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Chemo during pregnancy may impact baby’s fertility
Photo by Nina Matthews
Preclinical research suggests the chemotherapy drug etoposide may have adverse effects on the developing ovaries of female fetuses.
Researchers found that etoposide can damage the development of mouse ovary tissue in vitro.
However, if the drug is given after ovarian follicles have developed, the damage is not significant.
The researchers said further study is needed to assess whether etoposide has similar effects on human tissue.
“In a study involving mouse tissue, we have shown that etoposide can damage the development of the ovaries while a fetus is in the womb,” said study author Norah Spears, DPhil, of the University of Edinburgh in the UK.
“The drug affects the germ cells in the ovaries, which are the cells that give rise to eggs. This is important because it could mean that the fertility of the offspring could be affected in later life.”
Dr Spears and her colleagues reported these findings in BMC Cancer.
The researchers noted that etoposide is considered safe for use in the second and third trimester of pregnancy because it has a low risk of miscarriage and birth defects. However, little is known about the effects of the drug on the unborn baby in later life.
A woman’s reproductive lifespan is determined before birth, while the ovaries are developing in the womb. The second and third trimesters are particularly important, as that’s when female germ cells form ovarian follicles, which determine how many eggs a woman will be able to release in her lifetime.
Ovarian follicles each contain an oocyte. The process by which oocytes become enclosed in follicles starts about 17 weeks into fetal development and is only completed in late pregnancy.
Dr Spears and her colleagues found that exposing mouse ovaries to etoposide before follicles had formed caused the death of most germ cells. The few remaining germ cells went on to form unhealthy follicles. Once oocytes were enclosed in follicles, however, etoposide had no significant adverse effects.
The researchers collected fetal and neonatal ovaries from mice and cultured them in the lab. The team then exposed groups of 6 ovaries each to different doses of etoposide.
When fetal ovaries were treated with etoposide prior to follicle formation, this resulted in dose-dependent damage. Total follicle numbers declined by 72% to 90% in response to medium and high doses of etoposide, respectively.
In neonatal ovaries after follicle formation, etoposide only had minor effects, even at doses higher than those used to treat fetal ovaries.
“Our work indicates that female mouse germ cells are particularly susceptible to damage by etoposide at a specific early developmental stage, immediately prior to follicle formation, and that there could be possible consequences to the fertility of females born to women who were treated with etoposide during the second trimester of their pregnancy,” Dr Spears said.
She and her colleagues noted that additional research is needed to determine if these effects might occur in humans. And research is needed to determine whether the adverse effects of etoposide in germ cells are caused by damage to the DNA or because etoposide affects other processes such as transcription. 
Photo by Nina Matthews
Preclinical research suggests the chemotherapy drug etoposide may have adverse effects on the developing ovaries of female fetuses.
Researchers found that etoposide can damage the development of mouse ovary tissue in vitro.
However, if the drug is given after ovarian follicles have developed, the damage is not significant.
The researchers said further study is needed to assess whether etoposide has similar effects on human tissue.
“In a study involving mouse tissue, we have shown that etoposide can damage the development of the ovaries while a fetus is in the womb,” said study author Norah Spears, DPhil, of the University of Edinburgh in the UK.
“The drug affects the germ cells in the ovaries, which are the cells that give rise to eggs. This is important because it could mean that the fertility of the offspring could be affected in later life.”
Dr Spears and her colleagues reported these findings in BMC Cancer.
The researchers noted that etoposide is considered safe for use in the second and third trimester of pregnancy because it has a low risk of miscarriage and birth defects. However, little is known about the effects of the drug on the unborn baby in later life.
A woman’s reproductive lifespan is determined before birth, while the ovaries are developing in the womb. The second and third trimesters are particularly important, as that’s when female germ cells form ovarian follicles, which determine how many eggs a woman will be able to release in her lifetime.
Ovarian follicles each contain an oocyte. The process by which oocytes become enclosed in follicles starts about 17 weeks into fetal development and is only completed in late pregnancy.
Dr Spears and her colleagues found that exposing mouse ovaries to etoposide before follicles had formed caused the death of most germ cells. The few remaining germ cells went on to form unhealthy follicles. Once oocytes were enclosed in follicles, however, etoposide had no significant adverse effects.
The researchers collected fetal and neonatal ovaries from mice and cultured them in the lab. The team then exposed groups of 6 ovaries each to different doses of etoposide.
When fetal ovaries were treated with etoposide prior to follicle formation, this resulted in dose-dependent damage. Total follicle numbers declined by 72% to 90% in response to medium and high doses of etoposide, respectively.
In neonatal ovaries after follicle formation, etoposide only had minor effects, even at doses higher than those used to treat fetal ovaries.
“Our work indicates that female mouse germ cells are particularly susceptible to damage by etoposide at a specific early developmental stage, immediately prior to follicle formation, and that there could be possible consequences to the fertility of females born to women who were treated with etoposide during the second trimester of their pregnancy,” Dr Spears said.
She and her colleagues noted that additional research is needed to determine if these effects might occur in humans. And research is needed to determine whether the adverse effects of etoposide in germ cells are caused by damage to the DNA or because etoposide affects other processes such as transcription.
Photo by Nina Matthews
Preclinical research suggests the chemotherapy drug etoposide may have adverse effects on the developing ovaries of female fetuses.
Researchers found that etoposide can damage the development of mouse ovary tissue in vitro.
However, if the drug is given after ovarian follicles have developed, the damage is not significant.
The researchers said further study is needed to assess whether etoposide has similar effects on human tissue.
“In a study involving mouse tissue, we have shown that etoposide can damage the development of the ovaries while a fetus is in the womb,” said study author Norah Spears, DPhil, of the University of Edinburgh in the UK.
“The drug affects the germ cells in the ovaries, which are the cells that give rise to eggs. This is important because it could mean that the fertility of the offspring could be affected in later life.”
Dr Spears and her colleagues reported these findings in BMC Cancer.
The researchers noted that etoposide is considered safe for use in the second and third trimester of pregnancy because it has a low risk of miscarriage and birth defects. However, little is known about the effects of the drug on the unborn baby in later life.
A woman’s reproductive lifespan is determined before birth, while the ovaries are developing in the womb. The second and third trimesters are particularly important, as that’s when female germ cells form ovarian follicles, which determine how many eggs a woman will be able to release in her lifetime.
Ovarian follicles each contain an oocyte. The process by which oocytes become enclosed in follicles starts about 17 weeks into fetal development and is only completed in late pregnancy.
Dr Spears and her colleagues found that exposing mouse ovaries to etoposide before follicles had formed caused the death of most germ cells. The few remaining germ cells went on to form unhealthy follicles. Once oocytes were enclosed in follicles, however, etoposide had no significant adverse effects.
The researchers collected fetal and neonatal ovaries from mice and cultured them in the lab. The team then exposed groups of 6 ovaries each to different doses of etoposide.
When fetal ovaries were treated with etoposide prior to follicle formation, this resulted in dose-dependent damage. Total follicle numbers declined by 72% to 90% in response to medium and high doses of etoposide, respectively.
In neonatal ovaries after follicle formation, etoposide only had minor effects, even at doses higher than those used to treat fetal ovaries.
“Our work indicates that female mouse germ cells are particularly susceptible to damage by etoposide at a specific early developmental stage, immediately prior to follicle formation, and that there could be possible consequences to the fertility of females born to women who were treated with etoposide during the second trimester of their pregnancy,” Dr Spears said.
She and her colleagues noted that additional research is needed to determine if these effects might occur in humans. And research is needed to determine whether the adverse effects of etoposide in germ cells are caused by damage to the DNA or because etoposide affects other processes such as transcription.
Quality of life measures comparable for panobinostat or placebo in combination with bortezomib and dexamethasone
Quality of life measures were comparable for multiple myeloma patients whether they received panobinostat or placebo in combination with bortezomib and dexamethasone, Paul G. Richardson, MD, of Dana-Farber Cancer Institute, Boston, and his associates in the PANORAMA-1 trial reported at the annual meeting of the American Society of Clinical Oncology.
Symptoms, function, and health-related quality of life were measured using the EORTC-QLQ-30, QLQ-MY20, and FACT/GOG-Ntx scales at screening, the first day of the first therapy cycle, and every 6 weeks thereafter in multiple myeloma patients randomly assigned to receive 21-day cycles of either the triple regimen or a placebo plus bortezomib and dexamethasone.
Panobinostat, in combination with bortezomib and dexamethasone, is approved for multiple myeloma patients who have received at least two prior regimens, including bortezomib and an immunomodulatory drug
In the U.S.-label population of the PANORAMA-1 study, patient-reported outcomes data were available at baseline for 94 and 92 patients based on the EORTC QLQ-C30, Global Health Status/QoL scale and for 91 and 95 patients based on the QLQMY20, Disease Symptoms (DS) subscale and FACT/GOG-Ntx Neurotoxicity subscale.
After 24 weeks of therapy, FACT-GOG-Ntx scores were similar (32.03 vs. 33.92, respectively), suggesting no difference in neurotoxicity symptoms. In the QLQ-MY20 DS subscale, scores initially improved and stabilized, with no difference between the two groups of patients (20.65 vs. 15.85). After initially declining, EORTC QLQ-C30 Global Health Status/QoL scores were also comparable (54.84 vs. 58.55).
The study was sponsored by Novartis Pharmaceuticals, the maker of panobinostat. Dr. Richardson is an adviser to Novartis as well as several other drug companies.
On Twitter @maryjodales
Quality of life measures were comparable for multiple myeloma patients whether they received panobinostat or placebo in combination with bortezomib and dexamethasone, Paul G. Richardson, MD, of Dana-Farber Cancer Institute, Boston, and his associates in the PANORAMA-1 trial reported at the annual meeting of the American Society of Clinical Oncology.
Symptoms, function, and health-related quality of life were measured using the EORTC-QLQ-30, QLQ-MY20, and FACT/GOG-Ntx scales at screening, the first day of the first therapy cycle, and every 6 weeks thereafter in multiple myeloma patients randomly assigned to receive 21-day cycles of either the triple regimen or a placebo plus bortezomib and dexamethasone.
Panobinostat, in combination with bortezomib and dexamethasone, is approved for multiple myeloma patients who have received at least two prior regimens, including bortezomib and an immunomodulatory drug
In the U.S.-label population of the PANORAMA-1 study, patient-reported outcomes data were available at baseline for 94 and 92 patients based on the EORTC QLQ-C30, Global Health Status/QoL scale and for 91 and 95 patients based on the QLQMY20, Disease Symptoms (DS) subscale and FACT/GOG-Ntx Neurotoxicity subscale.
After 24 weeks of therapy, FACT-GOG-Ntx scores were similar (32.03 vs. 33.92, respectively), suggesting no difference in neurotoxicity symptoms. In the QLQ-MY20 DS subscale, scores initially improved and stabilized, with no difference between the two groups of patients (20.65 vs. 15.85). After initially declining, EORTC QLQ-C30 Global Health Status/QoL scores were also comparable (54.84 vs. 58.55).
The study was sponsored by Novartis Pharmaceuticals, the maker of panobinostat. Dr. Richardson is an adviser to Novartis as well as several other drug companies.
On Twitter @maryjodales
Quality of life measures were comparable for multiple myeloma patients whether they received panobinostat or placebo in combination with bortezomib and dexamethasone, Paul G. Richardson, MD, of Dana-Farber Cancer Institute, Boston, and his associates in the PANORAMA-1 trial reported at the annual meeting of the American Society of Clinical Oncology.
Symptoms, function, and health-related quality of life were measured using the EORTC-QLQ-30, QLQ-MY20, and FACT/GOG-Ntx scales at screening, the first day of the first therapy cycle, and every 6 weeks thereafter in multiple myeloma patients randomly assigned to receive 21-day cycles of either the triple regimen or a placebo plus bortezomib and dexamethasone.
Panobinostat, in combination with bortezomib and dexamethasone, is approved for multiple myeloma patients who have received at least two prior regimens, including bortezomib and an immunomodulatory drug
In the U.S.-label population of the PANORAMA-1 study, patient-reported outcomes data were available at baseline for 94 and 92 patients based on the EORTC QLQ-C30, Global Health Status/QoL scale and for 91 and 95 patients based on the QLQMY20, Disease Symptoms (DS) subscale and FACT/GOG-Ntx Neurotoxicity subscale.
After 24 weeks of therapy, FACT-GOG-Ntx scores were similar (32.03 vs. 33.92, respectively), suggesting no difference in neurotoxicity symptoms. In the QLQ-MY20 DS subscale, scores initially improved and stabilized, with no difference between the two groups of patients (20.65 vs. 15.85). After initially declining, EORTC QLQ-C30 Global Health Status/QoL scores were also comparable (54.84 vs. 58.55).
The study was sponsored by Novartis Pharmaceuticals, the maker of panobinostat. Dr. Richardson is an adviser to Novartis as well as several other drug companies.
On Twitter @maryjodales
FROM 2016 ASCO ANNUAL MEETING
Key clinical point: Quality of-life measures were comparable for multiple myeloma patients whether they received panobinostat or placebo in combination with bortezomib and dexamethasone.
Major finding: After 24 weeks of therapy, FACT-GOG-Ntx scores were similar (32.03 vs. 33.92, respectively), suggesting no difference in neurotoxicity symptoms.
Data source: U.S. participants in the PANORAMA-1 trial.
Disclosures: The study was sponsored by Novartis Pharmaceuticals, the maker of panobinostat. Dr. Richardson is an adviser to Novartis as well as several other drug companies.
FDA approves drug for prevention of CINV
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has approved granisetron extended-release injection (Sustol®) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adults.
Extended-release granisetron is a serotonin-3 (5-HT3) receptor antagonist that utilizes Biochronomer® polymer-based drug delivery technology to maintain therapeutic levels of granisetron for at least 5 days, covering both the acute and delayed phases of CINV.
The product is intended for use in combination with other anti-emetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.
“Despite advances in the management of CINV, up to half of patients receiving chemotherapy can still experience CINV, with delayed CINV being particularly challenging to control,” said Ralph V. Boccia, MD, of the Center for Cancer and Blood Disorders in Bethesda, Maryland.
“In our experience, other 5-HT3 receptor antagonists, including palonosetron, are generally effective for 48 hours or less. Sustol, due to its extended-release profile, represents a novel option that can protect patients from CINV for a full 5 days.”
Extended-release granisetron (formerly known as APF530) is a product of Heron Therapeutics, Inc. The US commercial launch of the drug is planned for the fourth quarter of 2016.
Phase 3 trials
The global phase 3 development program of extended-release granisetron consisted of 2 large, guideline-based clinical trials of more than 2000 cancer patients.
In one trial, researchers compared extended-release granisetron to palonosetron for the prevention of acute and delayed CINV after MEC or highly emetogenic chemotherapy (HEC).
Results suggested extended-release granisetron was non-inferior to palonosetron. The most common adverse events observed in patients receiving granisetron were injection-site reactions and constipation.
In another trial, researchers compared extended-release granisetron to ondansetron for control of delayed CINV after HEC. Patients received extended-release granisetron, dexamethasone, and fosaprepitant or ondansetron, dexamethasone, and fosaprepitant.
A higher percentage of patients in the granisetron arm had delayed-phase complete response. The incidence of treatment-emergent adverse events was similar between the treatment arms.
“The Sustol clinical trial populations and results are highly representative of cancer patients in our real-world clinical practice,” said Jeffrey Vacirca, MD, of North Shore Hematology Oncology Associates in East Setauket, New York.
“Use of MEC regimens is widespread, and AC-based regimens are among the most commonly prescribed highly emetogenic chemotherapy regimens. The most significant challenge for my breast cancer patients receiving AC is chemotherapy-induced nausea and vomiting. Sustol represents a better option to manage this devastating side effect of therapy.”
For more details on the drug, access the full prescribing information at www.SUSTOL.com.
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has approved granisetron extended-release injection (Sustol®) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adults.
Extended-release granisetron is a serotonin-3 (5-HT3) receptor antagonist that utilizes Biochronomer® polymer-based drug delivery technology to maintain therapeutic levels of granisetron for at least 5 days, covering both the acute and delayed phases of CINV.
The product is intended for use in combination with other anti-emetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.
“Despite advances in the management of CINV, up to half of patients receiving chemotherapy can still experience CINV, with delayed CINV being particularly challenging to control,” said Ralph V. Boccia, MD, of the Center for Cancer and Blood Disorders in Bethesda, Maryland.
“In our experience, other 5-HT3 receptor antagonists, including palonosetron, are generally effective for 48 hours or less. Sustol, due to its extended-release profile, represents a novel option that can protect patients from CINV for a full 5 days.”
Extended-release granisetron (formerly known as APF530) is a product of Heron Therapeutics, Inc. The US commercial launch of the drug is planned for the fourth quarter of 2016.
Phase 3 trials
The global phase 3 development program of extended-release granisetron consisted of 2 large, guideline-based clinical trials of more than 2000 cancer patients.
In one trial, researchers compared extended-release granisetron to palonosetron for the prevention of acute and delayed CINV after MEC or highly emetogenic chemotherapy (HEC).
Results suggested extended-release granisetron was non-inferior to palonosetron. The most common adverse events observed in patients receiving granisetron were injection-site reactions and constipation.
In another trial, researchers compared extended-release granisetron to ondansetron for control of delayed CINV after HEC. Patients received extended-release granisetron, dexamethasone, and fosaprepitant or ondansetron, dexamethasone, and fosaprepitant.
A higher percentage of patients in the granisetron arm had delayed-phase complete response. The incidence of treatment-emergent adverse events was similar between the treatment arms.
“The Sustol clinical trial populations and results are highly representative of cancer patients in our real-world clinical practice,” said Jeffrey Vacirca, MD, of North Shore Hematology Oncology Associates in East Setauket, New York.
“Use of MEC regimens is widespread, and AC-based regimens are among the most commonly prescribed highly emetogenic chemotherapy regimens. The most significant challenge for my breast cancer patients receiving AC is chemotherapy-induced nausea and vomiting. Sustol represents a better option to manage this devastating side effect of therapy.”
For more details on the drug, access the full prescribing information at www.SUSTOL.com.
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has approved granisetron extended-release injection (Sustol®) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adults.
Extended-release granisetron is a serotonin-3 (5-HT3) receptor antagonist that utilizes Biochronomer® polymer-based drug delivery technology to maintain therapeutic levels of granisetron for at least 5 days, covering both the acute and delayed phases of CINV.
The product is intended for use in combination with other anti-emetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.
“Despite advances in the management of CINV, up to half of patients receiving chemotherapy can still experience CINV, with delayed CINV being particularly challenging to control,” said Ralph V. Boccia, MD, of the Center for Cancer and Blood Disorders in Bethesda, Maryland.
“In our experience, other 5-HT3 receptor antagonists, including palonosetron, are generally effective for 48 hours or less. Sustol, due to its extended-release profile, represents a novel option that can protect patients from CINV for a full 5 days.”
Extended-release granisetron (formerly known as APF530) is a product of Heron Therapeutics, Inc. The US commercial launch of the drug is planned for the fourth quarter of 2016.
Phase 3 trials
The global phase 3 development program of extended-release granisetron consisted of 2 large, guideline-based clinical trials of more than 2000 cancer patients.
In one trial, researchers compared extended-release granisetron to palonosetron for the prevention of acute and delayed CINV after MEC or highly emetogenic chemotherapy (HEC).
Results suggested extended-release granisetron was non-inferior to palonosetron. The most common adverse events observed in patients receiving granisetron were injection-site reactions and constipation.
In another trial, researchers compared extended-release granisetron to ondansetron for control of delayed CINV after HEC. Patients received extended-release granisetron, dexamethasone, and fosaprepitant or ondansetron, dexamethasone, and fosaprepitant.
A higher percentage of patients in the granisetron arm had delayed-phase complete response. The incidence of treatment-emergent adverse events was similar between the treatment arms.
“The Sustol clinical trial populations and results are highly representative of cancer patients in our real-world clinical practice,” said Jeffrey Vacirca, MD, of North Shore Hematology Oncology Associates in East Setauket, New York.
“Use of MEC regimens is widespread, and AC-based regimens are among the most commonly prescribed highly emetogenic chemotherapy regimens. The most significant challenge for my breast cancer patients receiving AC is chemotherapy-induced nausea and vomiting. Sustol represents a better option to manage this devastating side effect of therapy.”
For more details on the drug, access the full prescribing information at www.SUSTOL.com.
Daratumumab Effective in Combo Regimen
Adding daratumumab to bortezomib (a protease inhibitor [PI]) and dexamethasone reduces the risk of disease progression or death by 61% in patients with multiple myeloma (MM), compared with bortezomib and dexamethasone alone, according to an interim analysis of phase 3 trial results.
Related: Multiple Myeloma: Updates on Diagnosis and Management
Daratumumab is a biologic that targets CD38, a surface protein that is highly expressed across MM cells, regardless of disease stage. “CD38 is the most important tumor antigen on myeloma plasma cells,” said Antonio Palumbo, MD, University of Torino, Italy, who presented the study findings at the 2016 American Society of Clinical Oncology Annual Meeting in June. Daratumumab has more than 1 immune-mediated mechanism of action and both direct and indirect antimyeloma activity: It depletes CD38+ immunosuppressive regulatory cells and promotes T-cell expansion and activation, all while directly killing myeloma cells.
The multinational study (CASTOR) included 498 patients with MM who had received a median of 2 prior lines of therapy: bortezomib, an immunomodulatory agent, or a PI and immunomodulatory agent. Prior treatments had been unsuccessful in one-third of patients. In this study, researchers randomly assigned 251 patients to combination treatment with daratumumab.
Related: Treating Patients With Multiple Myeloma in the VA
Daratumumab significantly increased the overall response rate (83% vs 63%) and doubled rates of complete response or better (19% vs 9%). It also doubled the rates of very good partial response (59% vs 29%). The combination therapy met the primary endpoint of improved progression-free survival at a median follow-up of 7.4 months (60.7% in the combination arm, compared with 26.9%). The treatment was unblinded after meeting the primary endpoint.
The treatment benefits of the combination regimen were maintained across clinically relevant subgroups, the researchers said. The most common adverse effects were thrombocytopenia ,sensory peripheral neuropathy, anaemia, and diarrhea.
“These compelling phase 3 results demonstrate that a regimen built on daratumumab deepens clinical responses and help to underscore its potential for multiple myeloma patients who have been previously treated,” said Dr. Palumbo.
Related: A Mysterious Massive Hemorrhage
In a discussion of the study, Paul Richardson, MD, of the Dana-Farber Cancer Institute, praised the study as “outstanding” and “potentially practice changing.” However, another panel member noted that with an added cost of more than $10,000 a month, the treatment could be out of reach for many.
Adding daratumumab to bortezomib (a protease inhibitor [PI]) and dexamethasone reduces the risk of disease progression or death by 61% in patients with multiple myeloma (MM), compared with bortezomib and dexamethasone alone, according to an interim analysis of phase 3 trial results.
Related: Multiple Myeloma: Updates on Diagnosis and Management
Daratumumab is a biologic that targets CD38, a surface protein that is highly expressed across MM cells, regardless of disease stage. “CD38 is the most important tumor antigen on myeloma plasma cells,” said Antonio Palumbo, MD, University of Torino, Italy, who presented the study findings at the 2016 American Society of Clinical Oncology Annual Meeting in June. Daratumumab has more than 1 immune-mediated mechanism of action and both direct and indirect antimyeloma activity: It depletes CD38+ immunosuppressive regulatory cells and promotes T-cell expansion and activation, all while directly killing myeloma cells.
The multinational study (CASTOR) included 498 patients with MM who had received a median of 2 prior lines of therapy: bortezomib, an immunomodulatory agent, or a PI and immunomodulatory agent. Prior treatments had been unsuccessful in one-third of patients. In this study, researchers randomly assigned 251 patients to combination treatment with daratumumab.
Related: Treating Patients With Multiple Myeloma in the VA
Daratumumab significantly increased the overall response rate (83% vs 63%) and doubled rates of complete response or better (19% vs 9%). It also doubled the rates of very good partial response (59% vs 29%). The combination therapy met the primary endpoint of improved progression-free survival at a median follow-up of 7.4 months (60.7% in the combination arm, compared with 26.9%). The treatment was unblinded after meeting the primary endpoint.
The treatment benefits of the combination regimen were maintained across clinically relevant subgroups, the researchers said. The most common adverse effects were thrombocytopenia ,sensory peripheral neuropathy, anaemia, and diarrhea.
“These compelling phase 3 results demonstrate that a regimen built on daratumumab deepens clinical responses and help to underscore its potential for multiple myeloma patients who have been previously treated,” said Dr. Palumbo.
Related: A Mysterious Massive Hemorrhage
In a discussion of the study, Paul Richardson, MD, of the Dana-Farber Cancer Institute, praised the study as “outstanding” and “potentially practice changing.” However, another panel member noted that with an added cost of more than $10,000 a month, the treatment could be out of reach for many.
Adding daratumumab to bortezomib (a protease inhibitor [PI]) and dexamethasone reduces the risk of disease progression or death by 61% in patients with multiple myeloma (MM), compared with bortezomib and dexamethasone alone, according to an interim analysis of phase 3 trial results.
Related: Multiple Myeloma: Updates on Diagnosis and Management
Daratumumab is a biologic that targets CD38, a surface protein that is highly expressed across MM cells, regardless of disease stage. “CD38 is the most important tumor antigen on myeloma plasma cells,” said Antonio Palumbo, MD, University of Torino, Italy, who presented the study findings at the 2016 American Society of Clinical Oncology Annual Meeting in June. Daratumumab has more than 1 immune-mediated mechanism of action and both direct and indirect antimyeloma activity: It depletes CD38+ immunosuppressive regulatory cells and promotes T-cell expansion and activation, all while directly killing myeloma cells.
The multinational study (CASTOR) included 498 patients with MM who had received a median of 2 prior lines of therapy: bortezomib, an immunomodulatory agent, or a PI and immunomodulatory agent. Prior treatments had been unsuccessful in one-third of patients. In this study, researchers randomly assigned 251 patients to combination treatment with daratumumab.
Related: Treating Patients With Multiple Myeloma in the VA
Daratumumab significantly increased the overall response rate (83% vs 63%) and doubled rates of complete response or better (19% vs 9%). It also doubled the rates of very good partial response (59% vs 29%). The combination therapy met the primary endpoint of improved progression-free survival at a median follow-up of 7.4 months (60.7% in the combination arm, compared with 26.9%). The treatment was unblinded after meeting the primary endpoint.
The treatment benefits of the combination regimen were maintained across clinically relevant subgroups, the researchers said. The most common adverse effects were thrombocytopenia ,sensory peripheral neuropathy, anaemia, and diarrhea.
“These compelling phase 3 results demonstrate that a regimen built on daratumumab deepens clinical responses and help to underscore its potential for multiple myeloma patients who have been previously treated,” said Dr. Palumbo.
Related: A Mysterious Massive Hemorrhage
In a discussion of the study, Paul Richardson, MD, of the Dana-Farber Cancer Institute, praised the study as “outstanding” and “potentially practice changing.” However, another panel member noted that with an added cost of more than $10,000 a month, the treatment could be out of reach for many.
Ixazomib approved to treat rel/ref MM in Canada
Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.
Ixazomib is the first oral proteasome inhibitor approved for this indication.
The approval was primarily based on results from the phase 3 trial TOURMALINE-MM1, which were presented at the 2015 ASH Annual Meeting.
The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).
Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.
Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).
At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).
At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.
The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. And the incidence of serious AEs was 47% and 49%, respectively.
Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).
Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:
- TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
- TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
- TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.
Ixazomib is marketed by Takeda Pharmaceutical Company Limited.
Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.
Ixazomib is the first oral proteasome inhibitor approved for this indication.
The approval was primarily based on results from the phase 3 trial TOURMALINE-MM1, which were presented at the 2015 ASH Annual Meeting.
The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).
Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.
Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).
At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).
At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.
The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. And the incidence of serious AEs was 47% and 49%, respectively.
Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).
Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:
- TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
- TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
- TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.
Ixazomib is marketed by Takeda Pharmaceutical Company Limited.
Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.
Ixazomib is the first oral proteasome inhibitor approved for this indication.
The approval was primarily based on results from the phase 3 trial TOURMALINE-MM1, which were presented at the 2015 ASH Annual Meeting.
The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).
Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.
Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).
At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).
At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.
The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. And the incidence of serious AEs was 47% and 49%, respectively.
Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).
Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:
- TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
- TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
- TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.
Ixazomib is marketed by Takeda Pharmaceutical Company Limited.
Inhibitors could treat majority of MM patients, team says
David Segal, and Yuan Yao
Photo from the Walter
and Eliza Hall Institute
A new class of inhibitors may be effective in treating a majority of patients with multiple myeloma (MM), according to research published in Blood.
Experiments in multiple MM cell lines suggested the majority of myelomas rely on the protein MCL1 to stay alive.
And targeting MCL1 inhibited disease progression in mouse models of MM.
Therefore, researchers believe drugs designed to inhibit MCL1 may be a promising treatment option for MM.
“Our research shows that switching off MCL1 has the potential to be an effective new treatment approach for the majority of patients with myeloma,” said Jianan Gong, PhD, of The Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.
For this study, Dr Gong and her colleagues investigated the survival proteins that keep MM cells alive.
The team found that a majority of MM cell lines—about 70%—died when MCL1 was switched off. This included well-established, immortalized MM cell lines (17/25) and low-passage MM cell lines (5/7).
“In contrast, only around one quarter [of the cell lines] were susceptible to inhibiting BCL2,” Dr Gong said. “This finding is in keeping with earlier research at the Walter and Eliza Hall Institute that pinpointed MCL1 as the likely protein that keeps myeloma cells alive.”
The researchers also found that targeting MCL1 hindered MM growth in vivo.
The team targeted MCL1 by expressing the MCL1-selective ligand BIM2A in mice inoculated with 1 of 2 MM cell lines—AMO1 and H929. In both models, targeting MCL1 resulted in delayed disease progression and reduced disease burden.
Finally, the researchers identified a subtype of MM that is highly dependent upon BCLXL, so they’ve theorized that targeting both MCL1 and BCLXL could prove useful.
The team concluded that MCL1 is pivotal for maintaining the survival of most myelomas, so targeting the protein should be prioritized once validated inhibitors become available.
“As yet, these inhibitors are still in preclinical development,” said study author Andrew Roberts, MBBS, PhD, of The Walter and Eliza Hall Institute of Medical Research.
“Our results suggest that, once necessary laboratory testing for safety is completed, clinical trials of their effectiveness in treating patients with multiple myeloma that is no longer responding to current therapies would be well justified.”
David Segal, and Yuan Yao
Photo from the Walter
and Eliza Hall Institute
A new class of inhibitors may be effective in treating a majority of patients with multiple myeloma (MM), according to research published in Blood.
Experiments in multiple MM cell lines suggested the majority of myelomas rely on the protein MCL1 to stay alive.
And targeting MCL1 inhibited disease progression in mouse models of MM.
Therefore, researchers believe drugs designed to inhibit MCL1 may be a promising treatment option for MM.
“Our research shows that switching off MCL1 has the potential to be an effective new treatment approach for the majority of patients with myeloma,” said Jianan Gong, PhD, of The Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.
For this study, Dr Gong and her colleagues investigated the survival proteins that keep MM cells alive.
The team found that a majority of MM cell lines—about 70%—died when MCL1 was switched off. This included well-established, immortalized MM cell lines (17/25) and low-passage MM cell lines (5/7).
“In contrast, only around one quarter [of the cell lines] were susceptible to inhibiting BCL2,” Dr Gong said. “This finding is in keeping with earlier research at the Walter and Eliza Hall Institute that pinpointed MCL1 as the likely protein that keeps myeloma cells alive.”
The researchers also found that targeting MCL1 hindered MM growth in vivo.
The team targeted MCL1 by expressing the MCL1-selective ligand BIM2A in mice inoculated with 1 of 2 MM cell lines—AMO1 and H929. In both models, targeting MCL1 resulted in delayed disease progression and reduced disease burden.
Finally, the researchers identified a subtype of MM that is highly dependent upon BCLXL, so they’ve theorized that targeting both MCL1 and BCLXL could prove useful.
The team concluded that MCL1 is pivotal for maintaining the survival of most myelomas, so targeting the protein should be prioritized once validated inhibitors become available.
“As yet, these inhibitors are still in preclinical development,” said study author Andrew Roberts, MBBS, PhD, of The Walter and Eliza Hall Institute of Medical Research.
“Our results suggest that, once necessary laboratory testing for safety is completed, clinical trials of their effectiveness in treating patients with multiple myeloma that is no longer responding to current therapies would be well justified.”
David Segal, and Yuan Yao
Photo from the Walter
and Eliza Hall Institute
A new class of inhibitors may be effective in treating a majority of patients with multiple myeloma (MM), according to research published in Blood.
Experiments in multiple MM cell lines suggested the majority of myelomas rely on the protein MCL1 to stay alive.
And targeting MCL1 inhibited disease progression in mouse models of MM.
Therefore, researchers believe drugs designed to inhibit MCL1 may be a promising treatment option for MM.
“Our research shows that switching off MCL1 has the potential to be an effective new treatment approach for the majority of patients with myeloma,” said Jianan Gong, PhD, of The Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.
For this study, Dr Gong and her colleagues investigated the survival proteins that keep MM cells alive.
The team found that a majority of MM cell lines—about 70%—died when MCL1 was switched off. This included well-established, immortalized MM cell lines (17/25) and low-passage MM cell lines (5/7).
“In contrast, only around one quarter [of the cell lines] were susceptible to inhibiting BCL2,” Dr Gong said. “This finding is in keeping with earlier research at the Walter and Eliza Hall Institute that pinpointed MCL1 as the likely protein that keeps myeloma cells alive.”
The researchers also found that targeting MCL1 hindered MM growth in vivo.
The team targeted MCL1 by expressing the MCL1-selective ligand BIM2A in mice inoculated with 1 of 2 MM cell lines—AMO1 and H929. In both models, targeting MCL1 resulted in delayed disease progression and reduced disease burden.
Finally, the researchers identified a subtype of MM that is highly dependent upon BCLXL, so they’ve theorized that targeting both MCL1 and BCLXL could prove useful.
The team concluded that MCL1 is pivotal for maintaining the survival of most myelomas, so targeting the protein should be prioritized once validated inhibitors become available.
“As yet, these inhibitors are still in preclinical development,” said study author Andrew Roberts, MBBS, PhD, of The Walter and Eliza Hall Institute of Medical Research.
“Our results suggest that, once necessary laboratory testing for safety is completed, clinical trials of their effectiveness in treating patients with multiple myeloma that is no longer responding to current therapies would be well justified.”
Drug interferes with testing for blood transfusion
Photo by Daniel Gay
Research has shown that daratumumab, a monoclonal antibody approved to treat multiple myeloma, interferes with routine compatibility testing for blood transfusion.
And this interference can cause delays in providing patients with compatible blood.
Investigators have discovered ways to eliminate or circumvent the interference, but implementing these methods in hospital blood banks may be challenging.
Michael F. Murphy, MD, of John Radcliffe Hospital in Oxford, UK, and his colleagues discussed this issue in a letter to NEJM.
In a phase 1/2 trial of daratumumab, investigators at different study sites observed that the drug consistently interfered with routine blood compatibility testing. This meant that daratumumab-treated patients sometimes experienced delays in receiving blood transfusions.
Investigation revealed that daratumumab in patient plasma directly binds to CD38 on reagent red blood cells used in the blood bank, which causes false-positive antibody screens.
Unfortunately, standard serological methods to eliminate panreactive antibodies did not affect daratumumab’s interference.
However, an investigator-initiated study revealed a dithiothreitol-based method that can eliminate the interference.1
Another method, involving an anti-daratumumab idiotype, also appears effective, though not readily available.2 And a third method is to issue phenotypically or genotypically matched red cell units.3,4
However, establishing these approaches as routine methods in hospital blood banks will be a major challenge, according to Dr Murphy and his colleagues.
The team also said this issue with daratumumab suggests there is a pressing need to investigate whether new drugs interfere with routine blood bank testing.
Investigations should be performed early during drug development. And if interference with compatibility tests is found, it should be brought to the attention of clinicians and blood banks with advice about how to overcome the interference.
Photo by Daniel Gay
Research has shown that daratumumab, a monoclonal antibody approved to treat multiple myeloma, interferes with routine compatibility testing for blood transfusion.
And this interference can cause delays in providing patients with compatible blood.
Investigators have discovered ways to eliminate or circumvent the interference, but implementing these methods in hospital blood banks may be challenging.
Michael F. Murphy, MD, of John Radcliffe Hospital in Oxford, UK, and his colleagues discussed this issue in a letter to NEJM.
In a phase 1/2 trial of daratumumab, investigators at different study sites observed that the drug consistently interfered with routine blood compatibility testing. This meant that daratumumab-treated patients sometimes experienced delays in receiving blood transfusions.
Investigation revealed that daratumumab in patient plasma directly binds to CD38 on reagent red blood cells used in the blood bank, which causes false-positive antibody screens.
Unfortunately, standard serological methods to eliminate panreactive antibodies did not affect daratumumab’s interference.
However, an investigator-initiated study revealed a dithiothreitol-based method that can eliminate the interference.1
Another method, involving an anti-daratumumab idiotype, also appears effective, though not readily available.2 And a third method is to issue phenotypically or genotypically matched red cell units.3,4
However, establishing these approaches as routine methods in hospital blood banks will be a major challenge, according to Dr Murphy and his colleagues.
The team also said this issue with daratumumab suggests there is a pressing need to investigate whether new drugs interfere with routine blood bank testing.
Investigations should be performed early during drug development. And if interference with compatibility tests is found, it should be brought to the attention of clinicians and blood banks with advice about how to overcome the interference.
Photo by Daniel Gay
Research has shown that daratumumab, a monoclonal antibody approved to treat multiple myeloma, interferes with routine compatibility testing for blood transfusion.
And this interference can cause delays in providing patients with compatible blood.
Investigators have discovered ways to eliminate or circumvent the interference, but implementing these methods in hospital blood banks may be challenging.
Michael F. Murphy, MD, of John Radcliffe Hospital in Oxford, UK, and his colleagues discussed this issue in a letter to NEJM.
In a phase 1/2 trial of daratumumab, investigators at different study sites observed that the drug consistently interfered with routine blood compatibility testing. This meant that daratumumab-treated patients sometimes experienced delays in receiving blood transfusions.
Investigation revealed that daratumumab in patient plasma directly binds to CD38 on reagent red blood cells used in the blood bank, which causes false-positive antibody screens.
Unfortunately, standard serological methods to eliminate panreactive antibodies did not affect daratumumab’s interference.
However, an investigator-initiated study revealed a dithiothreitol-based method that can eliminate the interference.1
Another method, involving an anti-daratumumab idiotype, also appears effective, though not readily available.2 And a third method is to issue phenotypically or genotypically matched red cell units.3,4
However, establishing these approaches as routine methods in hospital blood banks will be a major challenge, according to Dr Murphy and his colleagues.
The team also said this issue with daratumumab suggests there is a pressing need to investigate whether new drugs interfere with routine blood bank testing.
Investigations should be performed early during drug development. And if interference with compatibility tests is found, it should be brought to the attention of clinicians and blood banks with advice about how to overcome the interference.
ASCO issues guideline on chronic pain management in adult cancer survivors
Photo courtesy of NIH
The American Society of Clinical Oncology (ASCO) has issued a new clinical practice guideline on the management of chronic pain in adult cancer survivors.
ASCO’s recommendations comprise both long-standing and new approaches, including routine screening for chronic pain, the use of alternative pain management approaches, the use of medical cannabis in certain settings where it is legal, and assessing the potential for opioid overuse.
“Many oncologists and primary care physicians are not trained to recognize or treat long-term pain associated with cancer,” said Judith A. Paice, PhD, RN, a co-chair of the ASCO expert panel that developed the guideline.
“This guideline will help clinicians identify pain early and develop comprehensive treatment plans, using a broad range of approaches.”
The guideline recommendations were developed by a multidisciplinary panel of experts in medical oncology, hematology/oncology, pain medicine, palliative care, hospice, radiation oncology, social work, symptom management research, rehabilitation, psychology, and anesthesiology, as well as a patient representative.
The panel conducted a systematic review of the medical literature published from 1996 to 2015. The resulting guideline includes the following key recommendations.
Clinicians should screen for pain at each encounter with a patient. Recurrent disease, second malignancy, or late-onset treatment effects should be evaluated, treated, and monitored.
Clinicians may prescribe non-pharmacologic interventions such as physical medicine and rehabilitation, integrative therapies (eg, acupuncture and massage), interventional therapies, and psychological approaches (eg, guided imagery, hypnosis, and meditation).
Systemic non-opioid analgesics (NSAIDS, acetaminophen) and adjuvant analgesics (selected antidepressants and anticonvulsants) may be prescribed to relieve chronic pain and/or improve physical function.
Clinicians may follow specific state regulations that allow access to medical cannabis or cannabinoids for patients with chronic pain after considering the potential benefits and risks of the available formulations.
Clinicians may prescribe a trial of opioids in carefully selected cancer patients who do not respond to more conservative pain management and who continue to experience pain-related distress or impairment of physical function.
Clinicians should assess the risk of adverse effects of opioids used in pain management and incorporate universal precautions to minimize abuse, addiction, and adverse consequences.
“Of great importance is the attention to appropriate assessment, not only of the individual’s pain, but also of their potential for over-reliance on opioids,” Dr Paice said. “This guideline outlines precautions that help ensure cancer survivors with persistent pain use opioids safely and effectively, while limiting access to those who are struggling with addiction.”
Photo courtesy of NIH
The American Society of Clinical Oncology (ASCO) has issued a new clinical practice guideline on the management of chronic pain in adult cancer survivors.
ASCO’s recommendations comprise both long-standing and new approaches, including routine screening for chronic pain, the use of alternative pain management approaches, the use of medical cannabis in certain settings where it is legal, and assessing the potential for opioid overuse.
“Many oncologists and primary care physicians are not trained to recognize or treat long-term pain associated with cancer,” said Judith A. Paice, PhD, RN, a co-chair of the ASCO expert panel that developed the guideline.
“This guideline will help clinicians identify pain early and develop comprehensive treatment plans, using a broad range of approaches.”
The guideline recommendations were developed by a multidisciplinary panel of experts in medical oncology, hematology/oncology, pain medicine, palliative care, hospice, radiation oncology, social work, symptom management research, rehabilitation, psychology, and anesthesiology, as well as a patient representative.
The panel conducted a systematic review of the medical literature published from 1996 to 2015. The resulting guideline includes the following key recommendations.
Clinicians should screen for pain at each encounter with a patient. Recurrent disease, second malignancy, or late-onset treatment effects should be evaluated, treated, and monitored.
Clinicians may prescribe non-pharmacologic interventions such as physical medicine and rehabilitation, integrative therapies (eg, acupuncture and massage), interventional therapies, and psychological approaches (eg, guided imagery, hypnosis, and meditation).
Systemic non-opioid analgesics (NSAIDS, acetaminophen) and adjuvant analgesics (selected antidepressants and anticonvulsants) may be prescribed to relieve chronic pain and/or improve physical function.
Clinicians may follow specific state regulations that allow access to medical cannabis or cannabinoids for patients with chronic pain after considering the potential benefits and risks of the available formulations.
Clinicians may prescribe a trial of opioids in carefully selected cancer patients who do not respond to more conservative pain management and who continue to experience pain-related distress or impairment of physical function.
Clinicians should assess the risk of adverse effects of opioids used in pain management and incorporate universal precautions to minimize abuse, addiction, and adverse consequences.
“Of great importance is the attention to appropriate assessment, not only of the individual’s pain, but also of their potential for over-reliance on opioids,” Dr Paice said. “This guideline outlines precautions that help ensure cancer survivors with persistent pain use opioids safely and effectively, while limiting access to those who are struggling with addiction.”
Photo courtesy of NIH
The American Society of Clinical Oncology (ASCO) has issued a new clinical practice guideline on the management of chronic pain in adult cancer survivors.
ASCO’s recommendations comprise both long-standing and new approaches, including routine screening for chronic pain, the use of alternative pain management approaches, the use of medical cannabis in certain settings where it is legal, and assessing the potential for opioid overuse.
“Many oncologists and primary care physicians are not trained to recognize or treat long-term pain associated with cancer,” said Judith A. Paice, PhD, RN, a co-chair of the ASCO expert panel that developed the guideline.
“This guideline will help clinicians identify pain early and develop comprehensive treatment plans, using a broad range of approaches.”
The guideline recommendations were developed by a multidisciplinary panel of experts in medical oncology, hematology/oncology, pain medicine, palliative care, hospice, radiation oncology, social work, symptom management research, rehabilitation, psychology, and anesthesiology, as well as a patient representative.
The panel conducted a systematic review of the medical literature published from 1996 to 2015. The resulting guideline includes the following key recommendations.
Clinicians should screen for pain at each encounter with a patient. Recurrent disease, second malignancy, or late-onset treatment effects should be evaluated, treated, and monitored.
Clinicians may prescribe non-pharmacologic interventions such as physical medicine and rehabilitation, integrative therapies (eg, acupuncture and massage), interventional therapies, and psychological approaches (eg, guided imagery, hypnosis, and meditation).
Systemic non-opioid analgesics (NSAIDS, acetaminophen) and adjuvant analgesics (selected antidepressants and anticonvulsants) may be prescribed to relieve chronic pain and/or improve physical function.
Clinicians may follow specific state regulations that allow access to medical cannabis or cannabinoids for patients with chronic pain after considering the potential benefits and risks of the available formulations.
Clinicians may prescribe a trial of opioids in carefully selected cancer patients who do not respond to more conservative pain management and who continue to experience pain-related distress or impairment of physical function.
Clinicians should assess the risk of adverse effects of opioids used in pain management and incorporate universal precautions to minimize abuse, addiction, and adverse consequences.
“Of great importance is the attention to appropriate assessment, not only of the individual’s pain, but also of their potential for over-reliance on opioids,” Dr Paice said. “This guideline outlines precautions that help ensure cancer survivors with persistent pain use opioids safely and effectively, while limiting access to those who are struggling with addiction.”
mAb granted breakthrough designation for MM
Photo courtesy of Janssen
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for daratumumab (Darzalex), a CD38-directed monoclonal antibody (mAb), as part of combination therapy for patients with multiple myeloma (MM).
The designation is for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of MM patients who have received at least 1 prior therapy.
This is the second breakthrough designation the FDA has granted to daratumumab.
The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.
To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
In May 2013, the FDA granted daratumumab breakthrough designation for the treatment of MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
In November 2015, daratumumab received accelerated approval from the FDA for this indication. Continued approval of the mAb may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Phase 3 trials
The newest breakthrough designation for daratumumab was based on data from two phase 3 studies—CASTOR (MMY3004) and POLLUX (MMY3003). Both studies were sponsored by Janssen Biotech, Inc., the company developing daratumumab.
In the CASTOR trial, researchers compared daratumumab-bortezomib-dexamethasone to bortezomib-dexamethasone in MM patients who had received at least 1 prior therapy.
The researchers said the addition of daratumumab significantly improved progression-free survival without increasing the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.
Results from this trial were presented at the 2016 ASCO Annual Meeting.
In the POLLUX trial, researchers compared daratumumab-lenalidomide-dexamethasone to lenalidomide-dexamethasone in MM patients who had received at least 1 prior therapy.
According to the researchers, daratumumab-lenalidomide-dexamethasone conferred the highest response rate reported to date in the treatment of relapsed/refractory MM, significantly improved progression-free survival compared to lenalidomide-dexamethasone, and had a manageable safety profile.
These results were presented at the 21st Congress of the European Hematology Association.
Photo courtesy of Janssen
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for daratumumab (Darzalex), a CD38-directed monoclonal antibody (mAb), as part of combination therapy for patients with multiple myeloma (MM).
The designation is for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of MM patients who have received at least 1 prior therapy.
This is the second breakthrough designation the FDA has granted to daratumumab.
The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.
To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
In May 2013, the FDA granted daratumumab breakthrough designation for the treatment of MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
In November 2015, daratumumab received accelerated approval from the FDA for this indication. Continued approval of the mAb may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Phase 3 trials
The newest breakthrough designation for daratumumab was based on data from two phase 3 studies—CASTOR (MMY3004) and POLLUX (MMY3003). Both studies were sponsored by Janssen Biotech, Inc., the company developing daratumumab.
In the CASTOR trial, researchers compared daratumumab-bortezomib-dexamethasone to bortezomib-dexamethasone in MM patients who had received at least 1 prior therapy.
The researchers said the addition of daratumumab significantly improved progression-free survival without increasing the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.
Results from this trial were presented at the 2016 ASCO Annual Meeting.
In the POLLUX trial, researchers compared daratumumab-lenalidomide-dexamethasone to lenalidomide-dexamethasone in MM patients who had received at least 1 prior therapy.
According to the researchers, daratumumab-lenalidomide-dexamethasone conferred the highest response rate reported to date in the treatment of relapsed/refractory MM, significantly improved progression-free survival compared to lenalidomide-dexamethasone, and had a manageable safety profile.
These results were presented at the 21st Congress of the European Hematology Association.
Photo courtesy of Janssen
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for daratumumab (Darzalex), a CD38-directed monoclonal antibody (mAb), as part of combination therapy for patients with multiple myeloma (MM).
The designation is for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of MM patients who have received at least 1 prior therapy.
This is the second breakthrough designation the FDA has granted to daratumumab.
The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.
To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
In May 2013, the FDA granted daratumumab breakthrough designation for the treatment of MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
In November 2015, daratumumab received accelerated approval from the FDA for this indication. Continued approval of the mAb may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Phase 3 trials
The newest breakthrough designation for daratumumab was based on data from two phase 3 studies—CASTOR (MMY3004) and POLLUX (MMY3003). Both studies were sponsored by Janssen Biotech, Inc., the company developing daratumumab.
In the CASTOR trial, researchers compared daratumumab-bortezomib-dexamethasone to bortezomib-dexamethasone in MM patients who had received at least 1 prior therapy.
The researchers said the addition of daratumumab significantly improved progression-free survival without increasing the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.
Results from this trial were presented at the 2016 ASCO Annual Meeting.
In the POLLUX trial, researchers compared daratumumab-lenalidomide-dexamethasone to lenalidomide-dexamethasone in MM patients who had received at least 1 prior therapy.
According to the researchers, daratumumab-lenalidomide-dexamethasone conferred the highest response rate reported to date in the treatment of relapsed/refractory MM, significantly improved progression-free survival compared to lenalidomide-dexamethasone, and had a manageable safety profile.
These results were presented at the 21st Congress of the European Hematology Association.
Blood disorders prove costly for European economy
chemotherapy
Photo by Rhoda Baer
Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.
Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.
Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.
Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.
The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.
The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).
Malignant blood disorders
In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).
In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.
When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).
In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).
The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).
Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.
The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.
Non-malignant blood disorders
In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).
Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.
“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.
“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”
chemotherapy
Photo by Rhoda Baer
Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.
Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.
Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.
Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.
The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.
The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).
Malignant blood disorders
In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).
In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.
When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).
In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).
The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).
Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.
The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.
Non-malignant blood disorders
In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).
Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.
“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.
“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”
chemotherapy
Photo by Rhoda Baer
Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.
Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.
Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.
Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.
The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.
The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).
Malignant blood disorders
In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).
In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.
When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).
In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).
The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).
Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.
The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.
Non-malignant blood disorders
In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).
Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.
“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.
“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”