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Study supports palliative care in HSCT recipients
Photo by Chad McNeeley
Palliative care can be beneficial for patients undergoing hematopoietic stem cell transplant (HSCT) to treat hematologic malignancies, according to research published in JAMA.
The single-center study suggested that palliative care can improve HSCT recipients’ quality of life, relieve symptoms associated with the procedure, and reduce depression and anxiety.
Researchers observed such benefits during hospitalization for HSCT and a few months later.
In addition, caregivers of patients receiving palliative care experienced less depression and were better at coping with the stress associated with the illness of their loved one.
“Palliative care clinicians are increasingly asked to help care for patients with solid tumors but are rarely consulted for patients with hematologic malignancies, especially those receiving therapy designed to cure their disease,” said study author Areej El-Jawahri, MD, of Massachusette General Hospital in Boston.
“The physical and psychological symptoms associated with HSCT are sometimes regarded as expected and unavoidable, which, combined with the persistent misperception that equates palliative care with end-of-life care, has contributed to a lack of involvement of palliative care clinicians in the care of these patients.”
Intervention
Dr El-Jawahri and her colleagues studied 160 patients who underwent autologous or allogeneic HSCT to treat a variety of hematologic malignancies from August 2014 into January 2016.
Participants were randomized to receive either standard care (n=79) or the palliative care intervention (n=81).
Within 3 days of their admission to the hospital, patients in the intervention group had an initial meeting with a palliative care clinician—a physician or advance practice nurse—who continued to meet with them at least twice a week during their hospitalization.
At the meetings, which could be attended by a family member or friend of the patient, clinicians first focused on establishing a rapport with patients and their caregivers.
Clinicians addressed ways of managing the physical and psychological symptoms patients were experiencing and provided support and strategies for coping with distress. Patients received an average of 8 palliative care visits during their hospitalizations, which lasted on average 20 days.
At the outset of the study and 2 weeks into the process, a time when symptoms tend to be at their worst, patients in both groups and participating caregivers completed questionnaires assessing their mood and quality of life.
Patients also completed questionnaires asking about symptoms of their illness and those associated with the procedure. Patients completed additional assessments 3 months after HSCT as well.
Results
The study’s primary endpoint was change in quality of life from baseline to week 2. Patients receiving the palliative care intervention had significantly better quality of life scores at week 2 than patients in the control group.
Also at the 2-week mark, patients receiving the palliative care intervention reported lower levels of depression, anxiety, and symptoms than the control group, but there was no significant difference between the groups with regard to fatigue.
At 3 months, patients receiving the palliative care intervention still had higher quality of life scores and less depression than controls, but there were no significant between-group differences in anxiety, fatigue, or symptom burden.
Caregivers attended 42% of the palliative care sessions. At the 2-week assessment, caregivers in the intervention group were found to have fewer depressive symptoms and improved coping skills, compared with caregivers in the control group.
“Caregivers play a crucial role in supporting patients during the transplant process, and they are substantially impacted as they watch their loved ones struggle with side effects that can be emotionally challenging,” Dr El-Jawahri said.
She and her colleagues noted that additional, larger studies are needed to assess caregiver impacts more completely, to replicate patient results at centers with more diverse patient populations, to assess the inclusion of more complete palliative care teams, to collect cost data, and to adapt the palliative care intervention to assist patients receiving other potentially curative treatment for hematologic or other cancers. 
Photo by Chad McNeeley
Palliative care can be beneficial for patients undergoing hematopoietic stem cell transplant (HSCT) to treat hematologic malignancies, according to research published in JAMA.
The single-center study suggested that palliative care can improve HSCT recipients’ quality of life, relieve symptoms associated with the procedure, and reduce depression and anxiety.
Researchers observed such benefits during hospitalization for HSCT and a few months later.
In addition, caregivers of patients receiving palliative care experienced less depression and were better at coping with the stress associated with the illness of their loved one.
“Palliative care clinicians are increasingly asked to help care for patients with solid tumors but are rarely consulted for patients with hematologic malignancies, especially those receiving therapy designed to cure their disease,” said study author Areej El-Jawahri, MD, of Massachusette General Hospital in Boston.
“The physical and psychological symptoms associated with HSCT are sometimes regarded as expected and unavoidable, which, combined with the persistent misperception that equates palliative care with end-of-life care, has contributed to a lack of involvement of palliative care clinicians in the care of these patients.”
Intervention
Dr El-Jawahri and her colleagues studied 160 patients who underwent autologous or allogeneic HSCT to treat a variety of hematologic malignancies from August 2014 into January 2016.
Participants were randomized to receive either standard care (n=79) or the palliative care intervention (n=81).
Within 3 days of their admission to the hospital, patients in the intervention group had an initial meeting with a palliative care clinician—a physician or advance practice nurse—who continued to meet with them at least twice a week during their hospitalization.
At the meetings, which could be attended by a family member or friend of the patient, clinicians first focused on establishing a rapport with patients and their caregivers.
Clinicians addressed ways of managing the physical and psychological symptoms patients were experiencing and provided support and strategies for coping with distress. Patients received an average of 8 palliative care visits during their hospitalizations, which lasted on average 20 days.
At the outset of the study and 2 weeks into the process, a time when symptoms tend to be at their worst, patients in both groups and participating caregivers completed questionnaires assessing their mood and quality of life.
Patients also completed questionnaires asking about symptoms of their illness and those associated with the procedure. Patients completed additional assessments 3 months after HSCT as well.
Results
The study’s primary endpoint was change in quality of life from baseline to week 2. Patients receiving the palliative care intervention had significantly better quality of life scores at week 2 than patients in the control group.
Also at the 2-week mark, patients receiving the palliative care intervention reported lower levels of depression, anxiety, and symptoms than the control group, but there was no significant difference between the groups with regard to fatigue.
At 3 months, patients receiving the palliative care intervention still had higher quality of life scores and less depression than controls, but there were no significant between-group differences in anxiety, fatigue, or symptom burden.
Caregivers attended 42% of the palliative care sessions. At the 2-week assessment, caregivers in the intervention group were found to have fewer depressive symptoms and improved coping skills, compared with caregivers in the control group.
“Caregivers play a crucial role in supporting patients during the transplant process, and they are substantially impacted as they watch their loved ones struggle with side effects that can be emotionally challenging,” Dr El-Jawahri said.
She and her colleagues noted that additional, larger studies are needed to assess caregiver impacts more completely, to replicate patient results at centers with more diverse patient populations, to assess the inclusion of more complete palliative care teams, to collect cost data, and to adapt the palliative care intervention to assist patients receiving other potentially curative treatment for hematologic or other cancers.
Photo by Chad McNeeley
Palliative care can be beneficial for patients undergoing hematopoietic stem cell transplant (HSCT) to treat hematologic malignancies, according to research published in JAMA.
The single-center study suggested that palliative care can improve HSCT recipients’ quality of life, relieve symptoms associated with the procedure, and reduce depression and anxiety.
Researchers observed such benefits during hospitalization for HSCT and a few months later.
In addition, caregivers of patients receiving palliative care experienced less depression and were better at coping with the stress associated with the illness of their loved one.
“Palliative care clinicians are increasingly asked to help care for patients with solid tumors but are rarely consulted for patients with hematologic malignancies, especially those receiving therapy designed to cure their disease,” said study author Areej El-Jawahri, MD, of Massachusette General Hospital in Boston.
“The physical and psychological symptoms associated with HSCT are sometimes regarded as expected and unavoidable, which, combined with the persistent misperception that equates palliative care with end-of-life care, has contributed to a lack of involvement of palliative care clinicians in the care of these patients.”
Intervention
Dr El-Jawahri and her colleagues studied 160 patients who underwent autologous or allogeneic HSCT to treat a variety of hematologic malignancies from August 2014 into January 2016.
Participants were randomized to receive either standard care (n=79) or the palliative care intervention (n=81).
Within 3 days of their admission to the hospital, patients in the intervention group had an initial meeting with a palliative care clinician—a physician or advance practice nurse—who continued to meet with them at least twice a week during their hospitalization.
At the meetings, which could be attended by a family member or friend of the patient, clinicians first focused on establishing a rapport with patients and their caregivers.
Clinicians addressed ways of managing the physical and psychological symptoms patients were experiencing and provided support and strategies for coping with distress. Patients received an average of 8 palliative care visits during their hospitalizations, which lasted on average 20 days.
At the outset of the study and 2 weeks into the process, a time when symptoms tend to be at their worst, patients in both groups and participating caregivers completed questionnaires assessing their mood and quality of life.
Patients also completed questionnaires asking about symptoms of their illness and those associated with the procedure. Patients completed additional assessments 3 months after HSCT as well.
Results
The study’s primary endpoint was change in quality of life from baseline to week 2. Patients receiving the palliative care intervention had significantly better quality of life scores at week 2 than patients in the control group.
Also at the 2-week mark, patients receiving the palliative care intervention reported lower levels of depression, anxiety, and symptoms than the control group, but there was no significant difference between the groups with regard to fatigue.
At 3 months, patients receiving the palliative care intervention still had higher quality of life scores and less depression than controls, but there were no significant between-group differences in anxiety, fatigue, or symptom burden.
Caregivers attended 42% of the palliative care sessions. At the 2-week assessment, caregivers in the intervention group were found to have fewer depressive symptoms and improved coping skills, compared with caregivers in the control group.
“Caregivers play a crucial role in supporting patients during the transplant process, and they are substantially impacted as they watch their loved ones struggle with side effects that can be emotionally challenging,” Dr El-Jawahri said.
She and her colleagues noted that additional, larger studies are needed to assess caregiver impacts more completely, to replicate patient results at centers with more diverse patient populations, to assess the inclusion of more complete palliative care teams, to collect cost data, and to adapt the palliative care intervention to assist patients receiving other potentially curative treatment for hematologic or other cancers.
EC approves nivolumab for relapsed/refractory cHL
Photo from Business Wire
The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with relapsed or refractory classical Hodgkin lymphoma (cHL) who have already received an autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV).
Nivolumab is the first PD-1 inhibitor approved in the European Economic Area as a treatment for a hematologic malignancy.
The EC previously approved nivolumab to treat advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. In Europe, nivolumab is marketed by Bristol-Myers Squibb.
Trials in cHL
The EC’s approval of nivolumab in cHL is based on an integrated analysis of data from 2 trials—the phase 1 CheckMate -039 trial and the phase 2 CheckMate -205 trial.
In CheckMate -039, researchers evaluated nivolumab in patients with cHL, non-Hodgkin lymphoma, and multiple myeloma. Results from this trial were presented at the 13th International Congress on Malignant Lymphoma in June 2015.
In CheckMate -205, researchers are evaluating nivolumab in 4 cohorts of cHL patients. Cohort A includes patients who previously received auto-HSCT and were BV-naïve at enrollment (n=63). Cohort B includes patients who previously received auto-HSCT followed by BV (n=80).
Cohort C includes patients who previously received BV before and/or after auto-HSCT (n=100). And cohort D, which is currently enrolling, is an evaluation of nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).
Results from cohort B were presented at the 21st Congress of the European Hematology Association in June 2016. Results from cohort C were presented at the 10th International Symposium on Hodgkin Lymphoma last month.
Integrated analysis
The analysis included cHL patients from CheckMate -205 and -039 who had received auto-HSCT and BV.
In the efficacy population (n=95), the objective response rate was 66%. The percentage of patients with a complete response was 6%. Twenty-three percent of patients had stable disease.
The median time to response was 2.0 months (range, 0.7-11.1), and the median duration of response was 13.1 months (range, 0.0+, 23.1+). At 12 months, the progression-free survival rate was 57%.
The safety of nivolumab in cHL was evaluated in 263 patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Serious adverse events (AEs) occurred in 21% of these patients.
The most common serious AEs (reported in at least 1% of patients) were infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.
The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).
Twenty-three percent of patients had a dose delay resulting from an AE, and 4.2% of patients discontinued treatment due to AEs.
Forty patients went on to allogeneic HSCT after nivolumab, and 6 of these patients died from complications of the transplant. The 40 patients had a median follow-up from allogeneic HSCT of 2.9 months (range, 0-22).
Because of these deaths, the US Food and Drug Administration asked Bristol-Myers Squibb to study the safety of allogeneic HSCT after nivolumab.
Photo from Business Wire
The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with relapsed or refractory classical Hodgkin lymphoma (cHL) who have already received an autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV).
Nivolumab is the first PD-1 inhibitor approved in the European Economic Area as a treatment for a hematologic malignancy.
The EC previously approved nivolumab to treat advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. In Europe, nivolumab is marketed by Bristol-Myers Squibb.
Trials in cHL
The EC’s approval of nivolumab in cHL is based on an integrated analysis of data from 2 trials—the phase 1 CheckMate -039 trial and the phase 2 CheckMate -205 trial.
In CheckMate -039, researchers evaluated nivolumab in patients with cHL, non-Hodgkin lymphoma, and multiple myeloma. Results from this trial were presented at the 13th International Congress on Malignant Lymphoma in June 2015.
In CheckMate -205, researchers are evaluating nivolumab in 4 cohorts of cHL patients. Cohort A includes patients who previously received auto-HSCT and were BV-naïve at enrollment (n=63). Cohort B includes patients who previously received auto-HSCT followed by BV (n=80).
Cohort C includes patients who previously received BV before and/or after auto-HSCT (n=100). And cohort D, which is currently enrolling, is an evaluation of nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).
Results from cohort B were presented at the 21st Congress of the European Hematology Association in June 2016. Results from cohort C were presented at the 10th International Symposium on Hodgkin Lymphoma last month.
Integrated analysis
The analysis included cHL patients from CheckMate -205 and -039 who had received auto-HSCT and BV.
In the efficacy population (n=95), the objective response rate was 66%. The percentage of patients with a complete response was 6%. Twenty-three percent of patients had stable disease.
The median time to response was 2.0 months (range, 0.7-11.1), and the median duration of response was 13.1 months (range, 0.0+, 23.1+). At 12 months, the progression-free survival rate was 57%.
The safety of nivolumab in cHL was evaluated in 263 patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Serious adverse events (AEs) occurred in 21% of these patients.
The most common serious AEs (reported in at least 1% of patients) were infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.
The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).
Twenty-three percent of patients had a dose delay resulting from an AE, and 4.2% of patients discontinued treatment due to AEs.
Forty patients went on to allogeneic HSCT after nivolumab, and 6 of these patients died from complications of the transplant. The 40 patients had a median follow-up from allogeneic HSCT of 2.9 months (range, 0-22).
Because of these deaths, the US Food and Drug Administration asked Bristol-Myers Squibb to study the safety of allogeneic HSCT after nivolumab.
Photo from Business Wire
The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with relapsed or refractory classical Hodgkin lymphoma (cHL) who have already received an autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV).
Nivolumab is the first PD-1 inhibitor approved in the European Economic Area as a treatment for a hematologic malignancy.
The EC previously approved nivolumab to treat advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. In Europe, nivolumab is marketed by Bristol-Myers Squibb.
Trials in cHL
The EC’s approval of nivolumab in cHL is based on an integrated analysis of data from 2 trials—the phase 1 CheckMate -039 trial and the phase 2 CheckMate -205 trial.
In CheckMate -039, researchers evaluated nivolumab in patients with cHL, non-Hodgkin lymphoma, and multiple myeloma. Results from this trial were presented at the 13th International Congress on Malignant Lymphoma in June 2015.
In CheckMate -205, researchers are evaluating nivolumab in 4 cohorts of cHL patients. Cohort A includes patients who previously received auto-HSCT and were BV-naïve at enrollment (n=63). Cohort B includes patients who previously received auto-HSCT followed by BV (n=80).
Cohort C includes patients who previously received BV before and/or after auto-HSCT (n=100). And cohort D, which is currently enrolling, is an evaluation of nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).
Results from cohort B were presented at the 21st Congress of the European Hematology Association in June 2016. Results from cohort C were presented at the 10th International Symposium on Hodgkin Lymphoma last month.
Integrated analysis
The analysis included cHL patients from CheckMate -205 and -039 who had received auto-HSCT and BV.
In the efficacy population (n=95), the objective response rate was 66%. The percentage of patients with a complete response was 6%. Twenty-three percent of patients had stable disease.
The median time to response was 2.0 months (range, 0.7-11.1), and the median duration of response was 13.1 months (range, 0.0+, 23.1+). At 12 months, the progression-free survival rate was 57%.
The safety of nivolumab in cHL was evaluated in 263 patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Serious adverse events (AEs) occurred in 21% of these patients.
The most common serious AEs (reported in at least 1% of patients) were infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.
The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).
Twenty-three percent of patients had a dose delay resulting from an AE, and 4.2% of patients discontinued treatment due to AEs.
Forty patients went on to allogeneic HSCT after nivolumab, and 6 of these patients died from complications of the transplant. The 40 patients had a median follow-up from allogeneic HSCT of 2.9 months (range, 0-22).
Because of these deaths, the US Food and Drug Administration asked Bristol-Myers Squibb to study the safety of allogeneic HSCT after nivolumab.
Statins increase bleeding risk with dabigatran
Photo courtesy of
St. Michael’s Hospital
Two commonly used statins, lovastatin and simvastatin, can increase the risk of major hemorrhage in patients receiving the anticoagulant dabigatran etexilate, according to research published in the Canadian Medical Association Journal.
“We found no difference in the risk of stroke in patients receiving dabigatran who were prescribed lovastatin or simvastatin versus other statins,” said study author Tony Antoniou, PhD, of St. Michael’s Hospital in Toronto, Ontario, Canada.
“However, an increase in the risk of bleeding requiring hospital admission or emergency department visits was seen with lovastatin and simvastatin compared with the other statins.”
Dr Antoniou and his colleagues made these discoveries by conducting 2 population-based, nested case-control studies.
The studies included patients older than 65 years of age who started treatment with dabigatran etexilate between 2012 and 2014. All patients had nonvalvular atrial fibrillation and were receiving dabigatran etexilate for the prevention of stroke and systemic embolism.
In the first study, the cases were patients with ischemic stroke. In the second study, the cases were patients with major hemorrhage. Each case had up to 4 age- and sex-matched controls.
Both cases and controls received a statin. And the researchers set out to determine the association between each outcome and the use of simvastatin or lovastatin compared to other statins.
In the 45,991 patients studied, there were 397 cases of ischemic stroke and 1117 cases of major hemorrhage.
Multivariable analysis suggested that use of simvastatin or lovastatin was not associated with an increased risk of stroke or transient ischemic attack
relative to other statins. The adjusted odds ratio was 1.33.
However, the use of simvastatin and lovastatin was associated with an increased risk of major hemorrhage. The adjusted odds ratio was 1.46.
Dr Antoniou and his colleagues believe simvastatin and lovastatin increase the risk of bleeding by increasing the amount of dabigatran absorbed by the body.
The team noted that dabigatran etexilate is metabolized to dabigatran by carboxylesterase enzymes, intestinal absorption of the prodrug is opposed by P-glycoprotein, and simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase.
The researchers said the fact that the statins inhibit P-glycoprotein appears to explain the increased risk of bleeding they observed. And the fact that simvastatin and lovastatin were not associated with an increased risk of stroke suggests carboxylesterase inhibition is of little clinical relevance in this setting.
On the other hand, the researchers also noted that the number of cases receiving lovastatin and simvastatin was small. This may have influenced the team’s power to detect an association between these drugs and stroke.
Regardless, the researchers said the results of these studies suggest there is a clinically important drug interaction between dabigatran etexilate and both simvastatin and lovastatin. Therefore, other statins should be considered in patients receiving dabigatran etexilate.
Photo courtesy of
St. Michael’s Hospital
Two commonly used statins, lovastatin and simvastatin, can increase the risk of major hemorrhage in patients receiving the anticoagulant dabigatran etexilate, according to research published in the Canadian Medical Association Journal.
“We found no difference in the risk of stroke in patients receiving dabigatran who were prescribed lovastatin or simvastatin versus other statins,” said study author Tony Antoniou, PhD, of St. Michael’s Hospital in Toronto, Ontario, Canada.
“However, an increase in the risk of bleeding requiring hospital admission or emergency department visits was seen with lovastatin and simvastatin compared with the other statins.”
Dr Antoniou and his colleagues made these discoveries by conducting 2 population-based, nested case-control studies.
The studies included patients older than 65 years of age who started treatment with dabigatran etexilate between 2012 and 2014. All patients had nonvalvular atrial fibrillation and were receiving dabigatran etexilate for the prevention of stroke and systemic embolism.
In the first study, the cases were patients with ischemic stroke. In the second study, the cases were patients with major hemorrhage. Each case had up to 4 age- and sex-matched controls.
Both cases and controls received a statin. And the researchers set out to determine the association between each outcome and the use of simvastatin or lovastatin compared to other statins.
In the 45,991 patients studied, there were 397 cases of ischemic stroke and 1117 cases of major hemorrhage.
Multivariable analysis suggested that use of simvastatin or lovastatin was not associated with an increased risk of stroke or transient ischemic attack
relative to other statins. The adjusted odds ratio was 1.33.
However, the use of simvastatin and lovastatin was associated with an increased risk of major hemorrhage. The adjusted odds ratio was 1.46.
Dr Antoniou and his colleagues believe simvastatin and lovastatin increase the risk of bleeding by increasing the amount of dabigatran absorbed by the body.
The team noted that dabigatran etexilate is metabolized to dabigatran by carboxylesterase enzymes, intestinal absorption of the prodrug is opposed by P-glycoprotein, and simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase.
The researchers said the fact that the statins inhibit P-glycoprotein appears to explain the increased risk of bleeding they observed. And the fact that simvastatin and lovastatin were not associated with an increased risk of stroke suggests carboxylesterase inhibition is of little clinical relevance in this setting.
On the other hand, the researchers also noted that the number of cases receiving lovastatin and simvastatin was small. This may have influenced the team’s power to detect an association between these drugs and stroke.
Regardless, the researchers said the results of these studies suggest there is a clinically important drug interaction between dabigatran etexilate and both simvastatin and lovastatin. Therefore, other statins should be considered in patients receiving dabigatran etexilate.
Photo courtesy of
St. Michael’s Hospital
Two commonly used statins, lovastatin and simvastatin, can increase the risk of major hemorrhage in patients receiving the anticoagulant dabigatran etexilate, according to research published in the Canadian Medical Association Journal.
“We found no difference in the risk of stroke in patients receiving dabigatran who were prescribed lovastatin or simvastatin versus other statins,” said study author Tony Antoniou, PhD, of St. Michael’s Hospital in Toronto, Ontario, Canada.
“However, an increase in the risk of bleeding requiring hospital admission or emergency department visits was seen with lovastatin and simvastatin compared with the other statins.”
Dr Antoniou and his colleagues made these discoveries by conducting 2 population-based, nested case-control studies.
The studies included patients older than 65 years of age who started treatment with dabigatran etexilate between 2012 and 2014. All patients had nonvalvular atrial fibrillation and were receiving dabigatran etexilate for the prevention of stroke and systemic embolism.
In the first study, the cases were patients with ischemic stroke. In the second study, the cases were patients with major hemorrhage. Each case had up to 4 age- and sex-matched controls.
Both cases and controls received a statin. And the researchers set out to determine the association between each outcome and the use of simvastatin or lovastatin compared to other statins.
In the 45,991 patients studied, there were 397 cases of ischemic stroke and 1117 cases of major hemorrhage.
Multivariable analysis suggested that use of simvastatin or lovastatin was not associated with an increased risk of stroke or transient ischemic attack
relative to other statins. The adjusted odds ratio was 1.33.
However, the use of simvastatin and lovastatin was associated with an increased risk of major hemorrhage. The adjusted odds ratio was 1.46.
Dr Antoniou and his colleagues believe simvastatin and lovastatin increase the risk of bleeding by increasing the amount of dabigatran absorbed by the body.
The team noted that dabigatran etexilate is metabolized to dabigatran by carboxylesterase enzymes, intestinal absorption of the prodrug is opposed by P-glycoprotein, and simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase.
The researchers said the fact that the statins inhibit P-glycoprotein appears to explain the increased risk of bleeding they observed. And the fact that simvastatin and lovastatin were not associated with an increased risk of stroke suggests carboxylesterase inhibition is of little clinical relevance in this setting.
On the other hand, the researchers also noted that the number of cases receiving lovastatin and simvastatin was small. This may have influenced the team’s power to detect an association between these drugs and stroke.
Regardless, the researchers said the results of these studies suggest there is a clinically important drug interaction between dabigatran etexilate and both simvastatin and lovastatin. Therefore, other statins should be considered in patients receiving dabigatran etexilate.
EC expands indication for arsenic trioxide in APL
Image courtesy of the Armed
Forces Institute of Pathology
The European Commission (EC) has extended the approved indication for arsenic trioxide (Trisenox®) in patients with acute promyelocytic leukemia (APL).
The drug is now approved for use in combination with all-trans-retinoic acid (ATRA) to induce remission and for consolidation in adults with newly diagnosed low- to intermediate-risk APL (white blood cell count, ≤ 10 x 103/μL) characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene.
Arsenic trioxide was previously approved by the EC to induce remission and as consolidation in adults with relapsed/refractory APL, which is characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene, whose previous treatment included a retinoid and chemotherapy.
“This [expanded] approval by the European Commission is good news for APL patients, as we now have access to a cure for an acute leukemia without using chemotherapy,” said Francesco Lo-Coco, MD, of University of Rome Tor Vergata in Italy.
“Moreover, this decision is a very positive endorsement by the European Commission, as it was made based solely on published academic research and studies.”
Arsenic trioxide is marketed by Teva Pharmaceutical Industries Ltd.
Phase 3 study results
The EC’s expanded approval of arsenic trioxide is based on results from the APL0406 Intergroup GIMEMA-AMLSG-SAL study. Previous results from this phase 3 study were published in NEJM in 2013.
Updated results include 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.
A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).
After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).
At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).
After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.
In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.
Image courtesy of the Armed
Forces Institute of Pathology
The European Commission (EC) has extended the approved indication for arsenic trioxide (Trisenox®) in patients with acute promyelocytic leukemia (APL).
The drug is now approved for use in combination with all-trans-retinoic acid (ATRA) to induce remission and for consolidation in adults with newly diagnosed low- to intermediate-risk APL (white blood cell count, ≤ 10 x 103/μL) characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene.
Arsenic trioxide was previously approved by the EC to induce remission and as consolidation in adults with relapsed/refractory APL, which is characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene, whose previous treatment included a retinoid and chemotherapy.
“This [expanded] approval by the European Commission is good news for APL patients, as we now have access to a cure for an acute leukemia without using chemotherapy,” said Francesco Lo-Coco, MD, of University of Rome Tor Vergata in Italy.
“Moreover, this decision is a very positive endorsement by the European Commission, as it was made based solely on published academic research and studies.”
Arsenic trioxide is marketed by Teva Pharmaceutical Industries Ltd.
Phase 3 study results
The EC’s expanded approval of arsenic trioxide is based on results from the APL0406 Intergroup GIMEMA-AMLSG-SAL study. Previous results from this phase 3 study were published in NEJM in 2013.
Updated results include 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.
A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).
After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).
At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).
After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.
In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.
Image courtesy of the Armed
Forces Institute of Pathology
The European Commission (EC) has extended the approved indication for arsenic trioxide (Trisenox®) in patients with acute promyelocytic leukemia (APL).
The drug is now approved for use in combination with all-trans-retinoic acid (ATRA) to induce remission and for consolidation in adults with newly diagnosed low- to intermediate-risk APL (white blood cell count, ≤ 10 x 103/μL) characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene.
Arsenic trioxide was previously approved by the EC to induce remission and as consolidation in adults with relapsed/refractory APL, which is characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene, whose previous treatment included a retinoid and chemotherapy.
“This [expanded] approval by the European Commission is good news for APL patients, as we now have access to a cure for an acute leukemia without using chemotherapy,” said Francesco Lo-Coco, MD, of University of Rome Tor Vergata in Italy.
“Moreover, this decision is a very positive endorsement by the European Commission, as it was made based solely on published academic research and studies.”
Arsenic trioxide is marketed by Teva Pharmaceutical Industries Ltd.
Phase 3 study results
The EC’s expanded approval of arsenic trioxide is based on results from the APL0406 Intergroup GIMEMA-AMLSG-SAL study. Previous results from this phase 3 study were published in NEJM in 2013.
Updated results include 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.
A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).
After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).
At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).
After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.
In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.
FDA approves new uses for drug in MM
Photo courtesy of Janssen
The US Food and Drug Administration (FDA) has approved new indications for the monoclonal antibody daratumumab (Darzalex®).
The drug is now approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.
This approval comes 3 months after a supplemental biologics license application was submitted to the FDA.
The application was granted priority review last month, and the FDA granted daratumumab breakthrough therapy designation in July.
Daratumumab is the first CD38-directed cytolytic antibody approved anywhere in the world.
The drug received accelerated approval from the FDA in November of last year for use as monotherapy in MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or MM patients who are double refractory to a proteasome inhibitor and immunomodulatory agent.
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab. For the full prescribing information, visit www.DARZALEX.com.
Phase 3 trials
The FDA’s latest approval of daratumumab was based on data from the phase 3 POLLUX and CASTOR trials.
In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.
Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.
However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.
Results from this trial were published in NEJM in October.
In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.
Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.
Results from this trial were published in NEJM in August.
Photo courtesy of Janssen
The US Food and Drug Administration (FDA) has approved new indications for the monoclonal antibody daratumumab (Darzalex®).
The drug is now approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.
This approval comes 3 months after a supplemental biologics license application was submitted to the FDA.
The application was granted priority review last month, and the FDA granted daratumumab breakthrough therapy designation in July.
Daratumumab is the first CD38-directed cytolytic antibody approved anywhere in the world.
The drug received accelerated approval from the FDA in November of last year for use as monotherapy in MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or MM patients who are double refractory to a proteasome inhibitor and immunomodulatory agent.
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab. For the full prescribing information, visit www.DARZALEX.com.
Phase 3 trials
The FDA’s latest approval of daratumumab was based on data from the phase 3 POLLUX and CASTOR trials.
In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.
Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.
However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.
Results from this trial were published in NEJM in October.
In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.
Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.
Results from this trial were published in NEJM in August.
Photo courtesy of Janssen
The US Food and Drug Administration (FDA) has approved new indications for the monoclonal antibody daratumumab (Darzalex®).
The drug is now approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.
This approval comes 3 months after a supplemental biologics license application was submitted to the FDA.
The application was granted priority review last month, and the FDA granted daratumumab breakthrough therapy designation in July.
Daratumumab is the first CD38-directed cytolytic antibody approved anywhere in the world.
The drug received accelerated approval from the FDA in November of last year for use as monotherapy in MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or MM patients who are double refractory to a proteasome inhibitor and immunomodulatory agent.
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab. For the full prescribing information, visit www.DARZALEX.com.
Phase 3 trials
The FDA’s latest approval of daratumumab was based on data from the phase 3 POLLUX and CASTOR trials.
In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.
Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.
However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.
Results from this trial were published in NEJM in October.
In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.
Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.
Results from this trial were published in NEJM in August.
ALL subtype ‘highly prevalent’ in adults
Photo courtesy of St. Jude
Children’s Research Hospital
Researchers have found evidence to suggest that a high-risk subtype of acute lymphoblastic leukemia (ALL) is “highly prevalent” in adults with ALL.
In a study of nearly 800 adults with ALL, roughly a quarter of the patients had Philadelphia chromosome-like (Ph-like) ALL.
Patients with Ph-like ALL had inferior overall survival (OS) and event-free survival (EFS), but most of them also had kinase-activating alterations that suggest they might respond well to tyrosine kinase inhibitors.
The researchers reported these findings in the Journal of Clinical Oncology.
“This study establishes that a large percentage of adults with ALL have this high-risk subtype,” said study author Charles Mullighan, MD, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“The finding provides a compelling reason to identify those with Ph-like ALL and move forward with clinical trials of these targeted therapies in combination with current chemotherapeutic regimens.”
This study builds on previous research, which suggested that Ph-like ALL becomes more common with age, is associated with poor prognosis, and is characterized by genomic alterations that appear to make patients responsive to treatment with tyrosine kinase inhibitors.
“Our 2014 findings that the prevalence of Ph-like ALL increased with age and was particularly common in young adults generated tremendous interest because adult ALL is difficult to treat,” Dr Mullighan said. “In this study, we determined that the prevalence remains high across the age spectrum of adults with ALL.”
Prevalence and outcomes
The study included 798 adults who were between the ages of 21 and 86 when diagnosed with ALL. A total of 194 patients (24%) had Ph-like ALL.
The incidence of Ph-like ALL was 27.9% among young adults (ages 21 to 39), 20.4% in adults (ages 40 to 59), and 24.0% in older adults (ages 60 to 86).
Patients with Ph-like ALL had significantly inferior 5-year OS compared to patients with non-Ph-like ALL—23.8% and 52.4%, respectively (P<0.001). The same was true for 5-year EFS—22.5% and 49.3%, respectively (P<0.001).
Among Ph-like ALL patients, the 5-year EFS rates were 40.4% for young adults, 29.8% for adults, and 18.9% for older adults. The 5-year OS rates were 45.2%, 35.1%, and 16.2%, respectively.
Genomic analysis
The researchers performed genomic analysis of 180 of the Ph-like ALL cases and found that 88% had kinase-activating alterations.
This included CRLF2 rearrangements in 51% of cases, JAK2 or EPOR rearrangements in 12.4%, ABL class fusions in 9.8%, other JAK-STAT sequence mutations in 7.2%, other kinase alterations in 4.1%, and Ras pathway mutations in 3.6%.
“Our comprehensive sequencing showed that Ph-like ALL in adults is the most genetically diverse subtype of leukemia that has been described,” said study author Kathryn Roberts, PhD, of St. Jude.
“Cumulatively, more than 50 different chromosomal rearrangements involving 15 different kinases and cytokine receptors have been identified. In this study, we identified 11 chromosomal rearrangements that are new to Ph-like ALL.”
These 11 rearrangements are FIP1L1-PDGFRA, SNX29-PDGFRB, SMU1-JAK2, ZNF340-JAK2, THADA-EPOR, SMARCA4-TYK2, ZNF340-TYK2, ZYMM2-FLT3, DNTT-BLNK, TMEM2-PTK2B, and KANK1-CBL1.
The diversity of kinase-activating alterations in Ph-like ALL has important clinical implications, said study author Hagop Kantarjian, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“It is important that we now identify patients with Ph-like ALL at diagnosis to provide optimal treatment with targeted agents,” he said.
The findings also highlight the importance of centralized comprehensive genomic sequencing for patients, said study author Elisabeth Paietta, PhD, of the Montefiore Health System and Albert Einstein College of Medicine in Bronx, New York.
“Lymphoblasts from almost half of the patients with Ph-like ALL harbor a genomic rearrangement of CRLF2, which can be detected by flow cytometry using an antibody to CRLF2,” Dr Paietta said. “This is very important as it allows a quick characterization of this Ph-like ALL subtype prior to any detailed sequencing.”
Photo courtesy of St. Jude
Children’s Research Hospital
Researchers have found evidence to suggest that a high-risk subtype of acute lymphoblastic leukemia (ALL) is “highly prevalent” in adults with ALL.
In a study of nearly 800 adults with ALL, roughly a quarter of the patients had Philadelphia chromosome-like (Ph-like) ALL.
Patients with Ph-like ALL had inferior overall survival (OS) and event-free survival (EFS), but most of them also had kinase-activating alterations that suggest they might respond well to tyrosine kinase inhibitors.
The researchers reported these findings in the Journal of Clinical Oncology.
“This study establishes that a large percentage of adults with ALL have this high-risk subtype,” said study author Charles Mullighan, MD, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“The finding provides a compelling reason to identify those with Ph-like ALL and move forward with clinical trials of these targeted therapies in combination with current chemotherapeutic regimens.”
This study builds on previous research, which suggested that Ph-like ALL becomes more common with age, is associated with poor prognosis, and is characterized by genomic alterations that appear to make patients responsive to treatment with tyrosine kinase inhibitors.
“Our 2014 findings that the prevalence of Ph-like ALL increased with age and was particularly common in young adults generated tremendous interest because adult ALL is difficult to treat,” Dr Mullighan said. “In this study, we determined that the prevalence remains high across the age spectrum of adults with ALL.”
Prevalence and outcomes
The study included 798 adults who were between the ages of 21 and 86 when diagnosed with ALL. A total of 194 patients (24%) had Ph-like ALL.
The incidence of Ph-like ALL was 27.9% among young adults (ages 21 to 39), 20.4% in adults (ages 40 to 59), and 24.0% in older adults (ages 60 to 86).
Patients with Ph-like ALL had significantly inferior 5-year OS compared to patients with non-Ph-like ALL—23.8% and 52.4%, respectively (P<0.001). The same was true for 5-year EFS—22.5% and 49.3%, respectively (P<0.001).
Among Ph-like ALL patients, the 5-year EFS rates were 40.4% for young adults, 29.8% for adults, and 18.9% for older adults. The 5-year OS rates were 45.2%, 35.1%, and 16.2%, respectively.
Genomic analysis
The researchers performed genomic analysis of 180 of the Ph-like ALL cases and found that 88% had kinase-activating alterations.
This included CRLF2 rearrangements in 51% of cases, JAK2 or EPOR rearrangements in 12.4%, ABL class fusions in 9.8%, other JAK-STAT sequence mutations in 7.2%, other kinase alterations in 4.1%, and Ras pathway mutations in 3.6%.
“Our comprehensive sequencing showed that Ph-like ALL in adults is the most genetically diverse subtype of leukemia that has been described,” said study author Kathryn Roberts, PhD, of St. Jude.
“Cumulatively, more than 50 different chromosomal rearrangements involving 15 different kinases and cytokine receptors have been identified. In this study, we identified 11 chromosomal rearrangements that are new to Ph-like ALL.”
These 11 rearrangements are FIP1L1-PDGFRA, SNX29-PDGFRB, SMU1-JAK2, ZNF340-JAK2, THADA-EPOR, SMARCA4-TYK2, ZNF340-TYK2, ZYMM2-FLT3, DNTT-BLNK, TMEM2-PTK2B, and KANK1-CBL1.
The diversity of kinase-activating alterations in Ph-like ALL has important clinical implications, said study author Hagop Kantarjian, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“It is important that we now identify patients with Ph-like ALL at diagnosis to provide optimal treatment with targeted agents,” he said.
The findings also highlight the importance of centralized comprehensive genomic sequencing for patients, said study author Elisabeth Paietta, PhD, of the Montefiore Health System and Albert Einstein College of Medicine in Bronx, New York.
“Lymphoblasts from almost half of the patients with Ph-like ALL harbor a genomic rearrangement of CRLF2, which can be detected by flow cytometry using an antibody to CRLF2,” Dr Paietta said. “This is very important as it allows a quick characterization of this Ph-like ALL subtype prior to any detailed sequencing.”
Photo courtesy of St. Jude
Children’s Research Hospital
Researchers have found evidence to suggest that a high-risk subtype of acute lymphoblastic leukemia (ALL) is “highly prevalent” in adults with ALL.
In a study of nearly 800 adults with ALL, roughly a quarter of the patients had Philadelphia chromosome-like (Ph-like) ALL.
Patients with Ph-like ALL had inferior overall survival (OS) and event-free survival (EFS), but most of them also had kinase-activating alterations that suggest they might respond well to tyrosine kinase inhibitors.
The researchers reported these findings in the Journal of Clinical Oncology.
“This study establishes that a large percentage of adults with ALL have this high-risk subtype,” said study author Charles Mullighan, MD, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“The finding provides a compelling reason to identify those with Ph-like ALL and move forward with clinical trials of these targeted therapies in combination with current chemotherapeutic regimens.”
This study builds on previous research, which suggested that Ph-like ALL becomes more common with age, is associated with poor prognosis, and is characterized by genomic alterations that appear to make patients responsive to treatment with tyrosine kinase inhibitors.
“Our 2014 findings that the prevalence of Ph-like ALL increased with age and was particularly common in young adults generated tremendous interest because adult ALL is difficult to treat,” Dr Mullighan said. “In this study, we determined that the prevalence remains high across the age spectrum of adults with ALL.”
Prevalence and outcomes
The study included 798 adults who were between the ages of 21 and 86 when diagnosed with ALL. A total of 194 patients (24%) had Ph-like ALL.
The incidence of Ph-like ALL was 27.9% among young adults (ages 21 to 39), 20.4% in adults (ages 40 to 59), and 24.0% in older adults (ages 60 to 86).
Patients with Ph-like ALL had significantly inferior 5-year OS compared to patients with non-Ph-like ALL—23.8% and 52.4%, respectively (P<0.001). The same was true for 5-year EFS—22.5% and 49.3%, respectively (P<0.001).
Among Ph-like ALL patients, the 5-year EFS rates were 40.4% for young adults, 29.8% for adults, and 18.9% for older adults. The 5-year OS rates were 45.2%, 35.1%, and 16.2%, respectively.
Genomic analysis
The researchers performed genomic analysis of 180 of the Ph-like ALL cases and found that 88% had kinase-activating alterations.
This included CRLF2 rearrangements in 51% of cases, JAK2 or EPOR rearrangements in 12.4%, ABL class fusions in 9.8%, other JAK-STAT sequence mutations in 7.2%, other kinase alterations in 4.1%, and Ras pathway mutations in 3.6%.
“Our comprehensive sequencing showed that Ph-like ALL in adults is the most genetically diverse subtype of leukemia that has been described,” said study author Kathryn Roberts, PhD, of St. Jude.
“Cumulatively, more than 50 different chromosomal rearrangements involving 15 different kinases and cytokine receptors have been identified. In this study, we identified 11 chromosomal rearrangements that are new to Ph-like ALL.”
These 11 rearrangements are FIP1L1-PDGFRA, SNX29-PDGFRB, SMU1-JAK2, ZNF340-JAK2, THADA-EPOR, SMARCA4-TYK2, ZNF340-TYK2, ZYMM2-FLT3, DNTT-BLNK, TMEM2-PTK2B, and KANK1-CBL1.
The diversity of kinase-activating alterations in Ph-like ALL has important clinical implications, said study author Hagop Kantarjian, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“It is important that we now identify patients with Ph-like ALL at diagnosis to provide optimal treatment with targeted agents,” he said.
The findings also highlight the importance of centralized comprehensive genomic sequencing for patients, said study author Elisabeth Paietta, PhD, of the Montefiore Health System and Albert Einstein College of Medicine in Bronx, New York.
“Lymphoblasts from almost half of the patients with Ph-like ALL harbor a genomic rearrangement of CRLF2, which can be detected by flow cytometry using an antibody to CRLF2,” Dr Paietta said. “This is very important as it allows a quick characterization of this Ph-like ALL subtype prior to any detailed sequencing.”
Drug approved to treat hemophilia A in Kuwait
(Elocta) packaging
Photo courtesy of Sobi
The Ministry of Health in Kuwait has approved efmoroctocog alfa (Elocta®), a recombinant human factor VIII Fc-fusion protein, for the treatment of hemophilia A.
It is indicated for both on-demand and prophylactic treatment in hemophilia A patients of all ages.
Efmoroctocog alfa is the first recombinant factor VIII Fc fusion protein therapy approved for the treatment of hemophilia A in the Middle East region.
Efmoroctocog alfa is also approved in the European Union, Switzerland, Iceland, Liechtenstein, Norway, the US, Canada, Australia, New Zealand, Brazil, Taiwan, and Japan.
Efmoroctocog alfa was developed by fusing B-domain deleted factor VIII to the Fc portion of immunoglobulin G subclass 1. It is believed that this enables efmoroctocog alfa to utilize a naturally occurring pathway to prolong the time the therapy remains in the body.
Sobi and Biogen are collaborators in the development and commercialization of efmoroctocog alfa for hemophilia A.
The approval of efmoroctocog alfa in Kuwait was based on data from a pair of phase 3 studies: A-LONG and Kids A-LONG.
A-LONG
The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.
Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.
None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with recombinant factor VIII.
Kids A-LONG
The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to factor VIII therapies.
The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.
None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.
(Elocta) packaging
Photo courtesy of Sobi
The Ministry of Health in Kuwait has approved efmoroctocog alfa (Elocta®), a recombinant human factor VIII Fc-fusion protein, for the treatment of hemophilia A.
It is indicated for both on-demand and prophylactic treatment in hemophilia A patients of all ages.
Efmoroctocog alfa is the first recombinant factor VIII Fc fusion protein therapy approved for the treatment of hemophilia A in the Middle East region.
Efmoroctocog alfa is also approved in the European Union, Switzerland, Iceland, Liechtenstein, Norway, the US, Canada, Australia, New Zealand, Brazil, Taiwan, and Japan.
Efmoroctocog alfa was developed by fusing B-domain deleted factor VIII to the Fc portion of immunoglobulin G subclass 1. It is believed that this enables efmoroctocog alfa to utilize a naturally occurring pathway to prolong the time the therapy remains in the body.
Sobi and Biogen are collaborators in the development and commercialization of efmoroctocog alfa for hemophilia A.
The approval of efmoroctocog alfa in Kuwait was based on data from a pair of phase 3 studies: A-LONG and Kids A-LONG.
A-LONG
The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.
Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.
None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with recombinant factor VIII.
Kids A-LONG
The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to factor VIII therapies.
The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.
None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.
(Elocta) packaging
Photo courtesy of Sobi
The Ministry of Health in Kuwait has approved efmoroctocog alfa (Elocta®), a recombinant human factor VIII Fc-fusion protein, for the treatment of hemophilia A.
It is indicated for both on-demand and prophylactic treatment in hemophilia A patients of all ages.
Efmoroctocog alfa is the first recombinant factor VIII Fc fusion protein therapy approved for the treatment of hemophilia A in the Middle East region.
Efmoroctocog alfa is also approved in the European Union, Switzerland, Iceland, Liechtenstein, Norway, the US, Canada, Australia, New Zealand, Brazil, Taiwan, and Japan.
Efmoroctocog alfa was developed by fusing B-domain deleted factor VIII to the Fc portion of immunoglobulin G subclass 1. It is believed that this enables efmoroctocog alfa to utilize a naturally occurring pathway to prolong the time the therapy remains in the body.
Sobi and Biogen are collaborators in the development and commercialization of efmoroctocog alfa for hemophilia A.
The approval of efmoroctocog alfa in Kuwait was based on data from a pair of phase 3 studies: A-LONG and Kids A-LONG.
A-LONG
The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.
Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.
None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with recombinant factor VIII.
Kids A-LONG
The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to factor VIII therapies.
The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.
None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.
Novel CLL drugs could greatly increase costs
New research suggests the increasing use of oral targeted therapies for chronic lymphocytic leukemia (CLL) could raise US treatment costs for the disease by almost 600%.
Investigators modeled the evolving management of CLL from 2011 to 2025 and found that increasing use of the oral targeted therapies ibrutinib and idelalisib could greatly increase costs for both patients and payers.
The team detailed these findings in the Journal of Clinical Oncology.
“The rising cost of cancer care is a serious concern,” said study author Jagpreet Chhatwal, PhD, of Massachusetts General Hospital in Boston.
“The average cost of annual cancer treatment, which was below $10,000 per patient before 2000, has now increased to more than $100,000. Such increasing trends can limit access to new therapies, potentially undermining their clinical effectiveness. These new drugs are highly effective, but their high costs motivated us to project their changing economic burden and affordability.”
Dr Chhatwal and his colleagues noted that ibrutinib and idelalisib each cost around $130,000 per year, and treatment with these drugs may be continued indefinitely.
So the team set out to determine the potential financial impact of the drugs on payers’ budgets, as well as on Medicare-enrolled patients, who represent the majority of CLL patients in the US.
The investigators developed a model to simulate the evolving management of CLL from 2011 to 2025.
In one scenario, chemoimmunotherapy was the standard of care before 2014, while oral targeted therapies were used for patients with del(17p) and relapsed CLL from 2014 onward and for first-line treatment of CLL from 2016 onward.
The team also modeled a scenario in which chemoimmunotherapy was the standard of care throughout the entire time period and compared the costs between these scenarios.
The model projects that:
- Per-patient lifetime costs for CLL treatment will increase from $147,000 to $604,000 from 2016 onward
- The total out-of-pocket costs for Medicare patients will increase from $9200 to $57,000 for patients initiating treatment from 2016 onward
- The total annual cost of CLL management in the US will rise from $0.74 billion in 2011 to $5.13 billion in 2025, an increase of 590%.
“Such substantial increases in the cost are mainly driven by high drug prices, prolonged treatment duration, and the increase in the number of patients living with CLL,” said study author Qiushi Chen, PhD, of Massachusetts General Hospital.
The investigators also noted that the standard measure used to determine the cost-effectiveness of a medical intervention is whether it costs less than $100,000 for each additional year of life gained. The projected cost-effectiveness ratio of oral targeted therapy in CLL is $189,000 for each year gained.
“At the current average wholesale prices, oral targeted therapies for CLL are not cost-effective, and prices would need to drop by 50% to 70% to become cost-effective,” Dr Chhatwal said.
“We are not recommending that clinicians choose less effective CLL management strategies that do not include oral targeted therapies,” said study author Nitin Jain, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Instead, we propose that the prices of these drugs need to be reduced to make the treatment cost-effective and more affordable, something we hope may happen with all cancer drugs. We also believe more research is needed to explore whether we can discontinue targeted treatment of patients who have responded well without risking worsening of their health.”
New research suggests the increasing use of oral targeted therapies for chronic lymphocytic leukemia (CLL) could raise US treatment costs for the disease by almost 600%.
Investigators modeled the evolving management of CLL from 2011 to 2025 and found that increasing use of the oral targeted therapies ibrutinib and idelalisib could greatly increase costs for both patients and payers.
The team detailed these findings in the Journal of Clinical Oncology.
“The rising cost of cancer care is a serious concern,” said study author Jagpreet Chhatwal, PhD, of Massachusetts General Hospital in Boston.
“The average cost of annual cancer treatment, which was below $10,000 per patient before 2000, has now increased to more than $100,000. Such increasing trends can limit access to new therapies, potentially undermining their clinical effectiveness. These new drugs are highly effective, but their high costs motivated us to project their changing economic burden and affordability.”
Dr Chhatwal and his colleagues noted that ibrutinib and idelalisib each cost around $130,000 per year, and treatment with these drugs may be continued indefinitely.
So the team set out to determine the potential financial impact of the drugs on payers’ budgets, as well as on Medicare-enrolled patients, who represent the majority of CLL patients in the US.
The investigators developed a model to simulate the evolving management of CLL from 2011 to 2025.
In one scenario, chemoimmunotherapy was the standard of care before 2014, while oral targeted therapies were used for patients with del(17p) and relapsed CLL from 2014 onward and for first-line treatment of CLL from 2016 onward.
The team also modeled a scenario in which chemoimmunotherapy was the standard of care throughout the entire time period and compared the costs between these scenarios.
The model projects that:
- Per-patient lifetime costs for CLL treatment will increase from $147,000 to $604,000 from 2016 onward
- The total out-of-pocket costs for Medicare patients will increase from $9200 to $57,000 for patients initiating treatment from 2016 onward
- The total annual cost of CLL management in the US will rise from $0.74 billion in 2011 to $5.13 billion in 2025, an increase of 590%.
“Such substantial increases in the cost are mainly driven by high drug prices, prolonged treatment duration, and the increase in the number of patients living with CLL,” said study author Qiushi Chen, PhD, of Massachusetts General Hospital.
The investigators also noted that the standard measure used to determine the cost-effectiveness of a medical intervention is whether it costs less than $100,000 for each additional year of life gained. The projected cost-effectiveness ratio of oral targeted therapy in CLL is $189,000 for each year gained.
“At the current average wholesale prices, oral targeted therapies for CLL are not cost-effective, and prices would need to drop by 50% to 70% to become cost-effective,” Dr Chhatwal said.
“We are not recommending that clinicians choose less effective CLL management strategies that do not include oral targeted therapies,” said study author Nitin Jain, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Instead, we propose that the prices of these drugs need to be reduced to make the treatment cost-effective and more affordable, something we hope may happen with all cancer drugs. We also believe more research is needed to explore whether we can discontinue targeted treatment of patients who have responded well without risking worsening of their health.”
New research suggests the increasing use of oral targeted therapies for chronic lymphocytic leukemia (CLL) could raise US treatment costs for the disease by almost 600%.
Investigators modeled the evolving management of CLL from 2011 to 2025 and found that increasing use of the oral targeted therapies ibrutinib and idelalisib could greatly increase costs for both patients and payers.
The team detailed these findings in the Journal of Clinical Oncology.
“The rising cost of cancer care is a serious concern,” said study author Jagpreet Chhatwal, PhD, of Massachusetts General Hospital in Boston.
“The average cost of annual cancer treatment, which was below $10,000 per patient before 2000, has now increased to more than $100,000. Such increasing trends can limit access to new therapies, potentially undermining their clinical effectiveness. These new drugs are highly effective, but their high costs motivated us to project their changing economic burden and affordability.”
Dr Chhatwal and his colleagues noted that ibrutinib and idelalisib each cost around $130,000 per year, and treatment with these drugs may be continued indefinitely.
So the team set out to determine the potential financial impact of the drugs on payers’ budgets, as well as on Medicare-enrolled patients, who represent the majority of CLL patients in the US.
The investigators developed a model to simulate the evolving management of CLL from 2011 to 2025.
In one scenario, chemoimmunotherapy was the standard of care before 2014, while oral targeted therapies were used for patients with del(17p) and relapsed CLL from 2014 onward and for first-line treatment of CLL from 2016 onward.
The team also modeled a scenario in which chemoimmunotherapy was the standard of care throughout the entire time period and compared the costs between these scenarios.
The model projects that:
- Per-patient lifetime costs for CLL treatment will increase from $147,000 to $604,000 from 2016 onward
- The total out-of-pocket costs for Medicare patients will increase from $9200 to $57,000 for patients initiating treatment from 2016 onward
- The total annual cost of CLL management in the US will rise from $0.74 billion in 2011 to $5.13 billion in 2025, an increase of 590%.
“Such substantial increases in the cost are mainly driven by high drug prices, prolonged treatment duration, and the increase in the number of patients living with CLL,” said study author Qiushi Chen, PhD, of Massachusetts General Hospital.
The investigators also noted that the standard measure used to determine the cost-effectiveness of a medical intervention is whether it costs less than $100,000 for each additional year of life gained. The projected cost-effectiveness ratio of oral targeted therapy in CLL is $189,000 for each year gained.
“At the current average wholesale prices, oral targeted therapies for CLL are not cost-effective, and prices would need to drop by 50% to 70% to become cost-effective,” Dr Chhatwal said.
“We are not recommending that clinicians choose less effective CLL management strategies that do not include oral targeted therapies,” said study author Nitin Jain, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Instead, we propose that the prices of these drugs need to be reduced to make the treatment cost-effective and more affordable, something we hope may happen with all cancer drugs. We also believe more research is needed to explore whether we can discontinue targeted treatment of patients who have responded well without risking worsening of their health.”
NCCN guidelines on MM now include MRD testing
The National Comprehensive Cancer Network (NCCN) has revised its clinical practice guidelines on multiple myeloma (MM) to include response criteria developed by the International Myeloma Working Group (IMWG) and testing for minimal residual disease (MRD).
The NCCN develops practice guidelines to help physicians in making informed treatment decisions.
Its recommendations can facilitate reimbursement for testing or treatment.
“The NCCN’s action represents a further step toward broad use of MRD testing,” said Brian Durie, MD, chairman of the International Myeloma Foundation (IMF).
The importance of first identifying and then eliminating MRD is the key principle of the IMF’s Black Swan Research Initiative®, a collaborative effort launched in 2012 to cure MM.
“We’ve long believed early intervention with highly effective treatments is the pathway to curing myeloma, and we are currently testing this in clinical trials,” Dr Durie said.
Through the Black Swan Research Initiative, the IMF helped develop next-generation flow cytometry, 1 of 2 tests recommended by the NCCN to assess the presence of MRD in MM patients. The second test is next-generation sequencing.
The new MM response criteria, on which the NCCN based its most recent revision to the guidelines, were developed and agreed upon by the more than 200 members of the IMWG.
The new response criteria spell out exact definitions of “MRD negative” by next-generation flow cytometry or next-generation sequencing.
“We are pleased that the 2016 IMWG response criteria were adopted in full in the new NCCN recommendations,” said Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota.
The 2016 IMWG response criteria were published in The Lancet Oncology in August.
The National Comprehensive Cancer Network (NCCN) has revised its clinical practice guidelines on multiple myeloma (MM) to include response criteria developed by the International Myeloma Working Group (IMWG) and testing for minimal residual disease (MRD).
The NCCN develops practice guidelines to help physicians in making informed treatment decisions.
Its recommendations can facilitate reimbursement for testing or treatment.
“The NCCN’s action represents a further step toward broad use of MRD testing,” said Brian Durie, MD, chairman of the International Myeloma Foundation (IMF).
The importance of first identifying and then eliminating MRD is the key principle of the IMF’s Black Swan Research Initiative®, a collaborative effort launched in 2012 to cure MM.
“We’ve long believed early intervention with highly effective treatments is the pathway to curing myeloma, and we are currently testing this in clinical trials,” Dr Durie said.
Through the Black Swan Research Initiative, the IMF helped develop next-generation flow cytometry, 1 of 2 tests recommended by the NCCN to assess the presence of MRD in MM patients. The second test is next-generation sequencing.
The new MM response criteria, on which the NCCN based its most recent revision to the guidelines, were developed and agreed upon by the more than 200 members of the IMWG.
The new response criteria spell out exact definitions of “MRD negative” by next-generation flow cytometry or next-generation sequencing.
“We are pleased that the 2016 IMWG response criteria were adopted in full in the new NCCN recommendations,” said Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota.
The 2016 IMWG response criteria were published in The Lancet Oncology in August.
The National Comprehensive Cancer Network (NCCN) has revised its clinical practice guidelines on multiple myeloma (MM) to include response criteria developed by the International Myeloma Working Group (IMWG) and testing for minimal residual disease (MRD).
The NCCN develops practice guidelines to help physicians in making informed treatment decisions.
Its recommendations can facilitate reimbursement for testing or treatment.
“The NCCN’s action represents a further step toward broad use of MRD testing,” said Brian Durie, MD, chairman of the International Myeloma Foundation (IMF).
The importance of first identifying and then eliminating MRD is the key principle of the IMF’s Black Swan Research Initiative®, a collaborative effort launched in 2012 to cure MM.
“We’ve long believed early intervention with highly effective treatments is the pathway to curing myeloma, and we are currently testing this in clinical trials,” Dr Durie said.
Through the Black Swan Research Initiative, the IMF helped develop next-generation flow cytometry, 1 of 2 tests recommended by the NCCN to assess the presence of MRD in MM patients. The second test is next-generation sequencing.
The new MM response criteria, on which the NCCN based its most recent revision to the guidelines, were developed and agreed upon by the more than 200 members of the IMWG.
The new response criteria spell out exact definitions of “MRD negative” by next-generation flow cytometry or next-generation sequencing.
“We are pleased that the 2016 IMWG response criteria were adopted in full in the new NCCN recommendations,” said Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota.
The 2016 IMWG response criteria were published in The Lancet Oncology in August.
Large-scale tumor profiling deemed feasible, but challenges remain
Photo courtesy of the
National Institute of
General Medical Sciences
New research suggests large-scale genomic profiling is technically feasible in a broad population of cancer patients.
However, the study also revealed challenges and barriers to widespread implementation of precision medicine, according to researchers.
Specifically, half of the patients studied did not receive results of genomic profiling due to insufficient samples or sequencing failure.
Most patients who did receive results did not see a change in their care.
However, genomic profiling provided an accurate diagnosis and changed treatment for a handful of the patients studied.
Lynette M. Sholl, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and her colleagues reported these findings in JCI Insight.
The report contains data on pediatric and adult patients with a range of malignancies.
Patient samples were analyzed using OncoPanel. This platform sequences hundreds of known cancer-related genes to look for alterations that drive tumors and might be helpful in guiding treatment choice or enrolling the patient in an appropriate clinical trial.
This study began with 7397 patients, but many of these individuals did not have specimens adequate for sequencing. This left 3892 patients (53%) to undergo genomic profiling, but sequencing failed in 165 (4%) of them. So sequencing was successful in 3727 patients, or 50% of the overall population.
Of the 3727 patients in whom sequencing was successful, 73% had at least 1 genetic alteration that was considered “clinically actionable or informative” by the researchers.
This included 54% of patients with alterations that might be used to inform diagnosis or recommend enrollment in a clinical trial. It also included 19% of patients who had an alteration that “would inform standard-of-care therapeutic decision-making,” according to the researchers.
The team provided several examples of how genomic testing clarified or changed a patient’s diagnosis, which, in turn, altered treatment and prognosis.
One example was a patient who was originally diagnosed with peripheral T-cell lymphoma, which was later revised to myeloid sarcoma. Sequencing results suggested the patient actually had FIP1L1-PDGFRA-driven acute myeloid leukemia, which predicted responsiveness to imatinib.
The patient was treated with imatinib and experienced a “dramatic and sustained clinical response.” He then proceeded to allogeneic transplant and had no evidence of disease at 1 year of follow-up.
The researchers concluded that genomic sequencing results may alter the management of cancer patients in some cases, but certain barriers must be overcome to enable precision cancer medicine on a large scale.
Photo courtesy of the
National Institute of
General Medical Sciences
New research suggests large-scale genomic profiling is technically feasible in a broad population of cancer patients.
However, the study also revealed challenges and barriers to widespread implementation of precision medicine, according to researchers.
Specifically, half of the patients studied did not receive results of genomic profiling due to insufficient samples or sequencing failure.
Most patients who did receive results did not see a change in their care.
However, genomic profiling provided an accurate diagnosis and changed treatment for a handful of the patients studied.
Lynette M. Sholl, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and her colleagues reported these findings in JCI Insight.
The report contains data on pediatric and adult patients with a range of malignancies.
Patient samples were analyzed using OncoPanel. This platform sequences hundreds of known cancer-related genes to look for alterations that drive tumors and might be helpful in guiding treatment choice or enrolling the patient in an appropriate clinical trial.
This study began with 7397 patients, but many of these individuals did not have specimens adequate for sequencing. This left 3892 patients (53%) to undergo genomic profiling, but sequencing failed in 165 (4%) of them. So sequencing was successful in 3727 patients, or 50% of the overall population.
Of the 3727 patients in whom sequencing was successful, 73% had at least 1 genetic alteration that was considered “clinically actionable or informative” by the researchers.
This included 54% of patients with alterations that might be used to inform diagnosis or recommend enrollment in a clinical trial. It also included 19% of patients who had an alteration that “would inform standard-of-care therapeutic decision-making,” according to the researchers.
The team provided several examples of how genomic testing clarified or changed a patient’s diagnosis, which, in turn, altered treatment and prognosis.
One example was a patient who was originally diagnosed with peripheral T-cell lymphoma, which was later revised to myeloid sarcoma. Sequencing results suggested the patient actually had FIP1L1-PDGFRA-driven acute myeloid leukemia, which predicted responsiveness to imatinib.
The patient was treated with imatinib and experienced a “dramatic and sustained clinical response.” He then proceeded to allogeneic transplant and had no evidence of disease at 1 year of follow-up.
The researchers concluded that genomic sequencing results may alter the management of cancer patients in some cases, but certain barriers must be overcome to enable precision cancer medicine on a large scale.
Photo courtesy of the
National Institute of
General Medical Sciences
New research suggests large-scale genomic profiling is technically feasible in a broad population of cancer patients.
However, the study also revealed challenges and barriers to widespread implementation of precision medicine, according to researchers.
Specifically, half of the patients studied did not receive results of genomic profiling due to insufficient samples or sequencing failure.
Most patients who did receive results did not see a change in their care.
However, genomic profiling provided an accurate diagnosis and changed treatment for a handful of the patients studied.
Lynette M. Sholl, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and her colleagues reported these findings in JCI Insight.
The report contains data on pediatric and adult patients with a range of malignancies.
Patient samples were analyzed using OncoPanel. This platform sequences hundreds of known cancer-related genes to look for alterations that drive tumors and might be helpful in guiding treatment choice or enrolling the patient in an appropriate clinical trial.
This study began with 7397 patients, but many of these individuals did not have specimens adequate for sequencing. This left 3892 patients (53%) to undergo genomic profiling, but sequencing failed in 165 (4%) of them. So sequencing was successful in 3727 patients, or 50% of the overall population.
Of the 3727 patients in whom sequencing was successful, 73% had at least 1 genetic alteration that was considered “clinically actionable or informative” by the researchers.
This included 54% of patients with alterations that might be used to inform diagnosis or recommend enrollment in a clinical trial. It also included 19% of patients who had an alteration that “would inform standard-of-care therapeutic decision-making,” according to the researchers.
The team provided several examples of how genomic testing clarified or changed a patient’s diagnosis, which, in turn, altered treatment and prognosis.
One example was a patient who was originally diagnosed with peripheral T-cell lymphoma, which was later revised to myeloid sarcoma. Sequencing results suggested the patient actually had FIP1L1-PDGFRA-driven acute myeloid leukemia, which predicted responsiveness to imatinib.
The patient was treated with imatinib and experienced a “dramatic and sustained clinical response.” He then proceeded to allogeneic transplant and had no evidence of disease at 1 year of follow-up.
The researchers concluded that genomic sequencing results may alter the management of cancer patients in some cases, but certain barriers must be overcome to enable precision cancer medicine on a large scale.