Multiple Myeloma

Photo by Rhoda Baer

Research has shown an increase in the global incidence of leukemia and non-Hodgkin lymphoma (NHL) in recent years.

The Global Burden of Disease (GBD) study showed that, from 2006 to 2016, the incidence of NHL increased 45%, and the incidence of leukemia increased 26%.

These increases were largely due to population growth and aging.

Results from the GDB study were published in JAMA Oncology.

The study indicated that, in 2016, there were 17.2 million cases of cancer worldwide and 8.9 million cancer deaths.

One in 3 men were likely to get cancer during their lifetime, as were 1 in 5 women. Cancer was associated with 213.2 million disability-adjusted life years (DALYs).

The following table lists the 2016 global incidence and mortality figures for all cancers combined and for individual hematologic malignancies.

Leukemia

In 2016, there were 467,000 new cases of leukemia and 310,000 leukemia deaths. Leukemia was responsible for 10.2 million DALYs. Leukemia developed in 1 in 118 men and 1 in 194 women worldwide.

Between 2006 and 2016, the global leukemia incidence increased by 26%—from 370,482 to 466,802 cases.

The researchers said the factors contributing to this increase were population growth (12%), population aging (10%), and an increase in age-specific incidence rates (3%).

NHL

In 2016, there were 461,000 new cases of NHL and 240,000 NHL deaths. NHL was responsible for 6.8 million DALYs. NHL developed in 1 in 110 men and 1 in 161 women worldwide.

Between 2006 and 2016, NHL increased by 45%, from 319,078 to 461,164 cases.

The factors contributing to this increase were increasing age-specific incidence rates (17%), changing population age structure (15%), and population growth (12%).

“A large proportion of the increase in cancer incidence can be explained by improving life expectancy and population growth—a development that can at least partially be attributed to a reduced burden from other common diseases,” the study authors wrote.

The authors also pointed out that prevention efforts are less effective for hematologic malignancies than for other cancers.

Photo by Rhoda Baer

Research has shown an increase in the global incidence of leukemia and non-Hodgkin lymphoma (NHL) in recent years.

The Global Burden of Disease (GBD) study showed that, from 2006 to 2016, the incidence of NHL increased 45%, and the incidence of leukemia increased 26%.

These increases were largely due to population growth and aging.

Results from the GDB study were published in JAMA Oncology.

The study indicated that, in 2016, there were 17.2 million cases of cancer worldwide and 8.9 million cancer deaths.

One in 3 men were likely to get cancer during their lifetime, as were 1 in 5 women. Cancer was associated with 213.2 million disability-adjusted life years (DALYs).

The following table lists the 2016 global incidence and mortality figures for all cancers combined and for individual hematologic malignancies.

Leukemia

In 2016, there were 467,000 new cases of leukemia and 310,000 leukemia deaths. Leukemia was responsible for 10.2 million DALYs. Leukemia developed in 1 in 118 men and 1 in 194 women worldwide.

Between 2006 and 2016, the global leukemia incidence increased by 26%—from 370,482 to 466,802 cases.

The researchers said the factors contributing to this increase were population growth (12%), population aging (10%), and an increase in age-specific incidence rates (3%).

NHL

In 2016, there were 461,000 new cases of NHL and 240,000 NHL deaths. NHL was responsible for 6.8 million DALYs. NHL developed in 1 in 110 men and 1 in 161 women worldwide.

Between 2006 and 2016, NHL increased by 45%, from 319,078 to 461,164 cases.

The factors contributing to this increase were increasing age-specific incidence rates (17%), changing population age structure (15%), and population growth (12%).

“A large proportion of the increase in cancer incidence can be explained by improving life expectancy and population growth—a development that can at least partially be attributed to a reduced burden from other common diseases,” the study authors wrote.

The authors also pointed out that prevention efforts are less effective for hematologic malignancies than for other cancers.

Photo by Rhoda Baer

Research has shown an increase in the global incidence of leukemia and non-Hodgkin lymphoma (NHL) in recent years.

The Global Burden of Disease (GBD) study showed that, from 2006 to 2016, the incidence of NHL increased 45%, and the incidence of leukemia increased 26%.

These increases were largely due to population growth and aging.

Results from the GDB study were published in JAMA Oncology.

The study indicated that, in 2016, there were 17.2 million cases of cancer worldwide and 8.9 million cancer deaths.

One in 3 men were likely to get cancer during their lifetime, as were 1 in 5 women. Cancer was associated with 213.2 million disability-adjusted life years (DALYs).

The following table lists the 2016 global incidence and mortality figures for all cancers combined and for individual hematologic malignancies.

Leukemia

In 2016, there were 467,000 new cases of leukemia and 310,000 leukemia deaths. Leukemia was responsible for 10.2 million DALYs. Leukemia developed in 1 in 118 men and 1 in 194 women worldwide.

Between 2006 and 2016, the global leukemia incidence increased by 26%—from 370,482 to 466,802 cases.

The researchers said the factors contributing to this increase were population growth (12%), population aging (10%), and an increase in age-specific incidence rates (3%).

NHL

In 2016, there were 461,000 new cases of NHL and 240,000 NHL deaths. NHL was responsible for 6.8 million DALYs. NHL developed in 1 in 110 men and 1 in 161 women worldwide.

Between 2006 and 2016, NHL increased by 45%, from 319,078 to 461,164 cases.

The factors contributing to this increase were increasing age-specific incidence rates (17%), changing population age structure (15%), and population growth (12%).

“A large proportion of the increase in cancer incidence can be explained by improving life expectancy and population growth—a development that can at least partially be attributed to a reduced burden from other common diseases,” the study authors wrote.

The authors also pointed out that prevention efforts are less effective for hematologic malignancies than for other cancers.

Photo courtesy of NIH

Researchers say they have developed a frailty index that can predict overall survival (OS) in patients newly diagnosed with multiple myeloma (MM).

An increasing frailty index score was significantly associated with an increased risk of death in these patients, and frailty retained a significant association with OS even after the researchers controlled for patients’ chronological age.

“Our goal was to create a tool that could be widely applied using data sources at hand and that helps doctors provide better informed treatment recommendations for their patients,” said Tanya S. Wildes, MD, of the Washington University School of Medicine in St Louis, Missouri.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health.”

Dr Wildes and her colleagues reported these results in JCO Clinical Cancer Informatics.

Creating the index

The researchers began this study with data from 2,692,361 patients without cancer who were older than 66 years of age. The data were collected from the Medicare Health Outcomes Survey (MHOS), which is used to annually collect self-reported symptoms, functional status, and health-related quality of life data from Medicare beneficiaries enrolled in Medicare Advantage plans.

The researchers used the MHOS data to create a deficit accumulation frailty index made up of a 25-item scale and scoring system. The index includes criteria in 5 categories for scoring frailty:

• Activities of daily living (eg, difficulty dressing or eating)
• Chronic health conditions
• Functioning (eg, difficulty walking or climbing several sets of stairs)
• General health
• Mental health.

Patients whose scores exceed a certain threshold on the scale are classified as frail.

Applying the index

The researchers applied their frailty index to 305 patients with newly diagnosed MM. Data from these patients were obtained from the Surveillance, Epidemiology, and End Results (SEER)-MHOS linked database. In this dataset, data from MHOS are linked to demographics, tumor characteristics, and survival for individuals with a cancer diagnosis who reside in the coverage area of the 14 registries participating in the SEER-MHOS linkage.

The researchers compared findings in the MM patients to findings in the patients without cancer.

In the non-cancer patients, the median age was 74, and the mean frailty score was 0.23. In the MM patients, the median age was 76, and the mean frailty score was 0.28.

Chronological age was weakly correlated with a higher frailty score in MM patients. However, for non-cancer patients, an increase in chronological age was strongly correlated with a higher frailty score.

Among non-cancer patients, each 10% increase in frailty score was associated with a 40% increased risk for death (adjusted hazard ratio, 1.397; P<0.001).

Among MM patients, each 10% increase in frailty score was associated with a 16% increased risk of death (adjusted hazard ratio, 1.159; P<0.001).

The median OS was 33 months for the entire MM cohort, 26.8 months for frail MM patients, and 43.7 months for non-frail MM patients (P=0.015 for the frail to non-frail comparison).

“These findings underscore the need to place more consideration on biological age versus chronological age in multiple myeloma, recognizing that frailty is dynamic and encompasses many factors beyond the disease itself,” Dr Wildes said.

“Ultimately, the hope is that this tool will help us to better personalize care based on a fuller picture of our patients’ health so that we are not under-treating an older adult who can tolerate a more intense therapy or over-treating one who’s going to be vulnerable to the toxicities of therapy.”

Limitations and next steps

The researchers believe there are several options for optimizing the data in the frailty index, including turning it into a computerized program and examining patients who are not newly diagnosed and have subsequent relapses, disease burden, and treatment toxicities.

This study is limited in the fact that researchers only assessed OS and not progression-free survival, chemotherapy toxicity, or hospitalization rates.

Additionally, the MM data was derived from patients enrolled in the Medicare Advantage program, which may have contributed to selecting participants who are, overall, lower-risk due to the way the program incentivizes lower-cost enrollees.

Photo courtesy of NIH

Researchers say they have developed a frailty index that can predict overall survival (OS) in patients newly diagnosed with multiple myeloma (MM).

An increasing frailty index score was significantly associated with an increased risk of death in these patients, and frailty retained a significant association with OS even after the researchers controlled for patients’ chronological age.

“Our goal was to create a tool that could be widely applied using data sources at hand and that helps doctors provide better informed treatment recommendations for their patients,” said Tanya S. Wildes, MD, of the Washington University School of Medicine in St Louis, Missouri.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health.”

Dr Wildes and her colleagues reported these results in JCO Clinical Cancer Informatics.

Creating the index

The researchers began this study with data from 2,692,361 patients without cancer who were older than 66 years of age. The data were collected from the Medicare Health Outcomes Survey (MHOS), which is used to annually collect self-reported symptoms, functional status, and health-related quality of life data from Medicare beneficiaries enrolled in Medicare Advantage plans.

The researchers used the MHOS data to create a deficit accumulation frailty index made up of a 25-item scale and scoring system. The index includes criteria in 5 categories for scoring frailty:

• Activities of daily living (eg, difficulty dressing or eating)
• Chronic health conditions
• Functioning (eg, difficulty walking or climbing several sets of stairs)
• General health
• Mental health.

Patients whose scores exceed a certain threshold on the scale are classified as frail.

Applying the index

The researchers applied their frailty index to 305 patients with newly diagnosed MM. Data from these patients were obtained from the Surveillance, Epidemiology, and End Results (SEER)-MHOS linked database. In this dataset, data from MHOS are linked to demographics, tumor characteristics, and survival for individuals with a cancer diagnosis who reside in the coverage area of the 14 registries participating in the SEER-MHOS linkage.

The researchers compared findings in the MM patients to findings in the patients without cancer.

In the non-cancer patients, the median age was 74, and the mean frailty score was 0.23. In the MM patients, the median age was 76, and the mean frailty score was 0.28.

Chronological age was weakly correlated with a higher frailty score in MM patients. However, for non-cancer patients, an increase in chronological age was strongly correlated with a higher frailty score.

Among non-cancer patients, each 10% increase in frailty score was associated with a 40% increased risk for death (adjusted hazard ratio, 1.397; P<0.001).

Among MM patients, each 10% increase in frailty score was associated with a 16% increased risk of death (adjusted hazard ratio, 1.159; P<0.001).

The median OS was 33 months for the entire MM cohort, 26.8 months for frail MM patients, and 43.7 months for non-frail MM patients (P=0.015 for the frail to non-frail comparison).

“These findings underscore the need to place more consideration on biological age versus chronological age in multiple myeloma, recognizing that frailty is dynamic and encompasses many factors beyond the disease itself,” Dr Wildes said.

“Ultimately, the hope is that this tool will help us to better personalize care based on a fuller picture of our patients’ health so that we are not under-treating an older adult who can tolerate a more intense therapy or over-treating one who’s going to be vulnerable to the toxicities of therapy.”

Limitations and next steps

The researchers believe there are several options for optimizing the data in the frailty index, including turning it into a computerized program and examining patients who are not newly diagnosed and have subsequent relapses, disease burden, and treatment toxicities.

This study is limited in the fact that researchers only assessed OS and not progression-free survival, chemotherapy toxicity, or hospitalization rates.

Additionally, the MM data was derived from patients enrolled in the Medicare Advantage program, which may have contributed to selecting participants who are, overall, lower-risk due to the way the program incentivizes lower-cost enrollees.

Photo courtesy of NIH

Researchers say they have developed a frailty index that can predict overall survival (OS) in patients newly diagnosed with multiple myeloma (MM).

An increasing frailty index score was significantly associated with an increased risk of death in these patients, and frailty retained a significant association with OS even after the researchers controlled for patients’ chronological age.

“Our goal was to create a tool that could be widely applied using data sources at hand and that helps doctors provide better informed treatment recommendations for their patients,” said Tanya S. Wildes, MD, of the Washington University School of Medicine in St Louis, Missouri.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health.”

Dr Wildes and her colleagues reported these results in JCO Clinical Cancer Informatics.

Creating the index

The researchers began this study with data from 2,692,361 patients without cancer who were older than 66 years of age. The data were collected from the Medicare Health Outcomes Survey (MHOS), which is used to annually collect self-reported symptoms, functional status, and health-related quality of life data from Medicare beneficiaries enrolled in Medicare Advantage plans.

The researchers used the MHOS data to create a deficit accumulation frailty index made up of a 25-item scale and scoring system. The index includes criteria in 5 categories for scoring frailty:

• Activities of daily living (eg, difficulty dressing or eating)
• Chronic health conditions
• Functioning (eg, difficulty walking or climbing several sets of stairs)
• General health
• Mental health.

Patients whose scores exceed a certain threshold on the scale are classified as frail.

Applying the index

The researchers applied their frailty index to 305 patients with newly diagnosed MM. Data from these patients were obtained from the Surveillance, Epidemiology, and End Results (SEER)-MHOS linked database. In this dataset, data from MHOS are linked to demographics, tumor characteristics, and survival for individuals with a cancer diagnosis who reside in the coverage area of the 14 registries participating in the SEER-MHOS linkage.

The researchers compared findings in the MM patients to findings in the patients without cancer.

In the non-cancer patients, the median age was 74, and the mean frailty score was 0.23. In the MM patients, the median age was 76, and the mean frailty score was 0.28.

Chronological age was weakly correlated with a higher frailty score in MM patients. However, for non-cancer patients, an increase in chronological age was strongly correlated with a higher frailty score.

Among non-cancer patients, each 10% increase in frailty score was associated with a 40% increased risk for death (adjusted hazard ratio, 1.397; P<0.001).

Among MM patients, each 10% increase in frailty score was associated with a 16% increased risk of death (adjusted hazard ratio, 1.159; P<0.001).

The median OS was 33 months for the entire MM cohort, 26.8 months for frail MM patients, and 43.7 months for non-frail MM patients (P=0.015 for the frail to non-frail comparison).

“These findings underscore the need to place more consideration on biological age versus chronological age in multiple myeloma, recognizing that frailty is dynamic and encompasses many factors beyond the disease itself,” Dr Wildes said.

“Ultimately, the hope is that this tool will help us to better personalize care based on a fuller picture of our patients’ health so that we are not under-treating an older adult who can tolerate a more intense therapy or over-treating one who’s going to be vulnerable to the toxicities of therapy.”

Limitations and next steps

The researchers believe there are several options for optimizing the data in the frailty index, including turning it into a computerized program and examining patients who are not newly diagnosed and have subsequent relapses, disease burden, and treatment toxicities.

This study is limited in the fact that researchers only assessed OS and not progression-free survival, chemotherapy toxicity, or hospitalization rates.

Additionally, the MM data was derived from patients enrolled in the Medicare Advantage program, which may have contributed to selecting participants who are, overall, lower-risk due to the way the program incentivizes lower-cost enrollees.

A new index of frailty predicts survival in older patients with multiple myeloma based on accumulation of aging-associated deficits, rather than chronological age alone, investigators report. A 16% increased risk of death was seen for each 10% increase in the deficit-accumulation frailty index (DAFI), which includes 25 variables related health, function, and activities of daily living.

There was only a weak correlation between chronological age and increase in deficits tracked by the index, in contrast to a cohort without cancer, in which age and frailty were strongly correlated, the investigators reported in JCO Clinical Cancer Informatics.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health,” study author Tanya M. Wildes, MD, of Washington University, St. Louis, said in a news release from the American Society of Clinical Oncology.

Existing tools to assess frailty include an index proposed by the International Myeloma Working Group that looks at age plus other indexes related to comorbidities and activities of daily living, and the revised Myeloma Comorbidity Index that incorporates age with other prognostic factors.

“Although both tools provide prognostic information, chronological age automatically increases frailty without taking biologic or functional age into account,” Dr. Wildes and her coauthors wrote in their report.

By contrast, the DAFI is based on the concept of biologic age, in which the health status of an individual is measured based on the proportion of aging-associated deficits they have accumulated, according to the authors.

To create the DAFI, Dr. Wildes and her colleagues analyzed nearly 2.7 million records of noncancer patients aged 66 years or older in the SEER Medicare Health Outcomes Survey (MHOS) database. They identified 25 variables in the database representing chronic health conditions, activities of daily living, functioning, mental health, and general health.

An individual’s DAFI score was calculated as the sum of scores for each of the 25 variables as 0 for absent, 0.5 for limited, and 1 for present. Predicted DAFI means were calculated for each year of age and used to create age-specific cut points to determine whether an individual would be considered frail or not versus others of the same age.

“In other words, the same frailty score may qualify an 80-year-old individual as fit and a 70-year-old as frail, depending on the cutoff for their respective age group,” investigators explained in their report.

They applied the index to 305 patients with newly diagnosed myeloma in the SEER-MHOS database who were 66 years of age or older (median age, 76 years) and had completed the survey within 1 year of diagnosis.

The DAFI classified 52% of the myeloma patients as frail, and for that group, median overall survival was 26.8 months, versus 43.7 months for nonfrail patients (P = .015), according to the reported data. For each 10% increase in score, the risk of death increased by 16% (P less than .001).

Notably, advancing age was very weakly correlated with increased age-related deficits in the myeloma cohort (r2 = 0.15; P = .010), according to investigators, but very strongly correlated with deficits in the cohort of noncancer patients (r2 = 0.98; P less than .001).

“This suggests that, in patients with multiple myeloma, the prevalence of impairments across domains of function, chronic comorbidities, general health, and mental health are more related to the overall burden of myeloma rather than chronological age alone,” the investigators wrote.

The information used to calculate a DAFI score is easily obtainable during a clinic visit, according to the authors, who provided an overview of all 25 variables in the journal article.

Further development of a computerized program would further enhance usability in the clinic, allowing for real-time calculation during a patient visit, they said.

Survivorship expert Merry Jennifer Markham, MD, said in the ASCO news release that this frailty index is notable because it accounts for more than just chronological age. “Knowing this information can help oncologists have more informed discussions with patients about their prognosis, which in turn can empower patients and families as they weigh treatment options,” she said.

The research was supported by National Cancer Institute. Dr. Wildes reported honoraria from Carevive Systems and research funding from Janssen Oncology. Another coauthor reported honoraria from Celgene and Janssen, and a consulting or advisory role with Amgen and Takeda.

 

SOURCE: Mian HS et al. JCO Clin Cancer Inform. 2018 Jul 25. 2018 Jul 25. doi: 10.1200/CCI.18.00043.

A new index of frailty predicts survival in older patients with multiple myeloma based on accumulation of aging-associated deficits, rather than chronological age alone, investigators report. A 16% increased risk of death was seen for each 10% increase in the deficit-accumulation frailty index (DAFI), which includes 25 variables related health, function, and activities of daily living.

There was only a weak correlation between chronological age and increase in deficits tracked by the index, in contrast to a cohort without cancer, in which age and frailty were strongly correlated, the investigators reported in JCO Clinical Cancer Informatics.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health,” study author Tanya M. Wildes, MD, of Washington University, St. Louis, said in a news release from the American Society of Clinical Oncology.

Existing tools to assess frailty include an index proposed by the International Myeloma Working Group that looks at age plus other indexes related to comorbidities and activities of daily living, and the revised Myeloma Comorbidity Index that incorporates age with other prognostic factors.

“Although both tools provide prognostic information, chronological age automatically increases frailty without taking biologic or functional age into account,” Dr. Wildes and her coauthors wrote in their report.

By contrast, the DAFI is based on the concept of biologic age, in which the health status of an individual is measured based on the proportion of aging-associated deficits they have accumulated, according to the authors.

To create the DAFI, Dr. Wildes and her colleagues analyzed nearly 2.7 million records of noncancer patients aged 66 years or older in the SEER Medicare Health Outcomes Survey (MHOS) database. They identified 25 variables in the database representing chronic health conditions, activities of daily living, functioning, mental health, and general health.

An individual’s DAFI score was calculated as the sum of scores for each of the 25 variables as 0 for absent, 0.5 for limited, and 1 for present. Predicted DAFI means were calculated for each year of age and used to create age-specific cut points to determine whether an individual would be considered frail or not versus others of the same age.

“In other words, the same frailty score may qualify an 80-year-old individual as fit and a 70-year-old as frail, depending on the cutoff for their respective age group,” investigators explained in their report.

They applied the index to 305 patients with newly diagnosed myeloma in the SEER-MHOS database who were 66 years of age or older (median age, 76 years) and had completed the survey within 1 year of diagnosis.

The DAFI classified 52% of the myeloma patients as frail, and for that group, median overall survival was 26.8 months, versus 43.7 months for nonfrail patients (P = .015), according to the reported data. For each 10% increase in score, the risk of death increased by 16% (P less than .001).

Notably, advancing age was very weakly correlated with increased age-related deficits in the myeloma cohort (r2 = 0.15; P = .010), according to investigators, but very strongly correlated with deficits in the cohort of noncancer patients (r2 = 0.98; P less than .001).

“This suggests that, in patients with multiple myeloma, the prevalence of impairments across domains of function, chronic comorbidities, general health, and mental health are more related to the overall burden of myeloma rather than chronological age alone,” the investigators wrote.

The information used to calculate a DAFI score is easily obtainable during a clinic visit, according to the authors, who provided an overview of all 25 variables in the journal article.

Further development of a computerized program would further enhance usability in the clinic, allowing for real-time calculation during a patient visit, they said.

Survivorship expert Merry Jennifer Markham, MD, said in the ASCO news release that this frailty index is notable because it accounts for more than just chronological age. “Knowing this information can help oncologists have more informed discussions with patients about their prognosis, which in turn can empower patients and families as they weigh treatment options,” she said.

The research was supported by National Cancer Institute. Dr. Wildes reported honoraria from Carevive Systems and research funding from Janssen Oncology. Another coauthor reported honoraria from Celgene and Janssen, and a consulting or advisory role with Amgen and Takeda.

 

SOURCE: Mian HS et al. JCO Clin Cancer Inform. 2018 Jul 25. 2018 Jul 25. doi: 10.1200/CCI.18.00043.

A new index of frailty predicts survival in older patients with multiple myeloma based on accumulation of aging-associated deficits, rather than chronological age alone, investigators report. A 16% increased risk of death was seen for each 10% increase in the deficit-accumulation frailty index (DAFI), which includes 25 variables related health, function, and activities of daily living.

There was only a weak correlation between chronological age and increase in deficits tracked by the index, in contrast to a cohort without cancer, in which age and frailty were strongly correlated, the investigators reported in JCO Clinical Cancer Informatics.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health,” study author Tanya M. Wildes, MD, of Washington University, St. Louis, said in a news release from the American Society of Clinical Oncology.

Existing tools to assess frailty include an index proposed by the International Myeloma Working Group that looks at age plus other indexes related to comorbidities and activities of daily living, and the revised Myeloma Comorbidity Index that incorporates age with other prognostic factors.

“Although both tools provide prognostic information, chronological age automatically increases frailty without taking biologic or functional age into account,” Dr. Wildes and her coauthors wrote in their report.

By contrast, the DAFI is based on the concept of biologic age, in which the health status of an individual is measured based on the proportion of aging-associated deficits they have accumulated, according to the authors.

To create the DAFI, Dr. Wildes and her colleagues analyzed nearly 2.7 million records of noncancer patients aged 66 years or older in the SEER Medicare Health Outcomes Survey (MHOS) database. They identified 25 variables in the database representing chronic health conditions, activities of daily living, functioning, mental health, and general health.

An individual’s DAFI score was calculated as the sum of scores for each of the 25 variables as 0 for absent, 0.5 for limited, and 1 for present. Predicted DAFI means were calculated for each year of age and used to create age-specific cut points to determine whether an individual would be considered frail or not versus others of the same age.

“In other words, the same frailty score may qualify an 80-year-old individual as fit and a 70-year-old as frail, depending on the cutoff for their respective age group,” investigators explained in their report.

They applied the index to 305 patients with newly diagnosed myeloma in the SEER-MHOS database who were 66 years of age or older (median age, 76 years) and had completed the survey within 1 year of diagnosis.

The DAFI classified 52% of the myeloma patients as frail, and for that group, median overall survival was 26.8 months, versus 43.7 months for nonfrail patients (P = .015), according to the reported data. For each 10% increase in score, the risk of death increased by 16% (P less than .001).

Notably, advancing age was very weakly correlated with increased age-related deficits in the myeloma cohort (r2 = 0.15; P = .010), according to investigators, but very strongly correlated with deficits in the cohort of noncancer patients (r2 = 0.98; P less than .001).

“This suggests that, in patients with multiple myeloma, the prevalence of impairments across domains of function, chronic comorbidities, general health, and mental health are more related to the overall burden of myeloma rather than chronological age alone,” the investigators wrote.

The information used to calculate a DAFI score is easily obtainable during a clinic visit, according to the authors, who provided an overview of all 25 variables in the journal article.

Further development of a computerized program would further enhance usability in the clinic, allowing for real-time calculation during a patient visit, they said.

Survivorship expert Merry Jennifer Markham, MD, said in the ASCO news release that this frailty index is notable because it accounts for more than just chronological age. “Knowing this information can help oncologists have more informed discussions with patients about their prognosis, which in turn can empower patients and families as they weigh treatment options,” she said.

The research was supported by National Cancer Institute. Dr. Wildes reported honoraria from Carevive Systems and research funding from Janssen Oncology. Another coauthor reported honoraria from Celgene and Janssen, and a consulting or advisory role with Amgen and Takeda.

 

SOURCE: Mian HS et al. JCO Clin Cancer Inform. 2018 Jul 25. 2018 Jul 25. doi: 10.1200/CCI.18.00043.

showing multiple myeloma

The US Food and Drug Administration (FDA) has granted fast track designation to the cancer vaccine galinpepimut-S (GPS) for the treatment of multiple myeloma (MM).

GPS consists of 4 modified peptide chains that induce an innate immune response (CD4+/CD8+ T cells) against the Wilms’ tumor 1 (WT1) antigen.

GPS is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target.

GPS has been tested in a phase 2 trial of patients with MM. Results from this trial were presented at the 44th Annual Meeting of the EBMT in March.

Phase 2 trial

The study enrolled 19 MM patients. Fifteen of them had high-risk cytogenetics at diagnosis, and 18 were at least minimal residual disease-positive after autologous stem cell transplant (ASCT).

Patients began receiving GPS within 22 days of ASCT. Initially, they received 6 doses (administered subcutaneously with the oil emulsifier montanide) every 2 weeks. Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor (70 μg) on days -2 (± 1 day) and 0 of each GPS vaccination.

The patients underwent assessment 2 to 4 weeks after the 6th GPS dose. Then, they received 6 additional monthly doses of GPS in conjunction with lenalidomide maintenance (10 mg daily), starting on day 100 post-ASCT. Patients were assessed 2 to 4 weeks after the 12th GPS dose.

The researchers found that GPS stimulated time-dependent CD4+ or CD8+ T-cell immune responses specific for all 4 WT1 peptides within GPS, 2 of which are heteroclitic.

Immune responses were confirmed in up to 91% of patients, with multivalent immune responses in up to 64% of patients. Three-quarters of patients had multifunctional cross-epitope T-cell reactivity to antigenic epitopes against which the hosts were not specifically immunized, in a pattern akin to epitope spreading.

In patients who received all 12 doses of GPS (n=12), there was a “strong” association between clinical benefit—defined as complete response (CR) or very good partial response (VGPR)—and frequency of CD4/CD8 immune responses.

Of those patients who had achieved CR/VGPR upon completion of GPS treatment, 100% (n=11) had CD4 immune responses, and 81.8% (n=9) had CD8 immune responses.

The median progression-free survival was 23.6 months, and the median overall survival was not reached. At 18 months, the rate of progression-free survival was 62%, and the rate of overall survival was 88%.

About fast track designation

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.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

showing multiple myeloma

The US Food and Drug Administration (FDA) has granted fast track designation to the cancer vaccine galinpepimut-S (GPS) for the treatment of multiple myeloma (MM).

GPS consists of 4 modified peptide chains that induce an innate immune response (CD4+/CD8+ T cells) against the Wilms’ tumor 1 (WT1) antigen.

GPS is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target.

GPS has been tested in a phase 2 trial of patients with MM. Results from this trial were presented at the 44th Annual Meeting of the EBMT in March.

Phase 2 trial

The study enrolled 19 MM patients. Fifteen of them had high-risk cytogenetics at diagnosis, and 18 were at least minimal residual disease-positive after autologous stem cell transplant (ASCT).

Patients began receiving GPS within 22 days of ASCT. Initially, they received 6 doses (administered subcutaneously with the oil emulsifier montanide) every 2 weeks. Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor (70 μg) on days -2 (± 1 day) and 0 of each GPS vaccination.

The patients underwent assessment 2 to 4 weeks after the 6th GPS dose. Then, they received 6 additional monthly doses of GPS in conjunction with lenalidomide maintenance (10 mg daily), starting on day 100 post-ASCT. Patients were assessed 2 to 4 weeks after the 12th GPS dose.

The researchers found that GPS stimulated time-dependent CD4+ or CD8+ T-cell immune responses specific for all 4 WT1 peptides within GPS, 2 of which are heteroclitic.

Immune responses were confirmed in up to 91% of patients, with multivalent immune responses in up to 64% of patients. Three-quarters of patients had multifunctional cross-epitope T-cell reactivity to antigenic epitopes against which the hosts were not specifically immunized, in a pattern akin to epitope spreading.

In patients who received all 12 doses of GPS (n=12), there was a “strong” association between clinical benefit—defined as complete response (CR) or very good partial response (VGPR)—and frequency of CD4/CD8 immune responses.

Of those patients who had achieved CR/VGPR upon completion of GPS treatment, 100% (n=11) had CD4 immune responses, and 81.8% (n=9) had CD8 immune responses.

The median progression-free survival was 23.6 months, and the median overall survival was not reached. At 18 months, the rate of progression-free survival was 62%, and the rate of overall survival was 88%.

About fast track designation

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.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

showing multiple myeloma

The US Food and Drug Administration (FDA) has granted fast track designation to the cancer vaccine galinpepimut-S (GPS) for the treatment of multiple myeloma (MM).

GPS consists of 4 modified peptide chains that induce an innate immune response (CD4+/CD8+ T cells) against the Wilms’ tumor 1 (WT1) antigen.

GPS is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target.

GPS has been tested in a phase 2 trial of patients with MM. Results from this trial were presented at the 44th Annual Meeting of the EBMT in March.

Phase 2 trial

The study enrolled 19 MM patients. Fifteen of them had high-risk cytogenetics at diagnosis, and 18 were at least minimal residual disease-positive after autologous stem cell transplant (ASCT).

Patients began receiving GPS within 22 days of ASCT. Initially, they received 6 doses (administered subcutaneously with the oil emulsifier montanide) every 2 weeks. Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor (70 μg) on days -2 (± 1 day) and 0 of each GPS vaccination.

The patients underwent assessment 2 to 4 weeks after the 6th GPS dose. Then, they received 6 additional monthly doses of GPS in conjunction with lenalidomide maintenance (10 mg daily), starting on day 100 post-ASCT. Patients were assessed 2 to 4 weeks after the 12th GPS dose.

The researchers found that GPS stimulated time-dependent CD4+ or CD8+ T-cell immune responses specific for all 4 WT1 peptides within GPS, 2 of which are heteroclitic.

Immune responses were confirmed in up to 91% of patients, with multivalent immune responses in up to 64% of patients. Three-quarters of patients had multifunctional cross-epitope T-cell reactivity to antigenic epitopes against which the hosts were not specifically immunized, in a pattern akin to epitope spreading.

In patients who received all 12 doses of GPS (n=12), there was a “strong” association between clinical benefit—defined as complete response (CR) or very good partial response (VGPR)—and frequency of CD4/CD8 immune responses.

Of those patients who had achieved CR/VGPR upon completion of GPS treatment, 100% (n=11) had CD4 immune responses, and 81.8% (n=9) had CD8 immune responses.

The median progression-free survival was 23.6 months, and the median overall survival was not reached. At 18 months, the rate of progression-free survival was 62%, and the rate of overall survival was 88%.

About fast track designation

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.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Nivestym™ (filgrastim-aafi), a biosimilar to Neupogen (filgrastim).

Nivestym is approved to treat patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy or undergoing bone marrow transplant, acute myeloid leukemia patients receiving induction or consolidation chemotherapy, patients undergoing autologous peripheral blood progenitor cell collection, and patients with severe chronic neutropenia.

The FDA’s approval of Nivestym was based on a review of evidence suggesting the drug is highly similar to Neupogen, according to Pfizer, the company developing Nivestym.

The full approved indication for Nivestym is as follows:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
• To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in patients with acute myeloid leukemia
• To reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg, febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplant
• For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
• For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

For more details on Nivestym, see the full prescribing information.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Nivestym™ (filgrastim-aafi), a biosimilar to Neupogen (filgrastim).

Nivestym is approved to treat patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy or undergoing bone marrow transplant, acute myeloid leukemia patients receiving induction or consolidation chemotherapy, patients undergoing autologous peripheral blood progenitor cell collection, and patients with severe chronic neutropenia.

The FDA’s approval of Nivestym was based on a review of evidence suggesting the drug is highly similar to Neupogen, according to Pfizer, the company developing Nivestym.

The full approved indication for Nivestym is as follows:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
• To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in patients with acute myeloid leukemia
• To reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg, febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplant
• For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
• For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

For more details on Nivestym, see the full prescribing information.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Nivestym™ (filgrastim-aafi), a biosimilar to Neupogen (filgrastim).

Nivestym is approved to treat patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy or undergoing bone marrow transplant, acute myeloid leukemia patients receiving induction or consolidation chemotherapy, patients undergoing autologous peripheral blood progenitor cell collection, and patients with severe chronic neutropenia.

The FDA’s approval of Nivestym was based on a review of evidence suggesting the drug is highly similar to Neupogen, according to Pfizer, the company developing Nivestym.

The full approved indication for Nivestym is as follows:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
• To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in patients with acute myeloid leukemia
• To reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg, febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplant
• For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
• For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

For more details on Nivestym, see the full prescribing information.

Photo by Rhoda Baer

A review of data from more than 19 million people indicates that diabetes significantly raises a person’s risk of developing cancer.

When researchers compared patients with diabetes and without, both male and female diabetics had an increased risk of leukemias and lymphomas as well as certain solid tumors.

Researchers also found that diabetes conferred a higher cancer risk for women than men, both for all cancers combined and for some specific cancers, including leukemia.

“The link between diabetes and the risk of developing cancer is now firmly established,” said Toshiaki Ohkuma, PhD, of The George Institute for Global Health at the University of New South Wales in Australia.

“We have also demonstrated, for the first time, that women with diabetes are more likely to develop any form of cancer and have a significantly higher chance of developing kidney, oral, and stomach cancers and leukemia.”

Dr Ohkuma and his colleagues reported these findings in Diabetologia.

The researchers conducted a systematic search in PubMed MEDLINE to identify reports on the links between diabetes and cancer. Additional reports were identified from the reference lists of the relevant studies.

Only those cohort studies providing relative risks (RRs) for the association between diabetes and cancer for both women and men were included. In total, 107 relevant articles were identified, along with 36 cohorts of individual participant data.

RRs for cancer were obtained for patients with diabetes (types 1 and 2 combined) versus those without diabetes, for both men and women. The women-to-men ratios of these relative risk ratios (RRRs) were then calculated to determine the excess risk in women if present.

Data on all-site cancer was available from 47 studies, involving 121 cohorts and 19,239,302 individuals.

Diabetics vs non-diabetics

Women with diabetes had a 27% higher risk of all-site cancer compared to women without diabetes (RR=1.27; 95% CI 1.21, 1.32; P<0.001).

For men, the risk of all-site cancer was 19% higher among those with diabetes than those without (RR=1.19; 95% CI 1.13, 1.25; P<0.001).

There were several hematologic malignancies for which diabetics had an increased risk, as shown in the following table.

Sex comparison

Calculation of the women-to-men ratio revealed that women with diabetes had a 6% greater excess risk of all-site cancer compared to men with diabetes (RRR=1.06; 95% CI 1.03, 1.09; P<0.001).

The women-to-men ratios also showed significantly higher risks for female diabetics for:

• Kidney cancer—RRR=1.11 (99% CI 1.04, 1.18; P<0.001)
• Oral cancer—RRR=1.13 (99% CI 1.00, 1.28; P=0.009)
• Stomach cancer—RRR=1.14 (99% CI 1.07, 1.22; P<0.001)
• Leukemia—RRR=1.15 (99% CI 1.02, 1.28; P=0.002).

However, women had a significantly lower risk of liver cancer (RRR=0.88; 99% CI 0.79, 0.99; P=0.005).

There are several possible reasons for the excess cancer risk observed in women, according to study author Sanne Peters, PhD, of The George Institute for Global Health at the University of Oxford in the UK.

For example, on average, women are in the pre-diabetic state of impaired glucose tolerance 2 years longer than men.

“Historically, we know that women are often under-treated when they first present with symptoms of diabetes, are less likely to receive intensive care, and are not taking the same levels of medications as men,” Dr Peters said. “All of these could go some way into explaining why women are at greater risk of developing cancer, but, without more research, we can’t be certain.”

Photo by Rhoda Baer

A review of data from more than 19 million people indicates that diabetes significantly raises a person’s risk of developing cancer.

When researchers compared patients with diabetes and without, both male and female diabetics had an increased risk of leukemias and lymphomas as well as certain solid tumors.

Researchers also found that diabetes conferred a higher cancer risk for women than men, both for all cancers combined and for some specific cancers, including leukemia.

“The link between diabetes and the risk of developing cancer is now firmly established,” said Toshiaki Ohkuma, PhD, of The George Institute for Global Health at the University of New South Wales in Australia.

“We have also demonstrated, for the first time, that women with diabetes are more likely to develop any form of cancer and have a significantly higher chance of developing kidney, oral, and stomach cancers and leukemia.”

Dr Ohkuma and his colleagues reported these findings in Diabetologia.

The researchers conducted a systematic search in PubMed MEDLINE to identify reports on the links between diabetes and cancer. Additional reports were identified from the reference lists of the relevant studies.

Only those cohort studies providing relative risks (RRs) for the association between diabetes and cancer for both women and men were included. In total, 107 relevant articles were identified, along with 36 cohorts of individual participant data.

RRs for cancer were obtained for patients with diabetes (types 1 and 2 combined) versus those without diabetes, for both men and women. The women-to-men ratios of these relative risk ratios (RRRs) were then calculated to determine the excess risk in women if present.

Data on all-site cancer was available from 47 studies, involving 121 cohorts and 19,239,302 individuals.

Diabetics vs non-diabetics

Women with diabetes had a 27% higher risk of all-site cancer compared to women without diabetes (RR=1.27; 95% CI 1.21, 1.32; P<0.001).

For men, the risk of all-site cancer was 19% higher among those with diabetes than those without (RR=1.19; 95% CI 1.13, 1.25; P<0.001).

There were several hematologic malignancies for which diabetics had an increased risk, as shown in the following table.

Sex comparison

Calculation of the women-to-men ratio revealed that women with diabetes had a 6% greater excess risk of all-site cancer compared to men with diabetes (RRR=1.06; 95% CI 1.03, 1.09; P<0.001).

The women-to-men ratios also showed significantly higher risks for female diabetics for:

• Kidney cancer—RRR=1.11 (99% CI 1.04, 1.18; P<0.001)
• Oral cancer—RRR=1.13 (99% CI 1.00, 1.28; P=0.009)
• Stomach cancer—RRR=1.14 (99% CI 1.07, 1.22; P<0.001)
• Leukemia—RRR=1.15 (99% CI 1.02, 1.28; P=0.002).

However, women had a significantly lower risk of liver cancer (RRR=0.88; 99% CI 0.79, 0.99; P=0.005).

There are several possible reasons for the excess cancer risk observed in women, according to study author Sanne Peters, PhD, of The George Institute for Global Health at the University of Oxford in the UK.

For example, on average, women are in the pre-diabetic state of impaired glucose tolerance 2 years longer than men.

“Historically, we know that women are often under-treated when they first present with symptoms of diabetes, are less likely to receive intensive care, and are not taking the same levels of medications as men,” Dr Peters said. “All of these could go some way into explaining why women are at greater risk of developing cancer, but, without more research, we can’t be certain.”

Photo by Rhoda Baer

A review of data from more than 19 million people indicates that diabetes significantly raises a person’s risk of developing cancer.

When researchers compared patients with diabetes and without, both male and female diabetics had an increased risk of leukemias and lymphomas as well as certain solid tumors.

Researchers also found that diabetes conferred a higher cancer risk for women than men, both for all cancers combined and for some specific cancers, including leukemia.

“The link between diabetes and the risk of developing cancer is now firmly established,” said Toshiaki Ohkuma, PhD, of The George Institute for Global Health at the University of New South Wales in Australia.

“We have also demonstrated, for the first time, that women with diabetes are more likely to develop any form of cancer and have a significantly higher chance of developing kidney, oral, and stomach cancers and leukemia.”

Dr Ohkuma and his colleagues reported these findings in Diabetologia.

The researchers conducted a systematic search in PubMed MEDLINE to identify reports on the links between diabetes and cancer. Additional reports were identified from the reference lists of the relevant studies.

Only those cohort studies providing relative risks (RRs) for the association between diabetes and cancer for both women and men were included. In total, 107 relevant articles were identified, along with 36 cohorts of individual participant data.

RRs for cancer were obtained for patients with diabetes (types 1 and 2 combined) versus those without diabetes, for both men and women. The women-to-men ratios of these relative risk ratios (RRRs) were then calculated to determine the excess risk in women if present.

Data on all-site cancer was available from 47 studies, involving 121 cohorts and 19,239,302 individuals.

Diabetics vs non-diabetics

Women with diabetes had a 27% higher risk of all-site cancer compared to women without diabetes (RR=1.27; 95% CI 1.21, 1.32; P<0.001).

For men, the risk of all-site cancer was 19% higher among those with diabetes than those without (RR=1.19; 95% CI 1.13, 1.25; P<0.001).

There were several hematologic malignancies for which diabetics had an increased risk, as shown in the following table.

Sex comparison

Calculation of the women-to-men ratio revealed that women with diabetes had a 6% greater excess risk of all-site cancer compared to men with diabetes (RRR=1.06; 95% CI 1.03, 1.09; P<0.001).

The women-to-men ratios also showed significantly higher risks for female diabetics for:

• Kidney cancer—RRR=1.11 (99% CI 1.04, 1.18; P<0.001)
• Oral cancer—RRR=1.13 (99% CI 1.00, 1.28; P=0.009)
• Stomach cancer—RRR=1.14 (99% CI 1.07, 1.22; P<0.001)
• Leukemia—RRR=1.15 (99% CI 1.02, 1.28; P=0.002).

However, women had a significantly lower risk of liver cancer (RRR=0.88; 99% CI 0.79, 0.99; P=0.005).

There are several possible reasons for the excess cancer risk observed in women, according to study author Sanne Peters, PhD, of The George Institute for Global Health at the University of Oxford in the UK.

For example, on average, women are in the pre-diabetic state of impaired glucose tolerance 2 years longer than men.

“Historically, we know that women are often under-treated when they first present with symptoms of diabetes, are less likely to receive intensive care, and are not taking the same levels of medications as men,” Dr Peters said. “All of these could go some way into explaining why women are at greater risk of developing cancer, but, without more research, we can’t be certain.”

STOCKHOLM –Adding the monoclonal antibody elotuzumab to pomalidomide and dexamethasone nearly doubled the overall response rate and median progression-free survival in patients with relapsed/refractory multiple myeloma compared with pomalidomide and dexamethasone alone, results of the phase 2 ELOQUENT-3 trial showed.

Neil Osterweil/MDedge News

After a minimum follow-up of 9.1 months, median progression-free survival (PFS) for 60 patients assigned to receive elotuzumab (Empliciti), pomalidomide (Pomalyst), and dexamethasone (EPd) was 10.3 months, compared with 4.7 months for 60 patients assigned to pomalidomide and dexamethasone (Pd). This difference translated into a hazard ratio (HR) of 0.54 (P = .0078) favoring EPd, reported Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens (Greece).

“The study met its primary endpoint, which was specifically designed to detect a large treatment effect in a relatively small sample of patients. Elotuzumab with pomalidomide and dexamethasone showed a significant and clinically meaningful 46% reduction in the risk of progression or death,” he said at the annual congress of the European Hematology Association.

Elotuzumab is an immunoglobulin G (IgG) monoclonal antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7) expressed on multiple myeloma cells. Pomalidomide, an immunomodulator, may act synergistically with elotuzumab through several different mechanisms to increase killing of multiple myeloma cells, Dr. Dimopoulos said.

In ELOQUENT-3, patients with relapsed or refractory multiple myeloma after 2 or more prior lines of therapy, including lenalidomide (Revlimid) and a proteasome inhibitor and no prior pomalidomide were enrolled and randomly assigned to receive either pomalidomide 4 mg orally on days 1-21 of each 28-day cycle plus oral dexamethasone 40 mg equivalent weekly, or to the same regimen plus intravenous elotuzumab 10 mg/kg weekly for cycles 1 and 2, and 20 mg/kg every 4 weeks for cycle 3 and subsequent cycles.

The trial met its primary endpoint of investigator-assessed PFS, with a 46% reduction in the risk of progression or death with EPd compared with Pd.

An analysis of PFS by subgroups showed that EPd was significantly superior to Pd for patients younger than 65 years, those with International Staging System stage I-II at study entry, patients with lactate dehydrogenase levels below 300 IU/L at baseline, patients who had two or three prior lines of therapy vs. four or more, and those who had disease that was refractory to both lenalidomide and a proteasome inhibitor.

EPd was also associated with a trend toward better PFS in an analysis combining patients with high-risk cytogenetics (deletion 17p or translocation 14;16) or high LDH levels, with a median of 7.7 months compared with 3.6 months for Pd. However, the HR, 0.55, was not statistically significant, likely because of the small sample size.

Similarly, the elotuzumab-containing combination showed a nonsignificant trend toward better PFS among patients without high risk disease, with a median PFS not reached, vs. not reached, vs. 4.7 months for patients treated with Pd.

The overall response rate with EPd was 53%, compared with 26% for Pd (odds ratio 3.5, P = .0029). The responses in the elotuzumab arm consisted of 8% complete response, 12% very good partial responses, and 33% partial responses. The respective rates in the Pd group were 2%, 7%, and 18%.

The median duration of response with EPd was not reached at the time of the database lock, compared with 8.3 months with Pd.

A preliminary analysis of overall survival showed a trend favoring EPd (13 deaths out to 22 months of follow-up, compared with 18 deaths out to 20 months in the Pd arm; HR 0.62, nonsignificant).

There were five treatment-related deaths in the EPd arm, and eight in the Pd arm. Grade 1 or 2 infusion reactions occurred in three patients in the EPd arm.

Other adverse events were comparable between the arms, with 57% of patients in the EPd arm and 60% in the Pd arm having at least one grade 3 or 4 adverse event.

“The hematologic toxicity was driven by pomalidomide and low-dose dexamethasone. For unclear reasons, there was less grade 3 or 4 neutropenia with the addition of elotuzumab to pomalidomide/dexamethasone, and also the infection rate was lower in the EPd arm,” Dr. Dimopoulos said.
 

SOURCE: Dimopoulos MA et al. EHA Congress, Abstract LB2606.

STOCKHOLM –Adding the monoclonal antibody elotuzumab to pomalidomide and dexamethasone nearly doubled the overall response rate and median progression-free survival in patients with relapsed/refractory multiple myeloma compared with pomalidomide and dexamethasone alone, results of the phase 2 ELOQUENT-3 trial showed.

Neil Osterweil/MDedge News

After a minimum follow-up of 9.1 months, median progression-free survival (PFS) for 60 patients assigned to receive elotuzumab (Empliciti), pomalidomide (Pomalyst), and dexamethasone (EPd) was 10.3 months, compared with 4.7 months for 60 patients assigned to pomalidomide and dexamethasone (Pd). This difference translated into a hazard ratio (HR) of 0.54 (P = .0078) favoring EPd, reported Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens (Greece).

“The study met its primary endpoint, which was specifically designed to detect a large treatment effect in a relatively small sample of patients. Elotuzumab with pomalidomide and dexamethasone showed a significant and clinically meaningful 46% reduction in the risk of progression or death,” he said at the annual congress of the European Hematology Association.

Elotuzumab is an immunoglobulin G (IgG) monoclonal antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7) expressed on multiple myeloma cells. Pomalidomide, an immunomodulator, may act synergistically with elotuzumab through several different mechanisms to increase killing of multiple myeloma cells, Dr. Dimopoulos said.

In ELOQUENT-3, patients with relapsed or refractory multiple myeloma after 2 or more prior lines of therapy, including lenalidomide (Revlimid) and a proteasome inhibitor and no prior pomalidomide were enrolled and randomly assigned to receive either pomalidomide 4 mg orally on days 1-21 of each 28-day cycle plus oral dexamethasone 40 mg equivalent weekly, or to the same regimen plus intravenous elotuzumab 10 mg/kg weekly for cycles 1 and 2, and 20 mg/kg every 4 weeks for cycle 3 and subsequent cycles.

The trial met its primary endpoint of investigator-assessed PFS, with a 46% reduction in the risk of progression or death with EPd compared with Pd.

An analysis of PFS by subgroups showed that EPd was significantly superior to Pd for patients younger than 65 years, those with International Staging System stage I-II at study entry, patients with lactate dehydrogenase levels below 300 IU/L at baseline, patients who had two or three prior lines of therapy vs. four or more, and those who had disease that was refractory to both lenalidomide and a proteasome inhibitor.

EPd was also associated with a trend toward better PFS in an analysis combining patients with high-risk cytogenetics (deletion 17p or translocation 14;16) or high LDH levels, with a median of 7.7 months compared with 3.6 months for Pd. However, the HR, 0.55, was not statistically significant, likely because of the small sample size.

Similarly, the elotuzumab-containing combination showed a nonsignificant trend toward better PFS among patients without high risk disease, with a median PFS not reached, vs. not reached, vs. 4.7 months for patients treated with Pd.

The overall response rate with EPd was 53%, compared with 26% for Pd (odds ratio 3.5, P = .0029). The responses in the elotuzumab arm consisted of 8% complete response, 12% very good partial responses, and 33% partial responses. The respective rates in the Pd group were 2%, 7%, and 18%.

The median duration of response with EPd was not reached at the time of the database lock, compared with 8.3 months with Pd.

A preliminary analysis of overall survival showed a trend favoring EPd (13 deaths out to 22 months of follow-up, compared with 18 deaths out to 20 months in the Pd arm; HR 0.62, nonsignificant).

There were five treatment-related deaths in the EPd arm, and eight in the Pd arm. Grade 1 or 2 infusion reactions occurred in three patients in the EPd arm.

Other adverse events were comparable between the arms, with 57% of patients in the EPd arm and 60% in the Pd arm having at least one grade 3 or 4 adverse event.

“The hematologic toxicity was driven by pomalidomide and low-dose dexamethasone. For unclear reasons, there was less grade 3 or 4 neutropenia with the addition of elotuzumab to pomalidomide/dexamethasone, and also the infection rate was lower in the EPd arm,” Dr. Dimopoulos said.
 

SOURCE: Dimopoulos MA et al. EHA Congress, Abstract LB2606.

STOCKHOLM –Adding the monoclonal antibody elotuzumab to pomalidomide and dexamethasone nearly doubled the overall response rate and median progression-free survival in patients with relapsed/refractory multiple myeloma compared with pomalidomide and dexamethasone alone, results of the phase 2 ELOQUENT-3 trial showed.

Neil Osterweil/MDedge News

After a minimum follow-up of 9.1 months, median progression-free survival (PFS) for 60 patients assigned to receive elotuzumab (Empliciti), pomalidomide (Pomalyst), and dexamethasone (EPd) was 10.3 months, compared with 4.7 months for 60 patients assigned to pomalidomide and dexamethasone (Pd). This difference translated into a hazard ratio (HR) of 0.54 (P = .0078) favoring EPd, reported Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens (Greece).

“The study met its primary endpoint, which was specifically designed to detect a large treatment effect in a relatively small sample of patients. Elotuzumab with pomalidomide and dexamethasone showed a significant and clinically meaningful 46% reduction in the risk of progression or death,” he said at the annual congress of the European Hematology Association.

Elotuzumab is an immunoglobulin G (IgG) monoclonal antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7) expressed on multiple myeloma cells. Pomalidomide, an immunomodulator, may act synergistically with elotuzumab through several different mechanisms to increase killing of multiple myeloma cells, Dr. Dimopoulos said.

In ELOQUENT-3, patients with relapsed or refractory multiple myeloma after 2 or more prior lines of therapy, including lenalidomide (Revlimid) and a proteasome inhibitor and no prior pomalidomide were enrolled and randomly assigned to receive either pomalidomide 4 mg orally on days 1-21 of each 28-day cycle plus oral dexamethasone 40 mg equivalent weekly, or to the same regimen plus intravenous elotuzumab 10 mg/kg weekly for cycles 1 and 2, and 20 mg/kg every 4 weeks for cycle 3 and subsequent cycles.

The trial met its primary endpoint of investigator-assessed PFS, with a 46% reduction in the risk of progression or death with EPd compared with Pd.

An analysis of PFS by subgroups showed that EPd was significantly superior to Pd for patients younger than 65 years, those with International Staging System stage I-II at study entry, patients with lactate dehydrogenase levels below 300 IU/L at baseline, patients who had two or three prior lines of therapy vs. four or more, and those who had disease that was refractory to both lenalidomide and a proteasome inhibitor.

EPd was also associated with a trend toward better PFS in an analysis combining patients with high-risk cytogenetics (deletion 17p or translocation 14;16) or high LDH levels, with a median of 7.7 months compared with 3.6 months for Pd. However, the HR, 0.55, was not statistically significant, likely because of the small sample size.

Similarly, the elotuzumab-containing combination showed a nonsignificant trend toward better PFS among patients without high risk disease, with a median PFS not reached, vs. not reached, vs. 4.7 months for patients treated with Pd.

The overall response rate with EPd was 53%, compared with 26% for Pd (odds ratio 3.5, P = .0029). The responses in the elotuzumab arm consisted of 8% complete response, 12% very good partial responses, and 33% partial responses. The respective rates in the Pd group were 2%, 7%, and 18%.

The median duration of response with EPd was not reached at the time of the database lock, compared with 8.3 months with Pd.

A preliminary analysis of overall survival showed a trend favoring EPd (13 deaths out to 22 months of follow-up, compared with 18 deaths out to 20 months in the Pd arm; HR 0.62, nonsignificant).

There were five treatment-related deaths in the EPd arm, and eight in the Pd arm. Grade 1 or 2 infusion reactions occurred in three patients in the EPd arm.

Other adverse events were comparable between the arms, with 57% of patients in the EPd arm and 60% in the Pd arm having at least one grade 3 or 4 adverse event.

“The hematologic toxicity was driven by pomalidomide and low-dose dexamethasone. For unclear reasons, there was less grade 3 or 4 neutropenia with the addition of elotuzumab to pomalidomide/dexamethasone, and also the infection rate was lower in the EPd arm,” Dr. Dimopoulos said.
 

SOURCE: Dimopoulos MA et al. EHA Congress, Abstract LB2606.

Augusta University

Researchers are questioning the clinical usefulness of the serum free light chain assay (SFLCA) for patients with monoclonal gammopathies.

The investigators found evidence suggesting that, about 25% of the time, SFLCA provides a negative κ/λ ratio in patients with lambda chain monoclonal gammopathies who have free homogenous lambda light chains detectable in their urine.

“If you have a lambda chain-associated lesion and you don’t do a urine study—just rely on the serum free light chain assay—about 1 out of 4 times, the assay will tell you that you don’t have anything when you actually do,” explained Won Sok Lee, MD, of the Medical College of Georgia at Augusta University.

“When you test the serum, we suggest you also test the urine whenever you suspect that somebody has a tumor of the plasma cells,” said Gurmukh Singh, MD, PhD, also of the Medical College of Georgia.

Drs Singh and Lee made this recommendation and detailed the supporting research in the Journal of Clinical Medicine Research.

The researchers evaluated results of serum and urine tests in 175 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple/plasma cell myeloma (MM).

In addition to results of SFLCA, the investigators looked at results of serum protein electrophoresis, serum protein immunofixation electrophoresis, urine protein electrophoresis, and urine protein immunofixation electrophoresis.

This analysis revealed “systematic under-detection” of serum free lambda light chains by SFLCA as well as an under-detection of the lambda-dominant ratio.

The researchers integrated the results of this study with findings from an earlier study* and concluded that, as compared to kappa chain lesions:

• The excess false-negative rate of κ/λ ratio for lambda chain lesions in MGUS is 29%
• The excess false-negative rate of κ/λ ratio for lambda chain lesions in MM is 32%
• The excess false-negative rate of κ/λ ratio for lambda chain lesions in all neoplastic monoclonal gammopathies (MGUS, MM, and SMM) is approximately 30%.

The investigators said they believe that 5% of the 30% false-negative rate is a result of under-production of excess free lambda light chains, and about 25% could be due to under-detection of monoclonal lambda light chains by SFLCA.

“[A patient] may go undiagnosed because the serum free light chain test either is not picking up those abnormal proteins or the lambda lesions don’t make that many excess abnormal proteins,” Dr Singh said.

However, Drs Singh and Lee also said it’s possible that unknown factors, such as general over-production of polyclonal kappa light chains in tertiary care patients, may alter the κ/λ ratio.

*Singh, G. Serum Free Light Chain Assay and κ/λ Ratio: Performance in Patients With Monoclonal Gammopathy-High False Negative Rate for κ/λ Ratio. J Clin Med Res. 2017 Jan; 9(1): 46–57.

Augusta University

Researchers are questioning the clinical usefulness of the serum free light chain assay (SFLCA) for patients with monoclonal gammopathies.

The investigators found evidence suggesting that, about 25% of the time, SFLCA provides a negative κ/λ ratio in patients with lambda chain monoclonal gammopathies who have free homogenous lambda light chains detectable in their urine.

“If you have a lambda chain-associated lesion and you don’t do a urine study—just rely on the serum free light chain assay—about 1 out of 4 times, the assay will tell you that you don’t have anything when you actually do,” explained Won Sok Lee, MD, of the Medical College of Georgia at Augusta University.

“When you test the serum, we suggest you also test the urine whenever you suspect that somebody has a tumor of the plasma cells,” said Gurmukh Singh, MD, PhD, also of the Medical College of Georgia.

Drs Singh and Lee made this recommendation and detailed the supporting research in the Journal of Clinical Medicine Research.

The researchers evaluated results of serum and urine tests in 175 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple/plasma cell myeloma (MM).

In addition to results of SFLCA, the investigators looked at results of serum protein electrophoresis, serum protein immunofixation electrophoresis, urine protein electrophoresis, and urine protein immunofixation electrophoresis.

This analysis revealed “systematic under-detection” of serum free lambda light chains by SFLCA as well as an under-detection of the lambda-dominant ratio.

The researchers integrated the results of this study with findings from an earlier study* and concluded that, as compared to kappa chain lesions:

• The excess false-negative rate of κ/λ ratio for lambda chain lesions in MGUS is 29%
• The excess false-negative rate of κ/λ ratio for lambda chain lesions in MM is 32%
• The excess false-negative rate of κ/λ ratio for lambda chain lesions in all neoplastic monoclonal gammopathies (MGUS, MM, and SMM) is approximately 30%.

The investigators said they believe that 5% of the 30% false-negative rate is a result of under-production of excess free lambda light chains, and about 25% could be due to under-detection of monoclonal lambda light chains by SFLCA.

“[A patient] may go undiagnosed because the serum free light chain test either is not picking up those abnormal proteins or the lambda lesions don’t make that many excess abnormal proteins,” Dr Singh said.

However, Drs Singh and Lee also said it’s possible that unknown factors, such as general over-production of polyclonal kappa light chains in tertiary care patients, may alter the κ/λ ratio.

*Singh, G. Serum Free Light Chain Assay and κ/λ Ratio: Performance in Patients With Monoclonal Gammopathy-High False Negative Rate for κ/λ Ratio. J Clin Med Res. 2017 Jan; 9(1): 46–57.

Augusta University

Researchers are questioning the clinical usefulness of the serum free light chain assay (SFLCA) for patients with monoclonal gammopathies.

The investigators found evidence suggesting that, about 25% of the time, SFLCA provides a negative κ/λ ratio in patients with lambda chain monoclonal gammopathies who have free homogenous lambda light chains detectable in their urine.

“If you have a lambda chain-associated lesion and you don’t do a urine study—just rely on the serum free light chain assay—about 1 out of 4 times, the assay will tell you that you don’t have anything when you actually do,” explained Won Sok Lee, MD, of the Medical College of Georgia at Augusta University.

“When you test the serum, we suggest you also test the urine whenever you suspect that somebody has a tumor of the plasma cells,” said Gurmukh Singh, MD, PhD, also of the Medical College of Georgia.

Drs Singh and Lee made this recommendation and detailed the supporting research in the Journal of Clinical Medicine Research.

The researchers evaluated results of serum and urine tests in 175 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple/plasma cell myeloma (MM).

In addition to results of SFLCA, the investigators looked at results of serum protein electrophoresis, serum protein immunofixation electrophoresis, urine protein electrophoresis, and urine protein immunofixation electrophoresis.

This analysis revealed “systematic under-detection” of serum free lambda light chains by SFLCA as well as an under-detection of the lambda-dominant ratio.

The researchers integrated the results of this study with findings from an earlier study* and concluded that, as compared to kappa chain lesions:

• The excess false-negative rate of κ/λ ratio for lambda chain lesions in MGUS is 29%
• The excess false-negative rate of κ/λ ratio for lambda chain lesions in MM is 32%
• The excess false-negative rate of κ/λ ratio for lambda chain lesions in all neoplastic monoclonal gammopathies (MGUS, MM, and SMM) is approximately 30%.

The investigators said they believe that 5% of the 30% false-negative rate is a result of under-production of excess free lambda light chains, and about 25% could be due to under-detection of monoclonal lambda light chains by SFLCA.

“[A patient] may go undiagnosed because the serum free light chain test either is not picking up those abnormal proteins or the lambda lesions don’t make that many excess abnormal proteins,” Dr Singh said.

However, Drs Singh and Lee also said it’s possible that unknown factors, such as general over-production of polyclonal kappa light chains in tertiary care patients, may alter the κ/λ ratio.

*Singh, G. Serum Free Light Chain Assay and κ/λ Ratio: Performance in Patients With Monoclonal Gammopathy-High False Negative Rate for κ/λ Ratio. J Clin Med Res. 2017 Jan; 9(1): 46–57.

Release Date: July 15, 2018
Expiration Date: July 14, 2019

Note: This activity is no longer available for credit

Introductory Comments: (Duration: 9 minutes)

Aaron P. Rapoport, MD
Bone Marrow Transplant Program
University of Maryland School of Medicine
Baltimore, MD

Presentation: (Duration: 39 minutes)

Carl H. June, MD
Richard W. Vague Professor in Immunotherapy
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA

Provided by:

Learning Objectives

• Review clinical data and individual case studies to determine where CAR T-cell therapy might be appropriate in the treatment of adult and pediatric patients with leukemia, lymphoma, and multiple myeloma.

• Discuss the management of cytotoxicity of CAR T-cell therapy.

Target Audience

Hematologists, oncologists, and other members of the healthcare team who treat or manage patients with hematologic malignancies.

Statement of Need

It is critical that clinicians managing patients with acute leukemia and other hematologic malignancies are cognizant of exciting breakthroughs and are also able to integrate recent progress into practice. However, given the overwhelming influx of data, it is no surprise that many hematology professionals face difficulties in identifying the most relevant findings for clinical practice. Hematologists are unable to stay abreast of the latest evidence on investigational agents. Educational programs are thus crucial to address this important professional practice gap.

Faculty

Carl H. June, MD
Richard W. Vague Professor in Immunotherapy
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA
Disclosures: Consultant: Novartis; Grant/Research support and royalties/IPR: Novartis
Stockholder: Tmunity Therapeutics, Inc.

Aaron P. Rapoport, MD
Bone Marrow Transplant Program
University of Maryland School of Medicine
Baltimore, Maryland
Disclosures: No relevant financial relationships with a commercial supporter

Permissions

• Slide 3: Complex tumor, host and environmental factors govern the strength and timing of anti-cancer immune responses
  • Reprinted from Immunity, Vol 39/No 1, Chen DS, Mellman I, Oncology meets immunology: the cancer-immunity cycle, pp 1-10, 2013, with permission from Elsevier
• Slide 9: Genes differentially expressed in CART19 cellular infusion products from CLL patients
  • From Fraietta JA, Lacey SF, Orlando EJ, . . . June CH, Melenhorst JJ. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med 2018; 24:563-571
• Slide 10: Characterization of CLL CAR T cells in NSG CLL model
  • Same as slide 9
• Slide 15: First adult ALL patient
  • Photos originally published in Kaiser Health News/Photo courtesy of Dr Keith Eaton. Available at: https://khn.org/news/cascade-of-costs-could-push-new-gene-therapy-above-1-million-per-patient/
• Slide 21: Efficient trafficking of CTL019 T Cells to CNS in ALL
  • From N Engl J Med, Grupp SA, Kalos M, Barrett D, . . V. June CH, Chimeric antigen receptor-modified T cells for acute lymphoid leukemia, Volume No 368, pp 1509-1518. Copyright © 2013 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
• Slide 26: Long-term persistence and expression of CTL019 is associated with durable remission in leukemia: Predictive Biomarker
  • From Porter DL, Hwang WT, Frey NV . . . June CH. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 2015; 7(303):303ra139. Reprinted with permission from AAAS.
• Slide 28: Rapid massive expansion of clonal CART cell population in patient #10
  • Initially published in Fraietta JA, Nobles CL, Sammons MA, . . . June CH, Melenhors JJ. Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells. Nature 2018; 558(7709):307-312
• Slide 29: Mapping CAR integration site in Pt #10
  • Same as slide 28.
• Slide 31: Long-term stable persistence of TET2-deficient CAR T cells in Pt #10
  • Same as slide 28
• Slide 32: Epigenetic and genetic changes uncovered by ATAC-seq in Pt #10
  • Same as slide 28.
• Slide 33: TET2 knock down in healthy donor T cells
  • Same as slide 28.
• Slide 34: TET2 knock down in healthy donor T cells
  • Same as slide 28.
• Slide 36: CAR T for myeloma: BCMA
  • From Rickert RC, Jellusova J, Miletic AV. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev 2011; 244(1):115-33. Reprinted with permission from John Wiley and Sons.
• Slide 38: CAR T for myeloma: Patient #1
  • Photo originally published by UT Southwestern Medical Center. Available at: https://www.utsouthwestern.edu/newsroom/articles/year-2018/wright-car-t.html
• Slide 39: Autoimmunity is the “Achilles’ Heel” of immunotherapy
  • First published in June CH, Warshauer JT, and Bluestone JA. Is autoimmunity the Achilles’ heel of cancer immunotherapy? Nat Med 2017;23(5):540-7
• Slide 41: Multiplex CRISPR /Cas9 editing: Universal T cells TCR, HLA, PD-1, CTLA-4 and Fas
  • From Ren J, Zhang X, Liu X, Fang C, Jiang S, June CH, Zhao Y. A versatile system for rapid multiplex genome-edited CAR T cell generation. Oncotarget 2017; 8:17002-17011.
• Slide 45: CAR T-cell trials for cancer are now global
  • From June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science 2018; 359:1361-1365. Reprinted with permission from AAAS.

Disclaimer

The content and views presented in this educational activity are those of the author and do not necessarily reflect those of Hemedicus or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.

Release Date: July 15, 2018
Expiration Date: July 14, 2019

Note: This activity is no longer available for credit

Introductory Comments: (Duration: 9 minutes)

Aaron P. Rapoport, MD
Bone Marrow Transplant Program
University of Maryland School of Medicine
Baltimore, MD

Presentation: (Duration: 39 minutes)

Carl H. June, MD
Richard W. Vague Professor in Immunotherapy
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA

Provided by:

Learning Objectives

• Review clinical data and individual case studies to determine where CAR T-cell therapy might be appropriate in the treatment of adult and pediatric patients with leukemia, lymphoma, and multiple myeloma.

• Discuss the management of cytotoxicity of CAR T-cell therapy.

Target Audience

Hematologists, oncologists, and other members of the healthcare team who treat or manage patients with hematologic malignancies.

Statement of Need

It is critical that clinicians managing patients with acute leukemia and other hematologic malignancies are cognizant of exciting breakthroughs and are also able to integrate recent progress into practice. However, given the overwhelming influx of data, it is no surprise that many hematology professionals face difficulties in identifying the most relevant findings for clinical practice. Hematologists are unable to stay abreast of the latest evidence on investigational agents. Educational programs are thus crucial to address this important professional practice gap.

Faculty

Carl H. June, MD
Richard W. Vague Professor in Immunotherapy
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA
Disclosures: Consultant: Novartis; Grant/Research support and royalties/IPR: Novartis
Stockholder: Tmunity Therapeutics, Inc.

Aaron P. Rapoport, MD
Bone Marrow Transplant Program
University of Maryland School of Medicine
Baltimore, Maryland
Disclosures: No relevant financial relationships with a commercial supporter

Permissions

• Slide 3: Complex tumor, host and environmental factors govern the strength and timing of anti-cancer immune responses
  • Reprinted from Immunity, Vol 39/No 1, Chen DS, Mellman I, Oncology meets immunology: the cancer-immunity cycle, pp 1-10, 2013, with permission from Elsevier
• Slide 9: Genes differentially expressed in CART19 cellular infusion products from CLL patients
  • From Fraietta JA, Lacey SF, Orlando EJ, . . . June CH, Melenhorst JJ. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med 2018; 24:563-571
• Slide 10: Characterization of CLL CAR T cells in NSG CLL model
  • Same as slide 9
• Slide 15: First adult ALL patient
  • Photos originally published in Kaiser Health News/Photo courtesy of Dr Keith Eaton. Available at: https://khn.org/news/cascade-of-costs-could-push-new-gene-therapy-above-1-million-per-patient/
• Slide 21: Efficient trafficking of CTL019 T Cells to CNS in ALL
  • From N Engl J Med, Grupp SA, Kalos M, Barrett D, . . V. June CH, Chimeric antigen receptor-modified T cells for acute lymphoid leukemia, Volume No 368, pp 1509-1518. Copyright © 2013 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
• Slide 26: Long-term persistence and expression of CTL019 is associated with durable remission in leukemia: Predictive Biomarker
  • From Porter DL, Hwang WT, Frey NV . . . June CH. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 2015; 7(303):303ra139. Reprinted with permission from AAAS.
• Slide 28: Rapid massive expansion of clonal CART cell population in patient #10
  • Initially published in Fraietta JA, Nobles CL, Sammons MA, . . . June CH, Melenhors JJ. Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells. Nature 2018; 558(7709):307-312
• Slide 29: Mapping CAR integration site in Pt #10
  • Same as slide 28.
• Slide 31: Long-term stable persistence of TET2-deficient CAR T cells in Pt #10
  • Same as slide 28
• Slide 32: Epigenetic and genetic changes uncovered by ATAC-seq in Pt #10
  • Same as slide 28.
• Slide 33: TET2 knock down in healthy donor T cells
  • Same as slide 28.
• Slide 34: TET2 knock down in healthy donor T cells
  • Same as slide 28.
• Slide 36: CAR T for myeloma: BCMA
  • From Rickert RC, Jellusova J, Miletic AV. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev 2011; 244(1):115-33. Reprinted with permission from John Wiley and Sons.
• Slide 38: CAR T for myeloma: Patient #1
  • Photo originally published by UT Southwestern Medical Center. Available at: https://www.utsouthwestern.edu/newsroom/articles/year-2018/wright-car-t.html
• Slide 39: Autoimmunity is the “Achilles’ Heel” of immunotherapy
  • First published in June CH, Warshauer JT, and Bluestone JA. Is autoimmunity the Achilles’ heel of cancer immunotherapy? Nat Med 2017;23(5):540-7
• Slide 41: Multiplex CRISPR /Cas9 editing: Universal T cells TCR, HLA, PD-1, CTLA-4 and Fas
  • From Ren J, Zhang X, Liu X, Fang C, Jiang S, June CH, Zhao Y. A versatile system for rapid multiplex genome-edited CAR T cell generation. Oncotarget 2017; 8:17002-17011.
• Slide 45: CAR T-cell trials for cancer are now global
  • From June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science 2018; 359:1361-1365. Reprinted with permission from AAAS.

Disclaimer

The content and views presented in this educational activity are those of the author and do not necessarily reflect those of Hemedicus or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.

Release Date: July 15, 2018
Expiration Date: July 14, 2019

Note: This activity is no longer available for credit

Introductory Comments: (Duration: 9 minutes)

Aaron P. Rapoport, MD
Bone Marrow Transplant Program
University of Maryland School of Medicine
Baltimore, MD

Presentation: (Duration: 39 minutes)

Carl H. June, MD
Richard W. Vague Professor in Immunotherapy
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA

Provided by:

Learning Objectives

• Review clinical data and individual case studies to determine where CAR T-cell therapy might be appropriate in the treatment of adult and pediatric patients with leukemia, lymphoma, and multiple myeloma.

• Discuss the management of cytotoxicity of CAR T-cell therapy.

Target Audience

Hematologists, oncologists, and other members of the healthcare team who treat or manage patients with hematologic malignancies.

Statement of Need

It is critical that clinicians managing patients with acute leukemia and other hematologic malignancies are cognizant of exciting breakthroughs and are also able to integrate recent progress into practice. However, given the overwhelming influx of data, it is no surprise that many hematology professionals face difficulties in identifying the most relevant findings for clinical practice. Hematologists are unable to stay abreast of the latest evidence on investigational agents. Educational programs are thus crucial to address this important professional practice gap.

Faculty

Carl H. June, MD
Richard W. Vague Professor in Immunotherapy
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA
Disclosures: Consultant: Novartis; Grant/Research support and royalties/IPR: Novartis
Stockholder: Tmunity Therapeutics, Inc.

Aaron P. Rapoport, MD
Bone Marrow Transplant Program
University of Maryland School of Medicine
Baltimore, Maryland
Disclosures: No relevant financial relationships with a commercial supporter

Permissions

• Slide 3: Complex tumor, host and environmental factors govern the strength and timing of anti-cancer immune responses
  • Reprinted from Immunity, Vol 39/No 1, Chen DS, Mellman I, Oncology meets immunology: the cancer-immunity cycle, pp 1-10, 2013, with permission from Elsevier
• Slide 9: Genes differentially expressed in CART19 cellular infusion products from CLL patients
  • From Fraietta JA, Lacey SF, Orlando EJ, . . . June CH, Melenhorst JJ. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med 2018; 24:563-571
• Slide 10: Characterization of CLL CAR T cells in NSG CLL model
  • Same as slide 9
• Slide 15: First adult ALL patient
  • Photos originally published in Kaiser Health News/Photo courtesy of Dr Keith Eaton. Available at: https://khn.org/news/cascade-of-costs-could-push-new-gene-therapy-above-1-million-per-patient/
• Slide 21: Efficient trafficking of CTL019 T Cells to CNS in ALL
  • From N Engl J Med, Grupp SA, Kalos M, Barrett D, . . V. June CH, Chimeric antigen receptor-modified T cells for acute lymphoid leukemia, Volume No 368, pp 1509-1518. Copyright © 2013 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
• Slide 26: Long-term persistence and expression of CTL019 is associated with durable remission in leukemia: Predictive Biomarker
  • From Porter DL, Hwang WT, Frey NV . . . June CH. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 2015; 7(303):303ra139. Reprinted with permission from AAAS.
• Slide 28: Rapid massive expansion of clonal CART cell population in patient #10
  • Initially published in Fraietta JA, Nobles CL, Sammons MA, . . . June CH, Melenhors JJ. Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells. Nature 2018; 558(7709):307-312
• Slide 29: Mapping CAR integration site in Pt #10
  • Same as slide 28.
• Slide 31: Long-term stable persistence of TET2-deficient CAR T cells in Pt #10
  • Same as slide 28
• Slide 32: Epigenetic and genetic changes uncovered by ATAC-seq in Pt #10
  • Same as slide 28.
• Slide 33: TET2 knock down in healthy donor T cells
  • Same as slide 28.
• Slide 34: TET2 knock down in healthy donor T cells
  • Same as slide 28.
• Slide 36: CAR T for myeloma: BCMA
  • From Rickert RC, Jellusova J, Miletic AV. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev 2011; 244(1):115-33. Reprinted with permission from John Wiley and Sons.
• Slide 38: CAR T for myeloma: Patient #1
  • Photo originally published by UT Southwestern Medical Center. Available at: https://www.utsouthwestern.edu/newsroom/articles/year-2018/wright-car-t.html
• Slide 39: Autoimmunity is the “Achilles’ Heel” of immunotherapy
  • First published in June CH, Warshauer JT, and Bluestone JA. Is autoimmunity the Achilles’ heel of cancer immunotherapy? Nat Med 2017;23(5):540-7
• Slide 41: Multiplex CRISPR /Cas9 editing: Universal T cells TCR, HLA, PD-1, CTLA-4 and Fas
  • From Ren J, Zhang X, Liu X, Fang C, Jiang S, June CH, Zhao Y. A versatile system for rapid multiplex genome-edited CAR T cell generation. Oncotarget 2017; 8:17002-17011.
• Slide 45: CAR T-cell trials for cancer are now global
  • From June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science 2018; 359:1361-1365. Reprinted with permission from AAAS.

Disclaimer

The content and views presented in this educational activity are those of the author and do not necessarily reflect those of Hemedicus or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.

Ixazomib significantly improved progression-free survival as a maintenance therapy in adults with multiple myeloma who had responded to high-dose therapy and autologous stem cell transplant.

The drug’s sponsor, Takeda, announced that the oral proteasome inhibitor had met the primary endpoint – progression-free survival versus placebo – in the randomized, phase 3 TOURMALINE-MM3 study. They also reported that adverse events were consistent with previously reported results for single-agent use of ixazomib and that there were no new safety signals.

Full study results will be presented at the annual meeting of the American Society of Hematology. Company officials plan to submit the trial data to the Food and Drug Administration and regulatory agencies around the world to gain approval of ixazomib as a single-agent maintenance therapy, according to a Takeda announcement.

The TOURMALINE-MM3 study is a double-blind study of 656 patients with multiple myeloma who have had complete response, very good partial response, or partial response to induction therapy followed by high-dose therapy and autologous stem cell transplant. In addition to progression-free survival, the trial assessed overall survival.

[email protected]

Ixazomib significantly improved progression-free survival as a maintenance therapy in adults with multiple myeloma who had responded to high-dose therapy and autologous stem cell transplant.

The drug’s sponsor, Takeda, announced that the oral proteasome inhibitor had met the primary endpoint – progression-free survival versus placebo – in the randomized, phase 3 TOURMALINE-MM3 study. They also reported that adverse events were consistent with previously reported results for single-agent use of ixazomib and that there were no new safety signals.

Full study results will be presented at the annual meeting of the American Society of Hematology. Company officials plan to submit the trial data to the Food and Drug Administration and regulatory agencies around the world to gain approval of ixazomib as a single-agent maintenance therapy, according to a Takeda announcement.

The TOURMALINE-MM3 study is a double-blind study of 656 patients with multiple myeloma who have had complete response, very good partial response, or partial response to induction therapy followed by high-dose therapy and autologous stem cell transplant. In addition to progression-free survival, the trial assessed overall survival.

[email protected]

Ixazomib significantly improved progression-free survival as a maintenance therapy in adults with multiple myeloma who had responded to high-dose therapy and autologous stem cell transplant.

The drug’s sponsor, Takeda, announced that the oral proteasome inhibitor had met the primary endpoint – progression-free survival versus placebo – in the randomized, phase 3 TOURMALINE-MM3 study. They also reported that adverse events were consistent with previously reported results for single-agent use of ixazomib and that there were no new safety signals.

Full study results will be presented at the annual meeting of the American Society of Hematology. Company officials plan to submit the trial data to the Food and Drug Administration and regulatory agencies around the world to gain approval of ixazomib as a single-agent maintenance therapy, according to a Takeda announcement.

The TOURMALINE-MM3 study is a double-blind study of 656 patients with multiple myeloma who have had complete response, very good partial response, or partial response to induction therapy followed by high-dose therapy and autologous stem cell transplant. In addition to progression-free survival, the trial assessed overall survival.

[email protected]