CML

First responders exposed to toxic dusts and fibers in the aftermath of the World Trade Center (WTC) terror attacks show increased levels of clonal hematopoiesis linked to the development of blood cancers, new research finds. These results add to concerns about the long-term health effects of that exposure and further underscore a need for screening of those exposed.

“These data demonstrate that environmental exposure to the WTC disaster site is associated with a higher burden of clonal hematopoiesis, exceeding that expected in normal aging, and establish a rationale for mutational testing of the larger WTC-exposed population,” report the authors in the study, published March 7 in Nature Medicine.

The findings come from a study of blood samples from WTC first responders, including 429 firefighters and 52 emergency medical service workers, collected between December 2013 and October 2015.

For comparisons, the authors collected blood samples from 255 firefighters from in and around Nashville, Tenn., none of whom had been exposed to the 9/11 disaster.

Genetic analysis of the samples showed that 10% of those in the WTC-exposed cohort (n = 48) had unique somatic mutations considered to likely be pathogenic, and six of those individuals carried one or more of the mutations.

After a multivariate adjustment controlling for age, sex and race/ethnicity, those among the WTC-exposed first responders had a significantly increased odds of clonal hematopoiesis versus nonexposed workers (odds ratio [OR] = 3.14; P = .0006).

The higher risk was further observed in a comparison limited only to the WTC-exposed firefighters versus nonexposed firefighters (OR = 2.93; P = .0014) after the multivariate adjustment. The greater association between WTC exposure and clonal hematopoiesis remained after the researchers controlled for smoking as well as other risk factors among the WTC-exposed group overall (OR = 3.05; P = .0015) and the firefighters-only comparison (OR = 2.78; P = .004).

A history of smoking was not significantly associated with an increased risk of clonal hematopoiesis in either model.

As a risk factor for hematologic malignancy, cardiovascular events, and mortality, “clonal hematopoiesis is a concerning acquired risk not only for diseases that are already associated with WTC exposure but also as the population ages, this may exacerbate their risk profile,” Dr. Anna Nolan, coauthor of the study, and professor of medicine and environmental medicine in the division of pulmonary and critical care, New York University, said in an interview.

The most common gene mutations observed in the WTC-exposed group were those associated with myeloid malignancies, such as chronic myeloid leukemia; however, blood counts in the exposed group showed no association between exposure and mutations linked to cytopenias.

A further analysis on mice, investigating how WTC particulate matter uniquely affects DNA, surprisingly showed that just one exposure to the material was associated with clonal hematopoietic changes.

Courtesy NYU Langone Health

“Exposure to particulates, even at a single time point, can yield clonal mutations that may be risk for multisystem end-organ changes,” Dr. Nolan said.

While the serious health effects of WTC exposure on humans, have been extensively documented, including a study published in February showing increases in skin, prostate and thyroid cancers, clonal hematopoiesis suggests further heightened risks as the exposed population grows older, Dr. Nolan noted.

“[Clonal hematopoiesis] is a concerning acquired risk not only for diseases that are already associated with WTC exposure, but also, as the population ages, this may exacerbate their risk profile,” she said.

Due to the risk, “clinicians should be aware that WTC-exposed first responders have had a significant exposure and that they are at risk for developing several conditions.”

Commenting on this study, William K. Oh, MD, whose team at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, has reported in a previous study on the increased risk of prostate cancer among WTC first responders, noted that more time may be necessary to better understand the full effects of the increases in clonal hematopoiesis.

“Though these findings are of concern, there were still no differences in the cohorts in actual hematologic cancers or even cytopenias, suggesting that more time and additional DNA damaging events were needed to transform the clonal hematopoiesis findings to clinically relevant diseases,” Dr. Oh, clinical professor of medicine, said in an interview.

Nevertheless, “if a patient is found on testing to have clonal hematopoiesis, they should be screened more closely for blood disorders and cardiovascular issues than they might otherwise be, though this remains an area of active investigation,” Dr. Oh said.

Dr. Nolan had no disclosures to report. Dr. Oh is the chief medical science officer at Sema4, a genomic testing and data company. 

First responders exposed to toxic dusts and fibers in the aftermath of the World Trade Center (WTC) terror attacks show increased levels of clonal hematopoiesis linked to the development of blood cancers, new research finds. These results add to concerns about the long-term health effects of that exposure and further underscore a need for screening of those exposed.

“These data demonstrate that environmental exposure to the WTC disaster site is associated with a higher burden of clonal hematopoiesis, exceeding that expected in normal aging, and establish a rationale for mutational testing of the larger WTC-exposed population,” report the authors in the study, published March 7 in Nature Medicine.

The findings come from a study of blood samples from WTC first responders, including 429 firefighters and 52 emergency medical service workers, collected between December 2013 and October 2015.

For comparisons, the authors collected blood samples from 255 firefighters from in and around Nashville, Tenn., none of whom had been exposed to the 9/11 disaster.

Genetic analysis of the samples showed that 10% of those in the WTC-exposed cohort (n = 48) had unique somatic mutations considered to likely be pathogenic, and six of those individuals carried one or more of the mutations.

After a multivariate adjustment controlling for age, sex and race/ethnicity, those among the WTC-exposed first responders had a significantly increased odds of clonal hematopoiesis versus nonexposed workers (odds ratio [OR] = 3.14; P = .0006).

The higher risk was further observed in a comparison limited only to the WTC-exposed firefighters versus nonexposed firefighters (OR = 2.93; P = .0014) after the multivariate adjustment. The greater association between WTC exposure and clonal hematopoiesis remained after the researchers controlled for smoking as well as other risk factors among the WTC-exposed group overall (OR = 3.05; P = .0015) and the firefighters-only comparison (OR = 2.78; P = .004).

A history of smoking was not significantly associated with an increased risk of clonal hematopoiesis in either model.

As a risk factor for hematologic malignancy, cardiovascular events, and mortality, “clonal hematopoiesis is a concerning acquired risk not only for diseases that are already associated with WTC exposure but also as the population ages, this may exacerbate their risk profile,” Dr. Anna Nolan, coauthor of the study, and professor of medicine and environmental medicine in the division of pulmonary and critical care, New York University, said in an interview.

The most common gene mutations observed in the WTC-exposed group were those associated with myeloid malignancies, such as chronic myeloid leukemia; however, blood counts in the exposed group showed no association between exposure and mutations linked to cytopenias.

A further analysis on mice, investigating how WTC particulate matter uniquely affects DNA, surprisingly showed that just one exposure to the material was associated with clonal hematopoietic changes.

Courtesy NYU Langone Health

“Exposure to particulates, even at a single time point, can yield clonal mutations that may be risk for multisystem end-organ changes,” Dr. Nolan said.

While the serious health effects of WTC exposure on humans, have been extensively documented, including a study published in February showing increases in skin, prostate and thyroid cancers, clonal hematopoiesis suggests further heightened risks as the exposed population grows older, Dr. Nolan noted.

“[Clonal hematopoiesis] is a concerning acquired risk not only for diseases that are already associated with WTC exposure, but also, as the population ages, this may exacerbate their risk profile,” she said.

Due to the risk, “clinicians should be aware that WTC-exposed first responders have had a significant exposure and that they are at risk for developing several conditions.”

Commenting on this study, William K. Oh, MD, whose team at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, has reported in a previous study on the increased risk of prostate cancer among WTC first responders, noted that more time may be necessary to better understand the full effects of the increases in clonal hematopoiesis.

“Though these findings are of concern, there were still no differences in the cohorts in actual hematologic cancers or even cytopenias, suggesting that more time and additional DNA damaging events were needed to transform the clonal hematopoiesis findings to clinically relevant diseases,” Dr. Oh, clinical professor of medicine, said in an interview.

Nevertheless, “if a patient is found on testing to have clonal hematopoiesis, they should be screened more closely for blood disorders and cardiovascular issues than they might otherwise be, though this remains an area of active investigation,” Dr. Oh said.

Dr. Nolan had no disclosures to report. Dr. Oh is the chief medical science officer at Sema4, a genomic testing and data company. 

First responders exposed to toxic dusts and fibers in the aftermath of the World Trade Center (WTC) terror attacks show increased levels of clonal hematopoiesis linked to the development of blood cancers, new research finds. These results add to concerns about the long-term health effects of that exposure and further underscore a need for screening of those exposed.

“These data demonstrate that environmental exposure to the WTC disaster site is associated with a higher burden of clonal hematopoiesis, exceeding that expected in normal aging, and establish a rationale for mutational testing of the larger WTC-exposed population,” report the authors in the study, published March 7 in Nature Medicine.

The findings come from a study of blood samples from WTC first responders, including 429 firefighters and 52 emergency medical service workers, collected between December 2013 and October 2015.

For comparisons, the authors collected blood samples from 255 firefighters from in and around Nashville, Tenn., none of whom had been exposed to the 9/11 disaster.

Genetic analysis of the samples showed that 10% of those in the WTC-exposed cohort (n = 48) had unique somatic mutations considered to likely be pathogenic, and six of those individuals carried one or more of the mutations.

After a multivariate adjustment controlling for age, sex and race/ethnicity, those among the WTC-exposed first responders had a significantly increased odds of clonal hematopoiesis versus nonexposed workers (odds ratio [OR] = 3.14; P = .0006).

The higher risk was further observed in a comparison limited only to the WTC-exposed firefighters versus nonexposed firefighters (OR = 2.93; P = .0014) after the multivariate adjustment. The greater association between WTC exposure and clonal hematopoiesis remained after the researchers controlled for smoking as well as other risk factors among the WTC-exposed group overall (OR = 3.05; P = .0015) and the firefighters-only comparison (OR = 2.78; P = .004).

A history of smoking was not significantly associated with an increased risk of clonal hematopoiesis in either model.

As a risk factor for hematologic malignancy, cardiovascular events, and mortality, “clonal hematopoiesis is a concerning acquired risk not only for diseases that are already associated with WTC exposure but also as the population ages, this may exacerbate their risk profile,” Dr. Anna Nolan, coauthor of the study, and professor of medicine and environmental medicine in the division of pulmonary and critical care, New York University, said in an interview.

The most common gene mutations observed in the WTC-exposed group were those associated with myeloid malignancies, such as chronic myeloid leukemia; however, blood counts in the exposed group showed no association between exposure and mutations linked to cytopenias.

A further analysis on mice, investigating how WTC particulate matter uniquely affects DNA, surprisingly showed that just one exposure to the material was associated with clonal hematopoietic changes.

Courtesy NYU Langone Health

“Exposure to particulates, even at a single time point, can yield clonal mutations that may be risk for multisystem end-organ changes,” Dr. Nolan said.

While the serious health effects of WTC exposure on humans, have been extensively documented, including a study published in February showing increases in skin, prostate and thyroid cancers, clonal hematopoiesis suggests further heightened risks as the exposed population grows older, Dr. Nolan noted.

“[Clonal hematopoiesis] is a concerning acquired risk not only for diseases that are already associated with WTC exposure, but also, as the population ages, this may exacerbate their risk profile,” she said.

Due to the risk, “clinicians should be aware that WTC-exposed first responders have had a significant exposure and that they are at risk for developing several conditions.”

Commenting on this study, William K. Oh, MD, whose team at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, has reported in a previous study on the increased risk of prostate cancer among WTC first responders, noted that more time may be necessary to better understand the full effects of the increases in clonal hematopoiesis.

“Though these findings are of concern, there were still no differences in the cohorts in actual hematologic cancers or even cytopenias, suggesting that more time and additional DNA damaging events were needed to transform the clonal hematopoiesis findings to clinically relevant diseases,” Dr. Oh, clinical professor of medicine, said in an interview.

Nevertheless, “if a patient is found on testing to have clonal hematopoiesis, they should be screened more closely for blood disorders and cardiovascular issues than they might otherwise be, though this remains an area of active investigation,” Dr. Oh said.

Dr. Nolan had no disclosures to report. Dr. Oh is the chief medical science officer at Sema4, a genomic testing and data company. 

In the United States, the risk of death from cancer overall has been continuously dropping since 1991, the American Cancer Society (ACS) noted in its latest report.

There has been an overall decline of 32% in cancer deaths as of 2019, or approximately 3.5 million cancer deaths averted, the report noted.

“This success is largely because of reductions in smoking that resulted in downstream declines in lung and other smoking-related cancers,” lead author Rebecca L. Siegel of the ACS, and colleagues, noted in the latest edition of the society’s annual report on cancer rates and trends.

The paper was published online Jan. 12 in CA: A Cancer Journal for Clinicians.

In particular, there has been a fall in both the incidence of and mortality from lung cancer, largely due to successful efforts to get people to quit smoking, but also from earlier diagnosis at a stage when the disease is far more amenable to treatment, noted the authors.

For example, the incidence of lung cancer declined by almost 3% per year in men between the years 2009 and 2018 and by 1% a year in women. Currently, the historically large gender gap in lung cancer incidence is disappearing such that in 2018, lung cancer rates were 24% higher in men than they were in women, and rates in women were actually higher in some younger age groups than they were in men.

Moreover, 28% of lung cancers detected in 2018 were found at a localized stage of disease compared with 17% in 2004.

Patients diagnosed with lung cancer are also living longer, with almost one-third of lung cancer patients still alive 3 years after their diagnosis compared with 21% a decade ago.

However, lung cancer is still the biggest contributor to cancer-related mortality overall, at a death toll of 350 per day – more than breast, prostate, and pancreatic cancer combined, the authors wrote.

This is 2.5 times higher than the death rate from colorectal cancer (CRC), the second leading cause of cancer death in the United States, they added.

Nevertheless, the decrease in lung cancer mortality accelerated from 3.1% per year between 2010 and 2014 to 5.4% per year during 2015 to 2019 in men and from 1.8% to 4.3% in women. “Overall, the lung cancer death rate has dropped by 56% from 1990 to 2019 in men and by 32% from 2002 to 2019 in women,” Ms. Siegel and colleagues emphasized.

Overall, the ACS projects there will be over 1.9 million new cancer cases and over 600,000 cancer deaths across the United States in 2022.


 

Patterns are changing

With prostate cancer now accounting for some 27% of all cancer diagnoses in men, recent trends in the incidence of prostate cancer are somewhat worrisome, the authors wrote. While the incidence for local-stage disease remained stable from 2014 through to 2018, the incidence of advanced-stage disease has increased by 6% a year since 2011. “Consequently, the proportion of distant-stage diagnoses has more than doubled,” the authors noted, “from a low of 3.9% in 2007 to 8.2% in 2018.”

The incidence of breast cancer among women has been slowly increasing by 0.5% per year since about the mid-2000s. This increase is due at least in part to declines in fertility and increases in body weight among women, the authors suggested. Declines in breast cancer mortality have slowed in recent years, dropping from 1% per year from 2013 to 2019 from 2%-3% per year seen during the 1990s and the early 2000s.

As for CRC, incidence patterns are similar by sex but differ by age. For example, incidence rates of CRC declined by about 2% per year between 2014 and 2018 in individuals 50 years and older, but they increased by 1.5% per year in adults under the age of 50. Overall, however, mortality from CRC decreased by about 2% per year between 2010 and 2019, although this trend again masks increasing mortality from CRC among younger adults, where death rates rose by 1.2% per year from 2005 through 2019 in patients under the age of 50.

The third leading cause of death in men and women combined is pancreatic cancer. Here again, mortality rates slowly increased in men between 2000 and 2013 but have remained relatively stable in women.

Between 2010 and 2019, cancers of the tongue, tonsils, and oropharynx caused by human papilloma virus (HPV) increased by about 2% per year in men and by 1% per year in women.

Death from cervical cancer – despite its being one of the most preventable cancers overall – is still the second leading cause of cancer death in women between 20 and 39 years of age. “Most of these women have never been screened so this is low-hanging fruit easily addressed by increasing access to screening and [HPV] vaccination among underserved women,” Ms. Siegel said in a statement.

On the other hand, mortality from liver cancer – having increased rapidly over the past number of decades – appears to have stabilized in more recent years.
 

Survival at 5 years

For all cancers combined, survival at 5 years between the mid-1970s and 2011 through 2017 increased from 50% to 68% for White patients and by 39% to 63% for Black patients. “For all stages combined, survival is highest for prostate cancer (98%), melanoma of the skin (93%) and female breast cancer (90%),” the authors pointed out.

In contrast, survival at 5 years is lowest, at 11% for pancreatic cancer, 20% for cancers of the liver and esophagus, and 22% for lung cancer.

Indeed, for most of the common cancers, cancer survival has improved since the mid-1970s with the exception or uterine and cervical cancer, the latter because there have been few advancements in treatment.

Even among the more rare blood and lymphoid malignancies, improvements in treatment strategies, including the use of targeted therapies, have resulted in major survival gains from around 20% in the mid-1970s for chronic myeloid leukemia (CML) patients to over 70% for CML patients diagnosed between 2011 and 2017.

Similarly, the discovery and use of immunotherapy has doubled 5-year survival rates to 30% for patients with metastatic melanoma from 15% in 2004. On the other hand, racial disparities in survival odds continue to persist. For every cancer type except for cancer of the pancreas and kidney, survival rates were lower for Black patients than for White patients, the researchers pointed out.

“Black individuals also have lower stage-specific survival for most cancer types,” the report authors noted. Indeed, after adjustment for sex, age, and stage at diagnosis, the risk of death is 33% higher in Black patients than White patients and 51% higher in American Indian/Alaska Natives compared to White patients.

That said, the overall incidence of cancer is still highest among White individuals, in part because of high rates of breast cancer in White women, which may in part reflect overdiagnosis of breast cancer in this patient population, as the authors suggested.

“However, Black women have the highest cancer mortality rates – 12% higher than White women,” they observed. Even more striking, Black women have a 4% lower incidence of breast cancer than White women but a 41% higher mortality risk from it.

As for pediatric and adolescent cancers, incidence rates may be increasing slightly among both age groups, but dramatic reductions in death by 71% among children and by 61% among adolescents from the mid-70s until now continue as a singular success story in the treatment of cancer overall.

All the authors are employed by the ACS.

A version of this article first appeared on Medscape.com.

In the United States, the risk of death from cancer overall has been continuously dropping since 1991, the American Cancer Society (ACS) noted in its latest report.

There has been an overall decline of 32% in cancer deaths as of 2019, or approximately 3.5 million cancer deaths averted, the report noted.

“This success is largely because of reductions in smoking that resulted in downstream declines in lung and other smoking-related cancers,” lead author Rebecca L. Siegel of the ACS, and colleagues, noted in the latest edition of the society’s annual report on cancer rates and trends.

The paper was published online Jan. 12 in CA: A Cancer Journal for Clinicians.

In particular, there has been a fall in both the incidence of and mortality from lung cancer, largely due to successful efforts to get people to quit smoking, but also from earlier diagnosis at a stage when the disease is far more amenable to treatment, noted the authors.

For example, the incidence of lung cancer declined by almost 3% per year in men between the years 2009 and 2018 and by 1% a year in women. Currently, the historically large gender gap in lung cancer incidence is disappearing such that in 2018, lung cancer rates were 24% higher in men than they were in women, and rates in women were actually higher in some younger age groups than they were in men.

Moreover, 28% of lung cancers detected in 2018 were found at a localized stage of disease compared with 17% in 2004.

Patients diagnosed with lung cancer are also living longer, with almost one-third of lung cancer patients still alive 3 years after their diagnosis compared with 21% a decade ago.

However, lung cancer is still the biggest contributor to cancer-related mortality overall, at a death toll of 350 per day – more than breast, prostate, and pancreatic cancer combined, the authors wrote.

This is 2.5 times higher than the death rate from colorectal cancer (CRC), the second leading cause of cancer death in the United States, they added.

Nevertheless, the decrease in lung cancer mortality accelerated from 3.1% per year between 2010 and 2014 to 5.4% per year during 2015 to 2019 in men and from 1.8% to 4.3% in women. “Overall, the lung cancer death rate has dropped by 56% from 1990 to 2019 in men and by 32% from 2002 to 2019 in women,” Ms. Siegel and colleagues emphasized.

Overall, the ACS projects there will be over 1.9 million new cancer cases and over 600,000 cancer deaths across the United States in 2022.


 

Patterns are changing

With prostate cancer now accounting for some 27% of all cancer diagnoses in men, recent trends in the incidence of prostate cancer are somewhat worrisome, the authors wrote. While the incidence for local-stage disease remained stable from 2014 through to 2018, the incidence of advanced-stage disease has increased by 6% a year since 2011. “Consequently, the proportion of distant-stage diagnoses has more than doubled,” the authors noted, “from a low of 3.9% in 2007 to 8.2% in 2018.”

The incidence of breast cancer among women has been slowly increasing by 0.5% per year since about the mid-2000s. This increase is due at least in part to declines in fertility and increases in body weight among women, the authors suggested. Declines in breast cancer mortality have slowed in recent years, dropping from 1% per year from 2013 to 2019 from 2%-3% per year seen during the 1990s and the early 2000s.

As for CRC, incidence patterns are similar by sex but differ by age. For example, incidence rates of CRC declined by about 2% per year between 2014 and 2018 in individuals 50 years and older, but they increased by 1.5% per year in adults under the age of 50. Overall, however, mortality from CRC decreased by about 2% per year between 2010 and 2019, although this trend again masks increasing mortality from CRC among younger adults, where death rates rose by 1.2% per year from 2005 through 2019 in patients under the age of 50.

The third leading cause of death in men and women combined is pancreatic cancer. Here again, mortality rates slowly increased in men between 2000 and 2013 but have remained relatively stable in women.

Between 2010 and 2019, cancers of the tongue, tonsils, and oropharynx caused by human papilloma virus (HPV) increased by about 2% per year in men and by 1% per year in women.

Death from cervical cancer – despite its being one of the most preventable cancers overall – is still the second leading cause of cancer death in women between 20 and 39 years of age. “Most of these women have never been screened so this is low-hanging fruit easily addressed by increasing access to screening and [HPV] vaccination among underserved women,” Ms. Siegel said in a statement.

On the other hand, mortality from liver cancer – having increased rapidly over the past number of decades – appears to have stabilized in more recent years.
 

Survival at 5 years

For all cancers combined, survival at 5 years between the mid-1970s and 2011 through 2017 increased from 50% to 68% for White patients and by 39% to 63% for Black patients. “For all stages combined, survival is highest for prostate cancer (98%), melanoma of the skin (93%) and female breast cancer (90%),” the authors pointed out.

In contrast, survival at 5 years is lowest, at 11% for pancreatic cancer, 20% for cancers of the liver and esophagus, and 22% for lung cancer.

Indeed, for most of the common cancers, cancer survival has improved since the mid-1970s with the exception or uterine and cervical cancer, the latter because there have been few advancements in treatment.

Even among the more rare blood and lymphoid malignancies, improvements in treatment strategies, including the use of targeted therapies, have resulted in major survival gains from around 20% in the mid-1970s for chronic myeloid leukemia (CML) patients to over 70% for CML patients diagnosed between 2011 and 2017.

Similarly, the discovery and use of immunotherapy has doubled 5-year survival rates to 30% for patients with metastatic melanoma from 15% in 2004. On the other hand, racial disparities in survival odds continue to persist. For every cancer type except for cancer of the pancreas and kidney, survival rates were lower for Black patients than for White patients, the researchers pointed out.

“Black individuals also have lower stage-specific survival for most cancer types,” the report authors noted. Indeed, after adjustment for sex, age, and stage at diagnosis, the risk of death is 33% higher in Black patients than White patients and 51% higher in American Indian/Alaska Natives compared to White patients.

That said, the overall incidence of cancer is still highest among White individuals, in part because of high rates of breast cancer in White women, which may in part reflect overdiagnosis of breast cancer in this patient population, as the authors suggested.

“However, Black women have the highest cancer mortality rates – 12% higher than White women,” they observed. Even more striking, Black women have a 4% lower incidence of breast cancer than White women but a 41% higher mortality risk from it.

As for pediatric and adolescent cancers, incidence rates may be increasing slightly among both age groups, but dramatic reductions in death by 71% among children and by 61% among adolescents from the mid-70s until now continue as a singular success story in the treatment of cancer overall.

All the authors are employed by the ACS.

A version of this article first appeared on Medscape.com.

In the United States, the risk of death from cancer overall has been continuously dropping since 1991, the American Cancer Society (ACS) noted in its latest report.

There has been an overall decline of 32% in cancer deaths as of 2019, or approximately 3.5 million cancer deaths averted, the report noted.

“This success is largely because of reductions in smoking that resulted in downstream declines in lung and other smoking-related cancers,” lead author Rebecca L. Siegel of the ACS, and colleagues, noted in the latest edition of the society’s annual report on cancer rates and trends.

The paper was published online Jan. 12 in CA: A Cancer Journal for Clinicians.

In particular, there has been a fall in both the incidence of and mortality from lung cancer, largely due to successful efforts to get people to quit smoking, but also from earlier diagnosis at a stage when the disease is far more amenable to treatment, noted the authors.

For example, the incidence of lung cancer declined by almost 3% per year in men between the years 2009 and 2018 and by 1% a year in women. Currently, the historically large gender gap in lung cancer incidence is disappearing such that in 2018, lung cancer rates were 24% higher in men than they were in women, and rates in women were actually higher in some younger age groups than they were in men.

Moreover, 28% of lung cancers detected in 2018 were found at a localized stage of disease compared with 17% in 2004.

Patients diagnosed with lung cancer are also living longer, with almost one-third of lung cancer patients still alive 3 years after their diagnosis compared with 21% a decade ago.

However, lung cancer is still the biggest contributor to cancer-related mortality overall, at a death toll of 350 per day – more than breast, prostate, and pancreatic cancer combined, the authors wrote.

This is 2.5 times higher than the death rate from colorectal cancer (CRC), the second leading cause of cancer death in the United States, they added.

Nevertheless, the decrease in lung cancer mortality accelerated from 3.1% per year between 2010 and 2014 to 5.4% per year during 2015 to 2019 in men and from 1.8% to 4.3% in women. “Overall, the lung cancer death rate has dropped by 56% from 1990 to 2019 in men and by 32% from 2002 to 2019 in women,” Ms. Siegel and colleagues emphasized.

Overall, the ACS projects there will be over 1.9 million new cancer cases and over 600,000 cancer deaths across the United States in 2022.


 

Patterns are changing

With prostate cancer now accounting for some 27% of all cancer diagnoses in men, recent trends in the incidence of prostate cancer are somewhat worrisome, the authors wrote. While the incidence for local-stage disease remained stable from 2014 through to 2018, the incidence of advanced-stage disease has increased by 6% a year since 2011. “Consequently, the proportion of distant-stage diagnoses has more than doubled,” the authors noted, “from a low of 3.9% in 2007 to 8.2% in 2018.”

The incidence of breast cancer among women has been slowly increasing by 0.5% per year since about the mid-2000s. This increase is due at least in part to declines in fertility and increases in body weight among women, the authors suggested. Declines in breast cancer mortality have slowed in recent years, dropping from 1% per year from 2013 to 2019 from 2%-3% per year seen during the 1990s and the early 2000s.

As for CRC, incidence patterns are similar by sex but differ by age. For example, incidence rates of CRC declined by about 2% per year between 2014 and 2018 in individuals 50 years and older, but they increased by 1.5% per year in adults under the age of 50. Overall, however, mortality from CRC decreased by about 2% per year between 2010 and 2019, although this trend again masks increasing mortality from CRC among younger adults, where death rates rose by 1.2% per year from 2005 through 2019 in patients under the age of 50.

The third leading cause of death in men and women combined is pancreatic cancer. Here again, mortality rates slowly increased in men between 2000 and 2013 but have remained relatively stable in women.

Between 2010 and 2019, cancers of the tongue, tonsils, and oropharynx caused by human papilloma virus (HPV) increased by about 2% per year in men and by 1% per year in women.

Death from cervical cancer – despite its being one of the most preventable cancers overall – is still the second leading cause of cancer death in women between 20 and 39 years of age. “Most of these women have never been screened so this is low-hanging fruit easily addressed by increasing access to screening and [HPV] vaccination among underserved women,” Ms. Siegel said in a statement.

On the other hand, mortality from liver cancer – having increased rapidly over the past number of decades – appears to have stabilized in more recent years.
 

Survival at 5 years

For all cancers combined, survival at 5 years between the mid-1970s and 2011 through 2017 increased from 50% to 68% for White patients and by 39% to 63% for Black patients. “For all stages combined, survival is highest for prostate cancer (98%), melanoma of the skin (93%) and female breast cancer (90%),” the authors pointed out.

In contrast, survival at 5 years is lowest, at 11% for pancreatic cancer, 20% for cancers of the liver and esophagus, and 22% for lung cancer.

Indeed, for most of the common cancers, cancer survival has improved since the mid-1970s with the exception or uterine and cervical cancer, the latter because there have been few advancements in treatment.

Even among the more rare blood and lymphoid malignancies, improvements in treatment strategies, including the use of targeted therapies, have resulted in major survival gains from around 20% in the mid-1970s for chronic myeloid leukemia (CML) patients to over 70% for CML patients diagnosed between 2011 and 2017.

Similarly, the discovery and use of immunotherapy has doubled 5-year survival rates to 30% for patients with metastatic melanoma from 15% in 2004. On the other hand, racial disparities in survival odds continue to persist. For every cancer type except for cancer of the pancreas and kidney, survival rates were lower for Black patients than for White patients, the researchers pointed out.

“Black individuals also have lower stage-specific survival for most cancer types,” the report authors noted. Indeed, after adjustment for sex, age, and stage at diagnosis, the risk of death is 33% higher in Black patients than White patients and 51% higher in American Indian/Alaska Natives compared to White patients.

That said, the overall incidence of cancer is still highest among White individuals, in part because of high rates of breast cancer in White women, which may in part reflect overdiagnosis of breast cancer in this patient population, as the authors suggested.

“However, Black women have the highest cancer mortality rates – 12% higher than White women,” they observed. Even more striking, Black women have a 4% lower incidence of breast cancer than White women but a 41% higher mortality risk from it.

As for pediatric and adolescent cancers, incidence rates may be increasing slightly among both age groups, but dramatic reductions in death by 71% among children and by 61% among adolescents from the mid-70s until now continue as a singular success story in the treatment of cancer overall.

All the authors are employed by the ACS.

A version of this article first appeared on Medscape.com.

Patients who adhere to their tyrosine kinase inhibitor (TKI) medication regimen will achieve CML survival goals that would be expected for their age group. Imatinib is a first generation TKI inhibitor.  In a recent post hoc analysis of the ADAGIO study patients, Obeng-Kusi M et al¹ showed that compared with 90% adherence, a 100% adherence to imatinib was associated with a 2-fold increase in achieving or maintaining treatment response in patients with chronic myeloid leukemia (CML), highlighting the urgent need to assess and promote patient adherence. There is virtually no margin for nonadherence, if the objective is to optimize the likelihood of treatment response, and a minimal margin to avoid impaired treatment response.

On the same topic, Davis TC et al.²also recently reported a study of suboptimal adherence to TKI. From the 86 patients with CML studied, almost 17.9% of participants reported nonadherence, i.e., missing at least 1 dose of CML medication in the previous week. The main reason that patients reported nonadherence were side effects, a busy schedule, and the difficulty of complying daily with the TKI regimen.

Cardiovascular adverse events (AE) have been described with TKI treatment at different rates, but cardiovascular risk stratification was not included in the design of many trials. Baggio D et al³  in a retrospective study included 88 patients with CML treated with any TKI and a median follow up of 3.8 months. They described the rates of major cardiovascular AEs by combining age, history of prior cardiovascular diseases, and Framingham risk score, along with additional insights from coronary artery calcium scoring (CACS). The authors found cardiovascular AEs in 0%, 10%, and 19%, of the low-, intermediate-, and high-risk groups respectively. By using CACS score they were able to reclassify patients from intermediate to low risk and none of those patients experienced a major adverse cardiovascular event.

The use of kinase domain mutation analysis at diagnosis is not a recommended practice by the National Comprehensive Cancer Network (NCCN) or the European Leukemia Net (ELN), but is reserved for use in patents who failed first or subsequent lines of therapies. Furthermore, previous publications in the topic have showed discordant results. More recently, the use of ultra-deep sequencing has detected low-frequency genetic mutations with high sensitivity. Park H et al.⁴ recently described the most common mutations found in a population of 50 CML patients treated with nilotinib. V299 L mutation associated with dasatinib resistance and nilotinib sensitivity were observed in 98% of patients. Two uncommon mutations S417Y and the V371A were associated with reduced molecular response.

References

1. Obeng-Kusi M et al. No margin for non-adherence: Probabilistic Kaplan-Meier modeling of imatinib non-adherence and treatment response in CML (ADAGIO study). Leuk Res. 2021;111:106734 (Oct 21).
2. Davis TC et al. Assessment of oral chemotherapy nonadherence in chronic myeloid leukemia patients using brief measures in community cancer clinics: a pilot study. Int J Environ Res Public Health. 2021;18(21):11045 (Oct 21).
3. Baggio D et al. Prediction of cardiovascular events in patients with chronic myeloid leukaemia using baseline risk factors and coronary artery calcium scoring. Intern Med J. 2021;51(10):1736-40 (Oct 18).  
4. Park H et al. Ultra-deep sequencing mutation analysis of the BCR/ABL1 kinase domain in newly diagnosed chronic myeloid leukemia patients. Leuk Res. 2021;111:106728 (Oct 15).

Patients who adhere to their tyrosine kinase inhibitor (TKI) medication regimen will achieve CML survival goals that would be expected for their age group. Imatinib is a first generation TKI inhibitor.  In a recent post hoc analysis of the ADAGIO study patients, Obeng-Kusi M et al¹ showed that compared with 90% adherence, a 100% adherence to imatinib was associated with a 2-fold increase in achieving or maintaining treatment response in patients with chronic myeloid leukemia (CML), highlighting the urgent need to assess and promote patient adherence. There is virtually no margin for nonadherence, if the objective is to optimize the likelihood of treatment response, and a minimal margin to avoid impaired treatment response.

On the same topic, Davis TC et al.²also recently reported a study of suboptimal adherence to TKI. From the 86 patients with CML studied, almost 17.9% of participants reported nonadherence, i.e., missing at least 1 dose of CML medication in the previous week. The main reason that patients reported nonadherence were side effects, a busy schedule, and the difficulty of complying daily with the TKI regimen.

Cardiovascular adverse events (AE) have been described with TKI treatment at different rates, but cardiovascular risk stratification was not included in the design of many trials. Baggio D et al³  in a retrospective study included 88 patients with CML treated with any TKI and a median follow up of 3.8 months. They described the rates of major cardiovascular AEs by combining age, history of prior cardiovascular diseases, and Framingham risk score, along with additional insights from coronary artery calcium scoring (CACS). The authors found cardiovascular AEs in 0%, 10%, and 19%, of the low-, intermediate-, and high-risk groups respectively. By using CACS score they were able to reclassify patients from intermediate to low risk and none of those patients experienced a major adverse cardiovascular event.

The use of kinase domain mutation analysis at diagnosis is not a recommended practice by the National Comprehensive Cancer Network (NCCN) or the European Leukemia Net (ELN), but is reserved for use in patents who failed first or subsequent lines of therapies. Furthermore, previous publications in the topic have showed discordant results. More recently, the use of ultra-deep sequencing has detected low-frequency genetic mutations with high sensitivity. Park H et al.⁴ recently described the most common mutations found in a population of 50 CML patients treated with nilotinib. V299 L mutation associated with dasatinib resistance and nilotinib sensitivity were observed in 98% of patients. Two uncommon mutations S417Y and the V371A were associated with reduced molecular response.

References

1. Obeng-Kusi M et al. No margin for non-adherence: Probabilistic Kaplan-Meier modeling of imatinib non-adherence and treatment response in CML (ADAGIO study). Leuk Res. 2021;111:106734 (Oct 21).
2. Davis TC et al. Assessment of oral chemotherapy nonadherence in chronic myeloid leukemia patients using brief measures in community cancer clinics: a pilot study. Int J Environ Res Public Health. 2021;18(21):11045 (Oct 21).
3. Baggio D et al. Prediction of cardiovascular events in patients with chronic myeloid leukaemia using baseline risk factors and coronary artery calcium scoring. Intern Med J. 2021;51(10):1736-40 (Oct 18).  
4. Park H et al. Ultra-deep sequencing mutation analysis of the BCR/ABL1 kinase domain in newly diagnosed chronic myeloid leukemia patients. Leuk Res. 2021;111:106728 (Oct 15).

Patients who adhere to their tyrosine kinase inhibitor (TKI) medication regimen will achieve CML survival goals that would be expected for their age group. Imatinib is a first generation TKI inhibitor.  In a recent post hoc analysis of the ADAGIO study patients, Obeng-Kusi M et al¹ showed that compared with 90% adherence, a 100% adherence to imatinib was associated with a 2-fold increase in achieving or maintaining treatment response in patients with chronic myeloid leukemia (CML), highlighting the urgent need to assess and promote patient adherence. There is virtually no margin for nonadherence, if the objective is to optimize the likelihood of treatment response, and a minimal margin to avoid impaired treatment response.

On the same topic, Davis TC et al.²also recently reported a study of suboptimal adherence to TKI. From the 86 patients with CML studied, almost 17.9% of participants reported nonadherence, i.e., missing at least 1 dose of CML medication in the previous week. The main reason that patients reported nonadherence were side effects, a busy schedule, and the difficulty of complying daily with the TKI regimen.

Cardiovascular adverse events (AE) have been described with TKI treatment at different rates, but cardiovascular risk stratification was not included in the design of many trials. Baggio D et al³  in a retrospective study included 88 patients with CML treated with any TKI and a median follow up of 3.8 months. They described the rates of major cardiovascular AEs by combining age, history of prior cardiovascular diseases, and Framingham risk score, along with additional insights from coronary artery calcium scoring (CACS). The authors found cardiovascular AEs in 0%, 10%, and 19%, of the low-, intermediate-, and high-risk groups respectively. By using CACS score they were able to reclassify patients from intermediate to low risk and none of those patients experienced a major adverse cardiovascular event.

The use of kinase domain mutation analysis at diagnosis is not a recommended practice by the National Comprehensive Cancer Network (NCCN) or the European Leukemia Net (ELN), but is reserved for use in patents who failed first or subsequent lines of therapies. Furthermore, previous publications in the topic have showed discordant results. More recently, the use of ultra-deep sequencing has detected low-frequency genetic mutations with high sensitivity. Park H et al.⁴ recently described the most common mutations found in a population of 50 CML patients treated with nilotinib. V299 L mutation associated with dasatinib resistance and nilotinib sensitivity were observed in 98% of patients. Two uncommon mutations S417Y and the V371A were associated with reduced molecular response.

References

1. Obeng-Kusi M et al. No margin for non-adherence: Probabilistic Kaplan-Meier modeling of imatinib non-adherence and treatment response in CML (ADAGIO study). Leuk Res. 2021;111:106734 (Oct 21).
2. Davis TC et al. Assessment of oral chemotherapy nonadherence in chronic myeloid leukemia patients using brief measures in community cancer clinics: a pilot study. Int J Environ Res Public Health. 2021;18(21):11045 (Oct 21).
3. Baggio D et al. Prediction of cardiovascular events in patients with chronic myeloid leukaemia using baseline risk factors and coronary artery calcium scoring. Intern Med J. 2021;51(10):1736-40 (Oct 18).  
4. Park H et al. Ultra-deep sequencing mutation analysis of the BCR/ABL1 kinase domain in newly diagnosed chronic myeloid leukemia patients. Leuk Res. 2021;111:106728 (Oct 15).

Key clinical point: Mutations in a novel gene ANKRD36 were associated with disease progression in chronic myeloid leukemia (CML) and may help identify patients at risk of disease progression.

Major finding: Mutations in the ANKRD36 gene (c.1183_1184 delGC and c.1187_1188 dupTT) were exclusively found in all patients with CML in blast crisis (CML-BC) and accelerated phase (CML-AP) but not in those with chronic-phase CML (CML-CP) and healthy controls.

Study details: This study included 141 patients with either CML-CP (n = 123), CML-AP (n = 6), or CML-BC (n = 12) and 10 age- and gender-matched healthy controls.

Disclosures: This study was funded by the National Plan for Science, Technology and Innovation, King Abdul-Aziz City for Science and Technology, Kingdom of Saudi Arabia. The authors declared no conflict of interests.

Source: Iqbal Z et al. Biology. 2021;10(11):1182 (Nov 15). Doi: 10.3390/biology10111182.

Key clinical point: Mutations in a novel gene ANKRD36 were associated with disease progression in chronic myeloid leukemia (CML) and may help identify patients at risk of disease progression.

Major finding: Mutations in the ANKRD36 gene (c.1183_1184 delGC and c.1187_1188 dupTT) were exclusively found in all patients with CML in blast crisis (CML-BC) and accelerated phase (CML-AP) but not in those with chronic-phase CML (CML-CP) and healthy controls.

Study details: This study included 141 patients with either CML-CP (n = 123), CML-AP (n = 6), or CML-BC (n = 12) and 10 age- and gender-matched healthy controls.

Disclosures: This study was funded by the National Plan for Science, Technology and Innovation, King Abdul-Aziz City for Science and Technology, Kingdom of Saudi Arabia. The authors declared no conflict of interests.

Source: Iqbal Z et al. Biology. 2021;10(11):1182 (Nov 15). Doi: 10.3390/biology10111182.

Key clinical point: Mutations in a novel gene ANKRD36 were associated with disease progression in chronic myeloid leukemia (CML) and may help identify patients at risk of disease progression.

Major finding: Mutations in the ANKRD36 gene (c.1183_1184 delGC and c.1187_1188 dupTT) were exclusively found in all patients with CML in blast crisis (CML-BC) and accelerated phase (CML-AP) but not in those with chronic-phase CML (CML-CP) and healthy controls.

Study details: This study included 141 patients with either CML-CP (n = 123), CML-AP (n = 6), or CML-BC (n = 12) and 10 age- and gender-matched healthy controls.

Disclosures: This study was funded by the National Plan for Science, Technology and Innovation, King Abdul-Aziz City for Science and Technology, Kingdom of Saudi Arabia. The authors declared no conflict of interests.

Source: Iqbal Z et al. Biology. 2021;10(11):1182 (Nov 15). Doi: 10.3390/biology10111182.

Key clinical point: Female sex, tyrosine kinase inhibitor (TKI) therapy-related symptoms, older age at diagnosis, younger age at the time of the study, and low maternal education were associated with worse health-related quality of life (HRQoL) in children with chronic-phase chronic myeloid leukemia (CML-CP) receiving TKI therapy.

Major finding: Worse HRQoL was observed in children with symptoms (P < .001), children with mothers having low educational qualifications (P = .005), children at a younger age at the time of the study (P = .008), children with older age at the time of diagnosis (P = .007), and female children (P = .038).

Study details: Findings are from a cross-sectional study of 240 respondents including children with CML-CP (age < 18 years at diagnosis) receiving TKI therapy and whose parents responded to a cross-sectional questionnaire.

Disclosures: This study was funded by the National Natural Science Foundation of China. The authors declared no conflict of interests.

Source: Zheng F et al. J Cancer Res Clin Oncol. 2021(Oct 29). Doi: 10.1007/s00432-021-03832-y.

Key clinical point: Female sex, tyrosine kinase inhibitor (TKI) therapy-related symptoms, older age at diagnosis, younger age at the time of the study, and low maternal education were associated with worse health-related quality of life (HRQoL) in children with chronic-phase chronic myeloid leukemia (CML-CP) receiving TKI therapy.

Major finding: Worse HRQoL was observed in children with symptoms (P < .001), children with mothers having low educational qualifications (P = .005), children at a younger age at the time of the study (P = .008), children with older age at the time of diagnosis (P = .007), and female children (P = .038).

Study details: Findings are from a cross-sectional study of 240 respondents including children with CML-CP (age < 18 years at diagnosis) receiving TKI therapy and whose parents responded to a cross-sectional questionnaire.

Disclosures: This study was funded by the National Natural Science Foundation of China. The authors declared no conflict of interests.

Source: Zheng F et al. J Cancer Res Clin Oncol. 2021(Oct 29). Doi: 10.1007/s00432-021-03832-y.

Key clinical point: Female sex, tyrosine kinase inhibitor (TKI) therapy-related symptoms, older age at diagnosis, younger age at the time of the study, and low maternal education were associated with worse health-related quality of life (HRQoL) in children with chronic-phase chronic myeloid leukemia (CML-CP) receiving TKI therapy.

Major finding: Worse HRQoL was observed in children with symptoms (P < .001), children with mothers having low educational qualifications (P = .005), children at a younger age at the time of the study (P = .008), children with older age at the time of diagnosis (P = .007), and female children (P = .038).

Study details: Findings are from a cross-sectional study of 240 respondents including children with CML-CP (age < 18 years at diagnosis) receiving TKI therapy and whose parents responded to a cross-sectional questionnaire.

Disclosures: This study was funded by the National Natural Science Foundation of China. The authors declared no conflict of interests.

Source: Zheng F et al. J Cancer Res Clin Oncol. 2021(Oct 29). Doi: 10.1007/s00432-021-03832-y.

Key clinical point: Adjuvant therapy with interferon-a+sargramostim (IFN) vs. K562/granulocyte macrophage-colony stimulating factor (GM-CSF) vaccine led to better molecular responses with sustained treatment-free remission (TFR) in tyrosine kinase inhibitor (TKI)-treated patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Patients receiving IFN vs. K562/GM-CSF vaccine had a higher rate of undetectable minimal residual disease at 1 year (47.4%; 95% CI 16.7%-66.7% vs. 25%; 95% CI 0.5%-43.5%). TFR was maintained by 36.6% vs. 0.0% of patients receiving IFN vs. K562/GM-CSF vaccine. Treatment discontinuation because of side effects was higher in IFN-treated patients.

Study details: Findings are from a phase 2 trial including 34 adult patients with CML-CP receiving stable dosing of frontline TKI therapy for ≥1 year with a complete cytogenic response who were randomly assigned to IFN or K562/GM-CSF vaccine.

Disclosures: This study was supported by grants from US National Institute of Health. The authors declared no conflict of interests.

Source: Webster JA et al. Leuk Res. 2021;111:106737 (Nov 2). Doi: 10.1016/j.leukres.2021.106737.

Key clinical point: Adjuvant therapy with interferon-a+sargramostim (IFN) vs. K562/granulocyte macrophage-colony stimulating factor (GM-CSF) vaccine led to better molecular responses with sustained treatment-free remission (TFR) in tyrosine kinase inhibitor (TKI)-treated patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Patients receiving IFN vs. K562/GM-CSF vaccine had a higher rate of undetectable minimal residual disease at 1 year (47.4%; 95% CI 16.7%-66.7% vs. 25%; 95% CI 0.5%-43.5%). TFR was maintained by 36.6% vs. 0.0% of patients receiving IFN vs. K562/GM-CSF vaccine. Treatment discontinuation because of side effects was higher in IFN-treated patients.

Study details: Findings are from a phase 2 trial including 34 adult patients with CML-CP receiving stable dosing of frontline TKI therapy for ≥1 year with a complete cytogenic response who were randomly assigned to IFN or K562/GM-CSF vaccine.

Disclosures: This study was supported by grants from US National Institute of Health. The authors declared no conflict of interests.

Source: Webster JA et al. Leuk Res. 2021;111:106737 (Nov 2). Doi: 10.1016/j.leukres.2021.106737.

Key clinical point: Adjuvant therapy with interferon-a+sargramostim (IFN) vs. K562/granulocyte macrophage-colony stimulating factor (GM-CSF) vaccine led to better molecular responses with sustained treatment-free remission (TFR) in tyrosine kinase inhibitor (TKI)-treated patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Patients receiving IFN vs. K562/GM-CSF vaccine had a higher rate of undetectable minimal residual disease at 1 year (47.4%; 95% CI 16.7%-66.7% vs. 25%; 95% CI 0.5%-43.5%). TFR was maintained by 36.6% vs. 0.0% of patients receiving IFN vs. K562/GM-CSF vaccine. Treatment discontinuation because of side effects was higher in IFN-treated patients.

Study details: Findings are from a phase 2 trial including 34 adult patients with CML-CP receiving stable dosing of frontline TKI therapy for ≥1 year with a complete cytogenic response who were randomly assigned to IFN or K562/GM-CSF vaccine.

Disclosures: This study was supported by grants from US National Institute of Health. The authors declared no conflict of interests.

Source: Webster JA et al. Leuk Res. 2021;111:106737 (Nov 2). Doi: 10.1016/j.leukres.2021.106737.

Key clinical point: Statin use alongside imatinib therapy significantly improved deep molecular response (DMR) and major molecular response (MMR) in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Imatinib-treated patients receiving statins had higher rates of DMR (55.8% vs. 41.0%; P = .0016) and MMR (56.8% vs. 47.0%; P = .0048) at 5 years than those not receiving statins. Concomitant statin use was independently associated with DMR (hazard ratio [HR] 1.785; P = .001) and MMR (HR 1.541; P = .043).

Study details: Findings are from a retrospective analysis of 408 patients with CML-CP receiving imatinib therapy with (n = 88) or without (n = 320) statins.

Disclosures: This study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declared no conflict of interests.

Source: Jang HJ et al. Cancers. 2021;13(21):5543 (Nov 4). Doi: 10.3390/cancers13215543.

Key clinical point: Statin use alongside imatinib therapy significantly improved deep molecular response (DMR) and major molecular response (MMR) in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Imatinib-treated patients receiving statins had higher rates of DMR (55.8% vs. 41.0%; P = .0016) and MMR (56.8% vs. 47.0%; P = .0048) at 5 years than those not receiving statins. Concomitant statin use was independently associated with DMR (hazard ratio [HR] 1.785; P = .001) and MMR (HR 1.541; P = .043).

Study details: Findings are from a retrospective analysis of 408 patients with CML-CP receiving imatinib therapy with (n = 88) or without (n = 320) statins.

Disclosures: This study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declared no conflict of interests.

Source: Jang HJ et al. Cancers. 2021;13(21):5543 (Nov 4). Doi: 10.3390/cancers13215543.

Key clinical point: Statin use alongside imatinib therapy significantly improved deep molecular response (DMR) and major molecular response (MMR) in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Imatinib-treated patients receiving statins had higher rates of DMR (55.8% vs. 41.0%; P = .0016) and MMR (56.8% vs. 47.0%; P = .0048) at 5 years than those not receiving statins. Concomitant statin use was independently associated with DMR (hazard ratio [HR] 1.785; P = .001) and MMR (HR 1.541; P = .043).

Study details: Findings are from a retrospective analysis of 408 patients with CML-CP receiving imatinib therapy with (n = 88) or without (n = 320) statins.

Disclosures: This study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declared no conflict of interests.

Source: Jang HJ et al. Cancers. 2021;13(21):5543 (Nov 4). Doi: 10.3390/cancers13215543.

Key clinical point: Ultra-deep sequencing identified genetic mutations of the BCR/ABL1 tyrosine kinase domain in patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML-CP) receiving nilotinib that could have prognostic implications in predicting molecular response (MR) duration.

Major finding: V299 L mutation associated with dasatinib resistance and nilotinib sensitivity was observed in 98% of patients. Of all the detected mutations, only V371A mutation vs. no mutation was associated with shorter sustained major MR for 2 years (75% vs. 100%; P = .039) and sustained MR 4.5 for 15 months (25.0% vs. 94.1%; P = .002).

Study details: Findings are from a prospective analysis of 50 patients with newly diagnosed Ph+ CML-CP undergoing first-line nilotinib therapy.

Disclosures: This study was funded by Novartis Pharmaceuticals Corporation. The authors declared no conflict of interests.

Source: Park H et al. Leuk Res. 2021;111:106728 (Oct 15).Doi: 10.1016/j.leukres.2021.106728.

Key clinical point: Ultra-deep sequencing identified genetic mutations of the BCR/ABL1 tyrosine kinase domain in patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML-CP) receiving nilotinib that could have prognostic implications in predicting molecular response (MR) duration.

Major finding: V299 L mutation associated with dasatinib resistance and nilotinib sensitivity was observed in 98% of patients. Of all the detected mutations, only V371A mutation vs. no mutation was associated with shorter sustained major MR for 2 years (75% vs. 100%; P = .039) and sustained MR 4.5 for 15 months (25.0% vs. 94.1%; P = .002).

Study details: Findings are from a prospective analysis of 50 patients with newly diagnosed Ph+ CML-CP undergoing first-line nilotinib therapy.

Disclosures: This study was funded by Novartis Pharmaceuticals Corporation. The authors declared no conflict of interests.

Source: Park H et al. Leuk Res. 2021;111:106728 (Oct 15).Doi: 10.1016/j.leukres.2021.106728.

Key clinical point: Ultra-deep sequencing identified genetic mutations of the BCR/ABL1 tyrosine kinase domain in patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML-CP) receiving nilotinib that could have prognostic implications in predicting molecular response (MR) duration.

Major finding: V299 L mutation associated with dasatinib resistance and nilotinib sensitivity was observed in 98% of patients. Of all the detected mutations, only V371A mutation vs. no mutation was associated with shorter sustained major MR for 2 years (75% vs. 100%; P = .039) and sustained MR 4.5 for 15 months (25.0% vs. 94.1%; P = .002).

Study details: Findings are from a prospective analysis of 50 patients with newly diagnosed Ph+ CML-CP undergoing first-line nilotinib therapy.

Disclosures: This study was funded by Novartis Pharmaceuticals Corporation. The authors declared no conflict of interests.

Source: Park H et al. Leuk Res. 2021;111:106728 (Oct 15).Doi: 10.1016/j.leukres.2021.106728.

Key clinical point: Monitoring routine plasma levels of imatinib may help optimize treatment dosage, thereby enabling treatment individualization and improving clinical outcomes in patients with chronic myeloid leukemia (CML).

Major finding: Only 39.3% patients showed minimum imatinib plasma concentrations measured at steady state (Cssmin) within therapeutic range (750-1500 ng/mL). Optimal molecular response was achieved by 100% vs. 50% of patients with Cssmin ≥750 ng/mL vs. <750 ng/mL (P = .0004). The rate of toxicity was higher in patients with Cssmin >1500 ng/mL vs. ≤1500 ng/mL (36.4% vs. 5.9%; P = .039).

Study details: This cross-sectional study included 28 patients with CML treated with imatinib for >1 month.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Del Rosario García B et al. J Oncol Pharm Pract. 2021 (Oct 18). Doi: 10.1177/10781552211052535.

Key clinical point: Monitoring routine plasma levels of imatinib may help optimize treatment dosage, thereby enabling treatment individualization and improving clinical outcomes in patients with chronic myeloid leukemia (CML).

Major finding: Only 39.3% patients showed minimum imatinib plasma concentrations measured at steady state (Cssmin) within therapeutic range (750-1500 ng/mL). Optimal molecular response was achieved by 100% vs. 50% of patients with Cssmin ≥750 ng/mL vs. <750 ng/mL (P = .0004). The rate of toxicity was higher in patients with Cssmin >1500 ng/mL vs. ≤1500 ng/mL (36.4% vs. 5.9%; P = .039).

Study details: This cross-sectional study included 28 patients with CML treated with imatinib for >1 month.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Del Rosario García B et al. J Oncol Pharm Pract. 2021 (Oct 18). Doi: 10.1177/10781552211052535.

Key clinical point: Monitoring routine plasma levels of imatinib may help optimize treatment dosage, thereby enabling treatment individualization and improving clinical outcomes in patients with chronic myeloid leukemia (CML).

Major finding: Only 39.3% patients showed minimum imatinib plasma concentrations measured at steady state (Cssmin) within therapeutic range (750-1500 ng/mL). Optimal molecular response was achieved by 100% vs. 50% of patients with Cssmin ≥750 ng/mL vs. <750 ng/mL (P = .0004). The rate of toxicity was higher in patients with Cssmin >1500 ng/mL vs. ≤1500 ng/mL (36.4% vs. 5.9%; P = .039).

Study details: This cross-sectional study included 28 patients with CML treated with imatinib for >1 month.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Del Rosario García B et al. J Oncol Pharm Pract. 2021 (Oct 18). Doi: 10.1177/10781552211052535.

Key clinical point: Suboptimal adherence to oral anticancer (OAC) agents was observed among patients with chronic myeloid leukemia (CML), highlighting the need for implementation of personalized counseling to address the risk for nonadherence and enhance treatment outcomes.

Major finding: Almost 17.9% of participants reported nonadherence, i.e., missing at least 1 dose of CML medication in the previous week. Patients who missed at least 1 vs. 0 doses in the last 7 days reported that medication was somewhat to very hard to take (50.0% vs. 18.6%; P = .008) or they missed doses because of side effects (50.0% vs. 11.4%; P = .001) or busy schedule (37.5% vs. 2.9%; P = .004).

Study details: This study included 86 adult patients with CML with a prescription of OAC agents (imatinib, nilotinib, dasatinib, bosutinib, or ponatinib) for at least 30 days.

Disclosures: This study was funded by grants from the National Cancer Institute and partly by the Institute of General Medical Sciences of the National Institutes of Health. The authors declared no conflict of interests.

Source: Davis TC et al. Int J Environ Res Public Health. 2021;18(21):11045 (Oct 21). Doi: 10.3390/ijerph182111045.

Key clinical point: Suboptimal adherence to oral anticancer (OAC) agents was observed among patients with chronic myeloid leukemia (CML), highlighting the need for implementation of personalized counseling to address the risk for nonadherence and enhance treatment outcomes.

Major finding: Almost 17.9% of participants reported nonadherence, i.e., missing at least 1 dose of CML medication in the previous week. Patients who missed at least 1 vs. 0 doses in the last 7 days reported that medication was somewhat to very hard to take (50.0% vs. 18.6%; P = .008) or they missed doses because of side effects (50.0% vs. 11.4%; P = .001) or busy schedule (37.5% vs. 2.9%; P = .004).

Study details: This study included 86 adult patients with CML with a prescription of OAC agents (imatinib, nilotinib, dasatinib, bosutinib, or ponatinib) for at least 30 days.

Disclosures: This study was funded by grants from the National Cancer Institute and partly by the Institute of General Medical Sciences of the National Institutes of Health. The authors declared no conflict of interests.

Source: Davis TC et al. Int J Environ Res Public Health. 2021;18(21):11045 (Oct 21). Doi: 10.3390/ijerph182111045.

Key clinical point: Suboptimal adherence to oral anticancer (OAC) agents was observed among patients with chronic myeloid leukemia (CML), highlighting the need for implementation of personalized counseling to address the risk for nonadherence and enhance treatment outcomes.

Major finding: Almost 17.9% of participants reported nonadherence, i.e., missing at least 1 dose of CML medication in the previous week. Patients who missed at least 1 vs. 0 doses in the last 7 days reported that medication was somewhat to very hard to take (50.0% vs. 18.6%; P = .008) or they missed doses because of side effects (50.0% vs. 11.4%; P = .001) or busy schedule (37.5% vs. 2.9%; P = .004).

Study details: This study included 86 adult patients with CML with a prescription of OAC agents (imatinib, nilotinib, dasatinib, bosutinib, or ponatinib) for at least 30 days.

Disclosures: This study was funded by grants from the National Cancer Institute and partly by the Institute of General Medical Sciences of the National Institutes of Health. The authors declared no conflict of interests.

Source: Davis TC et al. Int J Environ Res Public Health. 2021;18(21):11045 (Oct 21). Doi: 10.3390/ijerph182111045.