Family meetings are never easy.

They’re difficult, and often held to discuss the case of a demented patient. In these situations, the family doesn’t want the patient to hear their concerns or is afraid they’ll be embarrassed or angry. Sometimes getting the patient to the appointment is simply too difficult.

Of course, most discussions of this type can be done by phone ... in theory. In practice, it doesn’t work that way.

It’s the subject matter that makes the impersonal nature of the phone difficult. Families have hard questions and want real answers at these times. A face-to-face meeting, with the human interaction, is often the best way to get things across clearly and still with compassion. It avoids the problem of the phone being passed around, having to repeat yourself to each person, and wondering who just asked what. Very few families, in my experience, want to do this on the phone.

These meetings are never quick, either. Depending on family and circumstances, they can take 30-60 minutes. Getting an insurance company to pay for that time is near impossible. Most plans only want to pay for visits where the patient is actually present, when in these cases the family is trying to avoid that. While there is a Medicare payment code for “advance care planning,” it doesn’t cover treatment discussions or other neurological issues they may bring up, and many patients are on non-Medicare plans.

I bill people for these times and have found that most families are willing to pay. I’m not fond of doing so, and certainly not trying to get rich off of them. But it’s still time that I’m in my office and have to pay my rent, staff, and utilities.

Part of this job – a big part – is helping patients and their loved ones understand and deal with difficult situations. Realistically, this is the best way to do it. Families understand that as well as I do.

Why won’t insurance companies cover them? I suppose their excuse is that they cover the patient, not the questions or emotional needs of their caregivers. Of course, those things are as important to the care of the patient as any treatment, but the bean counters don’t want to pay for them.

That is unfortunate, because someone has to. Good medical care depends on good communication with all involved.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Family meetings are never easy.

They’re difficult, and often held to discuss the case of a demented patient. In these situations, the family doesn’t want the patient to hear their concerns or is afraid they’ll be embarrassed or angry. Sometimes getting the patient to the appointment is simply too difficult.

Of course, most discussions of this type can be done by phone ... in theory. In practice, it doesn’t work that way.

It’s the subject matter that makes the impersonal nature of the phone difficult. Families have hard questions and want real answers at these times. A face-to-face meeting, with the human interaction, is often the best way to get things across clearly and still with compassion. It avoids the problem of the phone being passed around, having to repeat yourself to each person, and wondering who just asked what. Very few families, in my experience, want to do this on the phone.

These meetings are never quick, either. Depending on family and circumstances, they can take 30-60 minutes. Getting an insurance company to pay for that time is near impossible. Most plans only want to pay for visits where the patient is actually present, when in these cases the family is trying to avoid that. While there is a Medicare payment code for “advance care planning,” it doesn’t cover treatment discussions or other neurological issues they may bring up, and many patients are on non-Medicare plans.

I bill people for these times and have found that most families are willing to pay. I’m not fond of doing so, and certainly not trying to get rich off of them. But it’s still time that I’m in my office and have to pay my rent, staff, and utilities.

Part of this job – a big part – is helping patients and their loved ones understand and deal with difficult situations. Realistically, this is the best way to do it. Families understand that as well as I do.

Why won’t insurance companies cover them? I suppose their excuse is that they cover the patient, not the questions or emotional needs of their caregivers. Of course, those things are as important to the care of the patient as any treatment, but the bean counters don’t want to pay for them.

That is unfortunate, because someone has to. Good medical care depends on good communication with all involved.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Family meetings are never easy.

They’re difficult, and often held to discuss the case of a demented patient. In these situations, the family doesn’t want the patient to hear their concerns or is afraid they’ll be embarrassed or angry. Sometimes getting the patient to the appointment is simply too difficult.

Of course, most discussions of this type can be done by phone ... in theory. In practice, it doesn’t work that way.

It’s the subject matter that makes the impersonal nature of the phone difficult. Families have hard questions and want real answers at these times. A face-to-face meeting, with the human interaction, is often the best way to get things across clearly and still with compassion. It avoids the problem of the phone being passed around, having to repeat yourself to each person, and wondering who just asked what. Very few families, in my experience, want to do this on the phone.

These meetings are never quick, either. Depending on family and circumstances, they can take 30-60 minutes. Getting an insurance company to pay for that time is near impossible. Most plans only want to pay for visits where the patient is actually present, when in these cases the family is trying to avoid that. While there is a Medicare payment code for “advance care planning,” it doesn’t cover treatment discussions or other neurological issues they may bring up, and many patients are on non-Medicare plans.

I bill people for these times and have found that most families are willing to pay. I’m not fond of doing so, and certainly not trying to get rich off of them. But it’s still time that I’m in my office and have to pay my rent, staff, and utilities.

Part of this job – a big part – is helping patients and their loved ones understand and deal with difficult situations. Realistically, this is the best way to do it. Families understand that as well as I do.

Why won’t insurance companies cover them? I suppose their excuse is that they cover the patient, not the questions or emotional needs of their caregivers. Of course, those things are as important to the care of the patient as any treatment, but the bean counters don’t want to pay for them.

That is unfortunate, because someone has to. Good medical care depends on good communication with all involved.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

SAN DIEGO – Tensions among academic investigators, industry sponsors, and the Food and Drug Administration can hinder new drug approvals and slow or block communication of important results, experts said at the annual Digestive Disease Week.

Relationships between investigators and industry have become especially strained, according to Dr. M. Scott Harris, cofounder of Lyric Pharmaceuticals in San Francisco. “I can tell you as a former investigator, and someone who speaks to investigators all the time, they feel disenfranchised,” he said.

Several steps can help. Industry should focus on empowering investigators, “not study sites,” said Dr. Harris. “Have protocol development meetings, not investigator meetings. Have open dialogue so that investigators can share in the excitement of the study, the results, and the science.”

Intellectual property is a particularly hot topic, acknowledged Dr. Harris, who started out in academic gastroenterology before making the jump to working for pharmaceutical and biotechnology companies. “Intellectual property is the lifeblood of a company – the only thing that generates the likelihood of a return on investment,” he emphasized. “Please do not push back if some information cannot be shared with you.” But within those constraints, industry should “force itself to be as patient as possible,” he said. “A balance has to be struck between the need for IP [intellectual property] and the need to share knowledge.”

Sharing knowledge also means that industry sponsors need to commit to a clear publication strategy, said Dr. Harris. “Investigators want the results of the studies to be communicated, including reasons for failure. We have failed at this as an industry, and this is not acceptable.”

But academic investigators need to make some changes, too. Successfully joining a trial means engaging actively with the sponsor and protocol, Dr. Harris emphasized. “Don’t tell your staff you’re too busy to talk to me when I call. Focus on ethical study conduct, good clinical practice, training, data quality, and meeting timelines.”

Dr. Gary Lichtenstein agreed. A gastroenterologist at the University of Pennsylvania, Philadelphia, with more than 30 years of experience in clinical trials, he knows that successful academic study sites have “efficient and businesslike operations,” a proven internal audit system, and solid, reasonable budgeting for staff time, overhead, equipment, and storage. In particular, academic investigators should double-check training requirements, the qualifications of the study coordinator, and who will handle regulatory, legal, and budgeting concerns, he said.

Vetting a potential industry sponsor is just as important. Ask “if they have the staff, time, equipment, and space to do the study,” Dr. Lichtenstein stressed. “Communicate expectations in writing back and forth to avoid misunderstandings. An indemnification clause is also very important to hold the consultant harmless from and against any claim, loss, or damage whatsoever.”

The FDA, for its part, needs to respond faster to meeting requests and offer clearer guidance about appropriate study designs and outcome measures, both experts emphasized. The median time for FDA to approve a drug application is about 180 days, while approving new gastroenterology agents takes nearly twice as long, according to Dr. Lichtenstein. “There is clearly a discrepancy, and it would be nice if we moved the bar closer. As an investigator, I need to know which trials are acceptable in design, and what endpoints are clearly defined, with examples,” he said. “If I have a question, I need a point of contact to call to get an answer in rapid time, instead of having to wait for months, and I need to know which biomarkers are appropriate to use.”

Dr. Harris agreed. “There should be tension between FDA and industry – that is part of the process,” he said. “But open communication and rapid response to meeting requests are crucial.”

Timeliness and transparency are especially important as FDA transitions “from being a classic regulator to a proactive partner in drug development,” Dr. Harris said. “What industry needs and expects from FDA is greater certainty on the path. Companies may or may not like a particular FDA guidance document, but they greatly appreciate the clarity that guidance documents provide.”

Dr. Lichtenstein disclosed ties to AbbVie, Hospira, Pfizer, and numerous other pharmaceutical companies. Dr. Harris is employed by Lyric Pharmaceuticals and disclosed relationships with several other biopharmaceutical companies.

SAN DIEGO – Tensions among academic investigators, industry sponsors, and the Food and Drug Administration can hinder new drug approvals and slow or block communication of important results, experts said at the annual Digestive Disease Week.

Relationships between investigators and industry have become especially strained, according to Dr. M. Scott Harris, cofounder of Lyric Pharmaceuticals in San Francisco. “I can tell you as a former investigator, and someone who speaks to investigators all the time, they feel disenfranchised,” he said.

Several steps can help. Industry should focus on empowering investigators, “not study sites,” said Dr. Harris. “Have protocol development meetings, not investigator meetings. Have open dialogue so that investigators can share in the excitement of the study, the results, and the science.”

Intellectual property is a particularly hot topic, acknowledged Dr. Harris, who started out in academic gastroenterology before making the jump to working for pharmaceutical and biotechnology companies. “Intellectual property is the lifeblood of a company – the only thing that generates the likelihood of a return on investment,” he emphasized. “Please do not push back if some information cannot be shared with you.” But within those constraints, industry should “force itself to be as patient as possible,” he said. “A balance has to be struck between the need for IP [intellectual property] and the need to share knowledge.”

Sharing knowledge also means that industry sponsors need to commit to a clear publication strategy, said Dr. Harris. “Investigators want the results of the studies to be communicated, including reasons for failure. We have failed at this as an industry, and this is not acceptable.”

But academic investigators need to make some changes, too. Successfully joining a trial means engaging actively with the sponsor and protocol, Dr. Harris emphasized. “Don’t tell your staff you’re too busy to talk to me when I call. Focus on ethical study conduct, good clinical practice, training, data quality, and meeting timelines.”

Dr. Gary Lichtenstein agreed. A gastroenterologist at the University of Pennsylvania, Philadelphia, with more than 30 years of experience in clinical trials, he knows that successful academic study sites have “efficient and businesslike operations,” a proven internal audit system, and solid, reasonable budgeting for staff time, overhead, equipment, and storage. In particular, academic investigators should double-check training requirements, the qualifications of the study coordinator, and who will handle regulatory, legal, and budgeting concerns, he said.

Vetting a potential industry sponsor is just as important. Ask “if they have the staff, time, equipment, and space to do the study,” Dr. Lichtenstein stressed. “Communicate expectations in writing back and forth to avoid misunderstandings. An indemnification clause is also very important to hold the consultant harmless from and against any claim, loss, or damage whatsoever.”

The FDA, for its part, needs to respond faster to meeting requests and offer clearer guidance about appropriate study designs and outcome measures, both experts emphasized. The median time for FDA to approve a drug application is about 180 days, while approving new gastroenterology agents takes nearly twice as long, according to Dr. Lichtenstein. “There is clearly a discrepancy, and it would be nice if we moved the bar closer. As an investigator, I need to know which trials are acceptable in design, and what endpoints are clearly defined, with examples,” he said. “If I have a question, I need a point of contact to call to get an answer in rapid time, instead of having to wait for months, and I need to know which biomarkers are appropriate to use.”

Dr. Harris agreed. “There should be tension between FDA and industry – that is part of the process,” he said. “But open communication and rapid response to meeting requests are crucial.”

Timeliness and transparency are especially important as FDA transitions “from being a classic regulator to a proactive partner in drug development,” Dr. Harris said. “What industry needs and expects from FDA is greater certainty on the path. Companies may or may not like a particular FDA guidance document, but they greatly appreciate the clarity that guidance documents provide.”

Dr. Lichtenstein disclosed ties to AbbVie, Hospira, Pfizer, and numerous other pharmaceutical companies. Dr. Harris is employed by Lyric Pharmaceuticals and disclosed relationships with several other biopharmaceutical companies.

SAN DIEGO – Tensions among academic investigators, industry sponsors, and the Food and Drug Administration can hinder new drug approvals and slow or block communication of important results, experts said at the annual Digestive Disease Week.

Relationships between investigators and industry have become especially strained, according to Dr. M. Scott Harris, cofounder of Lyric Pharmaceuticals in San Francisco. “I can tell you as a former investigator, and someone who speaks to investigators all the time, they feel disenfranchised,” he said.

Several steps can help. Industry should focus on empowering investigators, “not study sites,” said Dr. Harris. “Have protocol development meetings, not investigator meetings. Have open dialogue so that investigators can share in the excitement of the study, the results, and the science.”

Intellectual property is a particularly hot topic, acknowledged Dr. Harris, who started out in academic gastroenterology before making the jump to working for pharmaceutical and biotechnology companies. “Intellectual property is the lifeblood of a company – the only thing that generates the likelihood of a return on investment,” he emphasized. “Please do not push back if some information cannot be shared with you.” But within those constraints, industry should “force itself to be as patient as possible,” he said. “A balance has to be struck between the need for IP [intellectual property] and the need to share knowledge.”

Sharing knowledge also means that industry sponsors need to commit to a clear publication strategy, said Dr. Harris. “Investigators want the results of the studies to be communicated, including reasons for failure. We have failed at this as an industry, and this is not acceptable.”

But academic investigators need to make some changes, too. Successfully joining a trial means engaging actively with the sponsor and protocol, Dr. Harris emphasized. “Don’t tell your staff you’re too busy to talk to me when I call. Focus on ethical study conduct, good clinical practice, training, data quality, and meeting timelines.”

Dr. Gary Lichtenstein agreed. A gastroenterologist at the University of Pennsylvania, Philadelphia, with more than 30 years of experience in clinical trials, he knows that successful academic study sites have “efficient and businesslike operations,” a proven internal audit system, and solid, reasonable budgeting for staff time, overhead, equipment, and storage. In particular, academic investigators should double-check training requirements, the qualifications of the study coordinator, and who will handle regulatory, legal, and budgeting concerns, he said.

Vetting a potential industry sponsor is just as important. Ask “if they have the staff, time, equipment, and space to do the study,” Dr. Lichtenstein stressed. “Communicate expectations in writing back and forth to avoid misunderstandings. An indemnification clause is also very important to hold the consultant harmless from and against any claim, loss, or damage whatsoever.”

The FDA, for its part, needs to respond faster to meeting requests and offer clearer guidance about appropriate study designs and outcome measures, both experts emphasized. The median time for FDA to approve a drug application is about 180 days, while approving new gastroenterology agents takes nearly twice as long, according to Dr. Lichtenstein. “There is clearly a discrepancy, and it would be nice if we moved the bar closer. As an investigator, I need to know which trials are acceptable in design, and what endpoints are clearly defined, with examples,” he said. “If I have a question, I need a point of contact to call to get an answer in rapid time, instead of having to wait for months, and I need to know which biomarkers are appropriate to use.”

Dr. Harris agreed. “There should be tension between FDA and industry – that is part of the process,” he said. “But open communication and rapid response to meeting requests are crucial.”

Timeliness and transparency are especially important as FDA transitions “from being a classic regulator to a proactive partner in drug development,” Dr. Harris said. “What industry needs and expects from FDA is greater certainty on the path. Companies may or may not like a particular FDA guidance document, but they greatly appreciate the clarity that guidance documents provide.”

Dr. Lichtenstein disclosed ties to AbbVie, Hospira, Pfizer, and numerous other pharmaceutical companies. Dr. Harris is employed by Lyric Pharmaceuticals and disclosed relationships with several other biopharmaceutical companies.

There have been three infants born with birth defects and three pregnancy losses as a result of likely maternal Zika virus infection among U.S. women, according to figures released by the Centers for Disease Control and Prevention.

The figures, posted by the CDC on June 16, reflect reporting to the U.S. Zika Pregnancy Registry as of June 9. This is not real-time data and reflects only pregnancy outcomes for women with any laboratory evidence of possible Zika virus infection, though it is not known if Zika virus was the cause of the poor outcomes. The numbers also do not reflect outcomes among ongoing pregnancies.

Zika-related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

The current numbers include outcomes reported in U.S. states and the District of Columbia. The CDC will begin reporting outcomes in U.S. territories in the coming weeks.

CDC officials plan to update the pregnancy outcome data every Thursday at http://www.cdc.gov/zika/geo/pregnancy-outcomes.html.

[email protected]

On Twitter @maryellenny

There have been three infants born with birth defects and three pregnancy losses as a result of likely maternal Zika virus infection among U.S. women, according to figures released by the Centers for Disease Control and Prevention.

The figures, posted by the CDC on June 16, reflect reporting to the U.S. Zika Pregnancy Registry as of June 9. This is not real-time data and reflects only pregnancy outcomes for women with any laboratory evidence of possible Zika virus infection, though it is not known if Zika virus was the cause of the poor outcomes. The numbers also do not reflect outcomes among ongoing pregnancies.

Zika-related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

The current numbers include outcomes reported in U.S. states and the District of Columbia. The CDC will begin reporting outcomes in U.S. territories in the coming weeks.

CDC officials plan to update the pregnancy outcome data every Thursday at http://www.cdc.gov/zika/geo/pregnancy-outcomes.html.

[email protected]

On Twitter @maryellenny

There have been three infants born with birth defects and three pregnancy losses as a result of likely maternal Zika virus infection among U.S. women, according to figures released by the Centers for Disease Control and Prevention.

The figures, posted by the CDC on June 16, reflect reporting to the U.S. Zika Pregnancy Registry as of June 9. This is not real-time data and reflects only pregnancy outcomes for women with any laboratory evidence of possible Zika virus infection, though it is not known if Zika virus was the cause of the poor outcomes. The numbers also do not reflect outcomes among ongoing pregnancies.

Zika-related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

The current numbers include outcomes reported in U.S. states and the District of Columbia. The CDC will begin reporting outcomes in U.S. territories in the coming weeks.

CDC officials plan to update the pregnancy outcome data every Thursday at http://www.cdc.gov/zika/geo/pregnancy-outcomes.html.

[email protected]

On Twitter @maryellenny

COPENHAGEN – Nivolumab may be an effective salvage therapy option for adults with Hodgkin lymphoma whose disease has progressed despite transplant and treatment with brentuximab vedotin, investigators reported.

In a subcohort of patients from the Checkmate 205 phase II trial, 80 patients with Hodgkin lymphoma who had disease progression following autologous stem cell transplant (ASCT) and brentuximab vedotin (Adcetris), nivolumab (Opdivo) therapy was associated with a 53% objective response rate according to independent reviewers, reported Dr. Anas Younes, chief of the lymphoma service at Memorial Sloan Kettering Cancer Center, New York.

“The PD-1 checkpoint inhibitor nivolumab is an important new treatment to address unmet needs in patients with classical Hodgkin lymphoma with progressive disease and limited treatment options, especially after autologous transplant,” he said at a briefing at the annual congress of the European Hematology Association.

Objective response rates as determined by both investigators and independent reviewers were “impressive,” and had “encouraging durability,” he added. The median duration of response at time of data cutoff was 7.8 months, and the majority of patients had ongoing responses at the time of the analysis, Dr. Younes said.

Nivolumab was recently approved by the Food and Drug Administration for the treatment of classical Hodgkin lymphoma that has relapsed or progressed after ASCT followed by brentuximab vedotin.

In the Checkmate 205 registrational trial, 80 patients (median age 37, range 18-72 years) were assigned to receive nivolumab 3 mg/kg intravenously every 2 weeks. Patients were evaluated for response by both an independent radiologic review committee (IRRC) and investigators, using 2007 International Working Group response criteria. After a median follow-up of 8.9 months, the IRRC-rated objective response rate, the primary endpoint, was 66%, including 8.8% complete remissions (CR), and 57.5% partial remissions (PR).

Dr. Younes showed a waterfall plot indicating that nearly all patients had some degree of tumor regression, and all but one patient among the responders had tumor reductions of 50% or greater from baseline.

Among 43 patients who had had no response to brentuximab vedotin, subsequent treatment with nivolumab was associated with an IRRC-rated objective response rate of 72%. As noted, the median duration of response was 7.8 months, and the median time to response was 2.1 months.

As of the last follow-up, 33 of the 53 patients with IRRC-rated responses had retained response. The IRRC-determined 6-month progression-free survival rate was 77%, and the overall survival rate was 99%.

In all, 72 patients (90%) had a treatment-related adverse event. The most common events occurring in 15% or more of patients were fatigue, infusion-related reactions, and rash. Most of the immune-mediated adverse events were of low grade and manageable, and there were no treatment-related deaths, Dr. Younes said.

Briefing moderator Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam, who was not involved in the study, asked whether nivolumab can be considered as a bridge to other therapies in this population.

Dr. Younes said that the “natural progression of a single-agent therapy that has efficacy is to combine it with other active agents, or use maybe in the adjuvant or maintenance setting in certain circumstances.”

“I don’t expect single-agent nivolumab to cure our patients,” he added.

A similarly designed clinical trial, MK-3457-087/KEYNOTE-087, is exploring the use of pembrolizumab (Keytruda). This trial is ongoing but does not have published data as yet.

Checkmate 205 is sponsored by Bristol-Myers Squibb. Dr. Younes has served as a consultant/advisor, received honoraria and/or research funding from Gilead Sciences, Curis, Incyte, Janssen, Seattle Genetics, Novartis, Celgene, Millennium, and Sanofi. Dr. Hagenbeek reported no relevant disclosures.

COPENHAGEN – Nivolumab may be an effective salvage therapy option for adults with Hodgkin lymphoma whose disease has progressed despite transplant and treatment with brentuximab vedotin, investigators reported.

In a subcohort of patients from the Checkmate 205 phase II trial, 80 patients with Hodgkin lymphoma who had disease progression following autologous stem cell transplant (ASCT) and brentuximab vedotin (Adcetris), nivolumab (Opdivo) therapy was associated with a 53% objective response rate according to independent reviewers, reported Dr. Anas Younes, chief of the lymphoma service at Memorial Sloan Kettering Cancer Center, New York.

“The PD-1 checkpoint inhibitor nivolumab is an important new treatment to address unmet needs in patients with classical Hodgkin lymphoma with progressive disease and limited treatment options, especially after autologous transplant,” he said at a briefing at the annual congress of the European Hematology Association.

Objective response rates as determined by both investigators and independent reviewers were “impressive,” and had “encouraging durability,” he added. The median duration of response at time of data cutoff was 7.8 months, and the majority of patients had ongoing responses at the time of the analysis, Dr. Younes said.

Nivolumab was recently approved by the Food and Drug Administration for the treatment of classical Hodgkin lymphoma that has relapsed or progressed after ASCT followed by brentuximab vedotin.

In the Checkmate 205 registrational trial, 80 patients (median age 37, range 18-72 years) were assigned to receive nivolumab 3 mg/kg intravenously every 2 weeks. Patients were evaluated for response by both an independent radiologic review committee (IRRC) and investigators, using 2007 International Working Group response criteria. After a median follow-up of 8.9 months, the IRRC-rated objective response rate, the primary endpoint, was 66%, including 8.8% complete remissions (CR), and 57.5% partial remissions (PR).

Dr. Younes showed a waterfall plot indicating that nearly all patients had some degree of tumor regression, and all but one patient among the responders had tumor reductions of 50% or greater from baseline.

Among 43 patients who had had no response to brentuximab vedotin, subsequent treatment with nivolumab was associated with an IRRC-rated objective response rate of 72%. As noted, the median duration of response was 7.8 months, and the median time to response was 2.1 months.

As of the last follow-up, 33 of the 53 patients with IRRC-rated responses had retained response. The IRRC-determined 6-month progression-free survival rate was 77%, and the overall survival rate was 99%.

In all, 72 patients (90%) had a treatment-related adverse event. The most common events occurring in 15% or more of patients were fatigue, infusion-related reactions, and rash. Most of the immune-mediated adverse events were of low grade and manageable, and there were no treatment-related deaths, Dr. Younes said.

Briefing moderator Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam, who was not involved in the study, asked whether nivolumab can be considered as a bridge to other therapies in this population.

Dr. Younes said that the “natural progression of a single-agent therapy that has efficacy is to combine it with other active agents, or use maybe in the adjuvant or maintenance setting in certain circumstances.”

“I don’t expect single-agent nivolumab to cure our patients,” he added.

A similarly designed clinical trial, MK-3457-087/KEYNOTE-087, is exploring the use of pembrolizumab (Keytruda). This trial is ongoing but does not have published data as yet.

Checkmate 205 is sponsored by Bristol-Myers Squibb. Dr. Younes has served as a consultant/advisor, received honoraria and/or research funding from Gilead Sciences, Curis, Incyte, Janssen, Seattle Genetics, Novartis, Celgene, Millennium, and Sanofi. Dr. Hagenbeek reported no relevant disclosures.

COPENHAGEN – Nivolumab may be an effective salvage therapy option for adults with Hodgkin lymphoma whose disease has progressed despite transplant and treatment with brentuximab vedotin, investigators reported.

In a subcohort of patients from the Checkmate 205 phase II trial, 80 patients with Hodgkin lymphoma who had disease progression following autologous stem cell transplant (ASCT) and brentuximab vedotin (Adcetris), nivolumab (Opdivo) therapy was associated with a 53% objective response rate according to independent reviewers, reported Dr. Anas Younes, chief of the lymphoma service at Memorial Sloan Kettering Cancer Center, New York.

“The PD-1 checkpoint inhibitor nivolumab is an important new treatment to address unmet needs in patients with classical Hodgkin lymphoma with progressive disease and limited treatment options, especially after autologous transplant,” he said at a briefing at the annual congress of the European Hematology Association.

Objective response rates as determined by both investigators and independent reviewers were “impressive,” and had “encouraging durability,” he added. The median duration of response at time of data cutoff was 7.8 months, and the majority of patients had ongoing responses at the time of the analysis, Dr. Younes said.

Nivolumab was recently approved by the Food and Drug Administration for the treatment of classical Hodgkin lymphoma that has relapsed or progressed after ASCT followed by brentuximab vedotin.

In the Checkmate 205 registrational trial, 80 patients (median age 37, range 18-72 years) were assigned to receive nivolumab 3 mg/kg intravenously every 2 weeks. Patients were evaluated for response by both an independent radiologic review committee (IRRC) and investigators, using 2007 International Working Group response criteria. After a median follow-up of 8.9 months, the IRRC-rated objective response rate, the primary endpoint, was 66%, including 8.8% complete remissions (CR), and 57.5% partial remissions (PR).

Dr. Younes showed a waterfall plot indicating that nearly all patients had some degree of tumor regression, and all but one patient among the responders had tumor reductions of 50% or greater from baseline.

Among 43 patients who had had no response to brentuximab vedotin, subsequent treatment with nivolumab was associated with an IRRC-rated objective response rate of 72%. As noted, the median duration of response was 7.8 months, and the median time to response was 2.1 months.

As of the last follow-up, 33 of the 53 patients with IRRC-rated responses had retained response. The IRRC-determined 6-month progression-free survival rate was 77%, and the overall survival rate was 99%.

In all, 72 patients (90%) had a treatment-related adverse event. The most common events occurring in 15% or more of patients were fatigue, infusion-related reactions, and rash. Most of the immune-mediated adverse events were of low grade and manageable, and there were no treatment-related deaths, Dr. Younes said.

Briefing moderator Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam, who was not involved in the study, asked whether nivolumab can be considered as a bridge to other therapies in this population.

Dr. Younes said that the “natural progression of a single-agent therapy that has efficacy is to combine it with other active agents, or use maybe in the adjuvant or maintenance setting in certain circumstances.”

“I don’t expect single-agent nivolumab to cure our patients,” he added.

A similarly designed clinical trial, MK-3457-087/KEYNOTE-087, is exploring the use of pembrolizumab (Keytruda). This trial is ongoing but does not have published data as yet.

Checkmate 205 is sponsored by Bristol-Myers Squibb. Dr. Younes has served as a consultant/advisor, received honoraria and/or research funding from Gilead Sciences, Curis, Incyte, Janssen, Seattle Genetics, Novartis, Celgene, Millennium, and Sanofi. Dr. Hagenbeek reported no relevant disclosures.

LONDON – Bone mineral density (BMD) and estimated bone strength in the hip significantly increased during 1 year of treatment with the investigational monoclonal antibody romosozumab in comparison with teriparatide in women with postmenopausal osteoporosis who had previous fracture history and had been taking bisphosphonates for at least the previous 3 years in an open-label, randomized trial.

The investigators in the phase III, international, multicenter STRUCTURE trial sought to compare the monoclonal anti-sclerostin antibody romosozumab, which works dually to increase bone formation and decrease bone resorption, against the bone-forming agent teriparatide (Forteo) to see if it would increase total hip bone mineral density to a significantly greater extent by 12 months. Teriparatide is known to take longer to build bone at the hip following bisphosphonate use.

“These results in our minds suggest that romosozumab may offer a unique benefit to patients at high risk for fracture, transitioning from bisphosphonates,” first author Bente L. Langdahl, Ph.D., of Aarhus (Denmark) University Hospital said at the European Congress of Rheumatology. She discussed the study results in this video interview.

When Dr. Langdahl was asked after her presentation about the foreseen role of the drug in clinical practice, she noted that ongoing phase III trials looking at fracture endpoints should indicate whether it works faster at preventing fractures. Because there does not seem to be a restriction to the repeated use of romosozumab, she suggested it might be given initially for 12 months to build bone, followed by bisphosphonates to stabilize gains made, and then it could be used again if needed in a treat-to-target fashion.

The trial randomized 436 patients to receive either subcutaneous romosozumab 210 mg once monthly or subcutaneous teriparatide 20 mcg once daily for 12 months. All patients received a loading dose of 50,000-60,000 IU vitamin D3 to make sure they were vitamin D replete. The patients were postmenopausal, aged 55-90 years, and required to have taken oral bisphosphonate therapy at a dose equivalent to 70 mg weekly of alendronate for at least 3 years before enrollment (with at least 1 year of alendronate therapy prior to enrollment). They had a T score of –2.5 or less in total hip, lumbar spine, or femoral neck BMD and a history of a nonvertebral fracture after 50 years of age or a vertebral fracture at any age.

At 12 months, the primary endpoint of total hip BMD percentage change from baseline, which was calculated by averaging dual-energy x-ray absorptiometry (DXA) measurements at 6 and 12 months, increased significantly by 2.6% in the romosozumab group, compared with a loss of –1.6% in the teriparatide group.

“Why did we choose this rather unusual endpoint? It’s because we wanted to capture what happened throughout the first year,” Dr. Langdahl said.

The respective changes from baseline total hip BMD at month 12 were 2.9% vs. –0.5%; in the femoral neck, the 12-month change was 3.2% vs. –0.2%; and in the lumbar spine, the change was 9.8% vs. 5.4%.

The trial participants had a mean age of about 71 years, and T scores ranging from –2.87 to –2.83 in the lumbar spine, –2.27 to –2.21 in total hip, and –2.49 to –2.43 in the femoral neck.

Secondary endpoints of volumetric BMD measured by quantitative CT at 12 months supported the results for DXA measurements at the total hip: integral BMD changed 3.4% with romosozumab vs. –0.2% with teriparatide, cortical BMD changed 1.1% with romosozumab vs. –3.6% with teriparatide, and trabecular BMD increased 15.6% vs. 9.9%, respectively. Total hip strength at 12 months as estimated by finite element analysis rose by 2.5% with romosozumab, compared with a loss of –0.7% with teriparatide. The loss in estimated bone strength at the hip occurred mainly in the first 6 months of treatment with teriparatide and had started to recover by 12 months.

The main difference between the two treatments in total hip BMD came from romosozumab’s bone-building effect on cortical bone, Dr. Langdahl said. The significant loss of total hip cortical BMD observed with teriparatide matches what has been seen in other studies, and it occurs “because the way that teriparatide works initially on cortical bone is to open up the remodeling space; therefore, a decrease in BMD is seen.”

While romosozumab’s speed in increasing BMD and building bone strength is likely to be clinically meaningful for patients at high risk of fracture, the short duration of the trial likely left out the possibility of seeing the same sort of late increases in hip BMD and bone strength during the second year of treatment with teriparatide that have been observed in other studies. Dr. Langdahl suggested that the decline in total hip cortical bone volumetric BMD may have increased had there been more time for measurement in the study; after bisphosphonate treatment, teriparatide’s mechanism of action is thought to open up the bone remodeling space by stimulating bone resorption and formation, particularly in cortical bone.

“You will see an increased porosity in the cortical bone, and I think that is what explains the initial decrease. You’ll also see that it’s kind of catching up [to romosozumab]. This is only a 12-month study, unfortunately. I’m sure if it had been continued for 24 months, there would be an increase in strength because that has been demonstrated in other studies.”

The trial’s comparison of romosozumab versus teriparatide alone also leaves open the question of whether adding teriparatide to bisphosphonate or switching to a combination of teriparatide plus denosumab or teriparatide plus zoledronic acid might have yielded results comparable with romosozumab alone.

Furthermore, The study is not large enough to determine the overall side-effect profile of romosozumab and will have to wait until the larger, ongoing phase III studies are completed, Dr. Langdahl said. In the STRUCTURE study, the overall side effect profile was well balanced between the two groups. More women who received teriparatide developed hypercalcemia, and patients who received romosozumab developed antibodies, although they did not neutralize the agent’s effects.

The study was sponsored by UCB Pharma and Amgen. One investigator is an employee of UCB, and one is an employee of Amgen. Dr. Langdahl reported receiving research grants, consulting fees, and/or honoraria from Amgen, UCB, Eli Lilly, Merck, and Orkla. Most other investigators also reported financial relationships to Amgen and other pharmaceutical companies.

[email protected]

LONDON – Bone mineral density (BMD) and estimated bone strength in the hip significantly increased during 1 year of treatment with the investigational monoclonal antibody romosozumab in comparison with teriparatide in women with postmenopausal osteoporosis who had previous fracture history and had been taking bisphosphonates for at least the previous 3 years in an open-label, randomized trial.

The investigators in the phase III, international, multicenter STRUCTURE trial sought to compare the monoclonal anti-sclerostin antibody romosozumab, which works dually to increase bone formation and decrease bone resorption, against the bone-forming agent teriparatide (Forteo) to see if it would increase total hip bone mineral density to a significantly greater extent by 12 months. Teriparatide is known to take longer to build bone at the hip following bisphosphonate use.

“These results in our minds suggest that romosozumab may offer a unique benefit to patients at high risk for fracture, transitioning from bisphosphonates,” first author Bente L. Langdahl, Ph.D., of Aarhus (Denmark) University Hospital said at the European Congress of Rheumatology. She discussed the study results in this video interview.

When Dr. Langdahl was asked after her presentation about the foreseen role of the drug in clinical practice, she noted that ongoing phase III trials looking at fracture endpoints should indicate whether it works faster at preventing fractures. Because there does not seem to be a restriction to the repeated use of romosozumab, she suggested it might be given initially for 12 months to build bone, followed by bisphosphonates to stabilize gains made, and then it could be used again if needed in a treat-to-target fashion.

The trial randomized 436 patients to receive either subcutaneous romosozumab 210 mg once monthly or subcutaneous teriparatide 20 mcg once daily for 12 months. All patients received a loading dose of 50,000-60,000 IU vitamin D3 to make sure they were vitamin D replete. The patients were postmenopausal, aged 55-90 years, and required to have taken oral bisphosphonate therapy at a dose equivalent to 70 mg weekly of alendronate for at least 3 years before enrollment (with at least 1 year of alendronate therapy prior to enrollment). They had a T score of –2.5 or less in total hip, lumbar spine, or femoral neck BMD and a history of a nonvertebral fracture after 50 years of age or a vertebral fracture at any age.

At 12 months, the primary endpoint of total hip BMD percentage change from baseline, which was calculated by averaging dual-energy x-ray absorptiometry (DXA) measurements at 6 and 12 months, increased significantly by 2.6% in the romosozumab group, compared with a loss of –1.6% in the teriparatide group.

“Why did we choose this rather unusual endpoint? It’s because we wanted to capture what happened throughout the first year,” Dr. Langdahl said.

The respective changes from baseline total hip BMD at month 12 were 2.9% vs. –0.5%; in the femoral neck, the 12-month change was 3.2% vs. –0.2%; and in the lumbar spine, the change was 9.8% vs. 5.4%.

The trial participants had a mean age of about 71 years, and T scores ranging from –2.87 to –2.83 in the lumbar spine, –2.27 to –2.21 in total hip, and –2.49 to –2.43 in the femoral neck.

Secondary endpoints of volumetric BMD measured by quantitative CT at 12 months supported the results for DXA measurements at the total hip: integral BMD changed 3.4% with romosozumab vs. –0.2% with teriparatide, cortical BMD changed 1.1% with romosozumab vs. –3.6% with teriparatide, and trabecular BMD increased 15.6% vs. 9.9%, respectively. Total hip strength at 12 months as estimated by finite element analysis rose by 2.5% with romosozumab, compared with a loss of –0.7% with teriparatide. The loss in estimated bone strength at the hip occurred mainly in the first 6 months of treatment with teriparatide and had started to recover by 12 months.

The main difference between the two treatments in total hip BMD came from romosozumab’s bone-building effect on cortical bone, Dr. Langdahl said. The significant loss of total hip cortical BMD observed with teriparatide matches what has been seen in other studies, and it occurs “because the way that teriparatide works initially on cortical bone is to open up the remodeling space; therefore, a decrease in BMD is seen.”

While romosozumab’s speed in increasing BMD and building bone strength is likely to be clinically meaningful for patients at high risk of fracture, the short duration of the trial likely left out the possibility of seeing the same sort of late increases in hip BMD and bone strength during the second year of treatment with teriparatide that have been observed in other studies. Dr. Langdahl suggested that the decline in total hip cortical bone volumetric BMD may have increased had there been more time for measurement in the study; after bisphosphonate treatment, teriparatide’s mechanism of action is thought to open up the bone remodeling space by stimulating bone resorption and formation, particularly in cortical bone.

“You will see an increased porosity in the cortical bone, and I think that is what explains the initial decrease. You’ll also see that it’s kind of catching up [to romosozumab]. This is only a 12-month study, unfortunately. I’m sure if it had been continued for 24 months, there would be an increase in strength because that has been demonstrated in other studies.”

The trial’s comparison of romosozumab versus teriparatide alone also leaves open the question of whether adding teriparatide to bisphosphonate or switching to a combination of teriparatide plus denosumab or teriparatide plus zoledronic acid might have yielded results comparable with romosozumab alone.

Furthermore, The study is not large enough to determine the overall side-effect profile of romosozumab and will have to wait until the larger, ongoing phase III studies are completed, Dr. Langdahl said. In the STRUCTURE study, the overall side effect profile was well balanced between the two groups. More women who received teriparatide developed hypercalcemia, and patients who received romosozumab developed antibodies, although they did not neutralize the agent’s effects.

The study was sponsored by UCB Pharma and Amgen. One investigator is an employee of UCB, and one is an employee of Amgen. Dr. Langdahl reported receiving research grants, consulting fees, and/or honoraria from Amgen, UCB, Eli Lilly, Merck, and Orkla. Most other investigators also reported financial relationships to Amgen and other pharmaceutical companies.

[email protected]

LONDON – Bone mineral density (BMD) and estimated bone strength in the hip significantly increased during 1 year of treatment with the investigational monoclonal antibody romosozumab in comparison with teriparatide in women with postmenopausal osteoporosis who had previous fracture history and had been taking bisphosphonates for at least the previous 3 years in an open-label, randomized trial.

The investigators in the phase III, international, multicenter STRUCTURE trial sought to compare the monoclonal anti-sclerostin antibody romosozumab, which works dually to increase bone formation and decrease bone resorption, against the bone-forming agent teriparatide (Forteo) to see if it would increase total hip bone mineral density to a significantly greater extent by 12 months. Teriparatide is known to take longer to build bone at the hip following bisphosphonate use.

“These results in our minds suggest that romosozumab may offer a unique benefit to patients at high risk for fracture, transitioning from bisphosphonates,” first author Bente L. Langdahl, Ph.D., of Aarhus (Denmark) University Hospital said at the European Congress of Rheumatology. She discussed the study results in this video interview.

When Dr. Langdahl was asked after her presentation about the foreseen role of the drug in clinical practice, she noted that ongoing phase III trials looking at fracture endpoints should indicate whether it works faster at preventing fractures. Because there does not seem to be a restriction to the repeated use of romosozumab, she suggested it might be given initially for 12 months to build bone, followed by bisphosphonates to stabilize gains made, and then it could be used again if needed in a treat-to-target fashion.

The trial randomized 436 patients to receive either subcutaneous romosozumab 210 mg once monthly or subcutaneous teriparatide 20 mcg once daily for 12 months. All patients received a loading dose of 50,000-60,000 IU vitamin D3 to make sure they were vitamin D replete. The patients were postmenopausal, aged 55-90 years, and required to have taken oral bisphosphonate therapy at a dose equivalent to 70 mg weekly of alendronate for at least 3 years before enrollment (with at least 1 year of alendronate therapy prior to enrollment). They had a T score of –2.5 or less in total hip, lumbar spine, or femoral neck BMD and a history of a nonvertebral fracture after 50 years of age or a vertebral fracture at any age.

At 12 months, the primary endpoint of total hip BMD percentage change from baseline, which was calculated by averaging dual-energy x-ray absorptiometry (DXA) measurements at 6 and 12 months, increased significantly by 2.6% in the romosozumab group, compared with a loss of –1.6% in the teriparatide group.

“Why did we choose this rather unusual endpoint? It’s because we wanted to capture what happened throughout the first year,” Dr. Langdahl said.

The respective changes from baseline total hip BMD at month 12 were 2.9% vs. –0.5%; in the femoral neck, the 12-month change was 3.2% vs. –0.2%; and in the lumbar spine, the change was 9.8% vs. 5.4%.

The trial participants had a mean age of about 71 years, and T scores ranging from –2.87 to –2.83 in the lumbar spine, –2.27 to –2.21 in total hip, and –2.49 to –2.43 in the femoral neck.

Secondary endpoints of volumetric BMD measured by quantitative CT at 12 months supported the results for DXA measurements at the total hip: integral BMD changed 3.4% with romosozumab vs. –0.2% with teriparatide, cortical BMD changed 1.1% with romosozumab vs. –3.6% with teriparatide, and trabecular BMD increased 15.6% vs. 9.9%, respectively. Total hip strength at 12 months as estimated by finite element analysis rose by 2.5% with romosozumab, compared with a loss of –0.7% with teriparatide. The loss in estimated bone strength at the hip occurred mainly in the first 6 months of treatment with teriparatide and had started to recover by 12 months.

The main difference between the two treatments in total hip BMD came from romosozumab’s bone-building effect on cortical bone, Dr. Langdahl said. The significant loss of total hip cortical BMD observed with teriparatide matches what has been seen in other studies, and it occurs “because the way that teriparatide works initially on cortical bone is to open up the remodeling space; therefore, a decrease in BMD is seen.”

While romosozumab’s speed in increasing BMD and building bone strength is likely to be clinically meaningful for patients at high risk of fracture, the short duration of the trial likely left out the possibility of seeing the same sort of late increases in hip BMD and bone strength during the second year of treatment with teriparatide that have been observed in other studies. Dr. Langdahl suggested that the decline in total hip cortical bone volumetric BMD may have increased had there been more time for measurement in the study; after bisphosphonate treatment, teriparatide’s mechanism of action is thought to open up the bone remodeling space by stimulating bone resorption and formation, particularly in cortical bone.

“You will see an increased porosity in the cortical bone, and I think that is what explains the initial decrease. You’ll also see that it’s kind of catching up [to romosozumab]. This is only a 12-month study, unfortunately. I’m sure if it had been continued for 24 months, there would be an increase in strength because that has been demonstrated in other studies.”

The trial’s comparison of romosozumab versus teriparatide alone also leaves open the question of whether adding teriparatide to bisphosphonate or switching to a combination of teriparatide plus denosumab or teriparatide plus zoledronic acid might have yielded results comparable with romosozumab alone.

Furthermore, The study is not large enough to determine the overall side-effect profile of romosozumab and will have to wait until the larger, ongoing phase III studies are completed, Dr. Langdahl said. In the STRUCTURE study, the overall side effect profile was well balanced between the two groups. More women who received teriparatide developed hypercalcemia, and patients who received romosozumab developed antibodies, although they did not neutralize the agent’s effects.

The study was sponsored by UCB Pharma and Amgen. One investigator is an employee of UCB, and one is an employee of Amgen. Dr. Langdahl reported receiving research grants, consulting fees, and/or honoraria from Amgen, UCB, Eli Lilly, Merck, and Orkla. Most other investigators also reported financial relationships to Amgen and other pharmaceutical companies.

[email protected]

COPENHAGEN – It’s early days yet, but results look highly promising for the ability of an experimental gene-transfer therapy to improve coagulation parameters in patients with severe hemophilia B.

In a phase I/II dose-escalation study, a single 1-hour infusion of the gene-transfer product, labeled SPK-9001, resulted in factor IX activity levels ranging from 25% to 39% of normal in four men with severe or moderately severe hemophilia B, reported Dr. Katherine A High, president and chief scientific officer of Spark Therapeutics, maker of the product.

©Kativ/iStockphoto

“One of the most remarkable features of the data in my mind has been a very consistent performance,” she said at a briefing at the annual congress of the European Hematology Association.

The product consists of a vector containing a novel bio-engineered adeno-associated virus (AAV) capsid with tropism for liver, and a factor IX cassette that carries a strong liver-specific promoter to drive the expression of the factor IX variant, dubbed factor IX Padua.

“The hypothesis of the work was that if we could engineer a vector efficient enough, we would be able to infuse it at a dose low enough that it would drive loads of expression greater than 12% of normal, which in previous work has been shown to be associated with an absence of joint bleeds in natural history studies of people with mild disease, and that infusion at a low dose would eliminate the need for any type of immune suppression with steroids,” Dr. High said.

Other attempts at genetic engineering in patients with hemophilia B have been hampered by the need to use high doses of vector that can induce an immune response, thereby negating the benefit of therapy.

In this ongoing study, conducted in Mississippi, Pennsylvania, and California, males 18 and older with a confirmed diagnosis of hemophilia B (defined as equal to or less than 2 IU/dL or 2% endogenous factor IX) who have received 50 or more days of exposure to factor IX products are enrolled. The patients must have a minimum average of four bleeding events per year requiring episodic treatment of factor IX infusions or prophylactic factor IX infusions, no measurable factor IX inhibitor as assessed by the central laboratory, and no prior history of inhibitors to factor IX protein.

In an oral session at the congress, Dr. Spencer Sullivan, assistant professor of pediatrics and medicine at the University of Mississippi Medical Center in Jackson, presented data on four men whose age ranges from 18 to 47 years.

In the dose-escalation phase of the study, the patients received single infusions of SPK-9001 at an initial starting dose of 5 x 1011 vector genomes of body weight. They were followed for 7-26 weeks after gene transfer for factor IX activity levels, liver enzymes, bleeding episode, and factor usage. As of May 22, 2016, the first four patients showed factor IX activity levels of 32%, 39%, 25%, and 27% of normal, respectively.

All subjects are currently off prophylactic factor IX infusions. During the course of follow-up, one patient infused himself with factor IX once, treating himself 2 days after vector infusion for a suspected ankle bleed.

Asked by a reporter how durable the effect was, Dr. High replied that in dog models of hemophilia B the effect of the gene transfer has been durable.

The best evidence to date of durability in humans, she said, comes from investigators at University College in London (England), who found that if patients can make it past the first 8-10 weeks without developing an immune response to the transfer product, they are likely to do well, and to have a durable effect, she said.

Dr. Anton Hagenbeek, from the Academic Medical Center, University of Amsterdam, who moderated the briefing but was not involved in the study, said that Dr. High was “to be congratulated for these best data ever seen.”

He asked, facetiously, whether she thought that “thousands of patients would buy a ticket to Philadelphia.” The “City of Brotherly Love” is home to one of the trial sites and to Spark headquarters.

The study is sponsored by Spark Therapeutics and Pfizer. Dr. High is president and chief scientific officer of Spark. Dr. Sullivan and Dr. Hagenbeek reported no relevant disclosures.

COPENHAGEN – It’s early days yet, but results look highly promising for the ability of an experimental gene-transfer therapy to improve coagulation parameters in patients with severe hemophilia B.

In a phase I/II dose-escalation study, a single 1-hour infusion of the gene-transfer product, labeled SPK-9001, resulted in factor IX activity levels ranging from 25% to 39% of normal in four men with severe or moderately severe hemophilia B, reported Dr. Katherine A High, president and chief scientific officer of Spark Therapeutics, maker of the product.

©Kativ/iStockphoto

“One of the most remarkable features of the data in my mind has been a very consistent performance,” she said at a briefing at the annual congress of the European Hematology Association.

The product consists of a vector containing a novel bio-engineered adeno-associated virus (AAV) capsid with tropism for liver, and a factor IX cassette that carries a strong liver-specific promoter to drive the expression of the factor IX variant, dubbed factor IX Padua.

“The hypothesis of the work was that if we could engineer a vector efficient enough, we would be able to infuse it at a dose low enough that it would drive loads of expression greater than 12% of normal, which in previous work has been shown to be associated with an absence of joint bleeds in natural history studies of people with mild disease, and that infusion at a low dose would eliminate the need for any type of immune suppression with steroids,” Dr. High said.

Other attempts at genetic engineering in patients with hemophilia B have been hampered by the need to use high doses of vector that can induce an immune response, thereby negating the benefit of therapy.

In this ongoing study, conducted in Mississippi, Pennsylvania, and California, males 18 and older with a confirmed diagnosis of hemophilia B (defined as equal to or less than 2 IU/dL or 2% endogenous factor IX) who have received 50 or more days of exposure to factor IX products are enrolled. The patients must have a minimum average of four bleeding events per year requiring episodic treatment of factor IX infusions or prophylactic factor IX infusions, no measurable factor IX inhibitor as assessed by the central laboratory, and no prior history of inhibitors to factor IX protein.

In an oral session at the congress, Dr. Spencer Sullivan, assistant professor of pediatrics and medicine at the University of Mississippi Medical Center in Jackson, presented data on four men whose age ranges from 18 to 47 years.

In the dose-escalation phase of the study, the patients received single infusions of SPK-9001 at an initial starting dose of 5 x 1011 vector genomes of body weight. They were followed for 7-26 weeks after gene transfer for factor IX activity levels, liver enzymes, bleeding episode, and factor usage. As of May 22, 2016, the first four patients showed factor IX activity levels of 32%, 39%, 25%, and 27% of normal, respectively.

All subjects are currently off prophylactic factor IX infusions. During the course of follow-up, one patient infused himself with factor IX once, treating himself 2 days after vector infusion for a suspected ankle bleed.

Asked by a reporter how durable the effect was, Dr. High replied that in dog models of hemophilia B the effect of the gene transfer has been durable.

The best evidence to date of durability in humans, she said, comes from investigators at University College in London (England), who found that if patients can make it past the first 8-10 weeks without developing an immune response to the transfer product, they are likely to do well, and to have a durable effect, she said.

Dr. Anton Hagenbeek, from the Academic Medical Center, University of Amsterdam, who moderated the briefing but was not involved in the study, said that Dr. High was “to be congratulated for these best data ever seen.”

He asked, facetiously, whether she thought that “thousands of patients would buy a ticket to Philadelphia.” The “City of Brotherly Love” is home to one of the trial sites and to Spark headquarters.

The study is sponsored by Spark Therapeutics and Pfizer. Dr. High is president and chief scientific officer of Spark. Dr. Sullivan and Dr. Hagenbeek reported no relevant disclosures.

COPENHAGEN – It’s early days yet, but results look highly promising for the ability of an experimental gene-transfer therapy to improve coagulation parameters in patients with severe hemophilia B.

In a phase I/II dose-escalation study, a single 1-hour infusion of the gene-transfer product, labeled SPK-9001, resulted in factor IX activity levels ranging from 25% to 39% of normal in four men with severe or moderately severe hemophilia B, reported Dr. Katherine A High, president and chief scientific officer of Spark Therapeutics, maker of the product.

©Kativ/iStockphoto

“One of the most remarkable features of the data in my mind has been a very consistent performance,” she said at a briefing at the annual congress of the European Hematology Association.

The product consists of a vector containing a novel bio-engineered adeno-associated virus (AAV) capsid with tropism for liver, and a factor IX cassette that carries a strong liver-specific promoter to drive the expression of the factor IX variant, dubbed factor IX Padua.

“The hypothesis of the work was that if we could engineer a vector efficient enough, we would be able to infuse it at a dose low enough that it would drive loads of expression greater than 12% of normal, which in previous work has been shown to be associated with an absence of joint bleeds in natural history studies of people with mild disease, and that infusion at a low dose would eliminate the need for any type of immune suppression with steroids,” Dr. High said.

Other attempts at genetic engineering in patients with hemophilia B have been hampered by the need to use high doses of vector that can induce an immune response, thereby negating the benefit of therapy.

In this ongoing study, conducted in Mississippi, Pennsylvania, and California, males 18 and older with a confirmed diagnosis of hemophilia B (defined as equal to or less than 2 IU/dL or 2% endogenous factor IX) who have received 50 or more days of exposure to factor IX products are enrolled. The patients must have a minimum average of four bleeding events per year requiring episodic treatment of factor IX infusions or prophylactic factor IX infusions, no measurable factor IX inhibitor as assessed by the central laboratory, and no prior history of inhibitors to factor IX protein.

In an oral session at the congress, Dr. Spencer Sullivan, assistant professor of pediatrics and medicine at the University of Mississippi Medical Center in Jackson, presented data on four men whose age ranges from 18 to 47 years.

In the dose-escalation phase of the study, the patients received single infusions of SPK-9001 at an initial starting dose of 5 x 1011 vector genomes of body weight. They were followed for 7-26 weeks after gene transfer for factor IX activity levels, liver enzymes, bleeding episode, and factor usage. As of May 22, 2016, the first four patients showed factor IX activity levels of 32%, 39%, 25%, and 27% of normal, respectively.

All subjects are currently off prophylactic factor IX infusions. During the course of follow-up, one patient infused himself with factor IX once, treating himself 2 days after vector infusion for a suspected ankle bleed.

Asked by a reporter how durable the effect was, Dr. High replied that in dog models of hemophilia B the effect of the gene transfer has been durable.

The best evidence to date of durability in humans, she said, comes from investigators at University College in London (England), who found that if patients can make it past the first 8-10 weeks without developing an immune response to the transfer product, they are likely to do well, and to have a durable effect, she said.

Dr. Anton Hagenbeek, from the Academic Medical Center, University of Amsterdam, who moderated the briefing but was not involved in the study, said that Dr. High was “to be congratulated for these best data ever seen.”

He asked, facetiously, whether she thought that “thousands of patients would buy a ticket to Philadelphia.” The “City of Brotherly Love” is home to one of the trial sites and to Spark headquarters.

The study is sponsored by Spark Therapeutics and Pfizer. Dr. High is president and chief scientific officer of Spark. Dr. Sullivan and Dr. Hagenbeek reported no relevant disclosures.

CHICAGO – Artificially prolonging the platinum-free interval by introducing a non–platinum-based chemotherapy before re-treatment with platinum-based chemotherapy in patients with partially platinum-sensitive recurrent ovarian cancer did not improve efficacy, and actually worsened the outcomes in patients in the randomized, open-label, phase III Multicentre Italian Trials in Ovarian Cancer 8 (MITO8) trial.

Based on the findings, immediate re-treatment with platinum-based chemotherapy remains the standard treatment strategy in such patients, Dr. Sandro Pignata reported at the annual meeting of the American Society of Clinical Oncology.

The idea that a non-platinum therapy might artificially extend the platinum-free interval, thereby improving outcomes in ovarian cancer patients who experience recurrence between 6 and 12 months after responding to platinum-based therapy, was first proposed more than 20 years ago. Despite a lack of prospective data with respect to this non–platinum-therapy approach, the idea has been used successfully to market non-platinum chemotherapy agents such as paclitaxel, topotecan, pegylated liposomal doxorubicin (PLD), and more recently, PLD-trabectedin for use before reinitiating platinum chemotherapy, explained Dr. Pignata of S.C. Oncologia Medica Ginecologica, Istituto Nazionale Tumori, Napoli.

In fact, a 2007 retrospective analysis (SOCRATES) showed that 35% of patients with recurrence at 6-12 months after platinum-based therapy were treated with a non-platinum single agent before re-treatment with a platinum-based therapy, and that the approach has been used as the control arm in multiple phase III trials that included patients with a platinum-free interval of 6-12 months. The findings indicate that the unproven hypothesis has been adapted into clinical practice, but the investigators were unable to demonstrate an advantage with the approach and concluded that further investigation was warranted.

MITO8, a multi-organization collaborative effort, was designed to test whether artificial prolongation of the platinum-free interval with a single-agent non-platinum treatment would improve overall survival in recurrent partially platinum-sensitive ovarian cancer patients.

In 107 such patients randomized to the experimental arm – receiving a non–platinum-based chemotherapy first to prolong the platinum-free interval, followed by platinum-based chemotherapy after progression – the median time from previous platinum to randomization was 8 months, and from randomization to platinum, 7.8 months. Median overall survival, the primary endpoint of the study, was 21.8 months.

In 108 patients randomized to immediate standard therapy with platinum-based chemotherapy followed by non-platinum therapy, median time from previous platinum to randomization was 8 months, and overall survival was 24.5 months (hazard ratio favoring platinum chemotherapy, 1.38), Dr. Pignata said, noting that the difference in overall survival approached but did not reach statistical significance.

A secondary endpoint of progression-free survival after the second treatment was 12.8 months in the experimental arm, vs. 16.4 months in the platinum-based chemotherapy arm (adjusted HR, 1.41). This difference was statistically significant.

No differences with respect to safety or toxicity were seen between the groups.

MITO8 subjects were women with ovarian cancer recurring between 6 and 12 months after previous platinum-based chemotherapy. The patients had received no more than two prior lines of chemotherapy, had good performance status, and had normal organ function.

Non–platinum-based therapy used in the study included pegylated liposomal doxorubicin, except during a period of the study when the agent was in short supply and other single agents were used, including gemcitabine and topotecan. Most patients, however, received PLD.

Platinum-based therapy was carboplatin plus paclitaxel or, in patients with neurotoxicity at baseline, carboplatin plus gemcitabine.

The shortage of PLD was just one of numerous challenges encountered during the course of the beleaguered study. Enrollment began in 2009, but was temporarily suspended in 2011 because of the PLD shortage. In 2012, the amendment to allow other non–platinum-based chemotherapies to be used was approved at most sites and enrollment resumed. However, accrual slowed and enrollment was closed in 2015. The study was stopped early, and the final analysis was conducted in March 2016 when events plateaued. The investigators, in conjunction with the independent data monitoring committee, determined that the results “still had to be presented early because they still may affect clinical practice.”

Dr. Pignata said that the hypothesis “was based on the fact that there were more responses in the patients treated with a platinum after a non-platinum, but this was not the case ... Responses were more frequent in the patients who received platinum first and then non-platinum later,” he said. The response rates for the experimental vs. standard approaches, respectively, were 43% vs. 56% among RECIST responders, and 70% vs. 75% among CA125 responders.

The findings of MITO8, one of the first clinical trials in ovarian cancer to evaluate two different sequences of chemotherapy, send “a strong message that even in the presence of a very nice hypothesis, we have to await the results of prospective clinical trials before changing clinical practice,” he said.

Dr. Maurie Markman of Cancer Treatment Centers of America in Boca Raton, Fla., the invited discussant, praised the work of Dr. Pignata and his colleagues, calling their study “elegant,” and “an extraordinary effort.”

“In this unbelievably important analysis, the hypothesis was flat-out wrong,” he said.

The study is an example of “a simple, provocative, and potentially highly clinically relevant hypothesis that should be able to be quickly tested in either a cooperative group setting, in multiple institutions interested in gynecologic malignancies ... when or very shortly after it is initially proposed,” he said.

Waiting 20 years is unacceptable, he said, adding: “This is tragic, this length of time to get an answer. And I must ask ... how many ovarian cancer patients over this many-year period have received second-line chemotherapy based on this conceptual approach, and may have actually been harmed?”

To prevent such outcomes in the future, Dr. Markman proposed heavier reliance on “nonrandomized population-based studies including real-world patients managed by a variety of approaches with securely privacy-protected data included within a public database,” to test noninvestigational approaches to disease management.

“And for this database, I would propose ASCO’s CancerLinq,” he said.

Dr. Pignata reported receiving honoraria from, and serving as a consultant or adviser for AstraZeneca, PharmaMar, and Roche, and receiving research funding from Roche. Dr. Markman is a consultant or advisor for Amgen, Celgene, CritiTech, and Pfizer; is on the speakers bureau for AstraZeneca and Genentech/Roche, and has provided expert testimony for several entities

[email protected]

CHICAGO – Artificially prolonging the platinum-free interval by introducing a non–platinum-based chemotherapy before re-treatment with platinum-based chemotherapy in patients with partially platinum-sensitive recurrent ovarian cancer did not improve efficacy, and actually worsened the outcomes in patients in the randomized, open-label, phase III Multicentre Italian Trials in Ovarian Cancer 8 (MITO8) trial.

Based on the findings, immediate re-treatment with platinum-based chemotherapy remains the standard treatment strategy in such patients, Dr. Sandro Pignata reported at the annual meeting of the American Society of Clinical Oncology.

The idea that a non-platinum therapy might artificially extend the platinum-free interval, thereby improving outcomes in ovarian cancer patients who experience recurrence between 6 and 12 months after responding to platinum-based therapy, was first proposed more than 20 years ago. Despite a lack of prospective data with respect to this non–platinum-therapy approach, the idea has been used successfully to market non-platinum chemotherapy agents such as paclitaxel, topotecan, pegylated liposomal doxorubicin (PLD), and more recently, PLD-trabectedin for use before reinitiating platinum chemotherapy, explained Dr. Pignata of S.C. Oncologia Medica Ginecologica, Istituto Nazionale Tumori, Napoli.

In fact, a 2007 retrospective analysis (SOCRATES) showed that 35% of patients with recurrence at 6-12 months after platinum-based therapy were treated with a non-platinum single agent before re-treatment with a platinum-based therapy, and that the approach has been used as the control arm in multiple phase III trials that included patients with a platinum-free interval of 6-12 months. The findings indicate that the unproven hypothesis has been adapted into clinical practice, but the investigators were unable to demonstrate an advantage with the approach and concluded that further investigation was warranted.

MITO8, a multi-organization collaborative effort, was designed to test whether artificial prolongation of the platinum-free interval with a single-agent non-platinum treatment would improve overall survival in recurrent partially platinum-sensitive ovarian cancer patients.

In 107 such patients randomized to the experimental arm – receiving a non–platinum-based chemotherapy first to prolong the platinum-free interval, followed by platinum-based chemotherapy after progression – the median time from previous platinum to randomization was 8 months, and from randomization to platinum, 7.8 months. Median overall survival, the primary endpoint of the study, was 21.8 months.

In 108 patients randomized to immediate standard therapy with platinum-based chemotherapy followed by non-platinum therapy, median time from previous platinum to randomization was 8 months, and overall survival was 24.5 months (hazard ratio favoring platinum chemotherapy, 1.38), Dr. Pignata said, noting that the difference in overall survival approached but did not reach statistical significance.

A secondary endpoint of progression-free survival after the second treatment was 12.8 months in the experimental arm, vs. 16.4 months in the platinum-based chemotherapy arm (adjusted HR, 1.41). This difference was statistically significant.

No differences with respect to safety or toxicity were seen between the groups.

MITO8 subjects were women with ovarian cancer recurring between 6 and 12 months after previous platinum-based chemotherapy. The patients had received no more than two prior lines of chemotherapy, had good performance status, and had normal organ function.

Non–platinum-based therapy used in the study included pegylated liposomal doxorubicin, except during a period of the study when the agent was in short supply and other single agents were used, including gemcitabine and topotecan. Most patients, however, received PLD.

Platinum-based therapy was carboplatin plus paclitaxel or, in patients with neurotoxicity at baseline, carboplatin plus gemcitabine.

The shortage of PLD was just one of numerous challenges encountered during the course of the beleaguered study. Enrollment began in 2009, but was temporarily suspended in 2011 because of the PLD shortage. In 2012, the amendment to allow other non–platinum-based chemotherapies to be used was approved at most sites and enrollment resumed. However, accrual slowed and enrollment was closed in 2015. The study was stopped early, and the final analysis was conducted in March 2016 when events plateaued. The investigators, in conjunction with the independent data monitoring committee, determined that the results “still had to be presented early because they still may affect clinical practice.”

Dr. Pignata said that the hypothesis “was based on the fact that there were more responses in the patients treated with a platinum after a non-platinum, but this was not the case ... Responses were more frequent in the patients who received platinum first and then non-platinum later,” he said. The response rates for the experimental vs. standard approaches, respectively, were 43% vs. 56% among RECIST responders, and 70% vs. 75% among CA125 responders.

The findings of MITO8, one of the first clinical trials in ovarian cancer to evaluate two different sequences of chemotherapy, send “a strong message that even in the presence of a very nice hypothesis, we have to await the results of prospective clinical trials before changing clinical practice,” he said.

Dr. Maurie Markman of Cancer Treatment Centers of America in Boca Raton, Fla., the invited discussant, praised the work of Dr. Pignata and his colleagues, calling their study “elegant,” and “an extraordinary effort.”

“In this unbelievably important analysis, the hypothesis was flat-out wrong,” he said.

The study is an example of “a simple, provocative, and potentially highly clinically relevant hypothesis that should be able to be quickly tested in either a cooperative group setting, in multiple institutions interested in gynecologic malignancies ... when or very shortly after it is initially proposed,” he said.

Waiting 20 years is unacceptable, he said, adding: “This is tragic, this length of time to get an answer. And I must ask ... how many ovarian cancer patients over this many-year period have received second-line chemotherapy based on this conceptual approach, and may have actually been harmed?”

To prevent such outcomes in the future, Dr. Markman proposed heavier reliance on “nonrandomized population-based studies including real-world patients managed by a variety of approaches with securely privacy-protected data included within a public database,” to test noninvestigational approaches to disease management.

“And for this database, I would propose ASCO’s CancerLinq,” he said.

Dr. Pignata reported receiving honoraria from, and serving as a consultant or adviser for AstraZeneca, PharmaMar, and Roche, and receiving research funding from Roche. Dr. Markman is a consultant or advisor for Amgen, Celgene, CritiTech, and Pfizer; is on the speakers bureau for AstraZeneca and Genentech/Roche, and has provided expert testimony for several entities

[email protected]

CHICAGO – Artificially prolonging the platinum-free interval by introducing a non–platinum-based chemotherapy before re-treatment with platinum-based chemotherapy in patients with partially platinum-sensitive recurrent ovarian cancer did not improve efficacy, and actually worsened the outcomes in patients in the randomized, open-label, phase III Multicentre Italian Trials in Ovarian Cancer 8 (MITO8) trial.

Based on the findings, immediate re-treatment with platinum-based chemotherapy remains the standard treatment strategy in such patients, Dr. Sandro Pignata reported at the annual meeting of the American Society of Clinical Oncology.

The idea that a non-platinum therapy might artificially extend the platinum-free interval, thereby improving outcomes in ovarian cancer patients who experience recurrence between 6 and 12 months after responding to platinum-based therapy, was first proposed more than 20 years ago. Despite a lack of prospective data with respect to this non–platinum-therapy approach, the idea has been used successfully to market non-platinum chemotherapy agents such as paclitaxel, topotecan, pegylated liposomal doxorubicin (PLD), and more recently, PLD-trabectedin for use before reinitiating platinum chemotherapy, explained Dr. Pignata of S.C. Oncologia Medica Ginecologica, Istituto Nazionale Tumori, Napoli.

In fact, a 2007 retrospective analysis (SOCRATES) showed that 35% of patients with recurrence at 6-12 months after platinum-based therapy were treated with a non-platinum single agent before re-treatment with a platinum-based therapy, and that the approach has been used as the control arm in multiple phase III trials that included patients with a platinum-free interval of 6-12 months. The findings indicate that the unproven hypothesis has been adapted into clinical practice, but the investigators were unable to demonstrate an advantage with the approach and concluded that further investigation was warranted.

MITO8, a multi-organization collaborative effort, was designed to test whether artificial prolongation of the platinum-free interval with a single-agent non-platinum treatment would improve overall survival in recurrent partially platinum-sensitive ovarian cancer patients.

In 107 such patients randomized to the experimental arm – receiving a non–platinum-based chemotherapy first to prolong the platinum-free interval, followed by platinum-based chemotherapy after progression – the median time from previous platinum to randomization was 8 months, and from randomization to platinum, 7.8 months. Median overall survival, the primary endpoint of the study, was 21.8 months.

In 108 patients randomized to immediate standard therapy with platinum-based chemotherapy followed by non-platinum therapy, median time from previous platinum to randomization was 8 months, and overall survival was 24.5 months (hazard ratio favoring platinum chemotherapy, 1.38), Dr. Pignata said, noting that the difference in overall survival approached but did not reach statistical significance.

A secondary endpoint of progression-free survival after the second treatment was 12.8 months in the experimental arm, vs. 16.4 months in the platinum-based chemotherapy arm (adjusted HR, 1.41). This difference was statistically significant.

No differences with respect to safety or toxicity were seen between the groups.

MITO8 subjects were women with ovarian cancer recurring between 6 and 12 months after previous platinum-based chemotherapy. The patients had received no more than two prior lines of chemotherapy, had good performance status, and had normal organ function.

Non–platinum-based therapy used in the study included pegylated liposomal doxorubicin, except during a period of the study when the agent was in short supply and other single agents were used, including gemcitabine and topotecan. Most patients, however, received PLD.

Platinum-based therapy was carboplatin plus paclitaxel or, in patients with neurotoxicity at baseline, carboplatin plus gemcitabine.

The shortage of PLD was just one of numerous challenges encountered during the course of the beleaguered study. Enrollment began in 2009, but was temporarily suspended in 2011 because of the PLD shortage. In 2012, the amendment to allow other non–platinum-based chemotherapies to be used was approved at most sites and enrollment resumed. However, accrual slowed and enrollment was closed in 2015. The study was stopped early, and the final analysis was conducted in March 2016 when events plateaued. The investigators, in conjunction with the independent data monitoring committee, determined that the results “still had to be presented early because they still may affect clinical practice.”

Dr. Pignata said that the hypothesis “was based on the fact that there were more responses in the patients treated with a platinum after a non-platinum, but this was not the case ... Responses were more frequent in the patients who received platinum first and then non-platinum later,” he said. The response rates for the experimental vs. standard approaches, respectively, were 43% vs. 56% among RECIST responders, and 70% vs. 75% among CA125 responders.

The findings of MITO8, one of the first clinical trials in ovarian cancer to evaluate two different sequences of chemotherapy, send “a strong message that even in the presence of a very nice hypothesis, we have to await the results of prospective clinical trials before changing clinical practice,” he said.

Dr. Maurie Markman of Cancer Treatment Centers of America in Boca Raton, Fla., the invited discussant, praised the work of Dr. Pignata and his colleagues, calling their study “elegant,” and “an extraordinary effort.”

“In this unbelievably important analysis, the hypothesis was flat-out wrong,” he said.

The study is an example of “a simple, provocative, and potentially highly clinically relevant hypothesis that should be able to be quickly tested in either a cooperative group setting, in multiple institutions interested in gynecologic malignancies ... when or very shortly after it is initially proposed,” he said.

Waiting 20 years is unacceptable, he said, adding: “This is tragic, this length of time to get an answer. And I must ask ... how many ovarian cancer patients over this many-year period have received second-line chemotherapy based on this conceptual approach, and may have actually been harmed?”

To prevent such outcomes in the future, Dr. Markman proposed heavier reliance on “nonrandomized population-based studies including real-world patients managed by a variety of approaches with securely privacy-protected data included within a public database,” to test noninvestigational approaches to disease management.

“And for this database, I would propose ASCO’s CancerLinq,” he said.

Dr. Pignata reported receiving honoraria from, and serving as a consultant or adviser for AstraZeneca, PharmaMar, and Roche, and receiving research funding from Roche. Dr. Markman is a consultant or advisor for Amgen, Celgene, CritiTech, and Pfizer; is on the speakers bureau for AstraZeneca and Genentech/Roche, and has provided expert testimony for several entities

[email protected]

COPENHAGEN – A study from seven Nordic and Baltic countries adds to the growing body of evidence that young adults with acute lymphoblastic leukemia do better when they are treated like children – that is, with a standard pediatric chemotherapy regimen.

In a study of 221 patients from the age of 18 to 45 with acute lymphoblastic leukemia (ALL) treated with a pediatric regimen and followed for a median of 4 years, the event-free survival rate was 73%, compared with 42% for historical controls, reported Dr. Nina Toft from Herlev (Denmark) University Hospital.

“We have improved the survival for ALL patients 18 to 45 years, and we show that the cure rates are close to those of children. If you compare an adult in the standard-risk group with a child in the standard-risk group, there’s no difference,” she said at a briefing at the annual congress of the European Hematology Association (EHA).

The findings support those from an earlier study reported at the 2014 annual meeting of the American Society of Hematology. That study, conducted by Dr. Wendy Stock of the University of Chicago Medical Center and her colleagues showed that among 296 adolescents and young adults with ALL treated with an intensive pediatric chemotherapy combination regimen rather than a less-intensive adult regimen, the rate of overall survival (OS) at 2 years was 78%, and the event-free survival (EFS) rate was 66%.

In the current study, Dr. Toft and her colleagues looked at event-free survival among 1,509 children and adults (up to age 45) diagnosed with Philadelphia chromosome-negative ALL from July 2008 through December 2014.

The patients were treated in Sweden, Norway, Iceland, Finland Denmark, Lithuania, and Estonia, and all received the Nordic Society for Pediatric Hematology and Oncology (NOPHO)–ALL 2008 protocol, consisting of induction with prednisolone, vincristine, doxorubicin, and pegylated (PEG) asparaginase; consolidation for patients with standard- and intermediate-risk disease, with mercaptopurine, vincristine, PEG asparaginase, and methotrexate; and additional intensive combination chemotherapy for patients with high-risk disease, followed by maintenance with mercaptopurine and/or methotrexate, PEG asparaginase, vincristine, and dexamethasone.

Of the 1,509 patients, 1,022 were children from 1 to 9 years, 266 were preteens/adolescents (10-17 years), and 221 were adults up to age 45.

All patients were stratified by clinical, cytogenetic, and other factors into one of four risk groups: standard, intermediate, high risk, or high risk in first remission after a hematopoietic stem cell transplant, and all were treated with the NOPHO-ALL 2008 protocol.

The investigators found that in general older patients had higher-risk disease. Nonetheless, treatment intervals and severe toxicities, with the exception of osteonecrosis and thrombosis, were “almost identical” between adults and children, Dr. Toft said.

After a median of 4 years of follow-up, 16 patients, 3 of whom were adults, had died during the induction phase, and 50 patients (12 adults) had died in first remission.

There were a total of 123 relapses (36 among adults), and 1 adult and 12 children were diagnosed with a second malignancy.

Overall 5-year EFS rates were 88% for patients aged 1-9 years, 79% for those 10-17 years, and 73% for those 18-45, and these differences were significant (P less than .001). However, when EFS was stratified by risk group, EFS rates were lower only for adults with intermediate-risk disease (78% vs. 90% for 1- to 9-year-olds and 82% for 10- to 17-year-olds, P = .002).

Although the investigators did not formally report overall survival data, it was approximately 95% among all children in the cohort, and approximately 76% among the adults, Dr. Toft said in response to a reporter.

“What we need now is further cooperation, because we need to unite and get more patients so that we can show new developments faster. We also need to find new risk criteria, because of the intermediate-risk group; something is missing for the adults. We need more cytogenetics, we need something to define the patients as high risk or not,” Dr. Toft said.

“We also need new drugs, because with this method we’ve reached the limit of toxicity,” she added.

The study was sponsored by health authorities in the participating countries. Dr. Toft reported no relevant financial disclosures.

COPENHAGEN – A study from seven Nordic and Baltic countries adds to the growing body of evidence that young adults with acute lymphoblastic leukemia do better when they are treated like children – that is, with a standard pediatric chemotherapy regimen.

In a study of 221 patients from the age of 18 to 45 with acute lymphoblastic leukemia (ALL) treated with a pediatric regimen and followed for a median of 4 years, the event-free survival rate was 73%, compared with 42% for historical controls, reported Dr. Nina Toft from Herlev (Denmark) University Hospital.

“We have improved the survival for ALL patients 18 to 45 years, and we show that the cure rates are close to those of children. If you compare an adult in the standard-risk group with a child in the standard-risk group, there’s no difference,” she said at a briefing at the annual congress of the European Hematology Association (EHA).

The findings support those from an earlier study reported at the 2014 annual meeting of the American Society of Hematology. That study, conducted by Dr. Wendy Stock of the University of Chicago Medical Center and her colleagues showed that among 296 adolescents and young adults with ALL treated with an intensive pediatric chemotherapy combination regimen rather than a less-intensive adult regimen, the rate of overall survival (OS) at 2 years was 78%, and the event-free survival (EFS) rate was 66%.

In the current study, Dr. Toft and her colleagues looked at event-free survival among 1,509 children and adults (up to age 45) diagnosed with Philadelphia chromosome-negative ALL from July 2008 through December 2014.

The patients were treated in Sweden, Norway, Iceland, Finland Denmark, Lithuania, and Estonia, and all received the Nordic Society for Pediatric Hematology and Oncology (NOPHO)–ALL 2008 protocol, consisting of induction with prednisolone, vincristine, doxorubicin, and pegylated (PEG) asparaginase; consolidation for patients with standard- and intermediate-risk disease, with mercaptopurine, vincristine, PEG asparaginase, and methotrexate; and additional intensive combination chemotherapy for patients with high-risk disease, followed by maintenance with mercaptopurine and/or methotrexate, PEG asparaginase, vincristine, and dexamethasone.

Of the 1,509 patients, 1,022 were children from 1 to 9 years, 266 were preteens/adolescents (10-17 years), and 221 were adults up to age 45.

All patients were stratified by clinical, cytogenetic, and other factors into one of four risk groups: standard, intermediate, high risk, or high risk in first remission after a hematopoietic stem cell transplant, and all were treated with the NOPHO-ALL 2008 protocol.

The investigators found that in general older patients had higher-risk disease. Nonetheless, treatment intervals and severe toxicities, with the exception of osteonecrosis and thrombosis, were “almost identical” between adults and children, Dr. Toft said.

After a median of 4 years of follow-up, 16 patients, 3 of whom were adults, had died during the induction phase, and 50 patients (12 adults) had died in first remission.

There were a total of 123 relapses (36 among adults), and 1 adult and 12 children were diagnosed with a second malignancy.

Overall 5-year EFS rates were 88% for patients aged 1-9 years, 79% for those 10-17 years, and 73% for those 18-45, and these differences were significant (P less than .001). However, when EFS was stratified by risk group, EFS rates were lower only for adults with intermediate-risk disease (78% vs. 90% for 1- to 9-year-olds and 82% for 10- to 17-year-olds, P = .002).

Although the investigators did not formally report overall survival data, it was approximately 95% among all children in the cohort, and approximately 76% among the adults, Dr. Toft said in response to a reporter.

“What we need now is further cooperation, because we need to unite and get more patients so that we can show new developments faster. We also need to find new risk criteria, because of the intermediate-risk group; something is missing for the adults. We need more cytogenetics, we need something to define the patients as high risk or not,” Dr. Toft said.

“We also need new drugs, because with this method we’ve reached the limit of toxicity,” she added.

The study was sponsored by health authorities in the participating countries. Dr. Toft reported no relevant financial disclosures.

COPENHAGEN – A study from seven Nordic and Baltic countries adds to the growing body of evidence that young adults with acute lymphoblastic leukemia do better when they are treated like children – that is, with a standard pediatric chemotherapy regimen.

In a study of 221 patients from the age of 18 to 45 with acute lymphoblastic leukemia (ALL) treated with a pediatric regimen and followed for a median of 4 years, the event-free survival rate was 73%, compared with 42% for historical controls, reported Dr. Nina Toft from Herlev (Denmark) University Hospital.

“We have improved the survival for ALL patients 18 to 45 years, and we show that the cure rates are close to those of children. If you compare an adult in the standard-risk group with a child in the standard-risk group, there’s no difference,” she said at a briefing at the annual congress of the European Hematology Association (EHA).

The findings support those from an earlier study reported at the 2014 annual meeting of the American Society of Hematology. That study, conducted by Dr. Wendy Stock of the University of Chicago Medical Center and her colleagues showed that among 296 adolescents and young adults with ALL treated with an intensive pediatric chemotherapy combination regimen rather than a less-intensive adult regimen, the rate of overall survival (OS) at 2 years was 78%, and the event-free survival (EFS) rate was 66%.

In the current study, Dr. Toft and her colleagues looked at event-free survival among 1,509 children and adults (up to age 45) diagnosed with Philadelphia chromosome-negative ALL from July 2008 through December 2014.

The patients were treated in Sweden, Norway, Iceland, Finland Denmark, Lithuania, and Estonia, and all received the Nordic Society for Pediatric Hematology and Oncology (NOPHO)–ALL 2008 protocol, consisting of induction with prednisolone, vincristine, doxorubicin, and pegylated (PEG) asparaginase; consolidation for patients with standard- and intermediate-risk disease, with mercaptopurine, vincristine, PEG asparaginase, and methotrexate; and additional intensive combination chemotherapy for patients with high-risk disease, followed by maintenance with mercaptopurine and/or methotrexate, PEG asparaginase, vincristine, and dexamethasone.

Of the 1,509 patients, 1,022 were children from 1 to 9 years, 266 were preteens/adolescents (10-17 years), and 221 were adults up to age 45.

All patients were stratified by clinical, cytogenetic, and other factors into one of four risk groups: standard, intermediate, high risk, or high risk in first remission after a hematopoietic stem cell transplant, and all were treated with the NOPHO-ALL 2008 protocol.

The investigators found that in general older patients had higher-risk disease. Nonetheless, treatment intervals and severe toxicities, with the exception of osteonecrosis and thrombosis, were “almost identical” between adults and children, Dr. Toft said.

After a median of 4 years of follow-up, 16 patients, 3 of whom were adults, had died during the induction phase, and 50 patients (12 adults) had died in first remission.

There were a total of 123 relapses (36 among adults), and 1 adult and 12 children were diagnosed with a second malignancy.

Overall 5-year EFS rates were 88% for patients aged 1-9 years, 79% for those 10-17 years, and 73% for those 18-45, and these differences were significant (P less than .001). However, when EFS was stratified by risk group, EFS rates were lower only for adults with intermediate-risk disease (78% vs. 90% for 1- to 9-year-olds and 82% for 10- to 17-year-olds, P = .002).

Although the investigators did not formally report overall survival data, it was approximately 95% among all children in the cohort, and approximately 76% among the adults, Dr. Toft said in response to a reporter.

“What we need now is further cooperation, because we need to unite and get more patients so that we can show new developments faster. We also need to find new risk criteria, because of the intermediate-risk group; something is missing for the adults. We need more cytogenetics, we need something to define the patients as high risk or not,” Dr. Toft said.

“We also need new drugs, because with this method we’ve reached the limit of toxicity,” she added.

The study was sponsored by health authorities in the participating countries. Dr. Toft reported no relevant financial disclosures.

CHICAGO – An inadequately designed medical practice website can pose serious legal dangers, said Michael J. Sacopulos, a medical malpractice defense attorney based in Terre Haute, Ind.

Here is a list of website to-dos that can reduce your legal risks:

• Post emergency information on the website contact page. Unlike the practice’s phone system, the website may fail to include a disclaimer that the patient should call 911 if experiencing a medical emergency.

• Provide disclaimers about doctor-patient relationship. In addition, it’s important that the website includes a warning that communications through the website do not constitute a doctor-patient relationship, Mr. Sacopulos said during an American Bar Association conference. “Most [websites] have a box where you can leave comments. [People need to be told] that it does not create a physician-patient relationship when they describe their medical condition, sometimes even posting photographs.”

• Advise regarding comment security. Under the Health Information Technology for Economic and Clinical Health (HITECH) Act, medical information sent through electronic channels must be encrypted unless a patient consents otherwise. If information can be transmitted through a website’s comment box, patients should be advised that the transmission is not secure before they send their information, Mr. Sacopulos said.

• Secure any online appointment scheduling. Make sure that patients’ names and personal information are not visible to other patients when they schedule appointments, he said. A cardiology practice in Phoenix learned this the hard way when it had to pay the U.S. Department of Health & Human Services $100,000 for lack of HIPAA safeguards online. An investigation by the Office for Civil Rights found the practice was posting clinical and surgical appointments for patients on an Internet-based calendar that was publicly accessible.

• Ensure patient anonymity. The accidental release of private medical information occurred on the website of a St. Louis physician who obtained consent from her patients to include their before and after photos. No names were posted with the photos, but the computer file names of the photos included the patients’ names, and when a person scrolled over a photo with a cursor, the file name popped up. This allowed the public to view the patient name associated with each photo and caused serious problems for the practice, including litigation, he noted.

• Be aware of state board requirements that pertain to physician practice websites. Several state boards do not allow testimonials to be posted on websites. States also differ on the inclusion of before and after photos. New Jersey, for example, allows before and after photos on websites, while New York does not. Some state boards allow doctors to cite that they are board certified on a website without specifics, while states such as Louisiana require that physicians announce the specific certifying board.

“These are ethical and affirmative duties on behalf of physicians that oftentimes come up in websites,” he said.

• Adhere to the Americans With Disabilities Act (ADA). A website is considered real estate for purposes of the ADA, meaning it must include an accessible format to patients with disabilities, Mr. Sacupulos said. Problems arise when certain website features make sites difficult or incompatible with assistance devices that disabled patients require, such as a screen reader or voice interactive software. The National Federation for the Blind has been active in this area and has filed multiple class action lawsuits against companies that did not have compliant websites, he said. An ADA tool kit for best website practices can be found online.

• Hire an experienced Web designer to create the practice’s website. Too often, practices use a family member or friend to set up the company’s page, Mr. Sacupulos said. In one such instance, a young designer became angry at his doctor employer and set up a false website in his name, alleging abuses against patients. “Work with someone credible,” he advised. “Make sure you own your own domain. Many of these Web designers will purchase the domain name and build a site around it, which is great until you want to move to the next Web designer, and then you have to buy your domain back.”

[email protected]

On Twitter @legal_med

CHICAGO – An inadequately designed medical practice website can pose serious legal dangers, said Michael J. Sacopulos, a medical malpractice defense attorney based in Terre Haute, Ind.

Here is a list of website to-dos that can reduce your legal risks:

• Post emergency information on the website contact page. Unlike the practice’s phone system, the website may fail to include a disclaimer that the patient should call 911 if experiencing a medical emergency.

• Provide disclaimers about doctor-patient relationship. In addition, it’s important that the website includes a warning that communications through the website do not constitute a doctor-patient relationship, Mr. Sacopulos said during an American Bar Association conference. “Most [websites] have a box where you can leave comments. [People need to be told] that it does not create a physician-patient relationship when they describe their medical condition, sometimes even posting photographs.”

• Advise regarding comment security. Under the Health Information Technology for Economic and Clinical Health (HITECH) Act, medical information sent through electronic channels must be encrypted unless a patient consents otherwise. If information can be transmitted through a website’s comment box, patients should be advised that the transmission is not secure before they send their information, Mr. Sacopulos said.

• Secure any online appointment scheduling. Make sure that patients’ names and personal information are not visible to other patients when they schedule appointments, he said. A cardiology practice in Phoenix learned this the hard way when it had to pay the U.S. Department of Health & Human Services $100,000 for lack of HIPAA safeguards online. An investigation by the Office for Civil Rights found the practice was posting clinical and surgical appointments for patients on an Internet-based calendar that was publicly accessible.

• Ensure patient anonymity. The accidental release of private medical information occurred on the website of a St. Louis physician who obtained consent from her patients to include their before and after photos. No names were posted with the photos, but the computer file names of the photos included the patients’ names, and when a person scrolled over a photo with a cursor, the file name popped up. This allowed the public to view the patient name associated with each photo and caused serious problems for the practice, including litigation, he noted.

• Be aware of state board requirements that pertain to physician practice websites. Several state boards do not allow testimonials to be posted on websites. States also differ on the inclusion of before and after photos. New Jersey, for example, allows before and after photos on websites, while New York does not. Some state boards allow doctors to cite that they are board certified on a website without specifics, while states such as Louisiana require that physicians announce the specific certifying board.

“These are ethical and affirmative duties on behalf of physicians that oftentimes come up in websites,” he said.

• Adhere to the Americans With Disabilities Act (ADA). A website is considered real estate for purposes of the ADA, meaning it must include an accessible format to patients with disabilities, Mr. Sacupulos said. Problems arise when certain website features make sites difficult or incompatible with assistance devices that disabled patients require, such as a screen reader or voice interactive software. The National Federation for the Blind has been active in this area and has filed multiple class action lawsuits against companies that did not have compliant websites, he said. An ADA tool kit for best website practices can be found online.

• Hire an experienced Web designer to create the practice’s website. Too often, practices use a family member or friend to set up the company’s page, Mr. Sacupulos said. In one such instance, a young designer became angry at his doctor employer and set up a false website in his name, alleging abuses against patients. “Work with someone credible,” he advised. “Make sure you own your own domain. Many of these Web designers will purchase the domain name and build a site around it, which is great until you want to move to the next Web designer, and then you have to buy your domain back.”

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CHICAGO – An inadequately designed medical practice website can pose serious legal dangers, said Michael J. Sacopulos, a medical malpractice defense attorney based in Terre Haute, Ind.

Here is a list of website to-dos that can reduce your legal risks:

• Post emergency information on the website contact page. Unlike the practice’s phone system, the website may fail to include a disclaimer that the patient should call 911 if experiencing a medical emergency.

• Provide disclaimers about doctor-patient relationship. In addition, it’s important that the website includes a warning that communications through the website do not constitute a doctor-patient relationship, Mr. Sacopulos said during an American Bar Association conference. “Most [websites] have a box where you can leave comments. [People need to be told] that it does not create a physician-patient relationship when they describe their medical condition, sometimes even posting photographs.”

• Advise regarding comment security. Under the Health Information Technology for Economic and Clinical Health (HITECH) Act, medical information sent through electronic channels must be encrypted unless a patient consents otherwise. If information can be transmitted through a website’s comment box, patients should be advised that the transmission is not secure before they send their information, Mr. Sacopulos said.

• Secure any online appointment scheduling. Make sure that patients’ names and personal information are not visible to other patients when they schedule appointments, he said. A cardiology practice in Phoenix learned this the hard way when it had to pay the U.S. Department of Health & Human Services $100,000 for lack of HIPAA safeguards online. An investigation by the Office for Civil Rights found the practice was posting clinical and surgical appointments for patients on an Internet-based calendar that was publicly accessible.

• Ensure patient anonymity. The accidental release of private medical information occurred on the website of a St. Louis physician who obtained consent from her patients to include their before and after photos. No names were posted with the photos, but the computer file names of the photos included the patients’ names, and when a person scrolled over a photo with a cursor, the file name popped up. This allowed the public to view the patient name associated with each photo and caused serious problems for the practice, including litigation, he noted.

• Be aware of state board requirements that pertain to physician practice websites. Several state boards do not allow testimonials to be posted on websites. States also differ on the inclusion of before and after photos. New Jersey, for example, allows before and after photos on websites, while New York does not. Some state boards allow doctors to cite that they are board certified on a website without specifics, while states such as Louisiana require that physicians announce the specific certifying board.

“These are ethical and affirmative duties on behalf of physicians that oftentimes come up in websites,” he said.

• Adhere to the Americans With Disabilities Act (ADA). A website is considered real estate for purposes of the ADA, meaning it must include an accessible format to patients with disabilities, Mr. Sacupulos said. Problems arise when certain website features make sites difficult or incompatible with assistance devices that disabled patients require, such as a screen reader or voice interactive software. The National Federation for the Blind has been active in this area and has filed multiple class action lawsuits against companies that did not have compliant websites, he said. An ADA tool kit for best website practices can be found online.

• Hire an experienced Web designer to create the practice’s website. Too often, practices use a family member or friend to set up the company’s page, Mr. Sacupulos said. In one such instance, a young designer became angry at his doctor employer and set up a false website in his name, alleging abuses against patients. “Work with someone credible,” he advised. “Make sure you own your own domain. Many of these Web designers will purchase the domain name and build a site around it, which is great until you want to move to the next Web designer, and then you have to buy your domain back.”

[email protected]

On Twitter @legal_med