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Insured cancer patients report ‘overwhelming’ financial distress
A study of 300 US cancer patients showed that paying for care can cause “overwhelming” financial distress, even when patients have health insurance.
Sixteen percent of the patients studied reported “high or overwhelming” financial distress, spending a median of 31% of their monthly household income on healthcare, not including insurance premiums.
They had a median monthly out-of-pocket cost of $728 (range, $6 to $47,250).
Fumiko Chino, MD, of Duke University Medical Center in Durham, North Carolina, and her colleagues reported these findings in a letter to JAMA Oncology.
The researchers interviewed 300 insured cancer patients for this study. They had a median age of 59.6, and 68.3% were married.
Fifty-six percent of patients had private insurance, 35.7% had Medicare, and 7.3% had Medicaid.
Annual household incomes were as follows:
- 45.7%, $60,000 or greater
- 15.7%, $40,000 to $59,999
- 17.7%, $20,000 to 39,999
- 13.7%, lower than $20,000
- 7.3%, unknown.
The median monthly out-of-pocket cost for care was $592 (range, $3-$47,250), not including insurance premiums. The median relative cost of care was 11% of a patient’s monthly household income.
“Those who spend more than 10% of their income on healthcare costs are considered underinsured,” Dr Chino said. “Learning about the cost-sharing burden on some insured patients is important right now, given the uncertainty in health insurance.”
Most of the patients studied (83.7%, n=251) reported no, low, or average financial distress. Their median relative cost of care was 10% of their monthly household income, and their median monthly out-of-pocket cost was $565 (range, $3 to $26,756). Six percent of these patients had Medicaid, 39% had Medicare, and 53.8% had private insurance.
For the 16.3% of patients (n=49) who reported high or overwhelming financial distress, 67.3% had private insurance, 18.4% had Medicare, and 14.3% had Medicaid. As stated above, their median relative cost of care was 31% of their monthly household income, and their median monthly out-of-pocket cost was $728 (range, $6 to $47,250).
“This study adds to the growing evidence that we need to intervene,” said study author Yousuf Zafar, MD, of Duke Cancer Institute.
“We know there are a lot of barriers that prevent patients from talking about cost with their providers. We need to create tools for patients at risk of financial toxicity and connect them with resources in a timely fashion so they can afford their care.” 
A study of 300 US cancer patients showed that paying for care can cause “overwhelming” financial distress, even when patients have health insurance.
Sixteen percent of the patients studied reported “high or overwhelming” financial distress, spending a median of 31% of their monthly household income on healthcare, not including insurance premiums.
They had a median monthly out-of-pocket cost of $728 (range, $6 to $47,250).
Fumiko Chino, MD, of Duke University Medical Center in Durham, North Carolina, and her colleagues reported these findings in a letter to JAMA Oncology.
The researchers interviewed 300 insured cancer patients for this study. They had a median age of 59.6, and 68.3% were married.
Fifty-six percent of patients had private insurance, 35.7% had Medicare, and 7.3% had Medicaid.
Annual household incomes were as follows:
- 45.7%, $60,000 or greater
- 15.7%, $40,000 to $59,999
- 17.7%, $20,000 to 39,999
- 13.7%, lower than $20,000
- 7.3%, unknown.
The median monthly out-of-pocket cost for care was $592 (range, $3-$47,250), not including insurance premiums. The median relative cost of care was 11% of a patient’s monthly household income.
“Those who spend more than 10% of their income on healthcare costs are considered underinsured,” Dr Chino said. “Learning about the cost-sharing burden on some insured patients is important right now, given the uncertainty in health insurance.”
Most of the patients studied (83.7%, n=251) reported no, low, or average financial distress. Their median relative cost of care was 10% of their monthly household income, and their median monthly out-of-pocket cost was $565 (range, $3 to $26,756). Six percent of these patients had Medicaid, 39% had Medicare, and 53.8% had private insurance.
For the 16.3% of patients (n=49) who reported high or overwhelming financial distress, 67.3% had private insurance, 18.4% had Medicare, and 14.3% had Medicaid. As stated above, their median relative cost of care was 31% of their monthly household income, and their median monthly out-of-pocket cost was $728 (range, $6 to $47,250).
“This study adds to the growing evidence that we need to intervene,” said study author Yousuf Zafar, MD, of Duke Cancer Institute.
“We know there are a lot of barriers that prevent patients from talking about cost with their providers. We need to create tools for patients at risk of financial toxicity and connect them with resources in a timely fashion so they can afford their care.”
A study of 300 US cancer patients showed that paying for care can cause “overwhelming” financial distress, even when patients have health insurance.
Sixteen percent of the patients studied reported “high or overwhelming” financial distress, spending a median of 31% of their monthly household income on healthcare, not including insurance premiums.
They had a median monthly out-of-pocket cost of $728 (range, $6 to $47,250).
Fumiko Chino, MD, of Duke University Medical Center in Durham, North Carolina, and her colleagues reported these findings in a letter to JAMA Oncology.
The researchers interviewed 300 insured cancer patients for this study. They had a median age of 59.6, and 68.3% were married.
Fifty-six percent of patients had private insurance, 35.7% had Medicare, and 7.3% had Medicaid.
Annual household incomes were as follows:
- 45.7%, $60,000 or greater
- 15.7%, $40,000 to $59,999
- 17.7%, $20,000 to 39,999
- 13.7%, lower than $20,000
- 7.3%, unknown.
The median monthly out-of-pocket cost for care was $592 (range, $3-$47,250), not including insurance premiums. The median relative cost of care was 11% of a patient’s monthly household income.
“Those who spend more than 10% of their income on healthcare costs are considered underinsured,” Dr Chino said. “Learning about the cost-sharing burden on some insured patients is important right now, given the uncertainty in health insurance.”
Most of the patients studied (83.7%, n=251) reported no, low, or average financial distress. Their median relative cost of care was 10% of their monthly household income, and their median monthly out-of-pocket cost was $565 (range, $3 to $26,756). Six percent of these patients had Medicaid, 39% had Medicare, and 53.8% had private insurance.
For the 16.3% of patients (n=49) who reported high or overwhelming financial distress, 67.3% had private insurance, 18.4% had Medicare, and 14.3% had Medicaid. As stated above, their median relative cost of care was 31% of their monthly household income, and their median monthly out-of-pocket cost was $728 (range, $6 to $47,250).
“This study adds to the growing evidence that we need to intervene,” said study author Yousuf Zafar, MD, of Duke Cancer Institute.
“We know there are a lot of barriers that prevent patients from talking about cost with their providers. We need to create tools for patients at risk of financial toxicity and connect them with resources in a timely fashion so they can afford their care.”
Advanced cancer patients have lower survival after cardiac arrest
A new study suggests patients with advanced cancer who suffer cardiac arrest in the hospital have a survival rate of less than 10%, which is about half the rate of patients without cancer who suffer cardiac arrest.
This finding helps to clear up some myths about cardiac arrest survival and can be used as a guidepost when hospitalized cancer patients and their families consider do-not-resuscitate (DNR) orders, said Jeffrey T. Bruckel, MD, of the University of Rochester Medical Center in New York.
“We’re hopeful that our study, in some way, will help doctors and cancer patients make more informed decisions about the end of life,” Dr Bruckel said. “It’s very important to have early, frank discussions around the goals of care.”
Dr Bruckel and his colleagues published their study in the Journal of Oncology Practice.
The researchers used a US-wide resuscitation registry to evaluate survival after cardiac arrest in patients treated at 369 hospitals.
The study excluded patients with implantable defibrillators and those who were admitted for surgery, emergency room treatment, rehabilitation, or treatment from cardiac catheterization labs or interventional radiology.
Of the 47,157 eligible patients who experienced cardiac arrest, 14% (n=6585) had advanced cancer, including hematologic malignancies.
After cardiac arrest, 57.5% of the advanced cancer patients were resuscitated successfully, as were 63% of non-cancer patients (P<0.001).
After resuscitation, 9.6% of the cancer patients survived to be discharged, compared to 19.2% of non-cancer patients (P<0.001).
When the researchers adjusted their analysis for potential confounders, results were similar. The rate of successful resuscitation was 52.3% in advanced cancer patients and 56.6% in non-cancer patients (P<0.001). The rate of survival to discharge was 7.4% and 13.4%, respectively (P<0.001).
Dr Bruckel said there was no evidence to suggest that patients with advanced cancer received less aggressive resuscitation care.
However, there was a significant difference in the mean duration of resuscitation time among non-survivors with cancer—22.5 minutes—and non-survivors without cancer—24.2 minutes (P<0.001). After adjustment, the mean duration of resuscitation was 22.5 minutes and 24.1 minutes, respectively (P<0.001).
Cancer patients were more likely than those without cancer to sign DNR orders after resuscitation—55.6% and 43%, respectively (P<0.001). Results were similar after adjustment—50.4% and 41.6%, respectively (P<0.001).
Dr Bruckel and his colleagues said there were several limitations to this study, including a lack of detailed data on the types of advanced cancer and cancer treatments being given at the time of cardiac arrest.
Therefore, the next step in advancing this work is to gather data on the types of cancer diagnosis and treatment plans of patients who undergo in-hospital cardiac arrest.
Dr Bruckel also believes it is important to know how patients feel about this data and how both patients and physicians are using this data in decision-making.
“A large component of end-of-life care involves patient and family care decision-making, and a lot of that is driven by the routine discussions that we have,” Dr Bruckel said. “Not every patient is going to want detailed information, but for those that do, it’s important to have it. It’s important to tell them what we know.”
A new study suggests patients with advanced cancer who suffer cardiac arrest in the hospital have a survival rate of less than 10%, which is about half the rate of patients without cancer who suffer cardiac arrest.
This finding helps to clear up some myths about cardiac arrest survival and can be used as a guidepost when hospitalized cancer patients and their families consider do-not-resuscitate (DNR) orders, said Jeffrey T. Bruckel, MD, of the University of Rochester Medical Center in New York.
“We’re hopeful that our study, in some way, will help doctors and cancer patients make more informed decisions about the end of life,” Dr Bruckel said. “It’s very important to have early, frank discussions around the goals of care.”
Dr Bruckel and his colleagues published their study in the Journal of Oncology Practice.
The researchers used a US-wide resuscitation registry to evaluate survival after cardiac arrest in patients treated at 369 hospitals.
The study excluded patients with implantable defibrillators and those who were admitted for surgery, emergency room treatment, rehabilitation, or treatment from cardiac catheterization labs or interventional radiology.
Of the 47,157 eligible patients who experienced cardiac arrest, 14% (n=6585) had advanced cancer, including hematologic malignancies.
After cardiac arrest, 57.5% of the advanced cancer patients were resuscitated successfully, as were 63% of non-cancer patients (P<0.001).
After resuscitation, 9.6% of the cancer patients survived to be discharged, compared to 19.2% of non-cancer patients (P<0.001).
When the researchers adjusted their analysis for potential confounders, results were similar. The rate of successful resuscitation was 52.3% in advanced cancer patients and 56.6% in non-cancer patients (P<0.001). The rate of survival to discharge was 7.4% and 13.4%, respectively (P<0.001).
Dr Bruckel said there was no evidence to suggest that patients with advanced cancer received less aggressive resuscitation care.
However, there was a significant difference in the mean duration of resuscitation time among non-survivors with cancer—22.5 minutes—and non-survivors without cancer—24.2 minutes (P<0.001). After adjustment, the mean duration of resuscitation was 22.5 minutes and 24.1 minutes, respectively (P<0.001).
Cancer patients were more likely than those without cancer to sign DNR orders after resuscitation—55.6% and 43%, respectively (P<0.001). Results were similar after adjustment—50.4% and 41.6%, respectively (P<0.001).
Dr Bruckel and his colleagues said there were several limitations to this study, including a lack of detailed data on the types of advanced cancer and cancer treatments being given at the time of cardiac arrest.
Therefore, the next step in advancing this work is to gather data on the types of cancer diagnosis and treatment plans of patients who undergo in-hospital cardiac arrest.
Dr Bruckel also believes it is important to know how patients feel about this data and how both patients and physicians are using this data in decision-making.
“A large component of end-of-life care involves patient and family care decision-making, and a lot of that is driven by the routine discussions that we have,” Dr Bruckel said. “Not every patient is going to want detailed information, but for those that do, it’s important to have it. It’s important to tell them what we know.”
A new study suggests patients with advanced cancer who suffer cardiac arrest in the hospital have a survival rate of less than 10%, which is about half the rate of patients without cancer who suffer cardiac arrest.
This finding helps to clear up some myths about cardiac arrest survival and can be used as a guidepost when hospitalized cancer patients and their families consider do-not-resuscitate (DNR) orders, said Jeffrey T. Bruckel, MD, of the University of Rochester Medical Center in New York.
“We’re hopeful that our study, in some way, will help doctors and cancer patients make more informed decisions about the end of life,” Dr Bruckel said. “It’s very important to have early, frank discussions around the goals of care.”
Dr Bruckel and his colleagues published their study in the Journal of Oncology Practice.
The researchers used a US-wide resuscitation registry to evaluate survival after cardiac arrest in patients treated at 369 hospitals.
The study excluded patients with implantable defibrillators and those who were admitted for surgery, emergency room treatment, rehabilitation, or treatment from cardiac catheterization labs or interventional radiology.
Of the 47,157 eligible patients who experienced cardiac arrest, 14% (n=6585) had advanced cancer, including hematologic malignancies.
After cardiac arrest, 57.5% of the advanced cancer patients were resuscitated successfully, as were 63% of non-cancer patients (P<0.001).
After resuscitation, 9.6% of the cancer patients survived to be discharged, compared to 19.2% of non-cancer patients (P<0.001).
When the researchers adjusted their analysis for potential confounders, results were similar. The rate of successful resuscitation was 52.3% in advanced cancer patients and 56.6% in non-cancer patients (P<0.001). The rate of survival to discharge was 7.4% and 13.4%, respectively (P<0.001).
Dr Bruckel said there was no evidence to suggest that patients with advanced cancer received less aggressive resuscitation care.
However, there was a significant difference in the mean duration of resuscitation time among non-survivors with cancer—22.5 minutes—and non-survivors without cancer—24.2 minutes (P<0.001). After adjustment, the mean duration of resuscitation was 22.5 minutes and 24.1 minutes, respectively (P<0.001).
Cancer patients were more likely than those without cancer to sign DNR orders after resuscitation—55.6% and 43%, respectively (P<0.001). Results were similar after adjustment—50.4% and 41.6%, respectively (P<0.001).
Dr Bruckel and his colleagues said there were several limitations to this study, including a lack of detailed data on the types of advanced cancer and cancer treatments being given at the time of cardiac arrest.
Therefore, the next step in advancing this work is to gather data on the types of cancer diagnosis and treatment plans of patients who undergo in-hospital cardiac arrest.
Dr Bruckel also believes it is important to know how patients feel about this data and how both patients and physicians are using this data in decision-making.
“A large component of end-of-life care involves patient and family care decision-making, and a lot of that is driven by the routine discussions that we have,” Dr Bruckel said. “Not every patient is going to want detailed information, but for those that do, it’s important to have it. It’s important to tell them what we know.”
Delirium linked to early death in advanced cancer patients
A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.
The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.
This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.
“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.
He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).
Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.
In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.
Results
The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).
The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).
Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.
He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.
“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.
He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.
A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.
The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.
This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.
“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.
He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).
Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.
In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.
Results
The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).
The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).
Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.
He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.
“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.
He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.
A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.
The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.
This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.
“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.
He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).
Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.
In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.
Results
The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).
The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).
Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.
He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.
“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.
He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.
Differential Response to Carfilzomib Based on Initial Therapy With Bortezomib in Multiple Myeloma
Background: Proteasome inhibitors (PIs) are efficacious in multiple myeloma (MM). In randomized phase 3 studies, carfilzomib doubled the progression free survival (PFS) compared to bortezomib from 9.4 mo to 18.7 mo (ENDEAVOR study) in relapsed and refractory MM. However, concern for suboptimal carfilzomib-based therapy (CBT) response in patients (pts) progressing on bortezomib-based therapy (BBT) suggests cross-resistance.
Methods: After IRB approval, all pts with symptomatic MM over the past 10 years at the Michael E. Debakey VA Medical Center with initial BBT followed by salvage CBT at progression were included. Primary aim was to evaluate ORR (PR + VGPR+CR) and PFS by IMWG criteria, in relapsed/refractory pts treated with salvage CBT based on initial BBT response (i.e., primary refractory + stable vs CR+PR+VGPR) or not.
Results: In this cohort, the median overall survival was 45 months. Pts initially treated with BBT had an ORR of 17/19 (89.4%) and median PFS of 7.7 mo. For 12 pts attaining PR, PFS was 4.3 mo. and for those achieving CR/VGPR, PFS was 9.1 mo. P = .03. Two pts were primary refractory to BBT and to CBT. For initial BBT responders, the ORR with CBT was 68.4% (13/19), median PFS was 5.26 mo 6/19 pts (32%) were CBT refractory. PFS during BBT for CBT responders vs CBT refractory pts was not statistically different. Among those who responded to both CBT and BBT, there was no significant correlation between the PFS (CR vs VGPR vs PR) with initial BBT and PFS with CBT.
Conclusions: In our retrospective analysis, pts who exhibited initial resistance to primary BBT did not benefit from salvage therapy with CBT, raising the possibility that hard-wired PI-resistance mechanisms exist. Among BBT responders, CBT ORR was 68%. However, the PFS with CBT
was significantly shorter than the published literature of CBT in RRMM naïve to PI leading us to hypothesize that uncharacterized resistance mechanisms from “priming” bortezomib leads to inferior outcome with salvage CBT. We conclude that CBT can be attempted in those who respond to BBT independent of depth of response or PFS duration. However, alternative therapies should be considered in pts with primary refractoriness to BBT.
Background: Proteasome inhibitors (PIs) are efficacious in multiple myeloma (MM). In randomized phase 3 studies, carfilzomib doubled the progression free survival (PFS) compared to bortezomib from 9.4 mo to 18.7 mo (ENDEAVOR study) in relapsed and refractory MM. However, concern for suboptimal carfilzomib-based therapy (CBT) response in patients (pts) progressing on bortezomib-based therapy (BBT) suggests cross-resistance.
Methods: After IRB approval, all pts with symptomatic MM over the past 10 years at the Michael E. Debakey VA Medical Center with initial BBT followed by salvage CBT at progression were included. Primary aim was to evaluate ORR (PR + VGPR+CR) and PFS by IMWG criteria, in relapsed/refractory pts treated with salvage CBT based on initial BBT response (i.e., primary refractory + stable vs CR+PR+VGPR) or not.
Results: In this cohort, the median overall survival was 45 months. Pts initially treated with BBT had an ORR of 17/19 (89.4%) and median PFS of 7.7 mo. For 12 pts attaining PR, PFS was 4.3 mo. and for those achieving CR/VGPR, PFS was 9.1 mo. P = .03. Two pts were primary refractory to BBT and to CBT. For initial BBT responders, the ORR with CBT was 68.4% (13/19), median PFS was 5.26 mo 6/19 pts (32%) were CBT refractory. PFS during BBT for CBT responders vs CBT refractory pts was not statistically different. Among those who responded to both CBT and BBT, there was no significant correlation between the PFS (CR vs VGPR vs PR) with initial BBT and PFS with CBT.
Conclusions: In our retrospective analysis, pts who exhibited initial resistance to primary BBT did not benefit from salvage therapy with CBT, raising the possibility that hard-wired PI-resistance mechanisms exist. Among BBT responders, CBT ORR was 68%. However, the PFS with CBT
was significantly shorter than the published literature of CBT in RRMM naïve to PI leading us to hypothesize that uncharacterized resistance mechanisms from “priming” bortezomib leads to inferior outcome with salvage CBT. We conclude that CBT can be attempted in those who respond to BBT independent of depth of response or PFS duration. However, alternative therapies should be considered in pts with primary refractoriness to BBT.
Background: Proteasome inhibitors (PIs) are efficacious in multiple myeloma (MM). In randomized phase 3 studies, carfilzomib doubled the progression free survival (PFS) compared to bortezomib from 9.4 mo to 18.7 mo (ENDEAVOR study) in relapsed and refractory MM. However, concern for suboptimal carfilzomib-based therapy (CBT) response in patients (pts) progressing on bortezomib-based therapy (BBT) suggests cross-resistance.
Methods: After IRB approval, all pts with symptomatic MM over the past 10 years at the Michael E. Debakey VA Medical Center with initial BBT followed by salvage CBT at progression were included. Primary aim was to evaluate ORR (PR + VGPR+CR) and PFS by IMWG criteria, in relapsed/refractory pts treated with salvage CBT based on initial BBT response (i.e., primary refractory + stable vs CR+PR+VGPR) or not.
Results: In this cohort, the median overall survival was 45 months. Pts initially treated with BBT had an ORR of 17/19 (89.4%) and median PFS of 7.7 mo. For 12 pts attaining PR, PFS was 4.3 mo. and for those achieving CR/VGPR, PFS was 9.1 mo. P = .03. Two pts were primary refractory to BBT and to CBT. For initial BBT responders, the ORR with CBT was 68.4% (13/19), median PFS was 5.26 mo 6/19 pts (32%) were CBT refractory. PFS during BBT for CBT responders vs CBT refractory pts was not statistically different. Among those who responded to both CBT and BBT, there was no significant correlation between the PFS (CR vs VGPR vs PR) with initial BBT and PFS with CBT.
Conclusions: In our retrospective analysis, pts who exhibited initial resistance to primary BBT did not benefit from salvage therapy with CBT, raising the possibility that hard-wired PI-resistance mechanisms exist. Among BBT responders, CBT ORR was 68%. However, the PFS with CBT
was significantly shorter than the published literature of CBT in RRMM naïve to PI leading us to hypothesize that uncharacterized resistance mechanisms from “priming” bortezomib leads to inferior outcome with salvage CBT. We conclude that CBT can be attempted in those who respond to BBT independent of depth of response or PFS duration. However, alternative therapies should be considered in pts with primary refractoriness to BBT.
ASCO updates guidelines on antiemetic use in cancer patients
The American Society of Clinical Oncology (ASCO) has updated its clinical practice guidelines on the use of antiemetics in cancer patients.
The update, published in the Journal of Clinical Oncology, provides new evidence-based information on the appropriate use of olanzapine, NK1 receptor antagonists, and dexamethasone.
“The adverse impact of inadequately controlled nausea and vomiting on patients’ quality of life is well documented,” said Paul J. Hesketh, MD, co-chair of the ASCO expert panel that updated the guidelines.
“By following the ASCO antiemetics guideline, clinicians have the opportunity to improve patients’ quality of life by minimizing treatment-induced emesis.”
To update ASCO’s guidelines on antiemetics, the expert panel conducted a systematic review of the medical literature published between November 2009 and June 2016. The panel included members with expertise in medical oncology, radiation oncology, nursing, pharmacy, and health services research, as well as a patient representative.
“Tremendous progress has been realized over the last 25 years in the prevention of chemotherapy-induced nausea and vomiting with the introduction of new classes of antiemetic agents,” said Mark G. Kris, MD, co-chair of the expert panel that updated the guidelines.
“The full benefit of these treatment advances will only be realized, however, if evidence-based guidelines are fully implemented.”
Key recommendations in the updated guidelines include:
For adults receiving chemotherapy with a high risk for nausea and vomiting (eg, cisplatin or the combination of cyclophosphamide and an anthracycline), olanzapine should be added to standard antiemetic regimens (the combination of a 5-HT3 receptor antagonist, an NK1 receptor antagonist, and dexamethasone). Olanzapine also helps individuals who experience symptoms despite receiving medicines to prevent vomiting before chemotherapy is given.
For adults receiving carboplatin-based chemotherapy or high-dose chemotherapy and children receiving chemotherapy with a high risk for nausea and vomiting, an NK1 receptor antagonist should be added to the standard antiemetic regimen (the combination of 5-HT3 receptor antagonist and dexamethasone).
Dexamethasone treatment can be limited to the day of chemotherapy administration in patients receiving an anthracycline and cyclophosphamide.
Dronabinol and nabilone, cannabinoids approved by the US Food and Drug Administration, can be used to treat nausea and vomiting that is resistant to standard antiemetic therapies. Evidence remains insufficient to recommend medical marijuana for either prevention or treatment of nausea and vomiting in patients with cancer receiving chemotherapy or radiation therapy.
The American Society of Clinical Oncology (ASCO) has updated its clinical practice guidelines on the use of antiemetics in cancer patients.
The update, published in the Journal of Clinical Oncology, provides new evidence-based information on the appropriate use of olanzapine, NK1 receptor antagonists, and dexamethasone.
“The adverse impact of inadequately controlled nausea and vomiting on patients’ quality of life is well documented,” said Paul J. Hesketh, MD, co-chair of the ASCO expert panel that updated the guidelines.
“By following the ASCO antiemetics guideline, clinicians have the opportunity to improve patients’ quality of life by minimizing treatment-induced emesis.”
To update ASCO’s guidelines on antiemetics, the expert panel conducted a systematic review of the medical literature published between November 2009 and June 2016. The panel included members with expertise in medical oncology, radiation oncology, nursing, pharmacy, and health services research, as well as a patient representative.
“Tremendous progress has been realized over the last 25 years in the prevention of chemotherapy-induced nausea and vomiting with the introduction of new classes of antiemetic agents,” said Mark G. Kris, MD, co-chair of the expert panel that updated the guidelines.
“The full benefit of these treatment advances will only be realized, however, if evidence-based guidelines are fully implemented.”
Key recommendations in the updated guidelines include:
For adults receiving chemotherapy with a high risk for nausea and vomiting (eg, cisplatin or the combination of cyclophosphamide and an anthracycline), olanzapine should be added to standard antiemetic regimens (the combination of a 5-HT3 receptor antagonist, an NK1 receptor antagonist, and dexamethasone). Olanzapine also helps individuals who experience symptoms despite receiving medicines to prevent vomiting before chemotherapy is given.
For adults receiving carboplatin-based chemotherapy or high-dose chemotherapy and children receiving chemotherapy with a high risk for nausea and vomiting, an NK1 receptor antagonist should be added to the standard antiemetic regimen (the combination of 5-HT3 receptor antagonist and dexamethasone).
Dexamethasone treatment can be limited to the day of chemotherapy administration in patients receiving an anthracycline and cyclophosphamide.
Dronabinol and nabilone, cannabinoids approved by the US Food and Drug Administration, can be used to treat nausea and vomiting that is resistant to standard antiemetic therapies. Evidence remains insufficient to recommend medical marijuana for either prevention or treatment of nausea and vomiting in patients with cancer receiving chemotherapy or radiation therapy.
The American Society of Clinical Oncology (ASCO) has updated its clinical practice guidelines on the use of antiemetics in cancer patients.
The update, published in the Journal of Clinical Oncology, provides new evidence-based information on the appropriate use of olanzapine, NK1 receptor antagonists, and dexamethasone.
“The adverse impact of inadequately controlled nausea and vomiting on patients’ quality of life is well documented,” said Paul J. Hesketh, MD, co-chair of the ASCO expert panel that updated the guidelines.
“By following the ASCO antiemetics guideline, clinicians have the opportunity to improve patients’ quality of life by minimizing treatment-induced emesis.”
To update ASCO’s guidelines on antiemetics, the expert panel conducted a systematic review of the medical literature published between November 2009 and June 2016. The panel included members with expertise in medical oncology, radiation oncology, nursing, pharmacy, and health services research, as well as a patient representative.
“Tremendous progress has been realized over the last 25 years in the prevention of chemotherapy-induced nausea and vomiting with the introduction of new classes of antiemetic agents,” said Mark G. Kris, MD, co-chair of the expert panel that updated the guidelines.
“The full benefit of these treatment advances will only be realized, however, if evidence-based guidelines are fully implemented.”
Key recommendations in the updated guidelines include:
For adults receiving chemotherapy with a high risk for nausea and vomiting (eg, cisplatin or the combination of cyclophosphamide and an anthracycline), olanzapine should be added to standard antiemetic regimens (the combination of a 5-HT3 receptor antagonist, an NK1 receptor antagonist, and dexamethasone). Olanzapine also helps individuals who experience symptoms despite receiving medicines to prevent vomiting before chemotherapy is given.
For adults receiving carboplatin-based chemotherapy or high-dose chemotherapy and children receiving chemotherapy with a high risk for nausea and vomiting, an NK1 receptor antagonist should be added to the standard antiemetic regimen (the combination of 5-HT3 receptor antagonist and dexamethasone).
Dexamethasone treatment can be limited to the day of chemotherapy administration in patients receiving an anthracycline and cyclophosphamide.
Dronabinol and nabilone, cannabinoids approved by the US Food and Drug Administration, can be used to treat nausea and vomiting that is resistant to standard antiemetic therapies. Evidence remains insufficient to recommend medical marijuana for either prevention or treatment of nausea and vomiting in patients with cancer receiving chemotherapy or radiation therapy.
Less lenalidomide may be more in frail elderly multiple myeloma patients
In frail elderly patients with multiple myeloma, starting lenalidomide at low doses was associated with fewer adverse events and less treatment discontinuation, and did not compromise overall response rates, in a single-center, retrospective study conducted in Japan.
Although most of the 56 study patients received 5-10 mg/day of lenalidomide, not the recommended 25-mg/day dose, their overall response rate was 73% (complete response in 17% of patients, very good partial response in 19%, and partial response in 37%), Aya Nakaya, MD, PhD, of Kansai Medical University, Hirakata, and colleagues wrote (Acta Haematol. 2017;138:55-60). In addition, 23% of patients had stable disease and 4% had disease progression. Nine patients developed other types of malignancies during treatment with lenalidomide.
Starting patients on a reduced dose and increasing it gradually while monitoring carefully for adverse events meant that patients did not have to stop treatment, the researchers said. Continuous treatment may improve survival, and “treatment with lenalidomide for long periods of time, even in small doses, may yield favorable outcomes.”
The 30 men and 26 women, mean age 76.5 years, were consecutively diagnosed as transplant-ineligible patients with relapsed/refractory multiple myeloma; 34%, 32%, and 34% had stages I-III disease, respectively. The M-protein consisted of IgG in 52% of patients and IgA in 30%, with Bence-Jones protein detected in 14%.
They were treated with lenalidomide plus dexamethasone at a starting dose determined by the treating physician; 73% were treated with lenalidomide as a second-line regimen and 14% as a third-line regimen. During each 28-day treatment cycle, patients received lenalidomide on days 1-21 and dexamethasone (20 or 40 mg) on days 1, 8, 15, and 22.
The most common starting lenalidomide dose was 10 mg/day (45%), followed by 5 mg/day (21%), 15 mg/day (20%), 20 mg/day (4%), and 25 mg/day (10%). The treatment dose used for the longest period was 10 mg/day (46% of patients), followed by 5 mg/day (25%), 15 mg/day (16%), 20 mg/day (4%), and 25 mg/day (9%).
The most frequent reasons for dose reduction were renal dysfunction (54%), fatigue (20%), hematologic disorder (14%), and rash (9%).
The median treatment period was 9 months (range 1-60 months) and the median follow-up period was 16 months.
The median time to disease progression was 11.8 months (range 8.4-21.9), and the median overall survival was 39.2 months. For those who took 5-10 mg of lenalidomide, the median time to progression was 14.5 months; for those who took lenalidomide at a dose of more than 10 mg, the median time to progression was 8.9 months. The median overall survival of the patients who received a 5- to 10-mg dose of lenalidomide was 38.9 months; the median overall survival of the patients given a dose of more than 10 mg was not available.
The authors declared no competing financial interests in relation to this work.
[email protected]
On Twitter @maryjodales
In frail elderly patients with multiple myeloma, starting lenalidomide at low doses was associated with fewer adverse events and less treatment discontinuation, and did not compromise overall response rates, in a single-center, retrospective study conducted in Japan.
Although most of the 56 study patients received 5-10 mg/day of lenalidomide, not the recommended 25-mg/day dose, their overall response rate was 73% (complete response in 17% of patients, very good partial response in 19%, and partial response in 37%), Aya Nakaya, MD, PhD, of Kansai Medical University, Hirakata, and colleagues wrote (Acta Haematol. 2017;138:55-60). In addition, 23% of patients had stable disease and 4% had disease progression. Nine patients developed other types of malignancies during treatment with lenalidomide.
Starting patients on a reduced dose and increasing it gradually while monitoring carefully for adverse events meant that patients did not have to stop treatment, the researchers said. Continuous treatment may improve survival, and “treatment with lenalidomide for long periods of time, even in small doses, may yield favorable outcomes.”
The 30 men and 26 women, mean age 76.5 years, were consecutively diagnosed as transplant-ineligible patients with relapsed/refractory multiple myeloma; 34%, 32%, and 34% had stages I-III disease, respectively. The M-protein consisted of IgG in 52% of patients and IgA in 30%, with Bence-Jones protein detected in 14%.
They were treated with lenalidomide plus dexamethasone at a starting dose determined by the treating physician; 73% were treated with lenalidomide as a second-line regimen and 14% as a third-line regimen. During each 28-day treatment cycle, patients received lenalidomide on days 1-21 and dexamethasone (20 or 40 mg) on days 1, 8, 15, and 22.
The most common starting lenalidomide dose was 10 mg/day (45%), followed by 5 mg/day (21%), 15 mg/day (20%), 20 mg/day (4%), and 25 mg/day (10%). The treatment dose used for the longest period was 10 mg/day (46% of patients), followed by 5 mg/day (25%), 15 mg/day (16%), 20 mg/day (4%), and 25 mg/day (9%).
The most frequent reasons for dose reduction were renal dysfunction (54%), fatigue (20%), hematologic disorder (14%), and rash (9%).
The median treatment period was 9 months (range 1-60 months) and the median follow-up period was 16 months.
The median time to disease progression was 11.8 months (range 8.4-21.9), and the median overall survival was 39.2 months. For those who took 5-10 mg of lenalidomide, the median time to progression was 14.5 months; for those who took lenalidomide at a dose of more than 10 mg, the median time to progression was 8.9 months. The median overall survival of the patients who received a 5- to 10-mg dose of lenalidomide was 38.9 months; the median overall survival of the patients given a dose of more than 10 mg was not available.
The authors declared no competing financial interests in relation to this work.
[email protected]
On Twitter @maryjodales
In frail elderly patients with multiple myeloma, starting lenalidomide at low doses was associated with fewer adverse events and less treatment discontinuation, and did not compromise overall response rates, in a single-center, retrospective study conducted in Japan.
Although most of the 56 study patients received 5-10 mg/day of lenalidomide, not the recommended 25-mg/day dose, their overall response rate was 73% (complete response in 17% of patients, very good partial response in 19%, and partial response in 37%), Aya Nakaya, MD, PhD, of Kansai Medical University, Hirakata, and colleagues wrote (Acta Haematol. 2017;138:55-60). In addition, 23% of patients had stable disease and 4% had disease progression. Nine patients developed other types of malignancies during treatment with lenalidomide.
Starting patients on a reduced dose and increasing it gradually while monitoring carefully for adverse events meant that patients did not have to stop treatment, the researchers said. Continuous treatment may improve survival, and “treatment with lenalidomide for long periods of time, even in small doses, may yield favorable outcomes.”
The 30 men and 26 women, mean age 76.5 years, were consecutively diagnosed as transplant-ineligible patients with relapsed/refractory multiple myeloma; 34%, 32%, and 34% had stages I-III disease, respectively. The M-protein consisted of IgG in 52% of patients and IgA in 30%, with Bence-Jones protein detected in 14%.
They were treated with lenalidomide plus dexamethasone at a starting dose determined by the treating physician; 73% were treated with lenalidomide as a second-line regimen and 14% as a third-line regimen. During each 28-day treatment cycle, patients received lenalidomide on days 1-21 and dexamethasone (20 or 40 mg) on days 1, 8, 15, and 22.
The most common starting lenalidomide dose was 10 mg/day (45%), followed by 5 mg/day (21%), 15 mg/day (20%), 20 mg/day (4%), and 25 mg/day (10%). The treatment dose used for the longest period was 10 mg/day (46% of patients), followed by 5 mg/day (25%), 15 mg/day (16%), 20 mg/day (4%), and 25 mg/day (9%).
The most frequent reasons for dose reduction were renal dysfunction (54%), fatigue (20%), hematologic disorder (14%), and rash (9%).
The median treatment period was 9 months (range 1-60 months) and the median follow-up period was 16 months.
The median time to disease progression was 11.8 months (range 8.4-21.9), and the median overall survival was 39.2 months. For those who took 5-10 mg of lenalidomide, the median time to progression was 14.5 months; for those who took lenalidomide at a dose of more than 10 mg, the median time to progression was 8.9 months. The median overall survival of the patients who received a 5- to 10-mg dose of lenalidomide was 38.9 months; the median overall survival of the patients given a dose of more than 10 mg was not available.
The authors declared no competing financial interests in relation to this work.
[email protected]
On Twitter @maryjodales
FROM ACTA HAEMATOLOGICA
Key clinical point:
Major finding: Although most of the 56 study patients received 5-10 mg/day of lenalidomide, not the recommended 25-mg/day dose, their overall response rate was 73%.
Data source: A single-center, retrospective study of 56 consecutively diagnosed transplant-ineligible patients in Japan.
Disclosures: The authors declared no competing financial interests in relation to this work.
GEP classifier predicts risk in MM
A gene expression profiling (GEP) classifier can accurately identify high- and low-risk patients with multiple myeloma (MM), according to research published in Clinical Lymphoma, Myeloma and Leukemia.
The GEP classifier is known as SKY92, and researchers found they could accurately identify high-risk MM patients using SKY92 alone.
By combining SKY92 with the International Staging System (ISS), the team was able to identify low-risk MM patients as well.
“We have demonstrated the prognostic value of SKY92 not only as a marker of high risk, but also as a marker of low risk when combined with ISS,” said study author Erik H. van Beers, PhD, vice president of genomics at SkylineDx, the company that developed SKY92.
“Both validated markers may serve as the basis for the discovery of improved individualized therapies for patients with multiple myeloma.”
Dr van Beers and his colleagues compared 8 risk-assessment platforms to analyze gene expression data from 91 newly diagnosed MM patients. The patients were included in an independent dataset amassed by the Multiple Myeloma Research Foundation and the Multiple Myeloma Genomics Initiative (MMRF/MMGI).
The researchers used the GEP classifiers SKY92, UAMS70, UAMS80, IFM15, HM19, Cancer Testis Antigen, Centrosome Index, and Proliferation Index to identify high-risk patients.
Of the 8 classifiers, SKY92 identified the largest proportion (21%) of high-risk cases and also attained the highest Cox proportional hazard ratio (8.2) for overall survival (OS).
Additionally, SKY92 predicted 9 of the 13 (60%) deaths that occurred at 2 years and 16 of the 31 (52%) deaths at 5 years, a predictive rate that was higher than any of the other classifiers.
Dr van Beers and his colleagues also combined the SKY92 standard-risk classifier with the ISS to identify low-risk patients in the MMRF/MMGI cohort. This combination was recently identified as a marker for detecting low-risk MM.*
The SKY92/ISS marker identified 42% of patients as low risk, with their median OS not reached at 96 months. The low-risk classification was strongly supported by the achieved hazard ratio of 10.
“The MMRF/MMGI dataset was not part of our previous discovery*, which demonstrated that the combination of SKY92 and ISS identifies the lowest-risk patients with high accuracy and leaves the smallest proportion of patients identified as intermediate risk,” Dr van Beers said. “Thus, the dataset remained available for independent validation—an important factor in the adoption of gene expression profiling tools.”
“We are pleased to have validated the SKY92/ISS low-risk marker by applying it to the well-characterized MMRF/MMGI cohort,” added study author Rafael Fonseca, MD, of the Mayo Clinic in Scottsdale, Arizona. “Our findings further strengthen the prognostic utility of the combination marker.”
*Kuiper R, van Duin M, van Vliet, MH, et al. Prediction of high- and low-risk multiple myeloma based on gene expression and the International Staging System. Blood. 2015;126(17):1996-2004.
A gene expression profiling (GEP) classifier can accurately identify high- and low-risk patients with multiple myeloma (MM), according to research published in Clinical Lymphoma, Myeloma and Leukemia.
The GEP classifier is known as SKY92, and researchers found they could accurately identify high-risk MM patients using SKY92 alone.
By combining SKY92 with the International Staging System (ISS), the team was able to identify low-risk MM patients as well.
“We have demonstrated the prognostic value of SKY92 not only as a marker of high risk, but also as a marker of low risk when combined with ISS,” said study author Erik H. van Beers, PhD, vice president of genomics at SkylineDx, the company that developed SKY92.
“Both validated markers may serve as the basis for the discovery of improved individualized therapies for patients with multiple myeloma.”
Dr van Beers and his colleagues compared 8 risk-assessment platforms to analyze gene expression data from 91 newly diagnosed MM patients. The patients were included in an independent dataset amassed by the Multiple Myeloma Research Foundation and the Multiple Myeloma Genomics Initiative (MMRF/MMGI).
The researchers used the GEP classifiers SKY92, UAMS70, UAMS80, IFM15, HM19, Cancer Testis Antigen, Centrosome Index, and Proliferation Index to identify high-risk patients.
Of the 8 classifiers, SKY92 identified the largest proportion (21%) of high-risk cases and also attained the highest Cox proportional hazard ratio (8.2) for overall survival (OS).
Additionally, SKY92 predicted 9 of the 13 (60%) deaths that occurred at 2 years and 16 of the 31 (52%) deaths at 5 years, a predictive rate that was higher than any of the other classifiers.
Dr van Beers and his colleagues also combined the SKY92 standard-risk classifier with the ISS to identify low-risk patients in the MMRF/MMGI cohort. This combination was recently identified as a marker for detecting low-risk MM.*
The SKY92/ISS marker identified 42% of patients as low risk, with their median OS not reached at 96 months. The low-risk classification was strongly supported by the achieved hazard ratio of 10.
“The MMRF/MMGI dataset was not part of our previous discovery*, which demonstrated that the combination of SKY92 and ISS identifies the lowest-risk patients with high accuracy and leaves the smallest proportion of patients identified as intermediate risk,” Dr van Beers said. “Thus, the dataset remained available for independent validation—an important factor in the adoption of gene expression profiling tools.”
“We are pleased to have validated the SKY92/ISS low-risk marker by applying it to the well-characterized MMRF/MMGI cohort,” added study author Rafael Fonseca, MD, of the Mayo Clinic in Scottsdale, Arizona. “Our findings further strengthen the prognostic utility of the combination marker.”
*Kuiper R, van Duin M, van Vliet, MH, et al. Prediction of high- and low-risk multiple myeloma based on gene expression and the International Staging System. Blood. 2015;126(17):1996-2004.
A gene expression profiling (GEP) classifier can accurately identify high- and low-risk patients with multiple myeloma (MM), according to research published in Clinical Lymphoma, Myeloma and Leukemia.
The GEP classifier is known as SKY92, and researchers found they could accurately identify high-risk MM patients using SKY92 alone.
By combining SKY92 with the International Staging System (ISS), the team was able to identify low-risk MM patients as well.
“We have demonstrated the prognostic value of SKY92 not only as a marker of high risk, but also as a marker of low risk when combined with ISS,” said study author Erik H. van Beers, PhD, vice president of genomics at SkylineDx, the company that developed SKY92.
“Both validated markers may serve as the basis for the discovery of improved individualized therapies for patients with multiple myeloma.”
Dr van Beers and his colleagues compared 8 risk-assessment platforms to analyze gene expression data from 91 newly diagnosed MM patients. The patients were included in an independent dataset amassed by the Multiple Myeloma Research Foundation and the Multiple Myeloma Genomics Initiative (MMRF/MMGI).
The researchers used the GEP classifiers SKY92, UAMS70, UAMS80, IFM15, HM19, Cancer Testis Antigen, Centrosome Index, and Proliferation Index to identify high-risk patients.
Of the 8 classifiers, SKY92 identified the largest proportion (21%) of high-risk cases and also attained the highest Cox proportional hazard ratio (8.2) for overall survival (OS).
Additionally, SKY92 predicted 9 of the 13 (60%) deaths that occurred at 2 years and 16 of the 31 (52%) deaths at 5 years, a predictive rate that was higher than any of the other classifiers.
Dr van Beers and his colleagues also combined the SKY92 standard-risk classifier with the ISS to identify low-risk patients in the MMRF/MMGI cohort. This combination was recently identified as a marker for detecting low-risk MM.*
The SKY92/ISS marker identified 42% of patients as low risk, with their median OS not reached at 96 months. The low-risk classification was strongly supported by the achieved hazard ratio of 10.
“The MMRF/MMGI dataset was not part of our previous discovery*, which demonstrated that the combination of SKY92 and ISS identifies the lowest-risk patients with high accuracy and leaves the smallest proportion of patients identified as intermediate risk,” Dr van Beers said. “Thus, the dataset remained available for independent validation—an important factor in the adoption of gene expression profiling tools.”
“We are pleased to have validated the SKY92/ISS low-risk marker by applying it to the well-characterized MMRF/MMGI cohort,” added study author Rafael Fonseca, MD, of the Mayo Clinic in Scottsdale, Arizona. “Our findings further strengthen the prognostic utility of the combination marker.”
*Kuiper R, van Duin M, van Vliet, MH, et al. Prediction of high- and low-risk multiple myeloma based on gene expression and the International Staging System. Blood. 2015;126(17):1996-2004.
FLT3-L level may point to relapsed/refractory multiple myeloma
FLT3-ligand (FLT3-L) levels exceeding 92 pg/mL in bone marrow and 121 pg/mL in peripheral blood are associated with relapsed and refractory disease in patients with multiple myeloma, Normann Steiner, MD, and his colleagues report in a study published in PLoS ONE.
In the study of 14 patients with monoclonal gamm opathy of undetermined significance (MGUS), 42 patients with newly diagnosed myeloma, and 27 patients with relapsed/refractory myeloma, there was a 61% probability that patients with FLT3-L levels above 92 pg/mL in bone marrow had relapsed or refractory multiple myeloma and a 79% probability that those with FLT3-L levels of 92 pg/mL or less had not relapsed and were not refractory. Based on FLT3-L levels in peripheral blood, values of 121 pg/mL or more were associated with a 71% probability of relapsed or refractory disease. The likelihood of not having relapses or refractory disease was 87% for patients with values less than 121 pg/mL.
“FLT3-L could be useful as a marker to identify (relapsed or refractory multiple myeloma) patients and should be evaluated as a potential target for future therapy strategies,” Dr. Steiner of Innsbruck (Austria) Medical University, and his fellow researchers wrote in PLoS ONE.
The researchers obtained bone marrow aspirates from all patients. Peripheral blood was examined from 4 MGUS patients, 31 patients with newly diagnosed myeloma, and 16 patients with relapsed or refractory myeloma. Peripheral blood was also obtained from 16 control subjects.
The levels of four potential risk factors were measured – soluble TIE2, FLT3-L, endostatin, and osteoactivin. The most significant association with risk was seen with FLT3-L levels.
Expression of soluble TIE2 in bone marrow differed significantly among the three patient cohorts and may be driven by the same factors that influence FLT3-L levels. However, soluble TIE2 levels were not as effective at differentiating patients at risk for disease progression, the researchers wrote.
Soluble TIE2 expression in bone marrow was highest in MGUS patients (median 4003.97 pg/mL) in comparison to relapsed or refractory disease (median 2223.26 pg/mL; P = .03) and to newly diagnosed patients with myeloma (median 861.98 pg/mL; P less than .001). A statistically significant difference among bone marrow levels of soluble TIE2 was observed for newly diagnosed patients and those with relapsed or refractory disease (P = .03).
However, soluble TIE2 in peripheral blood plasma did not differ significantly in the three cohorts nor did it differ between patients and controls.
In contrast to TIE2 and FLT3-L, levels of endostatin were lowest (median 146.50 ng/mL) in bone marrow plasma samples of patients with relapsed or refractory disease. Levels were higher in MGUS patients (median 190.37 mg/dL) than in newly diagnosed myeloma patients (median 170.15 mg/mL; P = .5).
Similar to soluble TIE2, plasma levels of endostatin in peripheral blood did not differ significantly in the three patient cohorts. Measurements of endostatin in bone marrow and peripheral blood correlated significantly (P less than .001), and peripheral blood levels differed significantly (P less than .001) for patients and control persons.
Osteoactivin expression was highest in the MGUS cohort, with median bone marrow plasma levels of 36 ng/mL as compared with median levels of 24.92 ng/mL in newly diagnosed myeloma patients and 22.30 ng/mL in patients with relapsed or refractory myeloma. Osteoactivin levels in peripheral blood did not differ significantly in the three cohorts, but differed between patients and control subjects. Osteoactivin measures in bone marrow and peripheral blood correlated significantly.
Citation: Steiner N, et al. High levels of FLT3-ligand in bone marrow and peripheral blood of patients with advanced multiple myeloma. PLoS ONE 2017 Jul 20;12:e0181487. doi. org/10.1371/journal.pone.0181487.
[email protected]
On Twitter @maryjodales
FLT3-ligand (FLT3-L) levels exceeding 92 pg/mL in bone marrow and 121 pg/mL in peripheral blood are associated with relapsed and refractory disease in patients with multiple myeloma, Normann Steiner, MD, and his colleagues report in a study published in PLoS ONE.
In the study of 14 patients with monoclonal gamm opathy of undetermined significance (MGUS), 42 patients with newly diagnosed myeloma, and 27 patients with relapsed/refractory myeloma, there was a 61% probability that patients with FLT3-L levels above 92 pg/mL in bone marrow had relapsed or refractory multiple myeloma and a 79% probability that those with FLT3-L levels of 92 pg/mL or less had not relapsed and were not refractory. Based on FLT3-L levels in peripheral blood, values of 121 pg/mL or more were associated with a 71% probability of relapsed or refractory disease. The likelihood of not having relapses or refractory disease was 87% for patients with values less than 121 pg/mL.
“FLT3-L could be useful as a marker to identify (relapsed or refractory multiple myeloma) patients and should be evaluated as a potential target for future therapy strategies,” Dr. Steiner of Innsbruck (Austria) Medical University, and his fellow researchers wrote in PLoS ONE.
The researchers obtained bone marrow aspirates from all patients. Peripheral blood was examined from 4 MGUS patients, 31 patients with newly diagnosed myeloma, and 16 patients with relapsed or refractory myeloma. Peripheral blood was also obtained from 16 control subjects.
The levels of four potential risk factors were measured – soluble TIE2, FLT3-L, endostatin, and osteoactivin. The most significant association with risk was seen with FLT3-L levels.
Expression of soluble TIE2 in bone marrow differed significantly among the three patient cohorts and may be driven by the same factors that influence FLT3-L levels. However, soluble TIE2 levels were not as effective at differentiating patients at risk for disease progression, the researchers wrote.
Soluble TIE2 expression in bone marrow was highest in MGUS patients (median 4003.97 pg/mL) in comparison to relapsed or refractory disease (median 2223.26 pg/mL; P = .03) and to newly diagnosed patients with myeloma (median 861.98 pg/mL; P less than .001). A statistically significant difference among bone marrow levels of soluble TIE2 was observed for newly diagnosed patients and those with relapsed or refractory disease (P = .03).
However, soluble TIE2 in peripheral blood plasma did not differ significantly in the three cohorts nor did it differ between patients and controls.
In contrast to TIE2 and FLT3-L, levels of endostatin were lowest (median 146.50 ng/mL) in bone marrow plasma samples of patients with relapsed or refractory disease. Levels were higher in MGUS patients (median 190.37 mg/dL) than in newly diagnosed myeloma patients (median 170.15 mg/mL; P = .5).
Similar to soluble TIE2, plasma levels of endostatin in peripheral blood did not differ significantly in the three patient cohorts. Measurements of endostatin in bone marrow and peripheral blood correlated significantly (P less than .001), and peripheral blood levels differed significantly (P less than .001) for patients and control persons.
Osteoactivin expression was highest in the MGUS cohort, with median bone marrow plasma levels of 36 ng/mL as compared with median levels of 24.92 ng/mL in newly diagnosed myeloma patients and 22.30 ng/mL in patients with relapsed or refractory myeloma. Osteoactivin levels in peripheral blood did not differ significantly in the three cohorts, but differed between patients and control subjects. Osteoactivin measures in bone marrow and peripheral blood correlated significantly.
Citation: Steiner N, et al. High levels of FLT3-ligand in bone marrow and peripheral blood of patients with advanced multiple myeloma. PLoS ONE 2017 Jul 20;12:e0181487. doi. org/10.1371/journal.pone.0181487.
[email protected]
On Twitter @maryjodales
FLT3-ligand (FLT3-L) levels exceeding 92 pg/mL in bone marrow and 121 pg/mL in peripheral blood are associated with relapsed and refractory disease in patients with multiple myeloma, Normann Steiner, MD, and his colleagues report in a study published in PLoS ONE.
In the study of 14 patients with monoclonal gamm opathy of undetermined significance (MGUS), 42 patients with newly diagnosed myeloma, and 27 patients with relapsed/refractory myeloma, there was a 61% probability that patients with FLT3-L levels above 92 pg/mL in bone marrow had relapsed or refractory multiple myeloma and a 79% probability that those with FLT3-L levels of 92 pg/mL or less had not relapsed and were not refractory. Based on FLT3-L levels in peripheral blood, values of 121 pg/mL or more were associated with a 71% probability of relapsed or refractory disease. The likelihood of not having relapses or refractory disease was 87% for patients with values less than 121 pg/mL.
“FLT3-L could be useful as a marker to identify (relapsed or refractory multiple myeloma) patients and should be evaluated as a potential target for future therapy strategies,” Dr. Steiner of Innsbruck (Austria) Medical University, and his fellow researchers wrote in PLoS ONE.
The researchers obtained bone marrow aspirates from all patients. Peripheral blood was examined from 4 MGUS patients, 31 patients with newly diagnosed myeloma, and 16 patients with relapsed or refractory myeloma. Peripheral blood was also obtained from 16 control subjects.
The levels of four potential risk factors were measured – soluble TIE2, FLT3-L, endostatin, and osteoactivin. The most significant association with risk was seen with FLT3-L levels.
Expression of soluble TIE2 in bone marrow differed significantly among the three patient cohorts and may be driven by the same factors that influence FLT3-L levels. However, soluble TIE2 levels were not as effective at differentiating patients at risk for disease progression, the researchers wrote.
Soluble TIE2 expression in bone marrow was highest in MGUS patients (median 4003.97 pg/mL) in comparison to relapsed or refractory disease (median 2223.26 pg/mL; P = .03) and to newly diagnosed patients with myeloma (median 861.98 pg/mL; P less than .001). A statistically significant difference among bone marrow levels of soluble TIE2 was observed for newly diagnosed patients and those with relapsed or refractory disease (P = .03).
However, soluble TIE2 in peripheral blood plasma did not differ significantly in the three cohorts nor did it differ between patients and controls.
In contrast to TIE2 and FLT3-L, levels of endostatin were lowest (median 146.50 ng/mL) in bone marrow plasma samples of patients with relapsed or refractory disease. Levels were higher in MGUS patients (median 190.37 mg/dL) than in newly diagnosed myeloma patients (median 170.15 mg/mL; P = .5).
Similar to soluble TIE2, plasma levels of endostatin in peripheral blood did not differ significantly in the three patient cohorts. Measurements of endostatin in bone marrow and peripheral blood correlated significantly (P less than .001), and peripheral blood levels differed significantly (P less than .001) for patients and control persons.
Osteoactivin expression was highest in the MGUS cohort, with median bone marrow plasma levels of 36 ng/mL as compared with median levels of 24.92 ng/mL in newly diagnosed myeloma patients and 22.30 ng/mL in patients with relapsed or refractory myeloma. Osteoactivin levels in peripheral blood did not differ significantly in the three cohorts, but differed between patients and control subjects. Osteoactivin measures in bone marrow and peripheral blood correlated significantly.
Citation: Steiner N, et al. High levels of FLT3-ligand in bone marrow and peripheral blood of patients with advanced multiple myeloma. PLoS ONE 2017 Jul 20;12:e0181487. doi. org/10.1371/journal.pone.0181487.
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FROM PLOS ONE
Key clinical point: .
Major finding: There was a 61% probability that patients with FLT3-L levels above 92 pg/mL in bone marrow had relapsed or refractory multiple myeloma and a 79% probability that those with FLT3-L levels of 92 pg/mL or less had not relapsed and were not refractory.
Data source: A study of 14 patients with monoclonal gammopathy of undetermined significance, 42 patients with newly diagnosed myeloma, and 27 patients with relapsed/refractory myeloma, plus 16 control subjects.
Disclosures: The study was not sponsored, and the authors had no relevant disclosures.
Citation: Steiner N, et al. High levels of FLT3-ligand in bone marrow and peripheral blood of patients with advanced multiple myeloma. PLoS ONE 2017 Jul 20;12:e0181487. doi. org/10.1371/journal.pone.0181487
Four drugs better than three for myeloma induction
MADRID – A four-drug induction regimen induced quicker and deeper remissions than sequential triplet regimens in patients with newly diagnosed multiple myeloma.
In addition, fast, deep remissions may lead to improved progression-free survival (PFS) following autologous stem cell transplantation (ASCT), said investigators from a U.K. Medical Research Council study.
In the phase 3 randomized, parallel group Myeloma XI study, very good partial responses (VGPR) or better were seen following induction in 79.5% of patients assigned to the quadruplet (KCRD) of carfilzomib (Kyprolis), cyclophosphamide, lenalidomide (Revlimid), and dexamethasone, compared with 60.8% for those assigned to cyclophosphamide, lenalidomide, and dexamethasone (CRD) and 52.8% for those assigned to cyclophosphamide, thalidomide, and dexamethasone (CTD), said Charlotte Pawlyn, MD, PhD, at the annual congress of the European Hematology Association.
“In our study, we see a very much deeper response after initial induction with the quadruplet regimen, compared with triplet regimens,” Dr. Pawlyn of the Institute of Cancer Research, London, said in an interview.
Medical Research Council investigators showed in the Myeloma IX study that among patients who had a less than VGPR to an immunomodulator-based triplet regimen such as CRD, a triplet regimen including the proteasome inhibitor bortezomib (Velcade) could improve both pre- and post-transplant response rates, and that the improved responses translated into improved PFS.
For the Myeloma XI study, the investigators employed the same response-adapted approach to compare outcomes following induction with the proteasome inhibitor–containing KCRD regimen and the lenalidomide- or thalidomide-based regimens.
They chose carfilzomib as the proteasome-inhibitor backbone of the quadruplet because of its selective, irreversible target binding, lower incidence of peripheral neuropathy (compared with bortezomib), and efficacy in both the frontline and relapsed/refractory setting, she said.
Asked why the comparator regimens did not contain a proteasome inhibitor, Dr. Pawlyn said that while the current standard for induction therapy in the United Kingdom is bortezomib, thalidomide, and dexamethasone, CTD was the standard of care at the time of study planning and initial enrollment.
The trial was open to all patients in the United Kingdom of all ages with newly diagnosed symptomatic multiple myeloma, with pathways for both transplant-eligible and transplant-ineligible patients. The only main exclusion criteria were for patients with dialysis-dependent renal failure and for those who had a prior or concurrent malignancy.
A total of 1,021 patients were assigned to each of the CTD and CRD cohorts, and 526 patients were assigned to the KCRD cohort. The cohorts were well balanced by sex, age, World Health Organization performance score, and other parameters.
Patients randomized to either CTD or CRD were assessed for response after a minimum of four induction cycles, with treatment continued until best response. Those with a VGPR or better went on to ASCT, while those with a partial response were randomized to either a second induction with cyclophosphamide, bortezomib, and dexamethasone (CVD) or no CVD, and then proceeded to transplant. Patients with stable disease or disease progression in either of these arms went on to CVD prior to ASCT.
In the KCRD arm, all patients went from induction to transplant. Following ASCT, patients were randomized to either observation or lenalidomide maintenance.
A higher proportion of patients assigned to KCRD completed the minimum of four induction cycles, and few patients in any trial arm had to stop induction therapy because of adverse events. Dose modifications were required in 63.9% of patients on KCRD, 56.3% of patients on CRD, and 82.2% of patients on CTD.
There was no significant cardiac signal seen in the study, and no difference in the incidence of venous thromboembolic events among the treatment arms.
As noted before, rates of VGPR or better after initial induction were highest in the KCRD arm, at 79.5%, compared with 60% for CRD, and 52.8% for CTD.
“The KCRD quadruplet achieved the highest speed and depth of response,” Dr. Pawlyn said.
The pattern of responses was similar across all cytogenetic risk groups, she added.
A higher proportion of patients treated with KCRD went on to ASCT, and the pattern of deeper responses among patients who underwent induction with KCRD persisted, with 92.1% of patients having a post-transplant VGPR or better, compared with 81.8% for CRD and 77.0% for CTD (statistical significance not shown).
Again, the pattern of responses post-transplant was similar across cytogenetic risk groups.
The investigators anticipate receiving PFS results from the Myeloma XI study in the third or fourth quarter of 2017.
The study was sponsored by the University of Leeds (England), with support from the U.K. National Cancer Research Institute, Cancer Research UK, and Myeloma UK, and collaboration with Celgene, Merck Sharp & Dohme, and Amgen. Dr. Pawlyn disclosed travel support from Celgene and Janssen, and honoraria from Celgene and Takeda.
MADRID – A four-drug induction regimen induced quicker and deeper remissions than sequential triplet regimens in patients with newly diagnosed multiple myeloma.
In addition, fast, deep remissions may lead to improved progression-free survival (PFS) following autologous stem cell transplantation (ASCT), said investigators from a U.K. Medical Research Council study.
In the phase 3 randomized, parallel group Myeloma XI study, very good partial responses (VGPR) or better were seen following induction in 79.5% of patients assigned to the quadruplet (KCRD) of carfilzomib (Kyprolis), cyclophosphamide, lenalidomide (Revlimid), and dexamethasone, compared with 60.8% for those assigned to cyclophosphamide, lenalidomide, and dexamethasone (CRD) and 52.8% for those assigned to cyclophosphamide, thalidomide, and dexamethasone (CTD), said Charlotte Pawlyn, MD, PhD, at the annual congress of the European Hematology Association.
“In our study, we see a very much deeper response after initial induction with the quadruplet regimen, compared with triplet regimens,” Dr. Pawlyn of the Institute of Cancer Research, London, said in an interview.
Medical Research Council investigators showed in the Myeloma IX study that among patients who had a less than VGPR to an immunomodulator-based triplet regimen such as CRD, a triplet regimen including the proteasome inhibitor bortezomib (Velcade) could improve both pre- and post-transplant response rates, and that the improved responses translated into improved PFS.
For the Myeloma XI study, the investigators employed the same response-adapted approach to compare outcomes following induction with the proteasome inhibitor–containing KCRD regimen and the lenalidomide- or thalidomide-based regimens.
They chose carfilzomib as the proteasome-inhibitor backbone of the quadruplet because of its selective, irreversible target binding, lower incidence of peripheral neuropathy (compared with bortezomib), and efficacy in both the frontline and relapsed/refractory setting, she said.
Asked why the comparator regimens did not contain a proteasome inhibitor, Dr. Pawlyn said that while the current standard for induction therapy in the United Kingdom is bortezomib, thalidomide, and dexamethasone, CTD was the standard of care at the time of study planning and initial enrollment.
The trial was open to all patients in the United Kingdom of all ages with newly diagnosed symptomatic multiple myeloma, with pathways for both transplant-eligible and transplant-ineligible patients. The only main exclusion criteria were for patients with dialysis-dependent renal failure and for those who had a prior or concurrent malignancy.
A total of 1,021 patients were assigned to each of the CTD and CRD cohorts, and 526 patients were assigned to the KCRD cohort. The cohorts were well balanced by sex, age, World Health Organization performance score, and other parameters.
Patients randomized to either CTD or CRD were assessed for response after a minimum of four induction cycles, with treatment continued until best response. Those with a VGPR or better went on to ASCT, while those with a partial response were randomized to either a second induction with cyclophosphamide, bortezomib, and dexamethasone (CVD) or no CVD, and then proceeded to transplant. Patients with stable disease or disease progression in either of these arms went on to CVD prior to ASCT.
In the KCRD arm, all patients went from induction to transplant. Following ASCT, patients were randomized to either observation or lenalidomide maintenance.
A higher proportion of patients assigned to KCRD completed the minimum of four induction cycles, and few patients in any trial arm had to stop induction therapy because of adverse events. Dose modifications were required in 63.9% of patients on KCRD, 56.3% of patients on CRD, and 82.2% of patients on CTD.
There was no significant cardiac signal seen in the study, and no difference in the incidence of venous thromboembolic events among the treatment arms.
As noted before, rates of VGPR or better after initial induction were highest in the KCRD arm, at 79.5%, compared with 60% for CRD, and 52.8% for CTD.
“The KCRD quadruplet achieved the highest speed and depth of response,” Dr. Pawlyn said.
The pattern of responses was similar across all cytogenetic risk groups, she added.
A higher proportion of patients treated with KCRD went on to ASCT, and the pattern of deeper responses among patients who underwent induction with KCRD persisted, with 92.1% of patients having a post-transplant VGPR or better, compared with 81.8% for CRD and 77.0% for CTD (statistical significance not shown).
Again, the pattern of responses post-transplant was similar across cytogenetic risk groups.
The investigators anticipate receiving PFS results from the Myeloma XI study in the third or fourth quarter of 2017.
The study was sponsored by the University of Leeds (England), with support from the U.K. National Cancer Research Institute, Cancer Research UK, and Myeloma UK, and collaboration with Celgene, Merck Sharp & Dohme, and Amgen. Dr. Pawlyn disclosed travel support from Celgene and Janssen, and honoraria from Celgene and Takeda.
MADRID – A four-drug induction regimen induced quicker and deeper remissions than sequential triplet regimens in patients with newly diagnosed multiple myeloma.
In addition, fast, deep remissions may lead to improved progression-free survival (PFS) following autologous stem cell transplantation (ASCT), said investigators from a U.K. Medical Research Council study.
In the phase 3 randomized, parallel group Myeloma XI study, very good partial responses (VGPR) or better were seen following induction in 79.5% of patients assigned to the quadruplet (KCRD) of carfilzomib (Kyprolis), cyclophosphamide, lenalidomide (Revlimid), and dexamethasone, compared with 60.8% for those assigned to cyclophosphamide, lenalidomide, and dexamethasone (CRD) and 52.8% for those assigned to cyclophosphamide, thalidomide, and dexamethasone (CTD), said Charlotte Pawlyn, MD, PhD, at the annual congress of the European Hematology Association.
“In our study, we see a very much deeper response after initial induction with the quadruplet regimen, compared with triplet regimens,” Dr. Pawlyn of the Institute of Cancer Research, London, said in an interview.
Medical Research Council investigators showed in the Myeloma IX study that among patients who had a less than VGPR to an immunomodulator-based triplet regimen such as CRD, a triplet regimen including the proteasome inhibitor bortezomib (Velcade) could improve both pre- and post-transplant response rates, and that the improved responses translated into improved PFS.
For the Myeloma XI study, the investigators employed the same response-adapted approach to compare outcomes following induction with the proteasome inhibitor–containing KCRD regimen and the lenalidomide- or thalidomide-based regimens.
They chose carfilzomib as the proteasome-inhibitor backbone of the quadruplet because of its selective, irreversible target binding, lower incidence of peripheral neuropathy (compared with bortezomib), and efficacy in both the frontline and relapsed/refractory setting, she said.
Asked why the comparator regimens did not contain a proteasome inhibitor, Dr. Pawlyn said that while the current standard for induction therapy in the United Kingdom is bortezomib, thalidomide, and dexamethasone, CTD was the standard of care at the time of study planning and initial enrollment.
The trial was open to all patients in the United Kingdom of all ages with newly diagnosed symptomatic multiple myeloma, with pathways for both transplant-eligible and transplant-ineligible patients. The only main exclusion criteria were for patients with dialysis-dependent renal failure and for those who had a prior or concurrent malignancy.
A total of 1,021 patients were assigned to each of the CTD and CRD cohorts, and 526 patients were assigned to the KCRD cohort. The cohorts were well balanced by sex, age, World Health Organization performance score, and other parameters.
Patients randomized to either CTD or CRD were assessed for response after a minimum of four induction cycles, with treatment continued until best response. Those with a VGPR or better went on to ASCT, while those with a partial response were randomized to either a second induction with cyclophosphamide, bortezomib, and dexamethasone (CVD) or no CVD, and then proceeded to transplant. Patients with stable disease or disease progression in either of these arms went on to CVD prior to ASCT.
In the KCRD arm, all patients went from induction to transplant. Following ASCT, patients were randomized to either observation or lenalidomide maintenance.
A higher proportion of patients assigned to KCRD completed the minimum of four induction cycles, and few patients in any trial arm had to stop induction therapy because of adverse events. Dose modifications were required in 63.9% of patients on KCRD, 56.3% of patients on CRD, and 82.2% of patients on CTD.
There was no significant cardiac signal seen in the study, and no difference in the incidence of venous thromboembolic events among the treatment arms.
As noted before, rates of VGPR or better after initial induction were highest in the KCRD arm, at 79.5%, compared with 60% for CRD, and 52.8% for CTD.
“The KCRD quadruplet achieved the highest speed and depth of response,” Dr. Pawlyn said.
The pattern of responses was similar across all cytogenetic risk groups, she added.
A higher proportion of patients treated with KCRD went on to ASCT, and the pattern of deeper responses among patients who underwent induction with KCRD persisted, with 92.1% of patients having a post-transplant VGPR or better, compared with 81.8% for CRD and 77.0% for CTD (statistical significance not shown).
Again, the pattern of responses post-transplant was similar across cytogenetic risk groups.
The investigators anticipate receiving PFS results from the Myeloma XI study in the third or fourth quarter of 2017.
The study was sponsored by the University of Leeds (England), with support from the U.K. National Cancer Research Institute, Cancer Research UK, and Myeloma UK, and collaboration with Celgene, Merck Sharp & Dohme, and Amgen. Dr. Pawlyn disclosed travel support from Celgene and Janssen, and honoraria from Celgene and Takeda.
AT THE EHA CONGRESS
Key clinical point:
Major finding: An induction quadruplet containing carfilzomib induced a higher rate of very good partial responses or better vs. regimens without a proteasome inhibitor.
Data source: A randomized, open-label, parallel group study of 2,568 patients with newly diagnosed multiple myeloma.
Disclosures: The study was sponsored by the University of Leeds (England), with support from the U.K. National Cancer Research Institute, Cancer Research UK, and Myeloma UK, and collaboration with Celgene, Merck Sharp & Dohme, and Amgen. Dr. Pawlyn disclosed travel support from Celgene and Janssen, and honoraria from Celgene and Takeda.
The Prognostic Value of Circulating Plasma Cells in Multiple Myeloma
Some studies have suggested that circulating plasma cells (CPCs) might have prognostic value in multiple myeloma (MM), but the findings remain controversial, say researchers from Zhengzhou University in the People’s Republic of China. However, the development of highly sensitive and specific diagnostic methods, such as polymerase chain reaction (PCR) and flow cytometry (FCM), the researchers say, make it possible to explore whether CPCs can serve as a biomarker in MM. To that end, they conducted the first meta-analysis to provide better insight into the prognostic value of CPCs in MM.
The researchers examined findings from 11 studies involving 2,943 patients in 5 countries. Peripheral blood samples were analyzed using FCM, PCR, slide-based immunofluorescence assay (IF), and conventional morphology (CM).
Circulating plasma cell status reflected aggressive disease more than tumor burden, the researchers say. Patients in the CPC-positive groups had more aggressive disease and a worse overall survival (OS) rate compared with patients in the CPC-negative groups. The presence of CPCs was “strikingly” associated with elevated the International Staging System score but not the Durie-Salm staging system (DS) score. This difference may be associated, the researchers suggest, with the fact that the DS stage predominantly reflects tumor burden, which is significantly reduced now by newer therapies.
In subgroup analyses, the patients in the FCM and CM groups had worse prognosis for both disease progression and OS. The PCR subgroup showed prognostic significance for disease progression but not OS, and the IF subgroup for OS but not disease progression.
One question the researchers were also interested in answering was whether it mattered when the sample was taken. However, pooled hazard ratios for OS and disease progression were “fairly stable,” they say, and not influenced by sampling time. Regardless of whether CPCs are detected in an early stage or in relapse patients, the researchers add, CPC status may serve as a useful tool to guide treatment and prognosis.
Source:
Li J, Wang N, Tesfaluul N, Gao X, Liu S, Yue B. PLoS One. 2017;12(7):e0181447.
doi: 10.1371/journal.pone.0181447.
Some studies have suggested that circulating plasma cells (CPCs) might have prognostic value in multiple myeloma (MM), but the findings remain controversial, say researchers from Zhengzhou University in the People’s Republic of China. However, the development of highly sensitive and specific diagnostic methods, such as polymerase chain reaction (PCR) and flow cytometry (FCM), the researchers say, make it possible to explore whether CPCs can serve as a biomarker in MM. To that end, they conducted the first meta-analysis to provide better insight into the prognostic value of CPCs in MM.
The researchers examined findings from 11 studies involving 2,943 patients in 5 countries. Peripheral blood samples were analyzed using FCM, PCR, slide-based immunofluorescence assay (IF), and conventional morphology (CM).
Circulating plasma cell status reflected aggressive disease more than tumor burden, the researchers say. Patients in the CPC-positive groups had more aggressive disease and a worse overall survival (OS) rate compared with patients in the CPC-negative groups. The presence of CPCs was “strikingly” associated with elevated the International Staging System score but not the Durie-Salm staging system (DS) score. This difference may be associated, the researchers suggest, with the fact that the DS stage predominantly reflects tumor burden, which is significantly reduced now by newer therapies.
In subgroup analyses, the patients in the FCM and CM groups had worse prognosis for both disease progression and OS. The PCR subgroup showed prognostic significance for disease progression but not OS, and the IF subgroup for OS but not disease progression.
One question the researchers were also interested in answering was whether it mattered when the sample was taken. However, pooled hazard ratios for OS and disease progression were “fairly stable,” they say, and not influenced by sampling time. Regardless of whether CPCs are detected in an early stage or in relapse patients, the researchers add, CPC status may serve as a useful tool to guide treatment and prognosis.
Source:
Li J, Wang N, Tesfaluul N, Gao X, Liu S, Yue B. PLoS One. 2017;12(7):e0181447.
doi: 10.1371/journal.pone.0181447.
Some studies have suggested that circulating plasma cells (CPCs) might have prognostic value in multiple myeloma (MM), but the findings remain controversial, say researchers from Zhengzhou University in the People’s Republic of China. However, the development of highly sensitive and specific diagnostic methods, such as polymerase chain reaction (PCR) and flow cytometry (FCM), the researchers say, make it possible to explore whether CPCs can serve as a biomarker in MM. To that end, they conducted the first meta-analysis to provide better insight into the prognostic value of CPCs in MM.
The researchers examined findings from 11 studies involving 2,943 patients in 5 countries. Peripheral blood samples were analyzed using FCM, PCR, slide-based immunofluorescence assay (IF), and conventional morphology (CM).
Circulating plasma cell status reflected aggressive disease more than tumor burden, the researchers say. Patients in the CPC-positive groups had more aggressive disease and a worse overall survival (OS) rate compared with patients in the CPC-negative groups. The presence of CPCs was “strikingly” associated with elevated the International Staging System score but not the Durie-Salm staging system (DS) score. This difference may be associated, the researchers suggest, with the fact that the DS stage predominantly reflects tumor burden, which is significantly reduced now by newer therapies.
In subgroup analyses, the patients in the FCM and CM groups had worse prognosis for both disease progression and OS. The PCR subgroup showed prognostic significance for disease progression but not OS, and the IF subgroup for OS but not disease progression.
One question the researchers were also interested in answering was whether it mattered when the sample was taken. However, pooled hazard ratios for OS and disease progression were “fairly stable,” they say, and not influenced by sampling time. Regardless of whether CPCs are detected in an early stage or in relapse patients, the researchers add, CPC status may serve as a useful tool to guide treatment and prognosis.
Source:
Li J, Wang N, Tesfaluul N, Gao X, Liu S, Yue B. PLoS One. 2017;12(7):e0181447.
doi: 10.1371/journal.pone.0181447.