AVAHO

The CDC developed the Colorectal Cancer Control Program (CRCCP) to provide direct colorectal cancer (CRC) screening services to low-income, uninsured, or underinsured populations known to have low CRC screening rates. However, early evaluators found the program was insufficient to detect impact at the state level. In response to those findings, the CDC redesigned CRCCP and funded a new 5-year grant period beginning in 2015. How did the program fare this time? CDC researchers say it “shows promise.”

The CRCCP funds 23 states, 6 universities, and 1 tribal organization to partner with health care systems, implementing evidence-based interventions (EBIs). In this study, the researchers analyzed data reported by 387 of 413 clinics of varying sizes, representing 3,438 providers, and serving a screening-eligible population of 722,925 patients.

The researchers say their evaluation suggests that the CRCCP is working as intended: Program reach was measurable and “substantial,” clinics enhanced EBIs in place or implemented new ones, and the overall average screening rate rose.

At baseline, the screening rate was low (43%), and lowest in rural clinics—although evidence indicates that death rates for CRC are highest among people living in rural areas. In the first year, the overall screening rate increased by 4.4 percentage points. Still, that 47.3% is “much lower” than the commonly cited 67.3% from the 2016 Behavioral Risk Factor Surveillance System, the researchers note. They add, though, that the results confirm that grantees are working with clinics serving the intended populations and indicate the significant gap in CRC screening rates between those reached by the CRCCP and the US population overall.

Many clinics had ≥ 1 EBI or supporting activity (SA) already in place. Grantees used CRCCP resources to implement new or to enhance EBIs in 95% of the clinics, most often patient reminder activities and provider assessment and feedback. Most of the clinics used CRCCP resources for SAs, such as small media and provider education. Only 12% of clinics used resources for supporting community health workers. However, nearly half the clinics conducted planning activities for future implementation of community health workers and patient navigators.

Nearly 80% of the clinics reported having a CRC screening champion, 73% had a CRC screening policy, and 50% had either 3 or 4 EBIs in place at the end of the first year—all factors that the researchers suggest may support greater screening rate increases.

The CDC developed the Colorectal Cancer Control Program (CRCCP) to provide direct colorectal cancer (CRC) screening services to low-income, uninsured, or underinsured populations known to have low CRC screening rates. However, early evaluators found the program was insufficient to detect impact at the state level. In response to those findings, the CDC redesigned CRCCP and funded a new 5-year grant period beginning in 2015. How did the program fare this time? CDC researchers say it “shows promise.”

The CRCCP funds 23 states, 6 universities, and 1 tribal organization to partner with health care systems, implementing evidence-based interventions (EBIs). In this study, the researchers analyzed data reported by 387 of 413 clinics of varying sizes, representing 3,438 providers, and serving a screening-eligible population of 722,925 patients.

The researchers say their evaluation suggests that the CRCCP is working as intended: Program reach was measurable and “substantial,” clinics enhanced EBIs in place or implemented new ones, and the overall average screening rate rose.

At baseline, the screening rate was low (43%), and lowest in rural clinics—although evidence indicates that death rates for CRC are highest among people living in rural areas. In the first year, the overall screening rate increased by 4.4 percentage points. Still, that 47.3% is “much lower” than the commonly cited 67.3% from the 2016 Behavioral Risk Factor Surveillance System, the researchers note. They add, though, that the results confirm that grantees are working with clinics serving the intended populations and indicate the significant gap in CRC screening rates between those reached by the CRCCP and the US population overall.

Many clinics had ≥ 1 EBI or supporting activity (SA) already in place. Grantees used CRCCP resources to implement new or to enhance EBIs in 95% of the clinics, most often patient reminder activities and provider assessment and feedback. Most of the clinics used CRCCP resources for SAs, such as small media and provider education. Only 12% of clinics used resources for supporting community health workers. However, nearly half the clinics conducted planning activities for future implementation of community health workers and patient navigators.

Nearly 80% of the clinics reported having a CRC screening champion, 73% had a CRC screening policy, and 50% had either 3 or 4 EBIs in place at the end of the first year—all factors that the researchers suggest may support greater screening rate increases.

The CDC developed the Colorectal Cancer Control Program (CRCCP) to provide direct colorectal cancer (CRC) screening services to low-income, uninsured, or underinsured populations known to have low CRC screening rates. However, early evaluators found the program was insufficient to detect impact at the state level. In response to those findings, the CDC redesigned CRCCP and funded a new 5-year grant period beginning in 2015. How did the program fare this time? CDC researchers say it “shows promise.”

The CRCCP funds 23 states, 6 universities, and 1 tribal organization to partner with health care systems, implementing evidence-based interventions (EBIs). In this study, the researchers analyzed data reported by 387 of 413 clinics of varying sizes, representing 3,438 providers, and serving a screening-eligible population of 722,925 patients.

The researchers say their evaluation suggests that the CRCCP is working as intended: Program reach was measurable and “substantial,” clinics enhanced EBIs in place or implemented new ones, and the overall average screening rate rose.

At baseline, the screening rate was low (43%), and lowest in rural clinics—although evidence indicates that death rates for CRC are highest among people living in rural areas. In the first year, the overall screening rate increased by 4.4 percentage points. Still, that 47.3% is “much lower” than the commonly cited 67.3% from the 2016 Behavioral Risk Factor Surveillance System, the researchers note. They add, though, that the results confirm that grantees are working with clinics serving the intended populations and indicate the significant gap in CRC screening rates between those reached by the CRCCP and the US population overall.

Many clinics had ≥ 1 EBI or supporting activity (SA) already in place. Grantees used CRCCP resources to implement new or to enhance EBIs in 95% of the clinics, most often patient reminder activities and provider assessment and feedback. Most of the clinics used CRCCP resources for SAs, such as small media and provider education. Only 12% of clinics used resources for supporting community health workers. However, nearly half the clinics conducted planning activities for future implementation of community health workers and patient navigators.

Nearly 80% of the clinics reported having a CRC screening champion, 73% had a CRC screening policy, and 50% had either 3 or 4 EBIs in place at the end of the first year—all factors that the researchers suggest may support greater screening rate increases.

In older patients with chronic lymphocytic leukemia (CLL), first-line treatment with ibrutinib resulted in a long-term progression-free survival benefit versus chemotherapy, according to extended follow-up results of a phase 3 trial.

The quality of response to ibrutinib continued to improve over time in the study, including a substantial increase in the proportion of patients achieving complete response, the updated results of the RESONATE-2 trial show.

Rates of serious adverse events decreased over time in the study, while common reasons for initiating treatment, such as marrow failure and disease symptoms, all improved to a greater extent than with chlorambucil, reported Paul M. Barr, MD, of the University of Rochester (N.Y.) and colleagues.

“These data support the use of ibrutinib in the first-line treatment of CLL as a chemotherapy-free option that can be taken continuously, achieving long-term disease control for the majority of patients, including those with high-risk features,” Dr. Barr and coauthors said in the journal Haematologica.

Previously reported primary results of the RESONATE-2 trial, which showed an 84% reduction in risk of death for ibrutinib versus chlorambucil with a median follow-up of 18 months, led to the approval of ibrutinib for first-line CLL treatment, the authors said.

The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized 1:1 to ibrutinib or chlorambucil.

Out of 136 ibrutinib-treated patients, 107 (79%) remained on therapy at this extended analysis, which had a median follow-up of 29 months.

The extended analysis also showed an 88% reduction in risk of progression or death for those patients randomized to ibrutinib (P less than .0001), with significant improvements in subgroups evaluated, which include groups typically considered high risk, according to Dr. Barr and colleagues.

The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months, to 15% at 24 months, and to 18% with a maximum of 36 months’ follow-up, they said.

The overall response rate for ibrutinib was 92% in this extended analysis, with comparable findings in high-risk subgroups, including those with del(11q) at 100% and unmutated IGHV at 95%, according to the report.

Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42% versus 7% with chlorambucil. Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients versus 52% for chlorambucil, with complete resolution in 56% of ibrutinib-treated patients and 22% of chlorambucil-treated patients.

Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time. Rates of grade 3 or greater neutropenia, anemia, and thrombocytopenia were 8.1%, 5.9%, and 2.2%, respectively, in the first 12 months of treatment; those decreased to 0%, 1%, and 0% in the third year.

The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up; however, investigators said ibrutinib dose reductions and discontinuations because of this adverse effect were uncommon and less frequent with extended treatment.

“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.

The study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.

SOURCE: Barr PM, et al. Haematologica. 2018;103(9):1502-10.

In older patients with chronic lymphocytic leukemia (CLL), first-line treatment with ibrutinib resulted in a long-term progression-free survival benefit versus chemotherapy, according to extended follow-up results of a phase 3 trial.

The quality of response to ibrutinib continued to improve over time in the study, including a substantial increase in the proportion of patients achieving complete response, the updated results of the RESONATE-2 trial show.

Rates of serious adverse events decreased over time in the study, while common reasons for initiating treatment, such as marrow failure and disease symptoms, all improved to a greater extent than with chlorambucil, reported Paul M. Barr, MD, of the University of Rochester (N.Y.) and colleagues.

“These data support the use of ibrutinib in the first-line treatment of CLL as a chemotherapy-free option that can be taken continuously, achieving long-term disease control for the majority of patients, including those with high-risk features,” Dr. Barr and coauthors said in the journal Haematologica.

Previously reported primary results of the RESONATE-2 trial, which showed an 84% reduction in risk of death for ibrutinib versus chlorambucil with a median follow-up of 18 months, led to the approval of ibrutinib for first-line CLL treatment, the authors said.

The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized 1:1 to ibrutinib or chlorambucil.

Out of 136 ibrutinib-treated patients, 107 (79%) remained on therapy at this extended analysis, which had a median follow-up of 29 months.

The extended analysis also showed an 88% reduction in risk of progression or death for those patients randomized to ibrutinib (P less than .0001), with significant improvements in subgroups evaluated, which include groups typically considered high risk, according to Dr. Barr and colleagues.

The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months, to 15% at 24 months, and to 18% with a maximum of 36 months’ follow-up, they said.

The overall response rate for ibrutinib was 92% in this extended analysis, with comparable findings in high-risk subgroups, including those with del(11q) at 100% and unmutated IGHV at 95%, according to the report.

Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42% versus 7% with chlorambucil. Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients versus 52% for chlorambucil, with complete resolution in 56% of ibrutinib-treated patients and 22% of chlorambucil-treated patients.

Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time. Rates of grade 3 or greater neutropenia, anemia, and thrombocytopenia were 8.1%, 5.9%, and 2.2%, respectively, in the first 12 months of treatment; those decreased to 0%, 1%, and 0% in the third year.

The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up; however, investigators said ibrutinib dose reductions and discontinuations because of this adverse effect were uncommon and less frequent with extended treatment.

“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.

The study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.

SOURCE: Barr PM, et al. Haematologica. 2018;103(9):1502-10.

In older patients with chronic lymphocytic leukemia (CLL), first-line treatment with ibrutinib resulted in a long-term progression-free survival benefit versus chemotherapy, according to extended follow-up results of a phase 3 trial.

The quality of response to ibrutinib continued to improve over time in the study, including a substantial increase in the proportion of patients achieving complete response, the updated results of the RESONATE-2 trial show.

Rates of serious adverse events decreased over time in the study, while common reasons for initiating treatment, such as marrow failure and disease symptoms, all improved to a greater extent than with chlorambucil, reported Paul M. Barr, MD, of the University of Rochester (N.Y.) and colleagues.

“These data support the use of ibrutinib in the first-line treatment of CLL as a chemotherapy-free option that can be taken continuously, achieving long-term disease control for the majority of patients, including those with high-risk features,” Dr. Barr and coauthors said in the journal Haematologica.

Previously reported primary results of the RESONATE-2 trial, which showed an 84% reduction in risk of death for ibrutinib versus chlorambucil with a median follow-up of 18 months, led to the approval of ibrutinib for first-line CLL treatment, the authors said.

The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized 1:1 to ibrutinib or chlorambucil.

Out of 136 ibrutinib-treated patients, 107 (79%) remained on therapy at this extended analysis, which had a median follow-up of 29 months.

The extended analysis also showed an 88% reduction in risk of progression or death for those patients randomized to ibrutinib (P less than .0001), with significant improvements in subgroups evaluated, which include groups typically considered high risk, according to Dr. Barr and colleagues.

The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months, to 15% at 24 months, and to 18% with a maximum of 36 months’ follow-up, they said.

The overall response rate for ibrutinib was 92% in this extended analysis, with comparable findings in high-risk subgroups, including those with del(11q) at 100% and unmutated IGHV at 95%, according to the report.

Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42% versus 7% with chlorambucil. Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients versus 52% for chlorambucil, with complete resolution in 56% of ibrutinib-treated patients and 22% of chlorambucil-treated patients.

Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time. Rates of grade 3 or greater neutropenia, anemia, and thrombocytopenia were 8.1%, 5.9%, and 2.2%, respectively, in the first 12 months of treatment; those decreased to 0%, 1%, and 0% in the third year.

The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up; however, investigators said ibrutinib dose reductions and discontinuations because of this adverse effect were uncommon and less frequent with extended treatment.

“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.

The study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.

SOURCE: Barr PM, et al. Haematologica. 2018;103(9):1502-10.

The Food and Drug Administration has granted fast-track designation to CX-01 as a treatment for patients older than 60 years receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).

CX-01 also has orphan drug designation from the FDA.

CX-01 is a polysaccharide derived from heparin thought to enhance chemotherapy by disrupting leukemia cell adhesion in bone marrow. Cantex Pharmaceuticals is conducting a randomized, phase 2b study to determine whether CX-01 can improve the efficacy of frontline chemotherapy in patients with AML.

This study builds upon results of a pilot study, which were published in Blood Advances (Blood Adv. 2018 Feb 27;2[4]:381-9). The pilot study enrolled 12 adults with newly diagnosed AML who received CX-01 as a continuous infusion for 7 days, along with standard induction chemotherapy (cytarabine and idarubicin).

The FDA’s fast-track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

jensmith@mdedge.com

The Food and Drug Administration has granted fast-track designation to CX-01 as a treatment for patients older than 60 years receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).

CX-01 also has orphan drug designation from the FDA.

CX-01 is a polysaccharide derived from heparin thought to enhance chemotherapy by disrupting leukemia cell adhesion in bone marrow. Cantex Pharmaceuticals is conducting a randomized, phase 2b study to determine whether CX-01 can improve the efficacy of frontline chemotherapy in patients with AML.

This study builds upon results of a pilot study, which were published in Blood Advances (Blood Adv. 2018 Feb 27;2[4]:381-9). The pilot study enrolled 12 adults with newly diagnosed AML who received CX-01 as a continuous infusion for 7 days, along with standard induction chemotherapy (cytarabine and idarubicin).

The FDA’s fast-track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

jensmith@mdedge.com

The Food and Drug Administration has granted fast-track designation to CX-01 as a treatment for patients older than 60 years receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).

CX-01 also has orphan drug designation from the FDA.

CX-01 is a polysaccharide derived from heparin thought to enhance chemotherapy by disrupting leukemia cell adhesion in bone marrow. Cantex Pharmaceuticals is conducting a randomized, phase 2b study to determine whether CX-01 can improve the efficacy of frontline chemotherapy in patients with AML.

This study builds upon results of a pilot study, which were published in Blood Advances (Blood Adv. 2018 Feb 27;2[4]:381-9). The pilot study enrolled 12 adults with newly diagnosed AML who received CX-01 as a continuous infusion for 7 days, along with standard induction chemotherapy (cytarabine and idarubicin).

The FDA’s fast-track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

jensmith@mdedge.com

Table of Contents

• Association of VA Hematology/Oncology 2018 Annual Meeting Schedule
• AVAHO 2018 Abstract Index
• Poster Abstracts

Table of Contents

• Association of VA Hematology/Oncology 2018 Annual Meeting Schedule
• AVAHO 2018 Abstract Index
• Poster Abstracts

Table of Contents

• Association of VA Hematology/Oncology 2018 Annual Meeting Schedule
• AVAHO 2018 Abstract Index
• Poster Abstracts

In a letter to Congressional leaders, President Trump has announced a pay freeze for all civilian federal employees in 2019. The decision will not impact active duty service members who are still are expected to receive a 2.6% pay raise next year.

The decision aims to circumvent a 2.1% across the board increase and additional locality pay increases that would average 25.7%. "We must maintain efforts to put our Nation on a fiscally sustainable course, and Federal agency budgets cannot sustain such increases. Accordingly, I have determined that it is appropriate to exercise my authority to set alternative across-the-board and locality pay adjustments for 2019."

In the letter, the President disputed the notion that locality pay was important for keeping and attracting quality applicants for positions. Currently, the Veterans Health Administration has more  than 40,000 job openings.

"I have determined that for 2019, both across‑the‑board pay increases and locality pay increases will be set at zero.  These alternative pay plan decisions will not materially affect our ability to attract and retain a well‑qualified Federal workforce.

President Trump had already included the pay freeze in his budget proposal. While Congress can override the President's decision, congressional action is not expected.

In a letter to Congressional leaders, President Trump has announced a pay freeze for all civilian federal employees in 2019. The decision will not impact active duty service members who are still are expected to receive a 2.6% pay raise next year.

The decision aims to circumvent a 2.1% across the board increase and additional locality pay increases that would average 25.7%. "We must maintain efforts to put our Nation on a fiscally sustainable course, and Federal agency budgets cannot sustain such increases. Accordingly, I have determined that it is appropriate to exercise my authority to set alternative across-the-board and locality pay adjustments for 2019."

In the letter, the President disputed the notion that locality pay was important for keeping and attracting quality applicants for positions. Currently, the Veterans Health Administration has more  than 40,000 job openings.

"I have determined that for 2019, both across‑the‑board pay increases and locality pay increases will be set at zero.  These alternative pay plan decisions will not materially affect our ability to attract and retain a well‑qualified Federal workforce.

President Trump had already included the pay freeze in his budget proposal. While Congress can override the President's decision, congressional action is not expected.

In a letter to Congressional leaders, President Trump has announced a pay freeze for all civilian federal employees in 2019. The decision will not impact active duty service members who are still are expected to receive a 2.6% pay raise next year.

The decision aims to circumvent a 2.1% across the board increase and additional locality pay increases that would average 25.7%. "We must maintain efforts to put our Nation on a fiscally sustainable course, and Federal agency budgets cannot sustain such increases. Accordingly, I have determined that it is appropriate to exercise my authority to set alternative across-the-board and locality pay adjustments for 2019."

In the letter, the President disputed the notion that locality pay was important for keeping and attracting quality applicants for positions. Currently, the Veterans Health Administration has more  than 40,000 job openings.

"I have determined that for 2019, both across‑the‑board pay increases and locality pay increases will be set at zero.  These alternative pay plan decisions will not materially affect our ability to attract and retain a well‑qualified Federal workforce.

President Trump had already included the pay freeze in his budget proposal. While Congress can override the President's decision, congressional action is not expected.

Preexisting osteoporosis is an important risk factor for mortality risk in cancer-free postmenopausal women who go on to develop multiple myeloma, results of a recent analysis suggest.

©eranicle/Thinkstock

High fracture risk was associated with an increased risk of death, independent of other clinical risk factors, in this analysis of postmenopausal women in the Women’s Health Initiative (WHI) data set.

The findings help define osteoporosis as an important prognostic factor associated with mortality in postmenopausal women who develop myeloma, according to study author Ashley E. Rosko, MD, of Ohio State University, Columbus, and her colleagues.

“Osteoporosis is highly prevalent in aging adults, and very little is known on how this comorbid condition contributes to outcomes in individuals who develop myeloma,” wrote Dr. Rosko and her coauthors. Their report is in the journal Clinical Lymphoma, Myeloma and Leukemia.

The analysis involved 362 women in the WHI data set who developed myeloma and had no history of any cancer at baseline. Women in the WHI were between 50 and 79 years of age and postmenopausal at baseline when originally recruited at 40 U.S. centers between 1993 and 1998.

Dr. Rosko and her colleagues calculated bone health for women in the data set using the Fracture Risk Assessment Tool (FRAX), a web-based tool that calculates 10-year probability of hip and other major osteoporotic fractures.

Of the 362 women who developed myeloma, 98 were classified as having high FRAX scores, defined as a 10-year probability of 3% or greater for hip fracture, or 20% or greater for other major osteoporosis-related fractures.

With a median follow-up of 10.5 years, the adjusted risk of death was elevated in women with high FRAX scores, according to investigators, with a covariate-adjusted hazard ratio of 1.51 (95% confidence interval, 1.01-2.25; P = .044) versus women with low FRAX scores.

Of the 362 patients who developed myeloma, 226 died during the follow-up period. That included 71 women with high FRAX scores, or 72% of that subset; and 155 women with low FRAX scores, or 59% of that subset, investigators reported.

These findings suggest osteoporosis is an “important comorbidity” in women who develop multiple myeloma, Dr. Rosko and her coauthors said in a discussion of the study results.

“Recognizing osteoporosis as a risk factor associated with multiple myeloma mortality is an important prognostic factor in postmenopausal women,” they said.

This investigation was supported in part by the National Cancer Institute. The researchers reported having no relevant financial disclosures.

SOURCE: Rosko AE et al. Clin Lymphoma Myeloma Leuk. 2018 Sep;18(9):597-602.e1.

Preexisting osteoporosis is an important risk factor for mortality risk in cancer-free postmenopausal women who go on to develop multiple myeloma, results of a recent analysis suggest.

©eranicle/Thinkstock

High fracture risk was associated with an increased risk of death, independent of other clinical risk factors, in this analysis of postmenopausal women in the Women’s Health Initiative (WHI) data set.

The findings help define osteoporosis as an important prognostic factor associated with mortality in postmenopausal women who develop myeloma, according to study author Ashley E. Rosko, MD, of Ohio State University, Columbus, and her colleagues.

“Osteoporosis is highly prevalent in aging adults, and very little is known on how this comorbid condition contributes to outcomes in individuals who develop myeloma,” wrote Dr. Rosko and her coauthors. Their report is in the journal Clinical Lymphoma, Myeloma and Leukemia.

The analysis involved 362 women in the WHI data set who developed myeloma and had no history of any cancer at baseline. Women in the WHI were between 50 and 79 years of age and postmenopausal at baseline when originally recruited at 40 U.S. centers between 1993 and 1998.

Dr. Rosko and her colleagues calculated bone health for women in the data set using the Fracture Risk Assessment Tool (FRAX), a web-based tool that calculates 10-year probability of hip and other major osteoporotic fractures.

Of the 362 women who developed myeloma, 98 were classified as having high FRAX scores, defined as a 10-year probability of 3% or greater for hip fracture, or 20% or greater for other major osteoporosis-related fractures.

With a median follow-up of 10.5 years, the adjusted risk of death was elevated in women with high FRAX scores, according to investigators, with a covariate-adjusted hazard ratio of 1.51 (95% confidence interval, 1.01-2.25; P = .044) versus women with low FRAX scores.

Of the 362 patients who developed myeloma, 226 died during the follow-up period. That included 71 women with high FRAX scores, or 72% of that subset; and 155 women with low FRAX scores, or 59% of that subset, investigators reported.

These findings suggest osteoporosis is an “important comorbidity” in women who develop multiple myeloma, Dr. Rosko and her coauthors said in a discussion of the study results.

“Recognizing osteoporosis as a risk factor associated with multiple myeloma mortality is an important prognostic factor in postmenopausal women,” they said.

This investigation was supported in part by the National Cancer Institute. The researchers reported having no relevant financial disclosures.

SOURCE: Rosko AE et al. Clin Lymphoma Myeloma Leuk. 2018 Sep;18(9):597-602.e1.

Preexisting osteoporosis is an important risk factor for mortality risk in cancer-free postmenopausal women who go on to develop multiple myeloma, results of a recent analysis suggest.

©eranicle/Thinkstock

High fracture risk was associated with an increased risk of death, independent of other clinical risk factors, in this analysis of postmenopausal women in the Women’s Health Initiative (WHI) data set.

The findings help define osteoporosis as an important prognostic factor associated with mortality in postmenopausal women who develop myeloma, according to study author Ashley E. Rosko, MD, of Ohio State University, Columbus, and her colleagues.

“Osteoporosis is highly prevalent in aging adults, and very little is known on how this comorbid condition contributes to outcomes in individuals who develop myeloma,” wrote Dr. Rosko and her coauthors. Their report is in the journal Clinical Lymphoma, Myeloma and Leukemia.

The analysis involved 362 women in the WHI data set who developed myeloma and had no history of any cancer at baseline. Women in the WHI were between 50 and 79 years of age and postmenopausal at baseline when originally recruited at 40 U.S. centers between 1993 and 1998.

Dr. Rosko and her colleagues calculated bone health for women in the data set using the Fracture Risk Assessment Tool (FRAX), a web-based tool that calculates 10-year probability of hip and other major osteoporotic fractures.

Of the 362 women who developed myeloma, 98 were classified as having high FRAX scores, defined as a 10-year probability of 3% or greater for hip fracture, or 20% or greater for other major osteoporosis-related fractures.

With a median follow-up of 10.5 years, the adjusted risk of death was elevated in women with high FRAX scores, according to investigators, with a covariate-adjusted hazard ratio of 1.51 (95% confidence interval, 1.01-2.25; P = .044) versus women with low FRAX scores.

Of the 362 patients who developed myeloma, 226 died during the follow-up period. That included 71 women with high FRAX scores, or 72% of that subset; and 155 women with low FRAX scores, or 59% of that subset, investigators reported.

These findings suggest osteoporosis is an “important comorbidity” in women who develop multiple myeloma, Dr. Rosko and her coauthors said in a discussion of the study results.

“Recognizing osteoporosis as a risk factor associated with multiple myeloma mortality is an important prognostic factor in postmenopausal women,” they said.

This investigation was supported in part by the National Cancer Institute. The researchers reported having no relevant financial disclosures.

SOURCE: Rosko AE et al. Clin Lymphoma Myeloma Leuk. 2018 Sep;18(9):597-602.e1.

The National Cancer Institute (NCI) and VA Interagency Group to Accelerate Trials Enrollment, or NAVIGATE, is launching at 12 VA sites. At each site, it will build infrastructure that will allow more veterans to take part in cutting-edge clinical trials, such as those testing promising experimental treatments.

The VA has a robust clinical research program but VA facilities often face challenges initiating and completing externally funded trials because of the need for partners to navigate the system, says NCI. The joint program is intended to overcome those challenges with dedicated staffing and a sustainable infrastructure, and to address barriers to trial enrollment that veterans, including minority patients, often experience.

The NCI will provide infrastructure funding needed for the VA facilities to participate in the National Clinical Trials Network and the NCI Community Oncology Research Program. In turn, the VA will manage organizational and operational activities to establish a network to focus on NCI trial goals.

The program will be jointly managed for up to 3 years, during which time the VA sites will establish long-term capabilities to keep the program going. They will also establish best practices and share insights with other VA sites nationwide.

The National Cancer Institute (NCI) and VA Interagency Group to Accelerate Trials Enrollment, or NAVIGATE, is launching at 12 VA sites. At each site, it will build infrastructure that will allow more veterans to take part in cutting-edge clinical trials, such as those testing promising experimental treatments.

The VA has a robust clinical research program but VA facilities often face challenges initiating and completing externally funded trials because of the need for partners to navigate the system, says NCI. The joint program is intended to overcome those challenges with dedicated staffing and a sustainable infrastructure, and to address barriers to trial enrollment that veterans, including minority patients, often experience.

The NCI will provide infrastructure funding needed for the VA facilities to participate in the National Clinical Trials Network and the NCI Community Oncology Research Program. In turn, the VA will manage organizational and operational activities to establish a network to focus on NCI trial goals.

The program will be jointly managed for up to 3 years, during which time the VA sites will establish long-term capabilities to keep the program going. They will also establish best practices and share insights with other VA sites nationwide.

The National Cancer Institute (NCI) and VA Interagency Group to Accelerate Trials Enrollment, or NAVIGATE, is launching at 12 VA sites. At each site, it will build infrastructure that will allow more veterans to take part in cutting-edge clinical trials, such as those testing promising experimental treatments.

The VA has a robust clinical research program but VA facilities often face challenges initiating and completing externally funded trials because of the need for partners to navigate the system, says NCI. The joint program is intended to overcome those challenges with dedicated staffing and a sustainable infrastructure, and to address barriers to trial enrollment that veterans, including minority patients, often experience.

The NCI will provide infrastructure funding needed for the VA facilities to participate in the National Clinical Trials Network and the NCI Community Oncology Research Program. In turn, the VA will manage organizational and operational activities to establish a network to focus on NCI trial goals.

The program will be jointly managed for up to 3 years, during which time the VA sites will establish long-term capabilities to keep the program going. They will also establish best practices and share insights with other VA sites nationwide.

Treatment with nivolumab plus ipilimumab resulted in clinically meaningful efficacy for melanoma patients with asymptomatic, previously untreated brain metastases, results of an open-label, multicenter, phase 2 study have shown.

The combination of these two immune checkpoint inhibitors produced intracranial responses in more than half of the patients treated, and perhaps more importantly, according to the study investigators, the combination treatment prevented intracranial progression for more than 6 months in 64% of the study population.

“These results are relevant in a population in whom progression can quickly result in substantial neurologic symptoms, functional impairment, and the need for glucocorticoid therapy,” the study investigators wrote in the New England Journal of Medicine.

The investigators, led by Hussein A. Tawbi, MD, PhD, of the University of Texas MD Anderson Cancer, Houston, initially enrolled 101 patients with histologically confirmed melanoma and metastases to the brain that were asymptomatic. All patients had an Eastern Cooperative Oncology Group performance status of 0-1 and had not received systemic glucocorticoid therapy within 10 days of study treatment.

The primary endpoint of the study was the rate of intracranial benefit, defined as the percentage of patients with complete response, partial response, or stable disease for at least 6 months after starting treatment.

For 94 patients with at least 6 months of follow-up at the time of analysis (median follow-up, 14 months), the rate of intracranial benefit was 57%, including complete responses in 26%, partial responses in 30%, and stable disease in 2%, the investigators reported. The rate of extracranial benefit was similar, at 56%.

The 6-month rate of progression-free survival was 64.2% for intracranial assessments, while the 6-month overall survival rate was 92.3%, according to results of an initial assessment.

Grade 3 or 4 adverse events thought to be related to treatment occurred in 55% of patients and led to treatment discontinuation in 20%; the most common were increased levels of ALT and AST.

Dr. Tawbi and his colleagues said that, while cross-trial comparisons have inherent limitations, the rate of intracranial response seen in this trial is similar to what was seen in the COMBI-MB study of dabrafenib plus trametinib in patients with BRAF-mutant melanoma and brain metastases. However, in that study, published in 2017 in the Lancet, the combination of a BRAF inhibitor and MEK inhibitor had rates of intracranial response and progression-free survival that were “substantially shorter” than the rates of extracranial response and progression-free survival.

“In our study, the use of immunotherapy seemed capable of inducing intracranial responses that were very similar to extracranial responses in character, depth, and duration,” they wrote.

Dr. Tawbi and his coinvestigators enrolled an additional 20 symptomatic patients with brain metastases following a study protocol amendment; however, results from that cohort are not being reported yet because of inadequate follow-up length, they said.

The study was supported by Bristol-Myers Squibb and a grant from the National Cancer Institute. Dr. Tawbi reported disclosures related to Bristol-Myers Squibb, Merck, Genentech, and Novartis. His coauthors reported additional disclosures related to MedImmune, AstraZeneca, Dynavax Technologies, Genoptix, Exelixis, Acceleron Pharma, and Eisai, among others.

SOURCE: Tawbi HA et al. N Engl J Med. 2018 Aug 23. doi: 10.1056/NEJMoa1805453.

Treatment with nivolumab plus ipilimumab resulted in clinically meaningful efficacy for melanoma patients with asymptomatic, previously untreated brain metastases, results of an open-label, multicenter, phase 2 study have shown.

The combination of these two immune checkpoint inhibitors produced intracranial responses in more than half of the patients treated, and perhaps more importantly, according to the study investigators, the combination treatment prevented intracranial progression for more than 6 months in 64% of the study population.

“These results are relevant in a population in whom progression can quickly result in substantial neurologic symptoms, functional impairment, and the need for glucocorticoid therapy,” the study investigators wrote in the New England Journal of Medicine.

The investigators, led by Hussein A. Tawbi, MD, PhD, of the University of Texas MD Anderson Cancer, Houston, initially enrolled 101 patients with histologically confirmed melanoma and metastases to the brain that were asymptomatic. All patients had an Eastern Cooperative Oncology Group performance status of 0-1 and had not received systemic glucocorticoid therapy within 10 days of study treatment.

The primary endpoint of the study was the rate of intracranial benefit, defined as the percentage of patients with complete response, partial response, or stable disease for at least 6 months after starting treatment.

For 94 patients with at least 6 months of follow-up at the time of analysis (median follow-up, 14 months), the rate of intracranial benefit was 57%, including complete responses in 26%, partial responses in 30%, and stable disease in 2%, the investigators reported. The rate of extracranial benefit was similar, at 56%.

The 6-month rate of progression-free survival was 64.2% for intracranial assessments, while the 6-month overall survival rate was 92.3%, according to results of an initial assessment.

Grade 3 or 4 adverse events thought to be related to treatment occurred in 55% of patients and led to treatment discontinuation in 20%; the most common were increased levels of ALT and AST.

Dr. Tawbi and his colleagues said that, while cross-trial comparisons have inherent limitations, the rate of intracranial response seen in this trial is similar to what was seen in the COMBI-MB study of dabrafenib plus trametinib in patients with BRAF-mutant melanoma and brain metastases. However, in that study, published in 2017 in the Lancet, the combination of a BRAF inhibitor and MEK inhibitor had rates of intracranial response and progression-free survival that were “substantially shorter” than the rates of extracranial response and progression-free survival.

“In our study, the use of immunotherapy seemed capable of inducing intracranial responses that were very similar to extracranial responses in character, depth, and duration,” they wrote.

Dr. Tawbi and his coinvestigators enrolled an additional 20 symptomatic patients with brain metastases following a study protocol amendment; however, results from that cohort are not being reported yet because of inadequate follow-up length, they said.

The study was supported by Bristol-Myers Squibb and a grant from the National Cancer Institute. Dr. Tawbi reported disclosures related to Bristol-Myers Squibb, Merck, Genentech, and Novartis. His coauthors reported additional disclosures related to MedImmune, AstraZeneca, Dynavax Technologies, Genoptix, Exelixis, Acceleron Pharma, and Eisai, among others.

SOURCE: Tawbi HA et al. N Engl J Med. 2018 Aug 23. doi: 10.1056/NEJMoa1805453.

Treatment with nivolumab plus ipilimumab resulted in clinically meaningful efficacy for melanoma patients with asymptomatic, previously untreated brain metastases, results of an open-label, multicenter, phase 2 study have shown.

The combination of these two immune checkpoint inhibitors produced intracranial responses in more than half of the patients treated, and perhaps more importantly, according to the study investigators, the combination treatment prevented intracranial progression for more than 6 months in 64% of the study population.

“These results are relevant in a population in whom progression can quickly result in substantial neurologic symptoms, functional impairment, and the need for glucocorticoid therapy,” the study investigators wrote in the New England Journal of Medicine.

The investigators, led by Hussein A. Tawbi, MD, PhD, of the University of Texas MD Anderson Cancer, Houston, initially enrolled 101 patients with histologically confirmed melanoma and metastases to the brain that were asymptomatic. All patients had an Eastern Cooperative Oncology Group performance status of 0-1 and had not received systemic glucocorticoid therapy within 10 days of study treatment.

The primary endpoint of the study was the rate of intracranial benefit, defined as the percentage of patients with complete response, partial response, or stable disease for at least 6 months after starting treatment.

For 94 patients with at least 6 months of follow-up at the time of analysis (median follow-up, 14 months), the rate of intracranial benefit was 57%, including complete responses in 26%, partial responses in 30%, and stable disease in 2%, the investigators reported. The rate of extracranial benefit was similar, at 56%.

The 6-month rate of progression-free survival was 64.2% for intracranial assessments, while the 6-month overall survival rate was 92.3%, according to results of an initial assessment.

Grade 3 or 4 adverse events thought to be related to treatment occurred in 55% of patients and led to treatment discontinuation in 20%; the most common were increased levels of ALT and AST.

Dr. Tawbi and his colleagues said that, while cross-trial comparisons have inherent limitations, the rate of intracranial response seen in this trial is similar to what was seen in the COMBI-MB study of dabrafenib plus trametinib in patients with BRAF-mutant melanoma and brain metastases. However, in that study, published in 2017 in the Lancet, the combination of a BRAF inhibitor and MEK inhibitor had rates of intracranial response and progression-free survival that were “substantially shorter” than the rates of extracranial response and progression-free survival.

“In our study, the use of immunotherapy seemed capable of inducing intracranial responses that were very similar to extracranial responses in character, depth, and duration,” they wrote.

Dr. Tawbi and his coinvestigators enrolled an additional 20 symptomatic patients with brain metastases following a study protocol amendment; however, results from that cohort are not being reported yet because of inadequate follow-up length, they said.

The study was supported by Bristol-Myers Squibb and a grant from the National Cancer Institute. Dr. Tawbi reported disclosures related to Bristol-Myers Squibb, Merck, Genentech, and Novartis. His coauthors reported additional disclosures related to MedImmune, AstraZeneca, Dynavax Technologies, Genoptix, Exelixis, Acceleron Pharma, and Eisai, among others.

SOURCE: Tawbi HA et al. N Engl J Med. 2018 Aug 23. doi: 10.1056/NEJMoa1805453.

An antibiotic drug used to treat acne, among other things, may turn out to have potential well beyond that. Researchers from University of Antioquiain Medellin, Colombia, suggest that minocycline could be a promising antileukemic drug.

Minocycline is a well-established tetracycline derivative, used clinically since 1971, with a safe track record. But it also has nonantibiotic properties, exerting both antioxidant and antiapoptotic effects. There is even “compelling” preclinical evidence, the researchers say, that minocycline induces apoptosis in an acute myeloid leukemia cell line and a chronic myeloid leukemia cell line. Would the same be true of acute lymphoblastic leukemia (ALL) cells? To test their hypothesis, the researchers examined minocycline’s mechanism of action in the Jurkat cell line, an ALL tumor line established in the 1970s from the peripheral blood of a 14-year-old boy. 

The researchers found that minocycline did in fact induce apoptosis in Jurkat cells through a hydrogen peroxide (H₂O₂)-mediated signaling pathway. Indeed, they add, H₂O₂ triggers a whole cascade of adverse effects, including up-regulation of pro-apoptotic proteins. The researchers suggest that minocycline might even be capable of generating H₂O₂, which could explain the cytotoxic effects not only of minocycline, but of other tetracycline analogues. “Interestingly,” the researchers say, minocycline did all that without inducing oxidative stress or apoptosis makers in human peripheral blood lymphocyte cells.

The significance of their study is twofold, the researchers say: First, that minocycline is a safe and specific apoptosis-inducing drug against Jurkat cells in vitro; second, that it is pharmacologically well characterized and widely available.

The researchers note that no information is available on whether minocycline might efficiently kill ALL cells in vivo. However, they also note that minocycline has been found to be safe and well tolerated in doses up to 10 mg/kg in stroke patients—a dose that could be a sufficient concentration to reduce the viability of leukemia cell lines.

Source:
Ruiz-Moreno C, Velez-Pardo C, Jimenez-Del-Rio M. Toxicol In Vitro. 2018;50:336-346.
doi: 10.1016/j.tiv.2018.03.012

An antibiotic drug used to treat acne, among other things, may turn out to have potential well beyond that. Researchers from University of Antioquiain Medellin, Colombia, suggest that minocycline could be a promising antileukemic drug.

Minocycline is a well-established tetracycline derivative, used clinically since 1971, with a safe track record. But it also has nonantibiotic properties, exerting both antioxidant and antiapoptotic effects. There is even “compelling” preclinical evidence, the researchers say, that minocycline induces apoptosis in an acute myeloid leukemia cell line and a chronic myeloid leukemia cell line. Would the same be true of acute lymphoblastic leukemia (ALL) cells? To test their hypothesis, the researchers examined minocycline’s mechanism of action in the Jurkat cell line, an ALL tumor line established in the 1970s from the peripheral blood of a 14-year-old boy. 

The researchers found that minocycline did in fact induce apoptosis in Jurkat cells through a hydrogen peroxide (H₂O₂)-mediated signaling pathway. Indeed, they add, H₂O₂ triggers a whole cascade of adverse effects, including up-regulation of pro-apoptotic proteins. The researchers suggest that minocycline might even be capable of generating H₂O₂, which could explain the cytotoxic effects not only of minocycline, but of other tetracycline analogues. “Interestingly,” the researchers say, minocycline did all that without inducing oxidative stress or apoptosis makers in human peripheral blood lymphocyte cells.

The significance of their study is twofold, the researchers say: First, that minocycline is a safe and specific apoptosis-inducing drug against Jurkat cells in vitro; second, that it is pharmacologically well characterized and widely available.

The researchers note that no information is available on whether minocycline might efficiently kill ALL cells in vivo. However, they also note that minocycline has been found to be safe and well tolerated in doses up to 10 mg/kg in stroke patients—a dose that could be a sufficient concentration to reduce the viability of leukemia cell lines.

Source:
Ruiz-Moreno C, Velez-Pardo C, Jimenez-Del-Rio M. Toxicol In Vitro. 2018;50:336-346.
doi: 10.1016/j.tiv.2018.03.012

An antibiotic drug used to treat acne, among other things, may turn out to have potential well beyond that. Researchers from University of Antioquiain Medellin, Colombia, suggest that minocycline could be a promising antileukemic drug.

Minocycline is a well-established tetracycline derivative, used clinically since 1971, with a safe track record. But it also has nonantibiotic properties, exerting both antioxidant and antiapoptotic effects. There is even “compelling” preclinical evidence, the researchers say, that minocycline induces apoptosis in an acute myeloid leukemia cell line and a chronic myeloid leukemia cell line. Would the same be true of acute lymphoblastic leukemia (ALL) cells? To test their hypothesis, the researchers examined minocycline’s mechanism of action in the Jurkat cell line, an ALL tumor line established in the 1970s from the peripheral blood of a 14-year-old boy. 

The researchers found that minocycline did in fact induce apoptosis in Jurkat cells through a hydrogen peroxide (H₂O₂)-mediated signaling pathway. Indeed, they add, H₂O₂ triggers a whole cascade of adverse effects, including up-regulation of pro-apoptotic proteins. The researchers suggest that minocycline might even be capable of generating H₂O₂, which could explain the cytotoxic effects not only of minocycline, but of other tetracycline analogues. “Interestingly,” the researchers say, minocycline did all that without inducing oxidative stress or apoptosis makers in human peripheral blood lymphocyte cells.

The significance of their study is twofold, the researchers say: First, that minocycline is a safe and specific apoptosis-inducing drug against Jurkat cells in vitro; second, that it is pharmacologically well characterized and widely available.

The researchers note that no information is available on whether minocycline might efficiently kill ALL cells in vivo. However, they also note that minocycline has been found to be safe and well tolerated in doses up to 10 mg/kg in stroke patients—a dose that could be a sufficient concentration to reduce the viability of leukemia cell lines.

Source:
Ruiz-Moreno C, Velez-Pardo C, Jimenez-Del-Rio M. Toxicol In Vitro. 2018;50:336-346.
doi: 10.1016/j.tiv.2018.03.012

University Hospitals Seidman Cancer Center in Cleveland has launched a phase 1 clinical trial to study the safety of CAR T therapy for non-Hodgkin lymphoma.

The trial will enroll 12-15 adult patients with non-Hodgkin lymphoma who have not responded to standard therapies, according to a statement from University Hospitals Seidman Cancer Center.

The principal investigator for the trial will be Paolo Caimi, MD, of UH Seidman and Case Western Reserve University.

UH Seidman, affiliated with Case Western Reserve University, is one of a handful of centers that has the ability to manufacture the CAR T cells from the patient’s own genetically modified T cells on site in the shared Case Western Reserve University National Center for Regenerative Medicine and the UH Seidman Cellular Therapy Laboratory, saving time for patients.

“Having the ability to make cells on-site means there will be a shorter turnaround time in having the cells available for the patient, compared to shipping them off-site,” said Dr. Caimi in the press statement.

lnikolaides@mdedge.com

University Hospitals Seidman Cancer Center in Cleveland has launched a phase 1 clinical trial to study the safety of CAR T therapy for non-Hodgkin lymphoma.

The trial will enroll 12-15 adult patients with non-Hodgkin lymphoma who have not responded to standard therapies, according to a statement from University Hospitals Seidman Cancer Center.

The principal investigator for the trial will be Paolo Caimi, MD, of UH Seidman and Case Western Reserve University.

UH Seidman, affiliated with Case Western Reserve University, is one of a handful of centers that has the ability to manufacture the CAR T cells from the patient’s own genetically modified T cells on site in the shared Case Western Reserve University National Center for Regenerative Medicine and the UH Seidman Cellular Therapy Laboratory, saving time for patients.

“Having the ability to make cells on-site means there will be a shorter turnaround time in having the cells available for the patient, compared to shipping them off-site,” said Dr. Caimi in the press statement.

lnikolaides@mdedge.com

University Hospitals Seidman Cancer Center in Cleveland has launched a phase 1 clinical trial to study the safety of CAR T therapy for non-Hodgkin lymphoma.

The trial will enroll 12-15 adult patients with non-Hodgkin lymphoma who have not responded to standard therapies, according to a statement from University Hospitals Seidman Cancer Center.

The principal investigator for the trial will be Paolo Caimi, MD, of UH Seidman and Case Western Reserve University.

UH Seidman, affiliated with Case Western Reserve University, is one of a handful of centers that has the ability to manufacture the CAR T cells from the patient’s own genetically modified T cells on site in the shared Case Western Reserve University National Center for Regenerative Medicine and the UH Seidman Cellular Therapy Laboratory, saving time for patients.

“Having the ability to make cells on-site means there will be a shorter turnaround time in having the cells available for the patient, compared to shipping them off-site,” said Dr. Caimi in the press statement.

lnikolaides@mdedge.com