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Minor surgeries appear safe for hemophilia patients on emicizumab
MELBOURNE – A majority of minor surgeries can be performed in hemophilia A patients receiving emicizumab therapy without requiring prophylactic treatment with coagulation factors, according to data presented at the International Society on Thrombosis and Haemostasis congress.
Elena Santagostino, MD, PhD, from the Hemophilia and Thrombosis Center at Ospedale Maggiore Policlinico in Milan presented data from 399 patients involved in the four HAVEN trials of the humanized bispecific monoclonal antibody emicizumab (Hemlibra), which is Food and Drug Administration–approved for the prevention of bleeding episodes in individuals with hemophilia A, with or without inhibitors.
The analysis focused on the 126 patients (31.6%) who underwent at least one surgical procedure during the studies. Of the 233 surgeries, there were 215 minor procedures performed in 115 patients, and 18 major surgeries in 18 patients. All patients were receiving ongoing treatment with emicizumab, and there was no change to that treatment regimen during surgery.
“It is clear that surgery is a challenge for hemophilia,” Dr. Santagostino said. “It is a challenge for bleeding, it is a challenge for thrombosis, it is a challenge for any new drug, and this is why there is a lot of interest around this topic.”
Overall, 65.6% of minor surgeries were performed without any prophylactic coagulation factor treatment, and 90.8% of minor surgeries were conducted without postoperative bleeds requiring treatment. There were no cases of thrombosis reported.
The surgeries that did not require prophylactic coagulation factor included 42 dental procedures, 25 central venous access devices, 17 endoscopic procedures, and 12 joint procedures.
While the HAVEN studies did not allow for elective major surgery, there were still 18 unplanned major surgical situations that arose during the course of the studies. These included three hip, one knee, and one ankle arthroplasties; three synovectomies; and some dental, central venous line, and endoscopic biopsy procedures.
Of these, 15 involved prophylactic coagulant factor administration, but three procedures – including one synovectomy – were performed without prophylaxis and none resulted in a bleed.
There was one complicated bleed that occurred in a patient undergoing multiple procedures including a synovectomy, joint debridement and chondroplasty, who received prolonged treatment with recombinant Factor VIIa.
Dr. Santagostino said the findings showed surgery could be safely performed in patients who were being treated with emicizumab, both with and without inhibitors.
“A large number of minor procedures can be done without adding coagulation factors,” she said in an interview. “This is true for less invasive surgeries, such as catheter-related central venous line procedures. Even several endoscopic procedures, like a single biopsy, can be done reasonably safely.”
However she said there was still a lack of experience in dealing with hemophilia A patients who were undergoing cancer surgery, or who had significant comorbidities that might put them at higher risk of thrombosis.
“These are special patients populations that are still not investigated in the trial setting,” she said.
Commenting on the data, session cochair Liane Khoo, MD, from the Haemophilia Treatment Centre at Royal Prince Alfred Hospital in Sydney, said the results showed surgery could be performed in hemophilia A patients with and without inhibitors.
“The more we have the medication and the more experience we have, then we become more confident in using it,” she said.
The study was funded by F. Hoffman-La Roche and Chugai Pharmaceutical. Dr. Santagostino reported consultancies and speakers bureau engagements with the pharmaceutical sector.
SOURCE: Santagostino E et al. 2019 ISTH Congress, Abstract OC 60.1.
MELBOURNE – A majority of minor surgeries can be performed in hemophilia A patients receiving emicizumab therapy without requiring prophylactic treatment with coagulation factors, according to data presented at the International Society on Thrombosis and Haemostasis congress.
Elena Santagostino, MD, PhD, from the Hemophilia and Thrombosis Center at Ospedale Maggiore Policlinico in Milan presented data from 399 patients involved in the four HAVEN trials of the humanized bispecific monoclonal antibody emicizumab (Hemlibra), which is Food and Drug Administration–approved for the prevention of bleeding episodes in individuals with hemophilia A, with or without inhibitors.
The analysis focused on the 126 patients (31.6%) who underwent at least one surgical procedure during the studies. Of the 233 surgeries, there were 215 minor procedures performed in 115 patients, and 18 major surgeries in 18 patients. All patients were receiving ongoing treatment with emicizumab, and there was no change to that treatment regimen during surgery.
“It is clear that surgery is a challenge for hemophilia,” Dr. Santagostino said. “It is a challenge for bleeding, it is a challenge for thrombosis, it is a challenge for any new drug, and this is why there is a lot of interest around this topic.”
Overall, 65.6% of minor surgeries were performed without any prophylactic coagulation factor treatment, and 90.8% of minor surgeries were conducted without postoperative bleeds requiring treatment. There were no cases of thrombosis reported.
The surgeries that did not require prophylactic coagulation factor included 42 dental procedures, 25 central venous access devices, 17 endoscopic procedures, and 12 joint procedures.
While the HAVEN studies did not allow for elective major surgery, there were still 18 unplanned major surgical situations that arose during the course of the studies. These included three hip, one knee, and one ankle arthroplasties; three synovectomies; and some dental, central venous line, and endoscopic biopsy procedures.
Of these, 15 involved prophylactic coagulant factor administration, but three procedures – including one synovectomy – were performed without prophylaxis and none resulted in a bleed.
There was one complicated bleed that occurred in a patient undergoing multiple procedures including a synovectomy, joint debridement and chondroplasty, who received prolonged treatment with recombinant Factor VIIa.
Dr. Santagostino said the findings showed surgery could be safely performed in patients who were being treated with emicizumab, both with and without inhibitors.
“A large number of minor procedures can be done without adding coagulation factors,” she said in an interview. “This is true for less invasive surgeries, such as catheter-related central venous line procedures. Even several endoscopic procedures, like a single biopsy, can be done reasonably safely.”
However she said there was still a lack of experience in dealing with hemophilia A patients who were undergoing cancer surgery, or who had significant comorbidities that might put them at higher risk of thrombosis.
“These are special patients populations that are still not investigated in the trial setting,” she said.
Commenting on the data, session cochair Liane Khoo, MD, from the Haemophilia Treatment Centre at Royal Prince Alfred Hospital in Sydney, said the results showed surgery could be performed in hemophilia A patients with and without inhibitors.
“The more we have the medication and the more experience we have, then we become more confident in using it,” she said.
The study was funded by F. Hoffman-La Roche and Chugai Pharmaceutical. Dr. Santagostino reported consultancies and speakers bureau engagements with the pharmaceutical sector.
SOURCE: Santagostino E et al. 2019 ISTH Congress, Abstract OC 60.1.
MELBOURNE – A majority of minor surgeries can be performed in hemophilia A patients receiving emicizumab therapy without requiring prophylactic treatment with coagulation factors, according to data presented at the International Society on Thrombosis and Haemostasis congress.
Elena Santagostino, MD, PhD, from the Hemophilia and Thrombosis Center at Ospedale Maggiore Policlinico in Milan presented data from 399 patients involved in the four HAVEN trials of the humanized bispecific monoclonal antibody emicizumab (Hemlibra), which is Food and Drug Administration–approved for the prevention of bleeding episodes in individuals with hemophilia A, with or without inhibitors.
The analysis focused on the 126 patients (31.6%) who underwent at least one surgical procedure during the studies. Of the 233 surgeries, there were 215 minor procedures performed in 115 patients, and 18 major surgeries in 18 patients. All patients were receiving ongoing treatment with emicizumab, and there was no change to that treatment regimen during surgery.
“It is clear that surgery is a challenge for hemophilia,” Dr. Santagostino said. “It is a challenge for bleeding, it is a challenge for thrombosis, it is a challenge for any new drug, and this is why there is a lot of interest around this topic.”
Overall, 65.6% of minor surgeries were performed without any prophylactic coagulation factor treatment, and 90.8% of minor surgeries were conducted without postoperative bleeds requiring treatment. There were no cases of thrombosis reported.
The surgeries that did not require prophylactic coagulation factor included 42 dental procedures, 25 central venous access devices, 17 endoscopic procedures, and 12 joint procedures.
While the HAVEN studies did not allow for elective major surgery, there were still 18 unplanned major surgical situations that arose during the course of the studies. These included three hip, one knee, and one ankle arthroplasties; three synovectomies; and some dental, central venous line, and endoscopic biopsy procedures.
Of these, 15 involved prophylactic coagulant factor administration, but three procedures – including one synovectomy – were performed without prophylaxis and none resulted in a bleed.
There was one complicated bleed that occurred in a patient undergoing multiple procedures including a synovectomy, joint debridement and chondroplasty, who received prolonged treatment with recombinant Factor VIIa.
Dr. Santagostino said the findings showed surgery could be safely performed in patients who were being treated with emicizumab, both with and without inhibitors.
“A large number of minor procedures can be done without adding coagulation factors,” she said in an interview. “This is true for less invasive surgeries, such as catheter-related central venous line procedures. Even several endoscopic procedures, like a single biopsy, can be done reasonably safely.”
However she said there was still a lack of experience in dealing with hemophilia A patients who were undergoing cancer surgery, or who had significant comorbidities that might put them at higher risk of thrombosis.
“These are special patients populations that are still not investigated in the trial setting,” she said.
Commenting on the data, session cochair Liane Khoo, MD, from the Haemophilia Treatment Centre at Royal Prince Alfred Hospital in Sydney, said the results showed surgery could be performed in hemophilia A patients with and without inhibitors.
“The more we have the medication and the more experience we have, then we become more confident in using it,” she said.
The study was funded by F. Hoffman-La Roche and Chugai Pharmaceutical. Dr. Santagostino reported consultancies and speakers bureau engagements with the pharmaceutical sector.
SOURCE: Santagostino E et al. 2019 ISTH Congress, Abstract OC 60.1.
REPORTING FROM 2019 ISTH CONGRESS
NOACs benefit early stage chronic kidney disease patients
Non–vitamin K oral anticoagulants (NOACs) significantly reduced the risk of stroke or systemic embolism compared to vitamin K antagonists (VKAs) for patients in the early stages of chronic kidney disease and comorbid atrial fibrillation, based on data from a meta-analysis of roughly 34,000 patients.
Chronic kidney disease increases the risk of complications including stroke, congestive heart failure, and death in patients who also have atrial fibrillation, but most trials of anticoagulant therapy to reduce the risk of such events have excluded these patients, wrote Jeffrey T. Ha, MBBS, of the George Institute for Global Health, Newtown, Australia, and colleagues.
To assess the benefits and harms of oral anticoagulants for multiple indications in chronic kidney disease patients, the researchers conducted a meta-analysis of 45 studies including 34,082 individuals. The findings were published in the Annals of Internal Medicine. The analysis included 8 trials of end stage kidney disease patients on dialysis; the remaining trials excluded patients with creatinine clearance less than 20 mL/min or an estimated glomerular filtration rate less than 15 mL/min per 1.73 m2. The interventional agents were rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, warfarin, and acenocoumarol.
A notable finding was the significant reduction in relative risk of stroke or systemic embolism (21%), hemorrhagic stroke (52%), and intracranial hemorrhage (51%) for early-stage chronic kidney disease patients with atrial fibrillation given NOACs, compared with those given VKAs.
The evidence for the superiority of NOACs over VKAs for reducing risk of venous thromboembolism (VTE) or VTE-related death was uncertain, as was the evidence to draw any conclusions about benefits and harms of either NOACs or VKAs for patients with advanced or end-stage kidney disease.
Across all trials, NOACs appeared to reduce the relative risk of major bleeding, compared with VKAs by roughly 25%, but the difference was not statistically significant, the researchers noted.
The findings were limited by the lack of evidence for oral anticoagulant use in patients with advanced chronic or end-stage kidney disease, as well as inability to assess differences among NOACs, the researchers noted. However, the results suggest that NOACs may be recommended over VKAs for the subgroup of early-stage chronic kidney disease patients with atrial fibrillation, they said.
Several additional trials are in progress, and future trials “should include not only participants with dialysis-dependent ESKD [end-stage kidney disease] but also those with CrCl [creatinine clearance of] less than 25 mL/min,” and compare NOACs with placebo as well, they noted.
Lead author Dr. Ha is supported by a University Postgraduate Award from University of New South Wales, Sydney, but had no financial conflicts to disclose; coauthors disclosed support from various organizations as well as pharmaceutical companies including Baxter, Amgen, Eli Lilly, Boehringer Ingelheim, Vifor Pharma, Janssen, Pfizer, Bristol-Myers Squibb, and GlaxoSmithKline.
SOURCE: Ha JT et al. Ann Intern Med. 2019 July 15. doi: 10.7326/M19-0087
The significant reduction in risk of hemorrhagic stroke, recurrent venous thromboembolism, and VTE-related deaths in patients with early-stage chronic kidney disease given a NOAC [non–vitamin K oral anticoagulants] in a meta-analysis supports clinical application, but is there a level of renal dysfunction for which clinicians should apply greater caution in extrapolating these findings? As the evidence supporting the safety and effectiveness of NOACs in the general population increases, there is a renewed interest in defining the role of anticoagulant therapy to prevent stroke and VTE in patients with chronic kidney disease and end-stage kidney disease. This interest is driven in part by uncertainty as to the benefits vs. harms of warfarin for patients with chronic kidney disease. The data in the meta-analysis by Ha and colleagues do not support any benefits for patients with end-stage disease, but the results of two ongoing clinical trials of patients with atrial fibrillation and end-stage kidney disease may offer insights.
Until the results of these trials become available, the decision to use anticoagulant therapy in patients with end-stage kidney disease will continue to require an individualized approach that balances potential benefits and harms.
Ainslie Hildebrand, MD, of University of Alberta, Edmonton; Christine Ribic, MD, of McMaster University, Hamilton, Ont.; and Deborah Zimmerman, MD, of the University of Ottawa, made these comments in an accompanying editorial (Ann Intern Med. 2019 July 15. doi:10.7326/M19-1504). Dr. Ribic disclosed grants from Pfizer, Leo Pharma, and Astellas Pharma. Dr. Hildebrand and Dr. Zimmerman had no financial conflicts to disclose.
The significant reduction in risk of hemorrhagic stroke, recurrent venous thromboembolism, and VTE-related deaths in patients with early-stage chronic kidney disease given a NOAC [non–vitamin K oral anticoagulants] in a meta-analysis supports clinical application, but is there a level of renal dysfunction for which clinicians should apply greater caution in extrapolating these findings? As the evidence supporting the safety and effectiveness of NOACs in the general population increases, there is a renewed interest in defining the role of anticoagulant therapy to prevent stroke and VTE in patients with chronic kidney disease and end-stage kidney disease. This interest is driven in part by uncertainty as to the benefits vs. harms of warfarin for patients with chronic kidney disease. The data in the meta-analysis by Ha and colleagues do not support any benefits for patients with end-stage disease, but the results of two ongoing clinical trials of patients with atrial fibrillation and end-stage kidney disease may offer insights.
Until the results of these trials become available, the decision to use anticoagulant therapy in patients with end-stage kidney disease will continue to require an individualized approach that balances potential benefits and harms.
Ainslie Hildebrand, MD, of University of Alberta, Edmonton; Christine Ribic, MD, of McMaster University, Hamilton, Ont.; and Deborah Zimmerman, MD, of the University of Ottawa, made these comments in an accompanying editorial (Ann Intern Med. 2019 July 15. doi:10.7326/M19-1504). Dr. Ribic disclosed grants from Pfizer, Leo Pharma, and Astellas Pharma. Dr. Hildebrand and Dr. Zimmerman had no financial conflicts to disclose.
The significant reduction in risk of hemorrhagic stroke, recurrent venous thromboembolism, and VTE-related deaths in patients with early-stage chronic kidney disease given a NOAC [non–vitamin K oral anticoagulants] in a meta-analysis supports clinical application, but is there a level of renal dysfunction for which clinicians should apply greater caution in extrapolating these findings? As the evidence supporting the safety and effectiveness of NOACs in the general population increases, there is a renewed interest in defining the role of anticoagulant therapy to prevent stroke and VTE in patients with chronic kidney disease and end-stage kidney disease. This interest is driven in part by uncertainty as to the benefits vs. harms of warfarin for patients with chronic kidney disease. The data in the meta-analysis by Ha and colleagues do not support any benefits for patients with end-stage disease, but the results of two ongoing clinical trials of patients with atrial fibrillation and end-stage kidney disease may offer insights.
Until the results of these trials become available, the decision to use anticoagulant therapy in patients with end-stage kidney disease will continue to require an individualized approach that balances potential benefits and harms.
Ainslie Hildebrand, MD, of University of Alberta, Edmonton; Christine Ribic, MD, of McMaster University, Hamilton, Ont.; and Deborah Zimmerman, MD, of the University of Ottawa, made these comments in an accompanying editorial (Ann Intern Med. 2019 July 15. doi:10.7326/M19-1504). Dr. Ribic disclosed grants from Pfizer, Leo Pharma, and Astellas Pharma. Dr. Hildebrand and Dr. Zimmerman had no financial conflicts to disclose.
Non–vitamin K oral anticoagulants (NOACs) significantly reduced the risk of stroke or systemic embolism compared to vitamin K antagonists (VKAs) for patients in the early stages of chronic kidney disease and comorbid atrial fibrillation, based on data from a meta-analysis of roughly 34,000 patients.
Chronic kidney disease increases the risk of complications including stroke, congestive heart failure, and death in patients who also have atrial fibrillation, but most trials of anticoagulant therapy to reduce the risk of such events have excluded these patients, wrote Jeffrey T. Ha, MBBS, of the George Institute for Global Health, Newtown, Australia, and colleagues.
To assess the benefits and harms of oral anticoagulants for multiple indications in chronic kidney disease patients, the researchers conducted a meta-analysis of 45 studies including 34,082 individuals. The findings were published in the Annals of Internal Medicine. The analysis included 8 trials of end stage kidney disease patients on dialysis; the remaining trials excluded patients with creatinine clearance less than 20 mL/min or an estimated glomerular filtration rate less than 15 mL/min per 1.73 m2. The interventional agents were rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, warfarin, and acenocoumarol.
A notable finding was the significant reduction in relative risk of stroke or systemic embolism (21%), hemorrhagic stroke (52%), and intracranial hemorrhage (51%) for early-stage chronic kidney disease patients with atrial fibrillation given NOACs, compared with those given VKAs.
The evidence for the superiority of NOACs over VKAs for reducing risk of venous thromboembolism (VTE) or VTE-related death was uncertain, as was the evidence to draw any conclusions about benefits and harms of either NOACs or VKAs for patients with advanced or end-stage kidney disease.
Across all trials, NOACs appeared to reduce the relative risk of major bleeding, compared with VKAs by roughly 25%, but the difference was not statistically significant, the researchers noted.
The findings were limited by the lack of evidence for oral anticoagulant use in patients with advanced chronic or end-stage kidney disease, as well as inability to assess differences among NOACs, the researchers noted. However, the results suggest that NOACs may be recommended over VKAs for the subgroup of early-stage chronic kidney disease patients with atrial fibrillation, they said.
Several additional trials are in progress, and future trials “should include not only participants with dialysis-dependent ESKD [end-stage kidney disease] but also those with CrCl [creatinine clearance of] less than 25 mL/min,” and compare NOACs with placebo as well, they noted.
Lead author Dr. Ha is supported by a University Postgraduate Award from University of New South Wales, Sydney, but had no financial conflicts to disclose; coauthors disclosed support from various organizations as well as pharmaceutical companies including Baxter, Amgen, Eli Lilly, Boehringer Ingelheim, Vifor Pharma, Janssen, Pfizer, Bristol-Myers Squibb, and GlaxoSmithKline.
SOURCE: Ha JT et al. Ann Intern Med. 2019 July 15. doi: 10.7326/M19-0087
Non–vitamin K oral anticoagulants (NOACs) significantly reduced the risk of stroke or systemic embolism compared to vitamin K antagonists (VKAs) for patients in the early stages of chronic kidney disease and comorbid atrial fibrillation, based on data from a meta-analysis of roughly 34,000 patients.
Chronic kidney disease increases the risk of complications including stroke, congestive heart failure, and death in patients who also have atrial fibrillation, but most trials of anticoagulant therapy to reduce the risk of such events have excluded these patients, wrote Jeffrey T. Ha, MBBS, of the George Institute for Global Health, Newtown, Australia, and colleagues.
To assess the benefits and harms of oral anticoagulants for multiple indications in chronic kidney disease patients, the researchers conducted a meta-analysis of 45 studies including 34,082 individuals. The findings were published in the Annals of Internal Medicine. The analysis included 8 trials of end stage kidney disease patients on dialysis; the remaining trials excluded patients with creatinine clearance less than 20 mL/min or an estimated glomerular filtration rate less than 15 mL/min per 1.73 m2. The interventional agents were rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, warfarin, and acenocoumarol.
A notable finding was the significant reduction in relative risk of stroke or systemic embolism (21%), hemorrhagic stroke (52%), and intracranial hemorrhage (51%) for early-stage chronic kidney disease patients with atrial fibrillation given NOACs, compared with those given VKAs.
The evidence for the superiority of NOACs over VKAs for reducing risk of venous thromboembolism (VTE) or VTE-related death was uncertain, as was the evidence to draw any conclusions about benefits and harms of either NOACs or VKAs for patients with advanced or end-stage kidney disease.
Across all trials, NOACs appeared to reduce the relative risk of major bleeding, compared with VKAs by roughly 25%, but the difference was not statistically significant, the researchers noted.
The findings were limited by the lack of evidence for oral anticoagulant use in patients with advanced chronic or end-stage kidney disease, as well as inability to assess differences among NOACs, the researchers noted. However, the results suggest that NOACs may be recommended over VKAs for the subgroup of early-stage chronic kidney disease patients with atrial fibrillation, they said.
Several additional trials are in progress, and future trials “should include not only participants with dialysis-dependent ESKD [end-stage kidney disease] but also those with CrCl [creatinine clearance of] less than 25 mL/min,” and compare NOACs with placebo as well, they noted.
Lead author Dr. Ha is supported by a University Postgraduate Award from University of New South Wales, Sydney, but had no financial conflicts to disclose; coauthors disclosed support from various organizations as well as pharmaceutical companies including Baxter, Amgen, Eli Lilly, Boehringer Ingelheim, Vifor Pharma, Janssen, Pfizer, Bristol-Myers Squibb, and GlaxoSmithKline.
SOURCE: Ha JT et al. Ann Intern Med. 2019 July 15. doi: 10.7326/M19-0087
FROM THE ANNALS OF INTERNAL MEDICINE
Gaps in patient-provider survivorship communication persist
There has been little to no recent improvement in the large share of cancer patients who are not receiving detailed information about survivorship care, suggests a nationally representative cross-sectional survey.
In 2006, the Institute of Medicine issued a seminal report recommending survivorship care planning to address the special needs of this patient population, noted the investigators, led by Ashish Rai, PhD, American Cancer Society, Framingham, Mass. Other organizations have since issued guidelines and policies in this area.
For the study, Dr. Rai and colleagues analyzed data from 2,266 survivors who completed the 2011 or 2016 Medical Expenditure Panel Survey – Experiences with Cancer questionnaire. Survivors were asked whether any clinician had ever discussed various aspects of survivorship care; responses were dichotomized as having had detailed discussion versus not (brief or no discussion, or not remembering).
Between 2011 and 2016, there was minimal change in the percentage of survivors who reported not receiving detailed information on follow-up care (from 35.1% to 35.4%), late or long-term adverse effects (from 54.2% to 55.5%), lifestyle recommendations (from 58.9% to 57.8%), and emotional or social needs (from 69.2% to 68.2%), the investigators wrote. Their report is in Journal of Oncology Practice.
When analyses were restricted to only those survivors who had received cancer-directed treatment within 3 years of the survey, findings were essentially the same.
About one-quarter of survivors reported having detailed discussions about all four topics in both 2011 (24.4%) and 2016 (21.9%).
In 2016, nearly half of survivors, 47.6%, reported not having detailed discussions with their providers about a summary of their cancer treatments. (This question was not asked in 2011.)
“Despite national efforts and organizations promoting survivorship care planning and highlighting the need for improved quality of survivorship care delivery, clear gaps in quality of communication between survivors of cancer and providers persist,” Dr. Rai and colleagues said.
“Continued efforts are needed to promote communication about survivorship issues, including implementation and evaluation of targeted interventions in key survivorship care areas,” they recommended. “These interventions may consist of furnishing guidance on optimal ways to identify and address survivors’ communication needs, streamlining the flow of information across provider types, ensuring better integration of primary care providers with the survivorship care paradigm, and augmenting the use of health information technology for collection and dissemination of information across the cancer control continuum.”
Dr. Rai did not disclose any relevant conflicts of interest. The study did not receive specific funding.
SOURCE: Rai A et al. J Oncol Pract. 2019 July 2. doi: 10.1200/JOP.19.00157.
There has been little to no recent improvement in the large share of cancer patients who are not receiving detailed information about survivorship care, suggests a nationally representative cross-sectional survey.
In 2006, the Institute of Medicine issued a seminal report recommending survivorship care planning to address the special needs of this patient population, noted the investigators, led by Ashish Rai, PhD, American Cancer Society, Framingham, Mass. Other organizations have since issued guidelines and policies in this area.
For the study, Dr. Rai and colleagues analyzed data from 2,266 survivors who completed the 2011 or 2016 Medical Expenditure Panel Survey – Experiences with Cancer questionnaire. Survivors were asked whether any clinician had ever discussed various aspects of survivorship care; responses were dichotomized as having had detailed discussion versus not (brief or no discussion, or not remembering).
Between 2011 and 2016, there was minimal change in the percentage of survivors who reported not receiving detailed information on follow-up care (from 35.1% to 35.4%), late or long-term adverse effects (from 54.2% to 55.5%), lifestyle recommendations (from 58.9% to 57.8%), and emotional or social needs (from 69.2% to 68.2%), the investigators wrote. Their report is in Journal of Oncology Practice.
When analyses were restricted to only those survivors who had received cancer-directed treatment within 3 years of the survey, findings were essentially the same.
About one-quarter of survivors reported having detailed discussions about all four topics in both 2011 (24.4%) and 2016 (21.9%).
In 2016, nearly half of survivors, 47.6%, reported not having detailed discussions with their providers about a summary of their cancer treatments. (This question was not asked in 2011.)
“Despite national efforts and organizations promoting survivorship care planning and highlighting the need for improved quality of survivorship care delivery, clear gaps in quality of communication between survivors of cancer and providers persist,” Dr. Rai and colleagues said.
“Continued efforts are needed to promote communication about survivorship issues, including implementation and evaluation of targeted interventions in key survivorship care areas,” they recommended. “These interventions may consist of furnishing guidance on optimal ways to identify and address survivors’ communication needs, streamlining the flow of information across provider types, ensuring better integration of primary care providers with the survivorship care paradigm, and augmenting the use of health information technology for collection and dissemination of information across the cancer control continuum.”
Dr. Rai did not disclose any relevant conflicts of interest. The study did not receive specific funding.
SOURCE: Rai A et al. J Oncol Pract. 2019 July 2. doi: 10.1200/JOP.19.00157.
There has been little to no recent improvement in the large share of cancer patients who are not receiving detailed information about survivorship care, suggests a nationally representative cross-sectional survey.
In 2006, the Institute of Medicine issued a seminal report recommending survivorship care planning to address the special needs of this patient population, noted the investigators, led by Ashish Rai, PhD, American Cancer Society, Framingham, Mass. Other organizations have since issued guidelines and policies in this area.
For the study, Dr. Rai and colleagues analyzed data from 2,266 survivors who completed the 2011 or 2016 Medical Expenditure Panel Survey – Experiences with Cancer questionnaire. Survivors were asked whether any clinician had ever discussed various aspects of survivorship care; responses were dichotomized as having had detailed discussion versus not (brief or no discussion, or not remembering).
Between 2011 and 2016, there was minimal change in the percentage of survivors who reported not receiving detailed information on follow-up care (from 35.1% to 35.4%), late or long-term adverse effects (from 54.2% to 55.5%), lifestyle recommendations (from 58.9% to 57.8%), and emotional or social needs (from 69.2% to 68.2%), the investigators wrote. Their report is in Journal of Oncology Practice.
When analyses were restricted to only those survivors who had received cancer-directed treatment within 3 years of the survey, findings were essentially the same.
About one-quarter of survivors reported having detailed discussions about all four topics in both 2011 (24.4%) and 2016 (21.9%).
In 2016, nearly half of survivors, 47.6%, reported not having detailed discussions with their providers about a summary of their cancer treatments. (This question was not asked in 2011.)
“Despite national efforts and organizations promoting survivorship care planning and highlighting the need for improved quality of survivorship care delivery, clear gaps in quality of communication between survivors of cancer and providers persist,” Dr. Rai and colleagues said.
“Continued efforts are needed to promote communication about survivorship issues, including implementation and evaluation of targeted interventions in key survivorship care areas,” they recommended. “These interventions may consist of furnishing guidance on optimal ways to identify and address survivors’ communication needs, streamlining the flow of information across provider types, ensuring better integration of primary care providers with the survivorship care paradigm, and augmenting the use of health information technology for collection and dissemination of information across the cancer control continuum.”
Dr. Rai did not disclose any relevant conflicts of interest. The study did not receive specific funding.
SOURCE: Rai A et al. J Oncol Pract. 2019 July 2. doi: 10.1200/JOP.19.00157.
FROM THE JOURNAL OF ONCOLOGY PRACTICE
Noninvasive prenatal test may detect sickle cell disease
FORT LAUDERDALE, FLA. — Researchers have developed an assay that can be used in noninvasive prenatal testing (NIPT) of cell-free fetal DNA present in maternal blood to identify sickle cell disease without using paternal DNA, which could provide an alternative to other invasive methods, according to results of a pilot study.
The novel NIPT assay had a sensitivity greater than 98% and a specificity greater than 99% in early-phase analysis, Vivien A. Sheehan, MD, PhD, of Baylor College of Medicine, Houston, reported at the annual meeting of the Foundation for Sickle Cell Disease Research.
“Noninvasive prenatal testing is a safe and affordable alternative to chorionic villus sampling or amniocentesis and can be performed earlier in pregnancy,” Dr. Sheehan said. “There is a lot of potential for the growth of this test and its impact not only in this country, but worldwide.”
The NIPT uses cell-free fetal DNA from the pregnant mother’s peripheral blood.
“We know that fetal DNA is present in maternal blood and can comprise about 10% by the 10th week of gestation, and it increases as pregnancy progresses,” Dr. Sheehan said.
Maternal alleles from the baby and mother, as well as paternal alleles from the baby, can be identified in maternal blood. “By analyzing cell-free DNA in maternal blood via next-generation sequencing, we can determine fetal disease status,” she said.
Dr. Sheehan noted some reports have supported the use of NIPT for identifying trisomy and aneuploidy, but NIPT has encountered some challenges in identifying autosomal recessive disorders such as sickle cell disease.
To accomplish this, researchers at Baylor and test developer BillionToOne, developed a novel sequencing-based molecular counting strategy that can help measure the ratio of mutant versus normal alleles, Dr. Sheehan said.
The results obtained to date indicate that the assay reliably detects fetal sickle cell disease status when the fetal fraction is as low as 5%, the same limit as aneuploidy NIPT.
The method uses a commercial DNA extraction kit to isolate and purify cell-free fetal DNA from a single blood draw, then performs sickle cell disease NIPT assays using proprietary reagents, Dr. Sheehan explained. The protocol includes bioinformatic analyses that are used to determine hemoglobin S (HbS) mutation ratio and fetal disease status.
The pilot study had two phases. In the first phase, which has been completed, researchers sought to optimize the beta-globin gene probes using cell-free fetal DNA from compound heterozygote patients with sickle cell disease to establish the expected ratio of HbS mutation.
In the second phase, the researchers validated the test on pregnant women with sickle cell trait or sickle cell disease by performing the assay in maternal samples collected between 10-35 weeks of gestation.
Among the six controls who have sickle cell trait, the NIPT reported no false positives when compared with the state newborn screen results, Dr. Sheehan said. For the one participant with sickle cell anemia, the NIPT and newborn screening concurred on two blood draws, but the NIPT was inconclusive on the first blood draw obtained at 10 weeks’ gestation because of low levels of cell-free fetal DNA.
Overall, the analysis showed an analytical sensitivity greater than 98% and a specificity greater than 99%, even in the absence of paternal DNA, the study found.
BillionToOne developed the test. Dr. Sheehan reported having no financial relationships to disclose.
SOURCE: Sheehan VA et al. FSCDR 2019, Abstract JSCDH-D-19-00048.
FORT LAUDERDALE, FLA. — Researchers have developed an assay that can be used in noninvasive prenatal testing (NIPT) of cell-free fetal DNA present in maternal blood to identify sickle cell disease without using paternal DNA, which could provide an alternative to other invasive methods, according to results of a pilot study.
The novel NIPT assay had a sensitivity greater than 98% and a specificity greater than 99% in early-phase analysis, Vivien A. Sheehan, MD, PhD, of Baylor College of Medicine, Houston, reported at the annual meeting of the Foundation for Sickle Cell Disease Research.
“Noninvasive prenatal testing is a safe and affordable alternative to chorionic villus sampling or amniocentesis and can be performed earlier in pregnancy,” Dr. Sheehan said. “There is a lot of potential for the growth of this test and its impact not only in this country, but worldwide.”
The NIPT uses cell-free fetal DNA from the pregnant mother’s peripheral blood.
“We know that fetal DNA is present in maternal blood and can comprise about 10% by the 10th week of gestation, and it increases as pregnancy progresses,” Dr. Sheehan said.
Maternal alleles from the baby and mother, as well as paternal alleles from the baby, can be identified in maternal blood. “By analyzing cell-free DNA in maternal blood via next-generation sequencing, we can determine fetal disease status,” she said.
Dr. Sheehan noted some reports have supported the use of NIPT for identifying trisomy and aneuploidy, but NIPT has encountered some challenges in identifying autosomal recessive disorders such as sickle cell disease.
To accomplish this, researchers at Baylor and test developer BillionToOne, developed a novel sequencing-based molecular counting strategy that can help measure the ratio of mutant versus normal alleles, Dr. Sheehan said.
The results obtained to date indicate that the assay reliably detects fetal sickle cell disease status when the fetal fraction is as low as 5%, the same limit as aneuploidy NIPT.
The method uses a commercial DNA extraction kit to isolate and purify cell-free fetal DNA from a single blood draw, then performs sickle cell disease NIPT assays using proprietary reagents, Dr. Sheehan explained. The protocol includes bioinformatic analyses that are used to determine hemoglobin S (HbS) mutation ratio and fetal disease status.
The pilot study had two phases. In the first phase, which has been completed, researchers sought to optimize the beta-globin gene probes using cell-free fetal DNA from compound heterozygote patients with sickle cell disease to establish the expected ratio of HbS mutation.
In the second phase, the researchers validated the test on pregnant women with sickle cell trait or sickle cell disease by performing the assay in maternal samples collected between 10-35 weeks of gestation.
Among the six controls who have sickle cell trait, the NIPT reported no false positives when compared with the state newborn screen results, Dr. Sheehan said. For the one participant with sickle cell anemia, the NIPT and newborn screening concurred on two blood draws, but the NIPT was inconclusive on the first blood draw obtained at 10 weeks’ gestation because of low levels of cell-free fetal DNA.
Overall, the analysis showed an analytical sensitivity greater than 98% and a specificity greater than 99%, even in the absence of paternal DNA, the study found.
BillionToOne developed the test. Dr. Sheehan reported having no financial relationships to disclose.
SOURCE: Sheehan VA et al. FSCDR 2019, Abstract JSCDH-D-19-00048.
FORT LAUDERDALE, FLA. — Researchers have developed an assay that can be used in noninvasive prenatal testing (NIPT) of cell-free fetal DNA present in maternal blood to identify sickle cell disease without using paternal DNA, which could provide an alternative to other invasive methods, according to results of a pilot study.
The novel NIPT assay had a sensitivity greater than 98% and a specificity greater than 99% in early-phase analysis, Vivien A. Sheehan, MD, PhD, of Baylor College of Medicine, Houston, reported at the annual meeting of the Foundation for Sickle Cell Disease Research.
“Noninvasive prenatal testing is a safe and affordable alternative to chorionic villus sampling or amniocentesis and can be performed earlier in pregnancy,” Dr. Sheehan said. “There is a lot of potential for the growth of this test and its impact not only in this country, but worldwide.”
The NIPT uses cell-free fetal DNA from the pregnant mother’s peripheral blood.
“We know that fetal DNA is present in maternal blood and can comprise about 10% by the 10th week of gestation, and it increases as pregnancy progresses,” Dr. Sheehan said.
Maternal alleles from the baby and mother, as well as paternal alleles from the baby, can be identified in maternal blood. “By analyzing cell-free DNA in maternal blood via next-generation sequencing, we can determine fetal disease status,” she said.
Dr. Sheehan noted some reports have supported the use of NIPT for identifying trisomy and aneuploidy, but NIPT has encountered some challenges in identifying autosomal recessive disorders such as sickle cell disease.
To accomplish this, researchers at Baylor and test developer BillionToOne, developed a novel sequencing-based molecular counting strategy that can help measure the ratio of mutant versus normal alleles, Dr. Sheehan said.
The results obtained to date indicate that the assay reliably detects fetal sickle cell disease status when the fetal fraction is as low as 5%, the same limit as aneuploidy NIPT.
The method uses a commercial DNA extraction kit to isolate and purify cell-free fetal DNA from a single blood draw, then performs sickle cell disease NIPT assays using proprietary reagents, Dr. Sheehan explained. The protocol includes bioinformatic analyses that are used to determine hemoglobin S (HbS) mutation ratio and fetal disease status.
The pilot study had two phases. In the first phase, which has been completed, researchers sought to optimize the beta-globin gene probes using cell-free fetal DNA from compound heterozygote patients with sickle cell disease to establish the expected ratio of HbS mutation.
In the second phase, the researchers validated the test on pregnant women with sickle cell trait or sickle cell disease by performing the assay in maternal samples collected between 10-35 weeks of gestation.
Among the six controls who have sickle cell trait, the NIPT reported no false positives when compared with the state newborn screen results, Dr. Sheehan said. For the one participant with sickle cell anemia, the NIPT and newborn screening concurred on two blood draws, but the NIPT was inconclusive on the first blood draw obtained at 10 weeks’ gestation because of low levels of cell-free fetal DNA.
Overall, the analysis showed an analytical sensitivity greater than 98% and a specificity greater than 99%, even in the absence of paternal DNA, the study found.
BillionToOne developed the test. Dr. Sheehan reported having no financial relationships to disclose.
SOURCE: Sheehan VA et al. FSCDR 2019, Abstract JSCDH-D-19-00048.
REPORTING FROM FSCDR 2019
Crizanlizumab shows posttreatment effect in sickle cell
FORT LAUDERDALE, FLA. – Sickle cell patients who received high-dose crizanlizumab had fewer vaso-occlusive crises (VOCs) than patients on a low-dose regimen a year after stopping the treatment, findings from a real-world follow-up study suggest.
But hospitalization rates and use of other health care resources were similar during and after therapy, regardless of dose, Nirmish Shah, MD, of Duke Health in Durham, N.C., reported at the annual meeting of the Foundation for Sickle Cell Disease Research.
“This is our attempt at a real-world study of patients after being in a big study that has good results and what happens to them afterward in regard to VOCs and health care utilization,” Dr. Shah said.
He reported results from the SUCCESSOR trial – a multicenter, retrospective cohort study – that evaluated a subset of 48 adult patients up to a year after they completed the SUSTAIN placebo-controlled phase 2 trial of crizanlizumab, a P-selectin inhibitor designed to control sickle cell pain crises.
In SUSTAIN, researchers evaluated two different dosages of crizanlizumab: 5 mg/kg and 2.5 mg/kg.
In the follow-up study, researchers obtained data from medical records over the study period November 2014 to March 2017. Crizanlizumab was not administered in the 52 weeks following the SUSTAIN trial.
They found that the subset of patients on the high dose of crizanlizumab had annual VOC rates of 2.7, compared with 4.0 among patients on the low dose of the drug. By comparison, VOC rates in SUSTAIN were 1.7 per year for the 5-mg/kg–dose group and 3.2 per year for the 2.5-mg/kg–dose group.
Overall, at least 60% of patients in the follow-up study had at least one hospitalization in the year after SUSTAIN. In the higher-dose group, the rates of hospitalization were similar in both SUSTAIN and SUCCESSOR – 53%. In the lower-dose group, hospitalization rates were 67% and 61% in SUCCESSOR and SUSTAIN, respectively.
“Among the previously treated patients with crizanlizumab, the total number of emergency department visits did seem to be higher in SUCCESSOR,” Dr. Shah said.
The study was limited by its retrospective nature and the fact that full data sets and follow-up were available on only a small number of patients, Dr. Shah said. “It was underpowered for a statistical analysis between groups,” he said. The goal was to determine the drug’s effect after treatment is discontinued, he said.
Dr. Shah reported a financial relationship with Novartis, which is developing crizanlizumab.
SOURCE: Shah N et al. FSCDR 2019, Abstract JSCDH-D-19-00031.
FORT LAUDERDALE, FLA. – Sickle cell patients who received high-dose crizanlizumab had fewer vaso-occlusive crises (VOCs) than patients on a low-dose regimen a year after stopping the treatment, findings from a real-world follow-up study suggest.
But hospitalization rates and use of other health care resources were similar during and after therapy, regardless of dose, Nirmish Shah, MD, of Duke Health in Durham, N.C., reported at the annual meeting of the Foundation for Sickle Cell Disease Research.
“This is our attempt at a real-world study of patients after being in a big study that has good results and what happens to them afterward in regard to VOCs and health care utilization,” Dr. Shah said.
He reported results from the SUCCESSOR trial – a multicenter, retrospective cohort study – that evaluated a subset of 48 adult patients up to a year after they completed the SUSTAIN placebo-controlled phase 2 trial of crizanlizumab, a P-selectin inhibitor designed to control sickle cell pain crises.
In SUSTAIN, researchers evaluated two different dosages of crizanlizumab: 5 mg/kg and 2.5 mg/kg.
In the follow-up study, researchers obtained data from medical records over the study period November 2014 to March 2017. Crizanlizumab was not administered in the 52 weeks following the SUSTAIN trial.
They found that the subset of patients on the high dose of crizanlizumab had annual VOC rates of 2.7, compared with 4.0 among patients on the low dose of the drug. By comparison, VOC rates in SUSTAIN were 1.7 per year for the 5-mg/kg–dose group and 3.2 per year for the 2.5-mg/kg–dose group.
Overall, at least 60% of patients in the follow-up study had at least one hospitalization in the year after SUSTAIN. In the higher-dose group, the rates of hospitalization were similar in both SUSTAIN and SUCCESSOR – 53%. In the lower-dose group, hospitalization rates were 67% and 61% in SUCCESSOR and SUSTAIN, respectively.
“Among the previously treated patients with crizanlizumab, the total number of emergency department visits did seem to be higher in SUCCESSOR,” Dr. Shah said.
The study was limited by its retrospective nature and the fact that full data sets and follow-up were available on only a small number of patients, Dr. Shah said. “It was underpowered for a statistical analysis between groups,” he said. The goal was to determine the drug’s effect after treatment is discontinued, he said.
Dr. Shah reported a financial relationship with Novartis, which is developing crizanlizumab.
SOURCE: Shah N et al. FSCDR 2019, Abstract JSCDH-D-19-00031.
FORT LAUDERDALE, FLA. – Sickle cell patients who received high-dose crizanlizumab had fewer vaso-occlusive crises (VOCs) than patients on a low-dose regimen a year after stopping the treatment, findings from a real-world follow-up study suggest.
But hospitalization rates and use of other health care resources were similar during and after therapy, regardless of dose, Nirmish Shah, MD, of Duke Health in Durham, N.C., reported at the annual meeting of the Foundation for Sickle Cell Disease Research.
“This is our attempt at a real-world study of patients after being in a big study that has good results and what happens to them afterward in regard to VOCs and health care utilization,” Dr. Shah said.
He reported results from the SUCCESSOR trial – a multicenter, retrospective cohort study – that evaluated a subset of 48 adult patients up to a year after they completed the SUSTAIN placebo-controlled phase 2 trial of crizanlizumab, a P-selectin inhibitor designed to control sickle cell pain crises.
In SUSTAIN, researchers evaluated two different dosages of crizanlizumab: 5 mg/kg and 2.5 mg/kg.
In the follow-up study, researchers obtained data from medical records over the study period November 2014 to March 2017. Crizanlizumab was not administered in the 52 weeks following the SUSTAIN trial.
They found that the subset of patients on the high dose of crizanlizumab had annual VOC rates of 2.7, compared with 4.0 among patients on the low dose of the drug. By comparison, VOC rates in SUSTAIN were 1.7 per year for the 5-mg/kg–dose group and 3.2 per year for the 2.5-mg/kg–dose group.
Overall, at least 60% of patients in the follow-up study had at least one hospitalization in the year after SUSTAIN. In the higher-dose group, the rates of hospitalization were similar in both SUSTAIN and SUCCESSOR – 53%. In the lower-dose group, hospitalization rates were 67% and 61% in SUCCESSOR and SUSTAIN, respectively.
“Among the previously treated patients with crizanlizumab, the total number of emergency department visits did seem to be higher in SUCCESSOR,” Dr. Shah said.
The study was limited by its retrospective nature and the fact that full data sets and follow-up were available on only a small number of patients, Dr. Shah said. “It was underpowered for a statistical analysis between groups,” he said. The goal was to determine the drug’s effect after treatment is discontinued, he said.
Dr. Shah reported a financial relationship with Novartis, which is developing crizanlizumab.
SOURCE: Shah N et al. FSCDR 2019, Abstract JSCDH-D-19-00031.
REPORTING FROM FSCDR 2019
SC daratumumab deemed feasible for every multiple myeloma patient
CHICAGO – Subcutaneous (SC) daratumumab is noninferior to intravenous (IV) daratumumab for patients with relapsed or refractory multiple myeloma (MM), according findings from a phase 3 trial.
In the COLUMBA trial, SC daratumumab proved noninferior to IV daratumumab with regard to overall response rate and maximum trough concentration (Ctrough).
The safety profiles of the two formulations were similar, although patients who received SC daratumumab had a lower rate of infusion-related reactions. SC daratumumab also had a lower treatment burden.
“The COLUMBA study shows that [SC daratumumab] can be used in every myeloma patient [as a] single agent or, maybe in the future, in combination with the different backbones,” said Maria-Victoria Mateos, MD, PhD, of University Hospital of Salamanca (Spain).
Dr. Mateos presented results from the COLUMBA trial at the annual meeting of the American Society of Clinical Oncology.
Dr. Mateos cited a previous phase 1b study that had suggested that SC daratumumab might produce similar results as IV daratumumab (Blood. 2017;130:838) while providing a more convenient delivery method. She pointed out that infusions of IV daratumumab can last hours, while the SC formulation can be delivered in minutes.
The aim of the phase 3 COLUMBA study was to compare the IV and SC formulations head-to-head. The trial enrolled 522 patients with relapsed/refractory multiple myeloma. They were randomized to receive daratumumab SC (n = 263) or IV (n = 259).
The median patient age was 68 years (range, 33-92 years) in the IV arm and 65 years (range, 42-84 years) in the SC arm. Patients had received a median of four prior lines of therapy (range, 1-15 in the IV arm and 2-12 in the SC arm). Most patients were refractory to their last line of therapy – 85% in the IV arm and 80% in the SC arm – and most patients had standard-risk cytogenetics – 83% and 74%, respectively.
Treatment
Patients received SC daratumumab at 1,800 mg and IV daratumumab at 16 mg/kg. Both were given weekly for cycles 1-2, every 2 weeks for cycles 3-6, and every 4 weeks thereafter until disease progression.
The median duration of the first infusion was 421 minutes in the IV arm and 5 minutes in the SC arm. The median duration of the second infusion was 255 minutes and 5 minutes, respectively, and the median duration of subsequent infusions was 205 minutes and 5 minutes, respectively.
At a median follow-up of 7.46 months, 57% of patients in each arm had discontinued the study treatment. The most common reasons for discontinuation were progression – 44% of the IV arm and 43% of the SC arm – and adverse events (AEs) – 8% and 7%, respectively.
Safety
Dr. Mateos said the safety profiles of IV and SC daratumumab were comparable. However, infusion-related reactions were significantly less likely in the SC arm, occurring in 12.7% of those patients and 34.5% of patients in the IV arm (P less than .0001).
Grade 3 or higher treatment-emergent AEs occurred in 49% of patients in the IV arm and 46% of those in the SC arm. Rates of grade 5 AEs were 7% and 5%, respectively. The most common grade 3/4 AEs (in the IV and SC arms, respectively) were anemia (14% and 13%), thrombocytopenia (14% for both), neutropenia (8% and 13%), lymphopenia (6% and 5%), and hypertension (6% and 3%).
Efficacy
One of the study’s primary endpoints was overall response rate, which was 37.1% in the IV arm and 41.1% in the SC arm (relative risk, 1.11; 95% CI, 0.89-1.37; P less than .0001). This met the criteria for noninferiority, and overall response rates were comparable across all patient subgroups, Dr. Mateos noted.
The rates of complete response or stringent complete response were also comparable at 2.7% in the IV arm and 1.9% in the SC arm. Rates of very good partial response were 17.0% and 19.0%, respectively.
The study’s other primary endpoint was maximum Ctrough predose on day 1 of cycle 3. The ratio of maximum Ctrough for daratumumab SC over IV was 107.93% (90% CI, 95.74%-121.67%), which met the noninferiority criterion.
Survival outcomes were also similar between the IV and SC arms. The median progression-free survival was 6.1 months and 5.6 months, respectively (P = .9258). The rate of overall survival at 6 months was 83.0% and 87.5%, respectively (P = .6032).
Considering these results together, Dr. Mateos and colleagues concluded that SC daratumumab is noninferior to IV daratumumab.
“[SC daratumumab] has a reduced treatment burden due to a considerably shorter administration duration, and patients treated with [SC daratumumab] reported higher satisfaction with therapy,” Dr. Mateos said.
The results support the use of flat-dose 1,800-mg SC daratumumab, which is comparable with the IV formulation, she said.
The COLUMBA trial was sponsored by Janssen Research & Development. Dr. Mateos reported relationships with Amgen, Celgene, Janssen-Cilag, and Takeda.
SOURCE: Mateos MV et al. ASCO 2019, Abstract 8005.
CHICAGO – Subcutaneous (SC) daratumumab is noninferior to intravenous (IV) daratumumab for patients with relapsed or refractory multiple myeloma (MM), according findings from a phase 3 trial.
In the COLUMBA trial, SC daratumumab proved noninferior to IV daratumumab with regard to overall response rate and maximum trough concentration (Ctrough).
The safety profiles of the two formulations were similar, although patients who received SC daratumumab had a lower rate of infusion-related reactions. SC daratumumab also had a lower treatment burden.
“The COLUMBA study shows that [SC daratumumab] can be used in every myeloma patient [as a] single agent or, maybe in the future, in combination with the different backbones,” said Maria-Victoria Mateos, MD, PhD, of University Hospital of Salamanca (Spain).
Dr. Mateos presented results from the COLUMBA trial at the annual meeting of the American Society of Clinical Oncology.
Dr. Mateos cited a previous phase 1b study that had suggested that SC daratumumab might produce similar results as IV daratumumab (Blood. 2017;130:838) while providing a more convenient delivery method. She pointed out that infusions of IV daratumumab can last hours, while the SC formulation can be delivered in minutes.
The aim of the phase 3 COLUMBA study was to compare the IV and SC formulations head-to-head. The trial enrolled 522 patients with relapsed/refractory multiple myeloma. They were randomized to receive daratumumab SC (n = 263) or IV (n = 259).
The median patient age was 68 years (range, 33-92 years) in the IV arm and 65 years (range, 42-84 years) in the SC arm. Patients had received a median of four prior lines of therapy (range, 1-15 in the IV arm and 2-12 in the SC arm). Most patients were refractory to their last line of therapy – 85% in the IV arm and 80% in the SC arm – and most patients had standard-risk cytogenetics – 83% and 74%, respectively.
Treatment
Patients received SC daratumumab at 1,800 mg and IV daratumumab at 16 mg/kg. Both were given weekly for cycles 1-2, every 2 weeks for cycles 3-6, and every 4 weeks thereafter until disease progression.
The median duration of the first infusion was 421 minutes in the IV arm and 5 minutes in the SC arm. The median duration of the second infusion was 255 minutes and 5 minutes, respectively, and the median duration of subsequent infusions was 205 minutes and 5 minutes, respectively.
At a median follow-up of 7.46 months, 57% of patients in each arm had discontinued the study treatment. The most common reasons for discontinuation were progression – 44% of the IV arm and 43% of the SC arm – and adverse events (AEs) – 8% and 7%, respectively.
Safety
Dr. Mateos said the safety profiles of IV and SC daratumumab were comparable. However, infusion-related reactions were significantly less likely in the SC arm, occurring in 12.7% of those patients and 34.5% of patients in the IV arm (P less than .0001).
Grade 3 or higher treatment-emergent AEs occurred in 49% of patients in the IV arm and 46% of those in the SC arm. Rates of grade 5 AEs were 7% and 5%, respectively. The most common grade 3/4 AEs (in the IV and SC arms, respectively) were anemia (14% and 13%), thrombocytopenia (14% for both), neutropenia (8% and 13%), lymphopenia (6% and 5%), and hypertension (6% and 3%).
Efficacy
One of the study’s primary endpoints was overall response rate, which was 37.1% in the IV arm and 41.1% in the SC arm (relative risk, 1.11; 95% CI, 0.89-1.37; P less than .0001). This met the criteria for noninferiority, and overall response rates were comparable across all patient subgroups, Dr. Mateos noted.
The rates of complete response or stringent complete response were also comparable at 2.7% in the IV arm and 1.9% in the SC arm. Rates of very good partial response were 17.0% and 19.0%, respectively.
The study’s other primary endpoint was maximum Ctrough predose on day 1 of cycle 3. The ratio of maximum Ctrough for daratumumab SC over IV was 107.93% (90% CI, 95.74%-121.67%), which met the noninferiority criterion.
Survival outcomes were also similar between the IV and SC arms. The median progression-free survival was 6.1 months and 5.6 months, respectively (P = .9258). The rate of overall survival at 6 months was 83.0% and 87.5%, respectively (P = .6032).
Considering these results together, Dr. Mateos and colleagues concluded that SC daratumumab is noninferior to IV daratumumab.
“[SC daratumumab] has a reduced treatment burden due to a considerably shorter administration duration, and patients treated with [SC daratumumab] reported higher satisfaction with therapy,” Dr. Mateos said.
The results support the use of flat-dose 1,800-mg SC daratumumab, which is comparable with the IV formulation, she said.
The COLUMBA trial was sponsored by Janssen Research & Development. Dr. Mateos reported relationships with Amgen, Celgene, Janssen-Cilag, and Takeda.
SOURCE: Mateos MV et al. ASCO 2019, Abstract 8005.
CHICAGO – Subcutaneous (SC) daratumumab is noninferior to intravenous (IV) daratumumab for patients with relapsed or refractory multiple myeloma (MM), according findings from a phase 3 trial.
In the COLUMBA trial, SC daratumumab proved noninferior to IV daratumumab with regard to overall response rate and maximum trough concentration (Ctrough).
The safety profiles of the two formulations were similar, although patients who received SC daratumumab had a lower rate of infusion-related reactions. SC daratumumab also had a lower treatment burden.
“The COLUMBA study shows that [SC daratumumab] can be used in every myeloma patient [as a] single agent or, maybe in the future, in combination with the different backbones,” said Maria-Victoria Mateos, MD, PhD, of University Hospital of Salamanca (Spain).
Dr. Mateos presented results from the COLUMBA trial at the annual meeting of the American Society of Clinical Oncology.
Dr. Mateos cited a previous phase 1b study that had suggested that SC daratumumab might produce similar results as IV daratumumab (Blood. 2017;130:838) while providing a more convenient delivery method. She pointed out that infusions of IV daratumumab can last hours, while the SC formulation can be delivered in minutes.
The aim of the phase 3 COLUMBA study was to compare the IV and SC formulations head-to-head. The trial enrolled 522 patients with relapsed/refractory multiple myeloma. They were randomized to receive daratumumab SC (n = 263) or IV (n = 259).
The median patient age was 68 years (range, 33-92 years) in the IV arm and 65 years (range, 42-84 years) in the SC arm. Patients had received a median of four prior lines of therapy (range, 1-15 in the IV arm and 2-12 in the SC arm). Most patients were refractory to their last line of therapy – 85% in the IV arm and 80% in the SC arm – and most patients had standard-risk cytogenetics – 83% and 74%, respectively.
Treatment
Patients received SC daratumumab at 1,800 mg and IV daratumumab at 16 mg/kg. Both were given weekly for cycles 1-2, every 2 weeks for cycles 3-6, and every 4 weeks thereafter until disease progression.
The median duration of the first infusion was 421 minutes in the IV arm and 5 minutes in the SC arm. The median duration of the second infusion was 255 minutes and 5 minutes, respectively, and the median duration of subsequent infusions was 205 minutes and 5 minutes, respectively.
At a median follow-up of 7.46 months, 57% of patients in each arm had discontinued the study treatment. The most common reasons for discontinuation were progression – 44% of the IV arm and 43% of the SC arm – and adverse events (AEs) – 8% and 7%, respectively.
Safety
Dr. Mateos said the safety profiles of IV and SC daratumumab were comparable. However, infusion-related reactions were significantly less likely in the SC arm, occurring in 12.7% of those patients and 34.5% of patients in the IV arm (P less than .0001).
Grade 3 or higher treatment-emergent AEs occurred in 49% of patients in the IV arm and 46% of those in the SC arm. Rates of grade 5 AEs were 7% and 5%, respectively. The most common grade 3/4 AEs (in the IV and SC arms, respectively) were anemia (14% and 13%), thrombocytopenia (14% for both), neutropenia (8% and 13%), lymphopenia (6% and 5%), and hypertension (6% and 3%).
Efficacy
One of the study’s primary endpoints was overall response rate, which was 37.1% in the IV arm and 41.1% in the SC arm (relative risk, 1.11; 95% CI, 0.89-1.37; P less than .0001). This met the criteria for noninferiority, and overall response rates were comparable across all patient subgroups, Dr. Mateos noted.
The rates of complete response or stringent complete response were also comparable at 2.7% in the IV arm and 1.9% in the SC arm. Rates of very good partial response were 17.0% and 19.0%, respectively.
The study’s other primary endpoint was maximum Ctrough predose on day 1 of cycle 3. The ratio of maximum Ctrough for daratumumab SC over IV was 107.93% (90% CI, 95.74%-121.67%), which met the noninferiority criterion.
Survival outcomes were also similar between the IV and SC arms. The median progression-free survival was 6.1 months and 5.6 months, respectively (P = .9258). The rate of overall survival at 6 months was 83.0% and 87.5%, respectively (P = .6032).
Considering these results together, Dr. Mateos and colleagues concluded that SC daratumumab is noninferior to IV daratumumab.
“[SC daratumumab] has a reduced treatment burden due to a considerably shorter administration duration, and patients treated with [SC daratumumab] reported higher satisfaction with therapy,” Dr. Mateos said.
The results support the use of flat-dose 1,800-mg SC daratumumab, which is comparable with the IV formulation, she said.
The COLUMBA trial was sponsored by Janssen Research & Development. Dr. Mateos reported relationships with Amgen, Celgene, Janssen-Cilag, and Takeda.
SOURCE: Mateos MV et al. ASCO 2019, Abstract 8005.
REPORTING FROM ASCO 2019
Another study supports safety of 2-cm margins for thick melanomas
based on data from a randomized, multicenter trial of 936 patients.
“Over time, and in light of the findings of several randomized studies, less extensive surgery for primary melanoma with tumor thickness greater than 2 mm has become more established,” and most recent guidelines recommend a 2-cm margin for these tumors, wrote Deborah Utjés, MD, of the Karolinska Institute in Stockholm and colleagues.
To reinforce the safety and effectiveness of the 2-cm margin, the researchers conducted an open-label, randomized trial of clinically staged melanoma patients aged 75 years and younger with localized cutaneous melanomas thicker than 2 mm, from January 1992 to May 2004. Patients were treated in Denmark, Estonia, Norway, and Sweden. The findings were published in the Lancet.
Patients were randomized to treatment with a 2-cm (471) or 4-cm excision margin (465). The melanomas were located on the trunk, upper extremities, or lower extremities.
The primary outcome of overall survival was similar between the groups. Over a median 20-year follow-up period, the death rate was approximately 50% in each group (49% in the 2-cm group and 51% in the 4-cm group). Disease-specific survival rates were similar as well. Of the 621 reported deaths, 397 were attributed to melanoma: 192 (48%) in the 2-cm group and 205 (52%) in the 4-cm group.
The study findings were limited by several factors, including a lower-than-expected number of patients, lack of nodal staging during the study period, and a focus only on the surgical margin without recording data on pathological excision margins.
However, the extended follow-up supports the safe use of the 2-cm margin for the treatment of melanomas thicker than 2 mm, the investigators wrote. In addition, results from an ongoing trial comparing 1-cm and 2-cm margins for melanomas at least 1 mm thick may yield more evidence to support still narrower surgical margins for some cutaneous melanomas.
The study notes that guidelines from organizations that include the American National Comprehensive Cancer Network and the American Academy of Dermatology recommend the 2-cm margin for tumors that are thicker than 2 mm.
The study was supported by the Swedish Cancer Society, Stockholm Cancer Society, Swedish Society for Medical Research, and the Stockholm County Council, and by funds from Radiumhemmet Research and Wallström. The authors reported no disclosures.
SOURCE: Utjés D et al. Lancet. 2019 Jul 4. doi: 10.1016/S0140-6736(19)31132-8.
based on data from a randomized, multicenter trial of 936 patients.
“Over time, and in light of the findings of several randomized studies, less extensive surgery for primary melanoma with tumor thickness greater than 2 mm has become more established,” and most recent guidelines recommend a 2-cm margin for these tumors, wrote Deborah Utjés, MD, of the Karolinska Institute in Stockholm and colleagues.
To reinforce the safety and effectiveness of the 2-cm margin, the researchers conducted an open-label, randomized trial of clinically staged melanoma patients aged 75 years and younger with localized cutaneous melanomas thicker than 2 mm, from January 1992 to May 2004. Patients were treated in Denmark, Estonia, Norway, and Sweden. The findings were published in the Lancet.
Patients were randomized to treatment with a 2-cm (471) or 4-cm excision margin (465). The melanomas were located on the trunk, upper extremities, or lower extremities.
The primary outcome of overall survival was similar between the groups. Over a median 20-year follow-up period, the death rate was approximately 50% in each group (49% in the 2-cm group and 51% in the 4-cm group). Disease-specific survival rates were similar as well. Of the 621 reported deaths, 397 were attributed to melanoma: 192 (48%) in the 2-cm group and 205 (52%) in the 4-cm group.
The study findings were limited by several factors, including a lower-than-expected number of patients, lack of nodal staging during the study period, and a focus only on the surgical margin without recording data on pathological excision margins.
However, the extended follow-up supports the safe use of the 2-cm margin for the treatment of melanomas thicker than 2 mm, the investigators wrote. In addition, results from an ongoing trial comparing 1-cm and 2-cm margins for melanomas at least 1 mm thick may yield more evidence to support still narrower surgical margins for some cutaneous melanomas.
The study notes that guidelines from organizations that include the American National Comprehensive Cancer Network and the American Academy of Dermatology recommend the 2-cm margin for tumors that are thicker than 2 mm.
The study was supported by the Swedish Cancer Society, Stockholm Cancer Society, Swedish Society for Medical Research, and the Stockholm County Council, and by funds from Radiumhemmet Research and Wallström. The authors reported no disclosures.
SOURCE: Utjés D et al. Lancet. 2019 Jul 4. doi: 10.1016/S0140-6736(19)31132-8.
based on data from a randomized, multicenter trial of 936 patients.
“Over time, and in light of the findings of several randomized studies, less extensive surgery for primary melanoma with tumor thickness greater than 2 mm has become more established,” and most recent guidelines recommend a 2-cm margin for these tumors, wrote Deborah Utjés, MD, of the Karolinska Institute in Stockholm and colleagues.
To reinforce the safety and effectiveness of the 2-cm margin, the researchers conducted an open-label, randomized trial of clinically staged melanoma patients aged 75 years and younger with localized cutaneous melanomas thicker than 2 mm, from January 1992 to May 2004. Patients were treated in Denmark, Estonia, Norway, and Sweden. The findings were published in the Lancet.
Patients were randomized to treatment with a 2-cm (471) or 4-cm excision margin (465). The melanomas were located on the trunk, upper extremities, or lower extremities.
The primary outcome of overall survival was similar between the groups. Over a median 20-year follow-up period, the death rate was approximately 50% in each group (49% in the 2-cm group and 51% in the 4-cm group). Disease-specific survival rates were similar as well. Of the 621 reported deaths, 397 were attributed to melanoma: 192 (48%) in the 2-cm group and 205 (52%) in the 4-cm group.
The study findings were limited by several factors, including a lower-than-expected number of patients, lack of nodal staging during the study period, and a focus only on the surgical margin without recording data on pathological excision margins.
However, the extended follow-up supports the safe use of the 2-cm margin for the treatment of melanomas thicker than 2 mm, the investigators wrote. In addition, results from an ongoing trial comparing 1-cm and 2-cm margins for melanomas at least 1 mm thick may yield more evidence to support still narrower surgical margins for some cutaneous melanomas.
The study notes that guidelines from organizations that include the American National Comprehensive Cancer Network and the American Academy of Dermatology recommend the 2-cm margin for tumors that are thicker than 2 mm.
The study was supported by the Swedish Cancer Society, Stockholm Cancer Society, Swedish Society for Medical Research, and the Stockholm County Council, and by funds from Radiumhemmet Research and Wallström. The authors reported no disclosures.
SOURCE: Utjés D et al. Lancet. 2019 Jul 4. doi: 10.1016/S0140-6736(19)31132-8.
FROM THE LANCET
Osteoporotic fracture risk appears higher in adults with hemophilia
Adults with newly diagnosed hemophilia may be at a higher risk of developing osteoporotic fractures, according to results from a retrospective study.
Sheng-Hui Tuan, MD, of Cishan Hospital in Kaohsiung, Taiwan, and colleagues conducted a population-based nationwide cohort study that included 75 patients with hemophilia and 300 control subjects without hemophilia matched for age and sex. Data was obtained from a national insurance database in Taiwan from January 2000 to December 2013. The findings were published in Haemophilia.
The primary outcome measured was newly diagnosed osteoporotic fractures, defined as wrist, vertebral, and hip fractures among individuals from both groups. Patients with osteoporotic fractures before hemophilia diagnosis were excluded.
In the analysis, the team calculated hazard ratios and incidence rates of new-onset osteoporotic fractures in both cohorts.
After analysis, the researchers found that the risk of developing new-onset osteoporotic fractures was greater in the hemophilia group versus the comparison group (HR, 5.41; 95% confidence interval, 2.42-12.1; P less than .001).
After adjusting for covariates, such as socioeconomic status, age, sex, and other comorbidities, patients with hemophilia had a 337% higher risk of developing osteoporotic fractures post diagnosis versus matched controls (95% CI, 1.88-10.17; P = .001).
“The risk of osteoporotic fractures following haemophilia increased with time and was significantly higher at 5 years after the diagnosis,” the researchers wrote.
The underlying mechanisms driving these associations remain unknown, according to the authors. Possible risk factors include reduced physical activity, HIV and hepatitis C virus infections, and arthropathy.
The researchers acknowledged that a key limitation of the study was the absence of some relevant clinical information within the database. As a result, information bias could have lowered the accuracy of the analysis.
No funding sources were reported. The authors reported having no conflicts of interest.
SOURCE: Tuan S-H et al. Haemophilia. 2019 Jul 7. doi: 10.1111/hae.13814.
Adults with newly diagnosed hemophilia may be at a higher risk of developing osteoporotic fractures, according to results from a retrospective study.
Sheng-Hui Tuan, MD, of Cishan Hospital in Kaohsiung, Taiwan, and colleagues conducted a population-based nationwide cohort study that included 75 patients with hemophilia and 300 control subjects without hemophilia matched for age and sex. Data was obtained from a national insurance database in Taiwan from January 2000 to December 2013. The findings were published in Haemophilia.
The primary outcome measured was newly diagnosed osteoporotic fractures, defined as wrist, vertebral, and hip fractures among individuals from both groups. Patients with osteoporotic fractures before hemophilia diagnosis were excluded.
In the analysis, the team calculated hazard ratios and incidence rates of new-onset osteoporotic fractures in both cohorts.
After analysis, the researchers found that the risk of developing new-onset osteoporotic fractures was greater in the hemophilia group versus the comparison group (HR, 5.41; 95% confidence interval, 2.42-12.1; P less than .001).
After adjusting for covariates, such as socioeconomic status, age, sex, and other comorbidities, patients with hemophilia had a 337% higher risk of developing osteoporotic fractures post diagnosis versus matched controls (95% CI, 1.88-10.17; P = .001).
“The risk of osteoporotic fractures following haemophilia increased with time and was significantly higher at 5 years after the diagnosis,” the researchers wrote.
The underlying mechanisms driving these associations remain unknown, according to the authors. Possible risk factors include reduced physical activity, HIV and hepatitis C virus infections, and arthropathy.
The researchers acknowledged that a key limitation of the study was the absence of some relevant clinical information within the database. As a result, information bias could have lowered the accuracy of the analysis.
No funding sources were reported. The authors reported having no conflicts of interest.
SOURCE: Tuan S-H et al. Haemophilia. 2019 Jul 7. doi: 10.1111/hae.13814.
Adults with newly diagnosed hemophilia may be at a higher risk of developing osteoporotic fractures, according to results from a retrospective study.
Sheng-Hui Tuan, MD, of Cishan Hospital in Kaohsiung, Taiwan, and colleagues conducted a population-based nationwide cohort study that included 75 patients with hemophilia and 300 control subjects without hemophilia matched for age and sex. Data was obtained from a national insurance database in Taiwan from January 2000 to December 2013. The findings were published in Haemophilia.
The primary outcome measured was newly diagnosed osteoporotic fractures, defined as wrist, vertebral, and hip fractures among individuals from both groups. Patients with osteoporotic fractures before hemophilia diagnosis were excluded.
In the analysis, the team calculated hazard ratios and incidence rates of new-onset osteoporotic fractures in both cohorts.
After analysis, the researchers found that the risk of developing new-onset osteoporotic fractures was greater in the hemophilia group versus the comparison group (HR, 5.41; 95% confidence interval, 2.42-12.1; P less than .001).
After adjusting for covariates, such as socioeconomic status, age, sex, and other comorbidities, patients with hemophilia had a 337% higher risk of developing osteoporotic fractures post diagnosis versus matched controls (95% CI, 1.88-10.17; P = .001).
“The risk of osteoporotic fractures following haemophilia increased with time and was significantly higher at 5 years after the diagnosis,” the researchers wrote.
The underlying mechanisms driving these associations remain unknown, according to the authors. Possible risk factors include reduced physical activity, HIV and hepatitis C virus infections, and arthropathy.
The researchers acknowledged that a key limitation of the study was the absence of some relevant clinical information within the database. As a result, information bias could have lowered the accuracy of the analysis.
No funding sources were reported. The authors reported having no conflicts of interest.
SOURCE: Tuan S-H et al. Haemophilia. 2019 Jul 7. doi: 10.1111/hae.13814.
FROM HAEMOPHILIA
Ibrutinib tops chlorambucil against CLL
AMSTERDAM – After 5 years, a large majority of patients with chronic lymphocytic leukemia treated with front-line ibrutinib (Imbruvica) have not experienced disease progression, and the median progression-free survival has still not been reached, long-term follow-up from the RESONATE-2 shows.
The 5-year estimated progression-free survival (PFS) rates were 70% for patients who had been randomized to receive ibrutinib monotherapy, compared with 12% for patients randomized to chlorambucil, reported Alessandra Tedeschi, MD, from Azienda Ospedaliera Niguarda Ca’ Granda in Milan.
Ibrutinib was also associated with a halving of risk for death, compared with chlorambucil, she said at the annual congress of the European Hematology Association.
“Importantly, the rate of progression during ibrutinib treatment was very low; only 8 – that is, 6% of patients” – experienced disease progression while receiving ibrutinib, she noted.
In the RESONATE-2 (PCYC-1115) trial, investigators enrolled 269 adults aged 65 years and older with previously untreated CLL/small lymphocytic lymphoma (SLL). Patients at the younger end of the age range (65-69 years) had to have comorbidities that would have made them ineligible for the FCR chemotherapy regimen (fludarabine, cyclophosphamide, and rituximab). Additionally, patients with the deleterious 17p deletion were excluded.
Patients were stratified by performance status and Rai stage and then randomized to receive either ibrutinib 420 mg once daily until disease progression or unacceptable toxicity (136 patients) or chlorambucil 0.5 mg/kg to a maximum of 0.8 mg/kg for up to 12 cycles (133 patients). The trial also had an extension study for patients who had disease progression as confirmed by an independent review committee or who had completed the RESONATE-2 trial. Of the 133 patients in the chlorambucil arm, 76 (57% of the intention-to-treat population) were crossed over to ibrutinib following disease progression.
The median duration of ibrutinib treatment was 57.1 months, with 73% of patients being on it for more than 3 years, 65% for more than 4 years, and 27% for more than 5 years. As of the data cutoff, 79 patients (58%) were continuing with ibrutinib on study.
At 5 years, 70% of ibrutinib-treated patients and 12% of chlorambucil-treated patients were estimated to be progression-free and alive (hazard ratio for PFS with ibrutinib 0.146 (95% confidence interval, 0.10-0.22). The benefit of ibrutinib was consistent for patients with high-risk genomic features, including the 11q deletion and unmutated immunoglobulin heavy-chain variable genes.
Estimated 5-year overall survival was also better with ibrutinib, at 83% vs. 68% (hazard ratio, 0.45; 95% CI, 0.266-0.761).
The most common grade 3 or greater adverse events occurring with ibrutinib were neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), hyponatremia (6%), atrial fibrillation (5%), and cataract (5%). The rates of most adverse events decreased over time, and dose reductions because of adverse events also diminished over time, from 5% of patients in the first year down to zero in years 4 through 5.
Patients responded to subsequent CLL therapies following ibrutinib discontinuation, including chemoimmunotherapy and other kinase inhibitors, Dr. Tedeschi said.
The trial was sponsored by Pharmacyclics with collaboration from Janssen Research & Development. Dr. Tedeschi reported advisory board activities with Janssen, AbbVie, and BeiGene.
SOURCE: Tedeschi A et al. EHA Congress, Abstract S107.
AMSTERDAM – After 5 years, a large majority of patients with chronic lymphocytic leukemia treated with front-line ibrutinib (Imbruvica) have not experienced disease progression, and the median progression-free survival has still not been reached, long-term follow-up from the RESONATE-2 shows.
The 5-year estimated progression-free survival (PFS) rates were 70% for patients who had been randomized to receive ibrutinib monotherapy, compared with 12% for patients randomized to chlorambucil, reported Alessandra Tedeschi, MD, from Azienda Ospedaliera Niguarda Ca’ Granda in Milan.
Ibrutinib was also associated with a halving of risk for death, compared with chlorambucil, she said at the annual congress of the European Hematology Association.
“Importantly, the rate of progression during ibrutinib treatment was very low; only 8 – that is, 6% of patients” – experienced disease progression while receiving ibrutinib, she noted.
In the RESONATE-2 (PCYC-1115) trial, investigators enrolled 269 adults aged 65 years and older with previously untreated CLL/small lymphocytic lymphoma (SLL). Patients at the younger end of the age range (65-69 years) had to have comorbidities that would have made them ineligible for the FCR chemotherapy regimen (fludarabine, cyclophosphamide, and rituximab). Additionally, patients with the deleterious 17p deletion were excluded.
Patients were stratified by performance status and Rai stage and then randomized to receive either ibrutinib 420 mg once daily until disease progression or unacceptable toxicity (136 patients) or chlorambucil 0.5 mg/kg to a maximum of 0.8 mg/kg for up to 12 cycles (133 patients). The trial also had an extension study for patients who had disease progression as confirmed by an independent review committee or who had completed the RESONATE-2 trial. Of the 133 patients in the chlorambucil arm, 76 (57% of the intention-to-treat population) were crossed over to ibrutinib following disease progression.
The median duration of ibrutinib treatment was 57.1 months, with 73% of patients being on it for more than 3 years, 65% for more than 4 years, and 27% for more than 5 years. As of the data cutoff, 79 patients (58%) were continuing with ibrutinib on study.
At 5 years, 70% of ibrutinib-treated patients and 12% of chlorambucil-treated patients were estimated to be progression-free and alive (hazard ratio for PFS with ibrutinib 0.146 (95% confidence interval, 0.10-0.22). The benefit of ibrutinib was consistent for patients with high-risk genomic features, including the 11q deletion and unmutated immunoglobulin heavy-chain variable genes.
Estimated 5-year overall survival was also better with ibrutinib, at 83% vs. 68% (hazard ratio, 0.45; 95% CI, 0.266-0.761).
The most common grade 3 or greater adverse events occurring with ibrutinib were neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), hyponatremia (6%), atrial fibrillation (5%), and cataract (5%). The rates of most adverse events decreased over time, and dose reductions because of adverse events also diminished over time, from 5% of patients in the first year down to zero in years 4 through 5.
Patients responded to subsequent CLL therapies following ibrutinib discontinuation, including chemoimmunotherapy and other kinase inhibitors, Dr. Tedeschi said.
The trial was sponsored by Pharmacyclics with collaboration from Janssen Research & Development. Dr. Tedeschi reported advisory board activities with Janssen, AbbVie, and BeiGene.
SOURCE: Tedeschi A et al. EHA Congress, Abstract S107.
AMSTERDAM – After 5 years, a large majority of patients with chronic lymphocytic leukemia treated with front-line ibrutinib (Imbruvica) have not experienced disease progression, and the median progression-free survival has still not been reached, long-term follow-up from the RESONATE-2 shows.
The 5-year estimated progression-free survival (PFS) rates were 70% for patients who had been randomized to receive ibrutinib monotherapy, compared with 12% for patients randomized to chlorambucil, reported Alessandra Tedeschi, MD, from Azienda Ospedaliera Niguarda Ca’ Granda in Milan.
Ibrutinib was also associated with a halving of risk for death, compared with chlorambucil, she said at the annual congress of the European Hematology Association.
“Importantly, the rate of progression during ibrutinib treatment was very low; only 8 – that is, 6% of patients” – experienced disease progression while receiving ibrutinib, she noted.
In the RESONATE-2 (PCYC-1115) trial, investigators enrolled 269 adults aged 65 years and older with previously untreated CLL/small lymphocytic lymphoma (SLL). Patients at the younger end of the age range (65-69 years) had to have comorbidities that would have made them ineligible for the FCR chemotherapy regimen (fludarabine, cyclophosphamide, and rituximab). Additionally, patients with the deleterious 17p deletion were excluded.
Patients were stratified by performance status and Rai stage and then randomized to receive either ibrutinib 420 mg once daily until disease progression or unacceptable toxicity (136 patients) or chlorambucil 0.5 mg/kg to a maximum of 0.8 mg/kg for up to 12 cycles (133 patients). The trial also had an extension study for patients who had disease progression as confirmed by an independent review committee or who had completed the RESONATE-2 trial. Of the 133 patients in the chlorambucil arm, 76 (57% of the intention-to-treat population) were crossed over to ibrutinib following disease progression.
The median duration of ibrutinib treatment was 57.1 months, with 73% of patients being on it for more than 3 years, 65% for more than 4 years, and 27% for more than 5 years. As of the data cutoff, 79 patients (58%) were continuing with ibrutinib on study.
At 5 years, 70% of ibrutinib-treated patients and 12% of chlorambucil-treated patients were estimated to be progression-free and alive (hazard ratio for PFS with ibrutinib 0.146 (95% confidence interval, 0.10-0.22). The benefit of ibrutinib was consistent for patients with high-risk genomic features, including the 11q deletion and unmutated immunoglobulin heavy-chain variable genes.
Estimated 5-year overall survival was also better with ibrutinib, at 83% vs. 68% (hazard ratio, 0.45; 95% CI, 0.266-0.761).
The most common grade 3 or greater adverse events occurring with ibrutinib were neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), hyponatremia (6%), atrial fibrillation (5%), and cataract (5%). The rates of most adverse events decreased over time, and dose reductions because of adverse events also diminished over time, from 5% of patients in the first year down to zero in years 4 through 5.
Patients responded to subsequent CLL therapies following ibrutinib discontinuation, including chemoimmunotherapy and other kinase inhibitors, Dr. Tedeschi said.
The trial was sponsored by Pharmacyclics with collaboration from Janssen Research & Development. Dr. Tedeschi reported advisory board activities with Janssen, AbbVie, and BeiGene.
SOURCE: Tedeschi A et al. EHA Congress, Abstract S107.
REPORTING FROM EHA CONGRESS
R2-CHOP doesn’t improve survival in DLBCL
LUGANO, Switzerland – Adding the immunomodulator lenalidomide (Revlimid) to standard chemotherapy for patients with newly diagnosed ABC-type diffuse large B-cell lymphoma (DLBCL) – the so-called R2-CHOP regimen – did not significantly improve either progression-free or overall survival, compared with R-CHOP alone, investigators in the phase 3 ROBUST trial found.
Among 570 patients with activated B-cell (ABC) type DLBCL followed for a median of 27.1 months, median progression-free survival (PFS) – the primary endpoint – had not been reached either for patients randomized to R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone) plus lenalidomide (R2-CHOP) or R-CHOP plus placebo.
The 1-year and 2-year PFS rate with R2-CHOP was 77%, compared with 75% for R-CHOP, and 2-year PFS rates were 67% and 64%, respectively, and neither comparison was statistically significant reported Umberto Vitolo, MD, from the Citta della Salute e della Scienzia Hospital and University in Turin, Italy.“The future direction is that promising preclinical data with next-generation immunomodulatory agents will be evaluated in future DLBCL clinical trials,” he said at the International Conference on Malignant Lymphoma.
The ROBUST trial is the latest in a long line of studies that failed to show improvement in outcomes with the addition of a novel agent to R-CHOP.
The rationale for adding lenalidomide to R-CHOP came from in-vitro studies showing antiproliferative and immunomodulatory action of lenalidomide against DLBCL, as well as two proof-of-concept clinical studies (REAL07 and MC078E) indicating efficacy against non–germinal center–like B (GCB) type DLBCL, Dr. Vitolo said.
In the ROBUST trial, investigators across 257 global sites enrolled 570 patients with ABC-type DLBCL, stratified them by International Prognostic Index (IPI) score (2 vs. 3 or greater), bulky disease (less than 7 cm vs. 7 cm or more), and age (younger than 65 years vs. 65 years and older) and randomly assigned them to receive R-CHOP with either oral lenalidomide 15 mg or placebo daily on days 1-14 of each 21-day cycle for six cycles.
All patients were required to have neutropenia prophylaxis according to local practice, with either a granulocyte- or granulocyte-macrophage colony-stimulating factor.
The efficacy analysis was by intention-to-treat and included 285 patients in each arm.
The investigators found no significant difference in the primary endpoint of PFS. Overall response rates (ORR) and complete response (CR) rates were high in both arms. The ORR was 91% in each arm, and the CR rate was 69% for R2-CHOP and 65% for R-CHOP.
Event-free survival (EFS) – a composite of first disease progression, death, or relapse after CR or start of second-line therapy – also did not differ significantly between the groups. The 1-year and 2-year EFS rates were 68% vs. 71% and 59% vs. 61%, respectively. The median EFS was not reached in either arm.
Similarly, overall survival did not differ between the groups. At 48 months of follow-up, 57 patients in the R2-CHOP arm and 62 patients in the R-CHOP arm had died. Respective 1- and 2-year overall survival rates were 91% vs. 90%, and 79% vs. 80%.
In the safety analysis, which included 283 patients in the R2-CHOP arm and 284 in the placebo/R-CHOP arm, there were no new safety signals observed. In all, 78% of patients in the lenalidomide arm and 71% in the placebo arm had at least one grade 3 or greater adverse events. The most common adverse events were hematologic, including neutropenia, febrile neutropenia, anemia, thrombocytopenia, and leukopenia.
The ROBUST study was funded by Celgene. Dr. Vitolo reported consulting and speaker’s bureau fees and research funding from the company.
SOURCE: Vitolo U et al. 15-ICML, Abstract 005.
LUGANO, Switzerland – Adding the immunomodulator lenalidomide (Revlimid) to standard chemotherapy for patients with newly diagnosed ABC-type diffuse large B-cell lymphoma (DLBCL) – the so-called R2-CHOP regimen – did not significantly improve either progression-free or overall survival, compared with R-CHOP alone, investigators in the phase 3 ROBUST trial found.
Among 570 patients with activated B-cell (ABC) type DLBCL followed for a median of 27.1 months, median progression-free survival (PFS) – the primary endpoint – had not been reached either for patients randomized to R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone) plus lenalidomide (R2-CHOP) or R-CHOP plus placebo.
The 1-year and 2-year PFS rate with R2-CHOP was 77%, compared with 75% for R-CHOP, and 2-year PFS rates were 67% and 64%, respectively, and neither comparison was statistically significant reported Umberto Vitolo, MD, from the Citta della Salute e della Scienzia Hospital and University in Turin, Italy.“The future direction is that promising preclinical data with next-generation immunomodulatory agents will be evaluated in future DLBCL clinical trials,” he said at the International Conference on Malignant Lymphoma.
The ROBUST trial is the latest in a long line of studies that failed to show improvement in outcomes with the addition of a novel agent to R-CHOP.
The rationale for adding lenalidomide to R-CHOP came from in-vitro studies showing antiproliferative and immunomodulatory action of lenalidomide against DLBCL, as well as two proof-of-concept clinical studies (REAL07 and MC078E) indicating efficacy against non–germinal center–like B (GCB) type DLBCL, Dr. Vitolo said.
In the ROBUST trial, investigators across 257 global sites enrolled 570 patients with ABC-type DLBCL, stratified them by International Prognostic Index (IPI) score (2 vs. 3 or greater), bulky disease (less than 7 cm vs. 7 cm or more), and age (younger than 65 years vs. 65 years and older) and randomly assigned them to receive R-CHOP with either oral lenalidomide 15 mg or placebo daily on days 1-14 of each 21-day cycle for six cycles.
All patients were required to have neutropenia prophylaxis according to local practice, with either a granulocyte- or granulocyte-macrophage colony-stimulating factor.
The efficacy analysis was by intention-to-treat and included 285 patients in each arm.
The investigators found no significant difference in the primary endpoint of PFS. Overall response rates (ORR) and complete response (CR) rates were high in both arms. The ORR was 91% in each arm, and the CR rate was 69% for R2-CHOP and 65% for R-CHOP.
Event-free survival (EFS) – a composite of first disease progression, death, or relapse after CR or start of second-line therapy – also did not differ significantly between the groups. The 1-year and 2-year EFS rates were 68% vs. 71% and 59% vs. 61%, respectively. The median EFS was not reached in either arm.
Similarly, overall survival did not differ between the groups. At 48 months of follow-up, 57 patients in the R2-CHOP arm and 62 patients in the R-CHOP arm had died. Respective 1- and 2-year overall survival rates were 91% vs. 90%, and 79% vs. 80%.
In the safety analysis, which included 283 patients in the R2-CHOP arm and 284 in the placebo/R-CHOP arm, there were no new safety signals observed. In all, 78% of patients in the lenalidomide arm and 71% in the placebo arm had at least one grade 3 or greater adverse events. The most common adverse events were hematologic, including neutropenia, febrile neutropenia, anemia, thrombocytopenia, and leukopenia.
The ROBUST study was funded by Celgene. Dr. Vitolo reported consulting and speaker’s bureau fees and research funding from the company.
SOURCE: Vitolo U et al. 15-ICML, Abstract 005.
LUGANO, Switzerland – Adding the immunomodulator lenalidomide (Revlimid) to standard chemotherapy for patients with newly diagnosed ABC-type diffuse large B-cell lymphoma (DLBCL) – the so-called R2-CHOP regimen – did not significantly improve either progression-free or overall survival, compared with R-CHOP alone, investigators in the phase 3 ROBUST trial found.
Among 570 patients with activated B-cell (ABC) type DLBCL followed for a median of 27.1 months, median progression-free survival (PFS) – the primary endpoint – had not been reached either for patients randomized to R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone) plus lenalidomide (R2-CHOP) or R-CHOP plus placebo.
The 1-year and 2-year PFS rate with R2-CHOP was 77%, compared with 75% for R-CHOP, and 2-year PFS rates were 67% and 64%, respectively, and neither comparison was statistically significant reported Umberto Vitolo, MD, from the Citta della Salute e della Scienzia Hospital and University in Turin, Italy.“The future direction is that promising preclinical data with next-generation immunomodulatory agents will be evaluated in future DLBCL clinical trials,” he said at the International Conference on Malignant Lymphoma.
The ROBUST trial is the latest in a long line of studies that failed to show improvement in outcomes with the addition of a novel agent to R-CHOP.
The rationale for adding lenalidomide to R-CHOP came from in-vitro studies showing antiproliferative and immunomodulatory action of lenalidomide against DLBCL, as well as two proof-of-concept clinical studies (REAL07 and MC078E) indicating efficacy against non–germinal center–like B (GCB) type DLBCL, Dr. Vitolo said.
In the ROBUST trial, investigators across 257 global sites enrolled 570 patients with ABC-type DLBCL, stratified them by International Prognostic Index (IPI) score (2 vs. 3 or greater), bulky disease (less than 7 cm vs. 7 cm or more), and age (younger than 65 years vs. 65 years and older) and randomly assigned them to receive R-CHOP with either oral lenalidomide 15 mg or placebo daily on days 1-14 of each 21-day cycle for six cycles.
All patients were required to have neutropenia prophylaxis according to local practice, with either a granulocyte- or granulocyte-macrophage colony-stimulating factor.
The efficacy analysis was by intention-to-treat and included 285 patients in each arm.
The investigators found no significant difference in the primary endpoint of PFS. Overall response rates (ORR) and complete response (CR) rates were high in both arms. The ORR was 91% in each arm, and the CR rate was 69% for R2-CHOP and 65% for R-CHOP.
Event-free survival (EFS) – a composite of first disease progression, death, or relapse after CR or start of second-line therapy – also did not differ significantly between the groups. The 1-year and 2-year EFS rates were 68% vs. 71% and 59% vs. 61%, respectively. The median EFS was not reached in either arm.
Similarly, overall survival did not differ between the groups. At 48 months of follow-up, 57 patients in the R2-CHOP arm and 62 patients in the R-CHOP arm had died. Respective 1- and 2-year overall survival rates were 91% vs. 90%, and 79% vs. 80%.
In the safety analysis, which included 283 patients in the R2-CHOP arm and 284 in the placebo/R-CHOP arm, there were no new safety signals observed. In all, 78% of patients in the lenalidomide arm and 71% in the placebo arm had at least one grade 3 or greater adverse events. The most common adverse events were hematologic, including neutropenia, febrile neutropenia, anemia, thrombocytopenia, and leukopenia.
The ROBUST study was funded by Celgene. Dr. Vitolo reported consulting and speaker’s bureau fees and research funding from the company.
SOURCE: Vitolo U et al. 15-ICML, Abstract 005.
REPORTING FROM 15-ICML