in patients with CR/CRi, partial response, hematologic improvement, or stable disease and 4.1 months in nonresponders (P less than .0001). This difference was still significant after the researchers censored the three patients who had gone on to SCT in CR/CRi (P less than .001).

The researchers also found that being in first salvage was associated with improved OS in a univariate analysis and in a comparison with historical controls.

Dr. Daver and his colleagues concluded that azacitidine and nivolumab “produced an encouraging response rate and overall survival” in patients with relapsed/refractory AML.

“We believe that implementation of clinical and immune biomarkers to select patients are likely to yield further improved outcomes with these types of therapies in AML,” Dr. Daver said.

This research was supported by Bristol-Myers Squibb, the University of Texas MD Anderson Cancer Center, and the Dick Clark Immunotherapy Research Fund. Individual researchers also reported financial relationships with Bristol-Myers Squibb.

jensmith@mdedge.com

SOURCE: Daver N et al. Cancer Discov. 2018 Nov 8. doi: 10.1158/2159-8290.CD-18-0774.

The combination of azacitidine and nivolumab produced “encouraging” results in a phase 2 trial of patients with relapsed or refractory acute myeloid leukemia (AML), according to researchers.

The overall response rate was 33%, and the median overall survival (OS) was 6.3 months. However, the researchers identified factors associated with improved response and survival that could be used to select patients for this treatment.

A quarter of patients on this trial had immune-related adverse events (AEs) that were considered related to treatment, and two patients died of AEs that may have been treatment related.

Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his colleagues reported these results in Cancer Discovery.

The trial included 70 patients with a median age of 70 years. More than half of the patients (56%) had de novo AML, and 44% had secondary AML. The median number of prior therapies was two; 64% of patients had received hypomethylating agents, 47% had received targeted therapies, and 19% had received allogeneic stem cell transplant (SCT).

For this trial, patients received azacitidine at 75 mg/m² on days 1 to 7 and nivolumab at 3 mg/kg on days 1 and 14 of each cycle. The median number of cycles was three. Patients had a median time on study of 3.5 months and reasons for discontinuation included primary refractory disease, relapse after initial response, proceeding to SCT, patient preference, and death.

The most common treatment-related, nonhematologic AEs were constipation, diarrhea, pneumonitis, nausea, and lung infection. The rate of immune-related AEs was 25% (n = 18), with grade 2-4 immune-related AEs occurring in 16 patients (8 with grade 3-4); 14 responded to steroids and were safely rechallenged with nivolumab, according to the researchers.

Nine patients (13%) discontinued nivolumab (but continued with azacitidine) because of AEs. Two patients died of AEs that were considered possibly related to treatment. One death was caused by progressive pneumonia/pneumonitis, and one was caused by hemophagocytic lymphohistiocytosis.

The overall response rate was 33% (n = 23), with 4 patients achieving a complete response (CR) and 11 achieving a CR with incomplete count recovery (CRi). One patient had a partial response, and seven had hematologic improvement in one or more parameter maintained for more than 6 months. Six patients had stable disease lasting more than 6 months.

The researchers noted that the response rate was higher among patients who had not received prior treatment with hypomethylating agents. Additionally, a higher frequency of pretherapy CD3 and CD8 cells in the bone marrow or peripheral blood appeared to predict response.

“In particular, CD3 appeared to have a high sensitivity and specificity rate for predicting response, indicating it might serve as a reliable biomarker for selecting patients for this combination therapy,” Dr. Daver said in a statement.

At a median follow-up of 21.4 months, 81% of patients (n = 57) had died; 16 died on study treatment and 41 died after discontinuation. The median OS overall was 6.3 months, and the median event-free survival was 4.5 months.

The median OS was 16.1 months in patients with CR/CRi, partial response, hematologic improvement, or stable disease and 4.1 months in nonresponders (P less than .0001). This difference was still significant after the researchers censored the three patients who had gone on to SCT in CR/CRi (P less than .001).

The researchers also found that being in first salvage was associated with improved OS in a univariate analysis and in a comparison with historical controls.

Dr. Daver and his colleagues concluded that azacitidine and nivolumab “produced an encouraging response rate and overall survival” in patients with relapsed/refractory AML.

“We believe that implementation of clinical and immune biomarkers to select patients are likely to yield further improved outcomes with these types of therapies in AML,” Dr. Daver said.

This research was supported by Bristol-Myers Squibb, the University of Texas MD Anderson Cancer Center, and the Dick Clark Immunotherapy Research Fund. Individual researchers also reported financial relationships with Bristol-Myers Squibb.

jensmith@mdedge.com

SOURCE: Daver N et al. Cancer Discov. 2018 Nov 8. doi: 10.1158/2159-8290.CD-18-0774.

The combination of azacitidine and nivolumab produced “encouraging” results in a phase 2 trial of patients with relapsed or refractory acute myeloid leukemia (AML), according to researchers.

The overall response rate was 33%, and the median overall survival (OS) was 6.3 months. However, the researchers identified factors associated with improved response and survival that could be used to select patients for this treatment.

A quarter of patients on this trial had immune-related adverse events (AEs) that were considered related to treatment, and two patients died of AEs that may have been treatment related.

Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his colleagues reported these results in Cancer Discovery.

The trial included 70 patients with a median age of 70 years. More than half of the patients (56%) had de novo AML, and 44% had secondary AML. The median number of prior therapies was two; 64% of patients had received hypomethylating agents, 47% had received targeted therapies, and 19% had received allogeneic stem cell transplant (SCT).

For this trial, patients received azacitidine at 75 mg/m² on days 1 to 7 and nivolumab at 3 mg/kg on days 1 and 14 of each cycle. The median number of cycles was three. Patients had a median time on study of 3.5 months and reasons for discontinuation included primary refractory disease, relapse after initial response, proceeding to SCT, patient preference, and death.

The most common treatment-related, nonhematologic AEs were constipation, diarrhea, pneumonitis, nausea, and lung infection. The rate of immune-related AEs was 25% (n = 18), with grade 2-4 immune-related AEs occurring in 16 patients (8 with grade 3-4); 14 responded to steroids and were safely rechallenged with nivolumab, according to the researchers.

Nine patients (13%) discontinued nivolumab (but continued with azacitidine) because of AEs. Two patients died of AEs that were considered possibly related to treatment. One death was caused by progressive pneumonia/pneumonitis, and one was caused by hemophagocytic lymphohistiocytosis.

The overall response rate was 33% (n = 23), with 4 patients achieving a complete response (CR) and 11 achieving a CR with incomplete count recovery (CRi). One patient had a partial response, and seven had hematologic improvement in one or more parameter maintained for more than 6 months. Six patients had stable disease lasting more than 6 months.

The researchers noted that the response rate was higher among patients who had not received prior treatment with hypomethylating agents. Additionally, a higher frequency of pretherapy CD3 and CD8 cells in the bone marrow or peripheral blood appeared to predict response.

“In particular, CD3 appeared to have a high sensitivity and specificity rate for predicting response, indicating it might serve as a reliable biomarker for selecting patients for this combination therapy,” Dr. Daver said in a statement.

At a median follow-up of 21.4 months, 81% of patients (n = 57) had died; 16 died on study treatment and 41 died after discontinuation. The median OS overall was 6.3 months, and the median event-free survival was 4.5 months.

The median OS was 16.1 months in patients with CR/CRi, partial response, hematologic improvement, or stable disease and 4.1 months in nonresponders (P less than .0001). This difference was still significant after the researchers censored the three patients who had gone on to SCT in CR/CRi (P less than .001).

The researchers also found that being in first salvage was associated with improved OS in a univariate analysis and in a comparison with historical controls.

Dr. Daver and his colleagues concluded that azacitidine and nivolumab “produced an encouraging response rate and overall survival” in patients with relapsed/refractory AML.

“We believe that implementation of clinical and immune biomarkers to select patients are likely to yield further improved outcomes with these types of therapies in AML,” Dr. Daver said.

This research was supported by Bristol-Myers Squibb, the University of Texas MD Anderson Cancer Center, and the Dick Clark Immunotherapy Research Fund. Individual researchers also reported financial relationships with Bristol-Myers Squibb.

jensmith@mdedge.com

SOURCE: Daver N et al. Cancer Discov. 2018 Nov 8. doi: 10.1158/2159-8290.CD-18-0774.

MUNICH – Men with metastatic hormone-naive prostate cancer may benefit from treatment with the combination of abiraterone (Zytiga), prednisolone, and androgen deprivation regardless of risk group or disease volume, STAMPEDE trialists contend.

Results of the STAMPEDE and LATITUDE trials, published in 2017 in the New England Journal of Medicine, showed significant improvements in overall survival with abiraterone, androgen deprivation therapy (ADT) and either prednisone (in LATITUDE) or prednisolone (in STAMPEDE) compared with ADT alone.

Data from the LATITUDE trial were used to support approval by both the Food and Drug Administration and European Medicines Agency of abiraterone in combination with ADT and a glucocorticoid for the new indication of treatment of men with metastatic high-risk castration-sensitive prostate cancer.

“So where we stand, at the minute, in terms of guidance: the EAU [European Urology Association] and the NCCN [National Comprehensive Cancer Network] have suggested that we consider treatment for men with hormone-naive metastatic prostatic cancer, but in 2018 the FDA and EMA licensed the drug for high-risk disease, so there’s therefore an evolving uncertainty about what we should be doing in low-risk disease,” Alex Hoyle, MBChB, of Christie NHS Foundation Trust, Manchester, England, said on behalf of colleagues in the STAMPEDE trial group.

The problem is that there is no international consensus on what constitutes low-risk disease, Dr. Hoyle said at the European Society for Medical Oncology Congress.

For example, in the CHAARTED trial, risk was defined by volume, with high-risk patients defined as those with visceral metastases and/or four or more bone metastases with one or more outside the vertebral column or pelvis. In contrast, the LATITUDE investigators defined high-risk patients as those with two or more high-risk features, including three or more bone metastases, visceral metastases, and/or a Gleason score of 8 or more.

To determine whether men with low-risk disease could also benefit from the combination, Dr. Hoyle and colleagues performed a retrospective analysis of the STAMPEDE trial, using staging scans to stratify patients with M1 disease into either high- or low-risk categories according to the LATITUDE risk criteria. The reviewers were blinded to the treatment arm for each patient. They also performed a secondary differential analysis by tumor volume according to the CHAARTED criteria.

The investigators then retrospectively reviewed outcomes for 901 evaluable patients, median age 67 years, with a median PSA of 96 ng/mL, followed for a median of 42 months. The sample included 428 patients determined to have low-risk disease, and 473 determined to have high-risk disease.

Overall survival (OS), the primary endpoint, was significantly better for patients treated with the combination vs. ADT alone in both high- and low-risk groups. The 3-year OS in high-risk patients treated with the abiraterone/prednisolone/ADT was 64.7% compared with 45% for patients treated with AD alone, an absolute difference of 19.7% that translated into a hazard ratio (HR) for death of 0.54 (P less than .001).

For patients in the low-risk group, 3-year OS was 82.4% with the combination vs. 78% with ADT alone, an absolute difference of 4.4%, translating into an HR of 0.66 (P = .041).

Three-year prostate cancer-specific survival, a secondary endpoint, was better with abiraterone in the high-risk (67% vs. 47.9%, HR 0.57, P less than .001) and low-risk (88.7% vs. 81.6%, HR 0.51, P = .008) populations.

The results were even more pronounced in favor of the abiraterone combination for the secondary endpoint of failure-free survival (FFS) in both groups, with 45.1% of high-risk patients on abiraterone having no biochemical failure at 3 years vs. 12.2% for those treated with ADT alone (HR 0.48, P less than .001). The respective FFS rates in the low-risk group were 80.8% vs. 56.4% (HR 0.66, P = .041).

ADT was superior in analyses of skeletal related event-free survival (HR 0.48 for high risk and 0.31 for low risk, P less than .001 for both comparisons), and metastasis progression-free survival (HR 0.54, P less than .001 for high risk, HR 0.66, P = .041 for low risk).

An exploratory analysis using the CHAARTED risk criteria showed similar results, with the combination significantly better in every category except prostate cancer–specific survival in patients with low-volume disease, although here, too, there was a clear trend favoring abiraterone.

“Abiraterone plus prednisolone in addition to ADT improves survival endpoints in metastatic hormone-naive prostate cancer,” Dr. Hoyle said.

Invited discussant Karim Fizazi, MD, PhD, of Gustave Roussy Cancer Institute at the University of Paris-Sud, France, said that the study, despite some limitations, was very important.

“For patients with high-risk de novo disease, until today we’ve had two standards of care: castration plus abiraterone or castration plus docetaxel. For patients with low risk, that was strongly debated – either castration alone or castration plus docetaxel. After this publication, I think it’s fair to say that for patients with high-risk disease the role of abiraterone is being strengthened, while for patients with low-risk disease, ADT plus abiraterone probably is going to become the new standard,” he said.

The STAMPEDE trial is supported by the Medical Research Council of the United Kingdom, the Salford Royal and the Christie NHS Foundation trusts, and Manchester Cancer Research Centre. Dr. Hoyle reported having no conflicts of interest. Dr. Fizazi reported advisory board participation and/or honoraria from Amgen, Astellas, AstraZeneca, Bayer, Clovis, CureVac, Essa, Genentech, Janssen, MSD, Orion, and Sanofi.

SOURCE: Hoyle AP et al. ESMO 2018. Abstract LBA4.

MUNICH – Men with metastatic hormone-naive prostate cancer may benefit from treatment with the combination of abiraterone (Zytiga), prednisolone, and androgen deprivation regardless of risk group or disease volume, STAMPEDE trialists contend.

Results of the STAMPEDE and LATITUDE trials, published in 2017 in the New England Journal of Medicine, showed significant improvements in overall survival with abiraterone, androgen deprivation therapy (ADT) and either prednisone (in LATITUDE) or prednisolone (in STAMPEDE) compared with ADT alone.

Data from the LATITUDE trial were used to support approval by both the Food and Drug Administration and European Medicines Agency of abiraterone in combination with ADT and a glucocorticoid for the new indication of treatment of men with metastatic high-risk castration-sensitive prostate cancer.

“So where we stand, at the minute, in terms of guidance: the EAU [European Urology Association] and the NCCN [National Comprehensive Cancer Network] have suggested that we consider treatment for men with hormone-naive metastatic prostatic cancer, but in 2018 the FDA and EMA licensed the drug for high-risk disease, so there’s therefore an evolving uncertainty about what we should be doing in low-risk disease,” Alex Hoyle, MBChB, of Christie NHS Foundation Trust, Manchester, England, said on behalf of colleagues in the STAMPEDE trial group.

The problem is that there is no international consensus on what constitutes low-risk disease, Dr. Hoyle said at the European Society for Medical Oncology Congress.

For example, in the CHAARTED trial, risk was defined by volume, with high-risk patients defined as those with visceral metastases and/or four or more bone metastases with one or more outside the vertebral column or pelvis. In contrast, the LATITUDE investigators defined high-risk patients as those with two or more high-risk features, including three or more bone metastases, visceral metastases, and/or a Gleason score of 8 or more.

To determine whether men with low-risk disease could also benefit from the combination, Dr. Hoyle and colleagues performed a retrospective analysis of the STAMPEDE trial, using staging scans to stratify patients with M1 disease into either high- or low-risk categories according to the LATITUDE risk criteria. The reviewers were blinded to the treatment arm for each patient. They also performed a secondary differential analysis by tumor volume according to the CHAARTED criteria.

The investigators then retrospectively reviewed outcomes for 901 evaluable patients, median age 67 years, with a median PSA of 96 ng/mL, followed for a median of 42 months. The sample included 428 patients determined to have low-risk disease, and 473 determined to have high-risk disease.

Overall survival (OS), the primary endpoint, was significantly better for patients treated with the combination vs. ADT alone in both high- and low-risk groups. The 3-year OS in high-risk patients treated with the abiraterone/prednisolone/ADT was 64.7% compared with 45% for patients treated with AD alone, an absolute difference of 19.7% that translated into a hazard ratio (HR) for death of 0.54 (P less than .001).

For patients in the low-risk group, 3-year OS was 82.4% with the combination vs. 78% with ADT alone, an absolute difference of 4.4%, translating into an HR of 0.66 (P = .041).

Three-year prostate cancer-specific survival, a secondary endpoint, was better with abiraterone in the high-risk (67% vs. 47.9%, HR 0.57, P less than .001) and low-risk (88.7% vs. 81.6%, HR 0.51, P = .008) populations.

The results were even more pronounced in favor of the abiraterone combination for the secondary endpoint of failure-free survival (FFS) in both groups, with 45.1% of high-risk patients on abiraterone having no biochemical failure at 3 years vs. 12.2% for those treated with ADT alone (HR 0.48, P less than .001). The respective FFS rates in the low-risk group were 80.8% vs. 56.4% (HR 0.66, P = .041).

ADT was superior in analyses of skeletal related event-free survival (HR 0.48 for high risk and 0.31 for low risk, P less than .001 for both comparisons), and metastasis progression-free survival (HR 0.54, P less than .001 for high risk, HR 0.66, P = .041 for low risk).

An exploratory analysis using the CHAARTED risk criteria showed similar results, with the combination significantly better in every category except prostate cancer–specific survival in patients with low-volume disease, although here, too, there was a clear trend favoring abiraterone.

“Abiraterone plus prednisolone in addition to ADT improves survival endpoints in metastatic hormone-naive prostate cancer,” Dr. Hoyle said.

Invited discussant Karim Fizazi, MD, PhD, of Gustave Roussy Cancer Institute at the University of Paris-Sud, France, said that the study, despite some limitations, was very important.

“For patients with high-risk de novo disease, until today we’ve had two standards of care: castration plus abiraterone or castration plus docetaxel. For patients with low risk, that was strongly debated – either castration alone or castration plus docetaxel. After this publication, I think it’s fair to say that for patients with high-risk disease the role of abiraterone is being strengthened, while for patients with low-risk disease, ADT plus abiraterone probably is going to become the new standard,” he said.

The STAMPEDE trial is supported by the Medical Research Council of the United Kingdom, the Salford Royal and the Christie NHS Foundation trusts, and Manchester Cancer Research Centre. Dr. Hoyle reported having no conflicts of interest. Dr. Fizazi reported advisory board participation and/or honoraria from Amgen, Astellas, AstraZeneca, Bayer, Clovis, CureVac, Essa, Genentech, Janssen, MSD, Orion, and Sanofi.

SOURCE: Hoyle AP et al. ESMO 2018. Abstract LBA4.

MUNICH – Men with metastatic hormone-naive prostate cancer may benefit from treatment with the combination of abiraterone (Zytiga), prednisolone, and androgen deprivation regardless of risk group or disease volume, STAMPEDE trialists contend.

Results of the STAMPEDE and LATITUDE trials, published in 2017 in the New England Journal of Medicine, showed significant improvements in overall survival with abiraterone, androgen deprivation therapy (ADT) and either prednisone (in LATITUDE) or prednisolone (in STAMPEDE) compared with ADT alone.

Data from the LATITUDE trial were used to support approval by both the Food and Drug Administration and European Medicines Agency of abiraterone in combination with ADT and a glucocorticoid for the new indication of treatment of men with metastatic high-risk castration-sensitive prostate cancer.

“So where we stand, at the minute, in terms of guidance: the EAU [European Urology Association] and the NCCN [National Comprehensive Cancer Network] have suggested that we consider treatment for men with hormone-naive metastatic prostatic cancer, but in 2018 the FDA and EMA licensed the drug for high-risk disease, so there’s therefore an evolving uncertainty about what we should be doing in low-risk disease,” Alex Hoyle, MBChB, of Christie NHS Foundation Trust, Manchester, England, said on behalf of colleagues in the STAMPEDE trial group.

The problem is that there is no international consensus on what constitutes low-risk disease, Dr. Hoyle said at the European Society for Medical Oncology Congress.

For example, in the CHAARTED trial, risk was defined by volume, with high-risk patients defined as those with visceral metastases and/or four or more bone metastases with one or more outside the vertebral column or pelvis. In contrast, the LATITUDE investigators defined high-risk patients as those with two or more high-risk features, including three or more bone metastases, visceral metastases, and/or a Gleason score of 8 or more.

To determine whether men with low-risk disease could also benefit from the combination, Dr. Hoyle and colleagues performed a retrospective analysis of the STAMPEDE trial, using staging scans to stratify patients with M1 disease into either high- or low-risk categories according to the LATITUDE risk criteria. The reviewers were blinded to the treatment arm for each patient. They also performed a secondary differential analysis by tumor volume according to the CHAARTED criteria.

The investigators then retrospectively reviewed outcomes for 901 evaluable patients, median age 67 years, with a median PSA of 96 ng/mL, followed for a median of 42 months. The sample included 428 patients determined to have low-risk disease, and 473 determined to have high-risk disease.

Overall survival (OS), the primary endpoint, was significantly better for patients treated with the combination vs. ADT alone in both high- and low-risk groups. The 3-year OS in high-risk patients treated with the abiraterone/prednisolone/ADT was 64.7% compared with 45% for patients treated with AD alone, an absolute difference of 19.7% that translated into a hazard ratio (HR) for death of 0.54 (P less than .001).

For patients in the low-risk group, 3-year OS was 82.4% with the combination vs. 78% with ADT alone, an absolute difference of 4.4%, translating into an HR of 0.66 (P = .041).

Three-year prostate cancer-specific survival, a secondary endpoint, was better with abiraterone in the high-risk (67% vs. 47.9%, HR 0.57, P less than .001) and low-risk (88.7% vs. 81.6%, HR 0.51, P = .008) populations.

The results were even more pronounced in favor of the abiraterone combination for the secondary endpoint of failure-free survival (FFS) in both groups, with 45.1% of high-risk patients on abiraterone having no biochemical failure at 3 years vs. 12.2% for those treated with ADT alone (HR 0.48, P less than .001). The respective FFS rates in the low-risk group were 80.8% vs. 56.4% (HR 0.66, P = .041).

ADT was superior in analyses of skeletal related event-free survival (HR 0.48 for high risk and 0.31 for low risk, P less than .001 for both comparisons), and metastasis progression-free survival (HR 0.54, P less than .001 for high risk, HR 0.66, P = .041 for low risk).

An exploratory analysis using the CHAARTED risk criteria showed similar results, with the combination significantly better in every category except prostate cancer–specific survival in patients with low-volume disease, although here, too, there was a clear trend favoring abiraterone.

“Abiraterone plus prednisolone in addition to ADT improves survival endpoints in metastatic hormone-naive prostate cancer,” Dr. Hoyle said.

Invited discussant Karim Fizazi, MD, PhD, of Gustave Roussy Cancer Institute at the University of Paris-Sud, France, said that the study, despite some limitations, was very important.

“For patients with high-risk de novo disease, until today we’ve had two standards of care: castration plus abiraterone or castration plus docetaxel. For patients with low risk, that was strongly debated – either castration alone or castration plus docetaxel. After this publication, I think it’s fair to say that for patients with high-risk disease the role of abiraterone is being strengthened, while for patients with low-risk disease, ADT plus abiraterone probably is going to become the new standard,” he said.

The STAMPEDE trial is supported by the Medical Research Council of the United Kingdom, the Salford Royal and the Christie NHS Foundation trusts, and Manchester Cancer Research Centre. Dr. Hoyle reported having no conflicts of interest. Dr. Fizazi reported advisory board participation and/or honoraria from Amgen, Astellas, AstraZeneca, Bayer, Clovis, CureVac, Essa, Genentech, Janssen, MSD, Orion, and Sanofi.

SOURCE: Hoyle AP et al. ESMO 2018. Abstract LBA4.

Osteoporosis is common among patients with multiple myeloma (MM), in part because both largely affect older adults. And more than half of MM patients will have MM skeletal-related events, which are painful, and can lead to complications (such as spinal cord compression) and death.

But how does pre-existing bone disease contribute to clinical outcomes in MM? Osteoporosis is a “silent condition” and very little is known about its role in MM, say researchers from The Ohio State University in Columbus and University of Massachusetts in Worcester. The standard diagnostic evaluation for MM does not include dual-energy x-ray absorptiometry, therefore assessments of underlying osteoporosis are not routine. Moreover, it is a challenge to distinguish osteoporotic fragility fractures from pathologic MM-induced fractures. Skeletal surveys underestimate bone involvement by about 40%, the researchers note, and are even less specific for distinguishing myeloma-related secondary osteoporosis from primary osteoporosis.

The researchers examined the relationship between the Fracture Risk Assessment Tool (FRAX) and the risk of death in women who developed MM. They analyzed data from 161,808 women in the Women’s Health Initiative (WHI). Of those, 409 developed MM; 362 had no history of cancer.

At baseline, 98 (27%) women had high FRAX scores, and 264 (73%) had low scores. The median follow-up period was 10.5 years from enrollment and 7.2 years from the time of MM diagnosis. Of the patients with MM, 226 died during the follow-up period, including 71 with high FRAX scores and 155 with low scores. MM mortality was higher among women with high FRAX scores: 72%, vs 59% of those with low scores. Poor bone health was associated with greater MM mortality but was not related to delay in time to diagnosis.

During the evaluation, 57 fractures were reported, 65% before MM diagnosis. Fewer than half of the women had a first fracture after diagnosis. The probability of fracture was similar among the women, regardless of FRAX score. Not surprisingly, older women with lower BMI were most at risk.

The WHI does not include information on staging, chemotherapy, or use of bisphosphonates. Therefore, the impact of bisphosphonates could not be determined in this study. The researchers also did not know how many patients might have had pre-existing monoclonal gammopathy of undetermined significance, a disorder in about 3% of the aging population that progresses to MM in 1% per year.

Source:
Rosko AE, Hade EM, Li W, et al. Clin Lymphoma Myeloma Leuk. 2018;18(9):597-602.

Osteoporosis is common among patients with multiple myeloma (MM), in part because both largely affect older adults. And more than half of MM patients will have MM skeletal-related events, which are painful, and can lead to complications (such as spinal cord compression) and death.

But how does pre-existing bone disease contribute to clinical outcomes in MM? Osteoporosis is a “silent condition” and very little is known about its role in MM, say researchers from The Ohio State University in Columbus and University of Massachusetts in Worcester. The standard diagnostic evaluation for MM does not include dual-energy x-ray absorptiometry, therefore assessments of underlying osteoporosis are not routine. Moreover, it is a challenge to distinguish osteoporotic fragility fractures from pathologic MM-induced fractures. Skeletal surveys underestimate bone involvement by about 40%, the researchers note, and are even less specific for distinguishing myeloma-related secondary osteoporosis from primary osteoporosis.

The researchers examined the relationship between the Fracture Risk Assessment Tool (FRAX) and the risk of death in women who developed MM. They analyzed data from 161,808 women in the Women’s Health Initiative (WHI). Of those, 409 developed MM; 362 had no history of cancer.

At baseline, 98 (27%) women had high FRAX scores, and 264 (73%) had low scores. The median follow-up period was 10.5 years from enrollment and 7.2 years from the time of MM diagnosis. Of the patients with MM, 226 died during the follow-up period, including 71 with high FRAX scores and 155 with low scores. MM mortality was higher among women with high FRAX scores: 72%, vs 59% of those with low scores. Poor bone health was associated with greater MM mortality but was not related to delay in time to diagnosis.

During the evaluation, 57 fractures were reported, 65% before MM diagnosis. Fewer than half of the women had a first fracture after diagnosis. The probability of fracture was similar among the women, regardless of FRAX score. Not surprisingly, older women with lower BMI were most at risk.

The WHI does not include information on staging, chemotherapy, or use of bisphosphonates. Therefore, the impact of bisphosphonates could not be determined in this study. The researchers also did not know how many patients might have had pre-existing monoclonal gammopathy of undetermined significance, a disorder in about 3% of the aging population that progresses to MM in 1% per year.

Source:
Rosko AE, Hade EM, Li W, et al. Clin Lymphoma Myeloma Leuk. 2018;18(9):597-602.

Osteoporosis is common among patients with multiple myeloma (MM), in part because both largely affect older adults. And more than half of MM patients will have MM skeletal-related events, which are painful, and can lead to complications (such as spinal cord compression) and death.

But how does pre-existing bone disease contribute to clinical outcomes in MM? Osteoporosis is a “silent condition” and very little is known about its role in MM, say researchers from The Ohio State University in Columbus and University of Massachusetts in Worcester. The standard diagnostic evaluation for MM does not include dual-energy x-ray absorptiometry, therefore assessments of underlying osteoporosis are not routine. Moreover, it is a challenge to distinguish osteoporotic fragility fractures from pathologic MM-induced fractures. Skeletal surveys underestimate bone involvement by about 40%, the researchers note, and are even less specific for distinguishing myeloma-related secondary osteoporosis from primary osteoporosis.

The researchers examined the relationship between the Fracture Risk Assessment Tool (FRAX) and the risk of death in women who developed MM. They analyzed data from 161,808 women in the Women’s Health Initiative (WHI). Of those, 409 developed MM; 362 had no history of cancer.

At baseline, 98 (27%) women had high FRAX scores, and 264 (73%) had low scores. The median follow-up period was 10.5 years from enrollment and 7.2 years from the time of MM diagnosis. Of the patients with MM, 226 died during the follow-up period, including 71 with high FRAX scores and 155 with low scores. MM mortality was higher among women with high FRAX scores: 72%, vs 59% of those with low scores. Poor bone health was associated with greater MM mortality but was not related to delay in time to diagnosis.

During the evaluation, 57 fractures were reported, 65% before MM diagnosis. Fewer than half of the women had a first fracture after diagnosis. The probability of fracture was similar among the women, regardless of FRAX score. Not surprisingly, older women with lower BMI were most at risk.

The WHI does not include information on staging, chemotherapy, or use of bisphosphonates. Therefore, the impact of bisphosphonates could not be determined in this study. The researchers also did not know how many patients might have had pre-existing monoclonal gammopathy of undetermined significance, a disorder in about 3% of the aging population that progresses to MM in 1% per year.

Source:
Rosko AE, Hade EM, Li W, et al. Clin Lymphoma Myeloma Leuk. 2018;18(9):597-602.

DUBROVNIK, CROATIA – New research suggests there is no association between the PTPN22 R620W polymorphism and chronic lymphocytic leukemia (CLL) or autoimmune hematologic disorders in patients from the Republic of Macedonia.

Past studies have shown an association between the PTPN22 R620W variant and both CLL and autoimmune diseases in patients from Northwest Europe. However, a new study of Macedonian patients suggests there is no association between the variant and CLL, autoimmune hemolytic anemia (AIHA), or idiopathic thrombocytopenic purpura (ITP) for patients from Southeast Europe.

Irina Panovska-Stavridis, PhD, of Ss. Cyril and Methodius University in Skopje, Republic of Macedonia, and her colleagues presented this finding at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.

“A lot of data from the literature suggests [the PTPN22 R620W variant ] has a role in developing multiple immune diseases, but it is validated just in patients from Northwest Europe,” Dr. Panovska-Stavridis noted.

She and her colleagues decided to assess the frequency of the PTPN22 R620W variant (C1858T, rs2476601) in individuals from Southeast Europe, particularly the Republic of Macedonia.

The researchers evaluated 320 patients – 168 with CLL, 66 with AIHA, and 86 with ITP – and 182 age- and sex-matched control subjects with no history of malignant or autoimmune disease.

The team found a similar frequency of the minor T allele and genotype distribution in control subjects and patients. For example, minor T allele was 0.107 in CLL, 0.067 in AIHA, 0.036 in ITP, and 0.05 in controls. Similarly, the frequency of the CC genotype was 0.809 in CLL, 0.166 in AIHA, 0.023 in ITP, and 0.901 in controls.

Dr. Panovska-Stavridis said these results suggest the PTPN22 R620W variant is not a risk factor for the development of CLL, AIHA, or ITP in patients from Southeast Europe.

She also said the results suggest the influence of the variant on lymphocytic homeostasis is affected by certain genetic and environmental factors, and the development of CLL and autoimmune diseases is influenced by race/ethnicity-based variations in the germline composition of the IGHV locus in correlation with environmental factors.

Dr. Panovska-Stavridis did not declare any conflicts of interest.

The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.
 

jensmith@mdedge.com

DUBROVNIK, CROATIA – New research suggests there is no association between the PTPN22 R620W polymorphism and chronic lymphocytic leukemia (CLL) or autoimmune hematologic disorders in patients from the Republic of Macedonia.

Past studies have shown an association between the PTPN22 R620W variant and both CLL and autoimmune diseases in patients from Northwest Europe. However, a new study of Macedonian patients suggests there is no association between the variant and CLL, autoimmune hemolytic anemia (AIHA), or idiopathic thrombocytopenic purpura (ITP) for patients from Southeast Europe.

Irina Panovska-Stavridis, PhD, of Ss. Cyril and Methodius University in Skopje, Republic of Macedonia, and her colleagues presented this finding at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.

“A lot of data from the literature suggests [the PTPN22 R620W variant ] has a role in developing multiple immune diseases, but it is validated just in patients from Northwest Europe,” Dr. Panovska-Stavridis noted.

She and her colleagues decided to assess the frequency of the PTPN22 R620W variant (C1858T, rs2476601) in individuals from Southeast Europe, particularly the Republic of Macedonia.

The researchers evaluated 320 patients – 168 with CLL, 66 with AIHA, and 86 with ITP – and 182 age- and sex-matched control subjects with no history of malignant or autoimmune disease.

The team found a similar frequency of the minor T allele and genotype distribution in control subjects and patients. For example, minor T allele was 0.107 in CLL, 0.067 in AIHA, 0.036 in ITP, and 0.05 in controls. Similarly, the frequency of the CC genotype was 0.809 in CLL, 0.166 in AIHA, 0.023 in ITP, and 0.901 in controls.

Dr. Panovska-Stavridis said these results suggest the PTPN22 R620W variant is not a risk factor for the development of CLL, AIHA, or ITP in patients from Southeast Europe.

She also said the results suggest the influence of the variant on lymphocytic homeostasis is affected by certain genetic and environmental factors, and the development of CLL and autoimmune diseases is influenced by race/ethnicity-based variations in the germline composition of the IGHV locus in correlation with environmental factors.

Dr. Panovska-Stavridis did not declare any conflicts of interest.

The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.
 

jensmith@mdedge.com

DUBROVNIK, CROATIA – New research suggests there is no association between the PTPN22 R620W polymorphism and chronic lymphocytic leukemia (CLL) or autoimmune hematologic disorders in patients from the Republic of Macedonia.

Past studies have shown an association between the PTPN22 R620W variant and both CLL and autoimmune diseases in patients from Northwest Europe. However, a new study of Macedonian patients suggests there is no association between the variant and CLL, autoimmune hemolytic anemia (AIHA), or idiopathic thrombocytopenic purpura (ITP) for patients from Southeast Europe.

Irina Panovska-Stavridis, PhD, of Ss. Cyril and Methodius University in Skopje, Republic of Macedonia, and her colleagues presented this finding at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.

“A lot of data from the literature suggests [the PTPN22 R620W variant ] has a role in developing multiple immune diseases, but it is validated just in patients from Northwest Europe,” Dr. Panovska-Stavridis noted.

She and her colleagues decided to assess the frequency of the PTPN22 R620W variant (C1858T, rs2476601) in individuals from Southeast Europe, particularly the Republic of Macedonia.

The researchers evaluated 320 patients – 168 with CLL, 66 with AIHA, and 86 with ITP – and 182 age- and sex-matched control subjects with no history of malignant or autoimmune disease.

The team found a similar frequency of the minor T allele and genotype distribution in control subjects and patients. For example, minor T allele was 0.107 in CLL, 0.067 in AIHA, 0.036 in ITP, and 0.05 in controls. Similarly, the frequency of the CC genotype was 0.809 in CLL, 0.166 in AIHA, 0.023 in ITP, and 0.901 in controls.

Dr. Panovska-Stavridis said these results suggest the PTPN22 R620W variant is not a risk factor for the development of CLL, AIHA, or ITP in patients from Southeast Europe.

She also said the results suggest the influence of the variant on lymphocytic homeostasis is affected by certain genetic and environmental factors, and the development of CLL and autoimmune diseases is influenced by race/ethnicity-based variations in the germline composition of the IGHV locus in correlation with environmental factors.

Dr. Panovska-Stavridis did not declare any conflicts of interest.

The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.
 

jensmith@mdedge.com

Obesity and weight gain are linked to increased risk of colorectal cancer in younger women, according to an analysis of a large, prospective U.S. cohort study.

Young women who were obese had a nearly twofold increase in risk of early-onset colorectal cancer, compared with women of normal weight, authors of the study reported in JAMA Oncology.

The findings suggest body weight could be used to “personalize and complement” early cancer screening strategies among adults younger than 50 years, said investigator Po-Hong Liu, MD, of Washington University, St. Louis, and coauthors.

“Given that most of these younger cases are diagnosed symptomatically with more advanced tumors and with a significant influence on years of life lost, our findings reinforce the benefits of maintaining a healthy weight throughout life,” Dr. Liu and coinvestigators said in their report.

Their analysis was based on the ongoing Nurses Health Study II, which began in 1989 and enrolled a total of 116,430 women between the ages of 25 and 42 years in 14 U.S. states. Women completed questionnaires on demographics, medical and health information, and lifestyle factors every 2 years after enrollment.

Dr. Liu and colleagues were able to document 114 cases of colorectal cancer over a median of 13.9 years of follow-up in 85,256 women who had no cancer or inflammatory bowel disease when they were enrolled in the study. The median age at diagnosis for these cancers was 45 years.

Obesity was independently associated with increased risk of these early-onset colorectal cancers, the investigators found in multivariable analysis.

Women with a body mass index of 30 kg/m² or higher had a relative risk of 1.93 (95% confidence interval, 1.15-3.25) versus women with normal BMIs in the 18.5 to 22.9-kg/m² range, according to results of the analysis, they reported.

There was an apparent linear trend between increasing weight and increasing colorectal cancer risk, they added in their report.

They also found links between BMI in early adulthood and risk of early-onset colorectal cancer, including a relative risk of 1.63 for women who reported a BMI of 23 kg/m² or higher at 18 years of age, versus women with a BMI of 18.5-20.9 kg/m² at that age.

Similarly, increase in weight since early adulthood was associated with increased cancer risk, they reported.

While the link between excess weight and colorectal cancer incidence and mortality is well established in previous studies, this study is one of few reports looking at the association in younger individuals, according to Dr. Liu and colleagues.

This is thought to be the first prospective study looking at the link between obesity and risk of colo-rectal cancer diagnosed before the age of 50, they added.

The study was funded by grants from the National Institutes of Health. Dr. Liu had no conflict of interest disclosures related to the study. One coauthor reported consulting fees from Bayer Pharma AG, Janssen, and Pfizer.

ginews@gastro.org

SOURCE: Liu P-H et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4280.

AGA Resource 

Visit the AGA GI Patient Center for education to share with your patients about obesity, colorectal cancer and other GI disorders at patient.gastro.org.

Obesity and weight gain are linked to increased risk of colorectal cancer in younger women, according to an analysis of a large, prospective U.S. cohort study.

Young women who were obese had a nearly twofold increase in risk of early-onset colorectal cancer, compared with women of normal weight, authors of the study reported in JAMA Oncology.

The findings suggest body weight could be used to “personalize and complement” early cancer screening strategies among adults younger than 50 years, said investigator Po-Hong Liu, MD, of Washington University, St. Louis, and coauthors.

“Given that most of these younger cases are diagnosed symptomatically with more advanced tumors and with a significant influence on years of life lost, our findings reinforce the benefits of maintaining a healthy weight throughout life,” Dr. Liu and coinvestigators said in their report.

Their analysis was based on the ongoing Nurses Health Study II, which began in 1989 and enrolled a total of 116,430 women between the ages of 25 and 42 years in 14 U.S. states. Women completed questionnaires on demographics, medical and health information, and lifestyle factors every 2 years after enrollment.

Dr. Liu and colleagues were able to document 114 cases of colorectal cancer over a median of 13.9 years of follow-up in 85,256 women who had no cancer or inflammatory bowel disease when they were enrolled in the study. The median age at diagnosis for these cancers was 45 years.

Obesity was independently associated with increased risk of these early-onset colorectal cancers, the investigators found in multivariable analysis.

Women with a body mass index of 30 kg/m² or higher had a relative risk of 1.93 (95% confidence interval, 1.15-3.25) versus women with normal BMIs in the 18.5 to 22.9-kg/m² range, according to results of the analysis, they reported.

There was an apparent linear trend between increasing weight and increasing colorectal cancer risk, they added in their report.

They also found links between BMI in early adulthood and risk of early-onset colorectal cancer, including a relative risk of 1.63 for women who reported a BMI of 23 kg/m² or higher at 18 years of age, versus women with a BMI of 18.5-20.9 kg/m² at that age.

Similarly, increase in weight since early adulthood was associated with increased cancer risk, they reported.

While the link between excess weight and colorectal cancer incidence and mortality is well established in previous studies, this study is one of few reports looking at the association in younger individuals, according to Dr. Liu and colleagues.

This is thought to be the first prospective study looking at the link between obesity and risk of colo-rectal cancer diagnosed before the age of 50, they added.

The study was funded by grants from the National Institutes of Health. Dr. Liu had no conflict of interest disclosures related to the study. One coauthor reported consulting fees from Bayer Pharma AG, Janssen, and Pfizer.

ginews@gastro.org

SOURCE: Liu P-H et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4280.

AGA Resource 

Visit the AGA GI Patient Center for education to share with your patients about obesity, colorectal cancer and other GI disorders at patient.gastro.org.

Obesity and weight gain are linked to increased risk of colorectal cancer in younger women, according to an analysis of a large, prospective U.S. cohort study.

Young women who were obese had a nearly twofold increase in risk of early-onset colorectal cancer, compared with women of normal weight, authors of the study reported in JAMA Oncology.

The findings suggest body weight could be used to “personalize and complement” early cancer screening strategies among adults younger than 50 years, said investigator Po-Hong Liu, MD, of Washington University, St. Louis, and coauthors.

“Given that most of these younger cases are diagnosed symptomatically with more advanced tumors and with a significant influence on years of life lost, our findings reinforce the benefits of maintaining a healthy weight throughout life,” Dr. Liu and coinvestigators said in their report.

Their analysis was based on the ongoing Nurses Health Study II, which began in 1989 and enrolled a total of 116,430 women between the ages of 25 and 42 years in 14 U.S. states. Women completed questionnaires on demographics, medical and health information, and lifestyle factors every 2 years after enrollment.

Dr. Liu and colleagues were able to document 114 cases of colorectal cancer over a median of 13.9 years of follow-up in 85,256 women who had no cancer or inflammatory bowel disease when they were enrolled in the study. The median age at diagnosis for these cancers was 45 years.

Obesity was independently associated with increased risk of these early-onset colorectal cancers, the investigators found in multivariable analysis.

Women with a body mass index of 30 kg/m² or higher had a relative risk of 1.93 (95% confidence interval, 1.15-3.25) versus women with normal BMIs in the 18.5 to 22.9-kg/m² range, according to results of the analysis, they reported.

There was an apparent linear trend between increasing weight and increasing colorectal cancer risk, they added in their report.

They also found links between BMI in early adulthood and risk of early-onset colorectal cancer, including a relative risk of 1.63 for women who reported a BMI of 23 kg/m² or higher at 18 years of age, versus women with a BMI of 18.5-20.9 kg/m² at that age.

Similarly, increase in weight since early adulthood was associated with increased cancer risk, they reported.

While the link between excess weight and colorectal cancer incidence and mortality is well established in previous studies, this study is one of few reports looking at the association in younger individuals, according to Dr. Liu and colleagues.

This is thought to be the first prospective study looking at the link between obesity and risk of colo-rectal cancer diagnosed before the age of 50, they added.

The study was funded by grants from the National Institutes of Health. Dr. Liu had no conflict of interest disclosures related to the study. One coauthor reported consulting fees from Bayer Pharma AG, Janssen, and Pfizer.

ginews@gastro.org

SOURCE: Liu P-H et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4280.

AGA Resource 

Visit the AGA GI Patient Center for education to share with your patients about obesity, colorectal cancer and other GI disorders at patient.gastro.org.