Q) All I hear about is the shortage of kidneys for transplantation. A friend of mine is on the local transplant list, and it is eight years long! Are there any ideas out there to grow your own kidneys?

Eight years is a long time for people dealing with the physical and emotional effects of kidney disease coupled with hemodialysis or peritoneal dialysis. Your friend is one of 110,000 patients (as of January 2015) in the United States on the United Network for Organ Sharing (UNOS) kidney transplant waiting list.¹ The UNOS/Organ Procurement and Transplant Network (OPTN) implemented new polices in 2014 to shorten the wait.

Among them: For pediatric patients (those younger than 18), the wait list time starts when the glomerular filtration rate (GFR) is ≤ 20 mL/min or the child starts dialysis. UNOS also has attempted to match posttransplant survival time of the graft with posttransplant survival time of the recipient through use of calculations that classify kidneys on the basis of how long they are likely to function once transplanted. Priority is now given to candidates with high immune system sensitivity or uncommon blood types, as they are less likely to obtain a kidney otherwise.²

The million-dollar question is how to obtain a kidney transplant in a timely fashion. Grave robbing, in case you are wondering, is not a viable option! Nor is transplant tourism (traveling outside the US to obtain an organ transplant), which confers a higher risk for severe infectious complications and acute rejection, possibly related to less extensive donor screening.³

There are other possibilities: Living donors can donate one kidney. Or, as is becoming increasingly common, paired organ transplants can be arranged. These occur when a patient in need of a kidney has a willing but incompatible donor; if a different match can be found, a “swap” is orchestrated, in which Donor A’s kidney is transplanted into Recipient B and Donor B’s kidney is given to Recipient A. This can be and has been done with multiple donors and recipients—in some cases, dozens—allowing the gift of donation to go on and on. (See “Trading Kidneys: Innovative Program Could Save Thousands of Lives” for an overview of how this concept started.)

Some exciting research is going on with regard to 3D printing of kidneys; they are miniature for now but showing survival of the printed cells. Another area of exploration is regenerative medicine; researchers in the field are investigating the bioengineering of organs by taking the “scaffolding” of an organ and implanting a patient’s own cells to “grow” a new organ (which, if successful, would also eliminate the need for immunosuppressants). Other signs of progress include recent news that scientists are getting lab-grown kidneys to work in ­animals.

It will be several years before any of these options will be viable. In the meantime, it never hurts to ask loved ones if they are willing to donate a kidney. Best wishes to your friend. —DC

Della Connor, PhD, RN, FNP-BC
East Texas Nephrology Associates, Lufkin, Texas

REFERENCES
1. Organ Procurement and Transplantation Network. http://optn.transplant.hrsa.gov. Accessed December 10, 2015.
2. Organ Procurement and Transplantation Network. New OPTN requirements and resources for the living donor kidney transplant programs. Prog Transplant. 2013;23(2):117.
3. Gill J, Madhira BR, Gjertson D, et al. Transplant tourism in the United States: a single-center experience. Clin J Am Soc Nephrol. 2008;3(6):1820-1828.

Q) All I hear about is the shortage of kidneys for transplantation. A friend of mine is on the local transplant list, and it is eight years long! Are there any ideas out there to grow your own kidneys?

Eight years is a long time for people dealing with the physical and emotional effects of kidney disease coupled with hemodialysis or peritoneal dialysis. Your friend is one of 110,000 patients (as of January 2015) in the United States on the United Network for Organ Sharing (UNOS) kidney transplant waiting list.¹ The UNOS/Organ Procurement and Transplant Network (OPTN) implemented new polices in 2014 to shorten the wait.

Among them: For pediatric patients (those younger than 18), the wait list time starts when the glomerular filtration rate (GFR) is ≤ 20 mL/min or the child starts dialysis. UNOS also has attempted to match posttransplant survival time of the graft with posttransplant survival time of the recipient through use of calculations that classify kidneys on the basis of how long they are likely to function once transplanted. Priority is now given to candidates with high immune system sensitivity or uncommon blood types, as they are less likely to obtain a kidney otherwise.²

The million-dollar question is how to obtain a kidney transplant in a timely fashion. Grave robbing, in case you are wondering, is not a viable option! Nor is transplant tourism (traveling outside the US to obtain an organ transplant), which confers a higher risk for severe infectious complications and acute rejection, possibly related to less extensive donor screening.³

There are other possibilities: Living donors can donate one kidney. Or, as is becoming increasingly common, paired organ transplants can be arranged. These occur when a patient in need of a kidney has a willing but incompatible donor; if a different match can be found, a “swap” is orchestrated, in which Donor A’s kidney is transplanted into Recipient B and Donor B’s kidney is given to Recipient A. This can be and has been done with multiple donors and recipients—in some cases, dozens—allowing the gift of donation to go on and on. (See “Trading Kidneys: Innovative Program Could Save Thousands of Lives” for an overview of how this concept started.)

Some exciting research is going on with regard to 3D printing of kidneys; they are miniature for now but showing survival of the printed cells. Another area of exploration is regenerative medicine; researchers in the field are investigating the bioengineering of organs by taking the “scaffolding” of an organ and implanting a patient’s own cells to “grow” a new organ (which, if successful, would also eliminate the need for immunosuppressants). Other signs of progress include recent news that scientists are getting lab-grown kidneys to work in ­animals.

It will be several years before any of these options will be viable. In the meantime, it never hurts to ask loved ones if they are willing to donate a kidney. Best wishes to your friend. —DC

Della Connor, PhD, RN, FNP-BC
East Texas Nephrology Associates, Lufkin, Texas

REFERENCES
1. Organ Procurement and Transplantation Network. http://optn.transplant.hrsa.gov. Accessed December 10, 2015.
2. Organ Procurement and Transplantation Network. New OPTN requirements and resources for the living donor kidney transplant programs. Prog Transplant. 2013;23(2):117.
3. Gill J, Madhira BR, Gjertson D, et al. Transplant tourism in the United States: a single-center experience. Clin J Am Soc Nephrol. 2008;3(6):1820-1828.

Q) All I hear about is the shortage of kidneys for transplantation. A friend of mine is on the local transplant list, and it is eight years long! Are there any ideas out there to grow your own kidneys?

Eight years is a long time for people dealing with the physical and emotional effects of kidney disease coupled with hemodialysis or peritoneal dialysis. Your friend is one of 110,000 patients (as of January 2015) in the United States on the United Network for Organ Sharing (UNOS) kidney transplant waiting list.¹ The UNOS/Organ Procurement and Transplant Network (OPTN) implemented new polices in 2014 to shorten the wait.

Among them: For pediatric patients (those younger than 18), the wait list time starts when the glomerular filtration rate (GFR) is ≤ 20 mL/min or the child starts dialysis. UNOS also has attempted to match posttransplant survival time of the graft with posttransplant survival time of the recipient through use of calculations that classify kidneys on the basis of how long they are likely to function once transplanted. Priority is now given to candidates with high immune system sensitivity or uncommon blood types, as they are less likely to obtain a kidney otherwise.²

The million-dollar question is how to obtain a kidney transplant in a timely fashion. Grave robbing, in case you are wondering, is not a viable option! Nor is transplant tourism (traveling outside the US to obtain an organ transplant), which confers a higher risk for severe infectious complications and acute rejection, possibly related to less extensive donor screening.³

There are other possibilities: Living donors can donate one kidney. Or, as is becoming increasingly common, paired organ transplants can be arranged. These occur when a patient in need of a kidney has a willing but incompatible donor; if a different match can be found, a “swap” is orchestrated, in which Donor A’s kidney is transplanted into Recipient B and Donor B’s kidney is given to Recipient A. This can be and has been done with multiple donors and recipients—in some cases, dozens—allowing the gift of donation to go on and on. (See “Trading Kidneys: Innovative Program Could Save Thousands of Lives” for an overview of how this concept started.)

Some exciting research is going on with regard to 3D printing of kidneys; they are miniature for now but showing survival of the printed cells. Another area of exploration is regenerative medicine; researchers in the field are investigating the bioengineering of organs by taking the “scaffolding” of an organ and implanting a patient’s own cells to “grow” a new organ (which, if successful, would also eliminate the need for immunosuppressants). Other signs of progress include recent news that scientists are getting lab-grown kidneys to work in ­animals.

It will be several years before any of these options will be viable. In the meantime, it never hurts to ask loved ones if they are willing to donate a kidney. Best wishes to your friend. —DC

Della Connor, PhD, RN, FNP-BC
East Texas Nephrology Associates, Lufkin, Texas

REFERENCES
1. Organ Procurement and Transplantation Network. http://optn.transplant.hrsa.gov. Accessed December 10, 2015.
2. Organ Procurement and Transplantation Network. New OPTN requirements and resources for the living donor kidney transplant programs. Prog Transplant. 2013;23(2):117.
3. Gill J, Madhira BR, Gjertson D, et al. Transplant tourism in the United States: a single-center experience. Clin J Am Soc Nephrol. 2008;3(6):1820-1828.

X-ray of the hand of a patient

with Fanconi anemia

Researchers say they have established the cause of a subtype of Fanconi anemia (FA)—a de novo mutation in 1 allele of RAD51, a gene responsible for repairing DNA damage.

The team made this discovery in a child with an FA-like syndrome who has healthy parents and a healthy sister.

“The particular mutation in this patient was a surprise to us,” said Patrick May, PhD, of the University of Luxembourg.

“It occurred only in 1 of the 2 RAD51 gene copies, which every person carries in the genome, but every RAD51 gene copy was normal in the child’s parents.”

Dr May and his colleagues described the mutation in Nature Communications.

Specifically, the researchers found a de novo g.41022153G>A; p.Ala293Thr (NM_002875) missense mutation in 1 allele of RAD51.

They said this heterozygous mutation causes a novel FA subtype, dubbed “FA-R,” which appears to be the first subtype of FA caused by a dominant-negative mutation.

The patient the researchers analyzed has microcephaly and mental retardation but has reached adulthood without the bone marrow failure and pediatric cancers typically observed in patients with FA.

Until this case, researchers believed that mutations leading to FA showed recessive inheritance and therefore had to be derived from both parents to lead to FA. Spontaneous mutations of the RAD51 gene like in this case had not been observed.

Dr May and his colleagues said their finding has implications for genetic counseling of families with a high risk for FA. Previously, people who wanted to have children but had relatives suffering from FA were screened for mutations in 1 of the 17 genes connected with the disease. Now, the risk of having a child with FA has to be recalculated.

“Furthermore, understanding this mutation teaches us more about how the RAD51 gene product protects the DNA and how disruptions of DNA repair may lead to leukemia and solid tumors,” Dr May said. “Of course, understanding the origins of human cancer will help us diagnose it with more confidence earlier and devise new therapies to prevent or mitigate it.”

X-ray of the hand of a patient

with Fanconi anemia

Researchers say they have established the cause of a subtype of Fanconi anemia (FA)—a de novo mutation in 1 allele of RAD51, a gene responsible for repairing DNA damage.

The team made this discovery in a child with an FA-like syndrome who has healthy parents and a healthy sister.

“The particular mutation in this patient was a surprise to us,” said Patrick May, PhD, of the University of Luxembourg.

“It occurred only in 1 of the 2 RAD51 gene copies, which every person carries in the genome, but every RAD51 gene copy was normal in the child’s parents.”

Dr May and his colleagues described the mutation in Nature Communications.

Specifically, the researchers found a de novo g.41022153G>A; p.Ala293Thr (NM_002875) missense mutation in 1 allele of RAD51.

They said this heterozygous mutation causes a novel FA subtype, dubbed “FA-R,” which appears to be the first subtype of FA caused by a dominant-negative mutation.

The patient the researchers analyzed has microcephaly and mental retardation but has reached adulthood without the bone marrow failure and pediatric cancers typically observed in patients with FA.

Until this case, researchers believed that mutations leading to FA showed recessive inheritance and therefore had to be derived from both parents to lead to FA. Spontaneous mutations of the RAD51 gene like in this case had not been observed.

Dr May and his colleagues said their finding has implications for genetic counseling of families with a high risk for FA. Previously, people who wanted to have children but had relatives suffering from FA were screened for mutations in 1 of the 17 genes connected with the disease. Now, the risk of having a child with FA has to be recalculated.

“Furthermore, understanding this mutation teaches us more about how the RAD51 gene product protects the DNA and how disruptions of DNA repair may lead to leukemia and solid tumors,” Dr May said. “Of course, understanding the origins of human cancer will help us diagnose it with more confidence earlier and devise new therapies to prevent or mitigate it.”

X-ray of the hand of a patient

with Fanconi anemia

Researchers say they have established the cause of a subtype of Fanconi anemia (FA)—a de novo mutation in 1 allele of RAD51, a gene responsible for repairing DNA damage.

The team made this discovery in a child with an FA-like syndrome who has healthy parents and a healthy sister.

“The particular mutation in this patient was a surprise to us,” said Patrick May, PhD, of the University of Luxembourg.

“It occurred only in 1 of the 2 RAD51 gene copies, which every person carries in the genome, but every RAD51 gene copy was normal in the child’s parents.”

Dr May and his colleagues described the mutation in Nature Communications.

Specifically, the researchers found a de novo g.41022153G>A; p.Ala293Thr (NM_002875) missense mutation in 1 allele of RAD51.

They said this heterozygous mutation causes a novel FA subtype, dubbed “FA-R,” which appears to be the first subtype of FA caused by a dominant-negative mutation.

The patient the researchers analyzed has microcephaly and mental retardation but has reached adulthood without the bone marrow failure and pediatric cancers typically observed in patients with FA.

Until this case, researchers believed that mutations leading to FA showed recessive inheritance and therefore had to be derived from both parents to lead to FA. Spontaneous mutations of the RAD51 gene like in this case had not been observed.

Dr May and his colleagues said their finding has implications for genetic counseling of families with a high risk for FA. Previously, people who wanted to have children but had relatives suffering from FA were screened for mutations in 1 of the 17 genes connected with the disease. Now, the risk of having a child with FA has to be recalculated.

“Furthermore, understanding this mutation teaches us more about how the RAD51 gene product protects the DNA and how disruptions of DNA repair may lead to leukemia and solid tumors,” Dr May said. “Of course, understanding the origins of human cancer will help us diagnose it with more confidence earlier and devise new therapies to prevent or mitigate it.”

Birth control pills

A study published in Blood indicates that women on anticoagulants can take estrogen-containing contraception or hormone replacement therapy

without an increased risk of venous thromboembolism (VTE) or uterine bleeding.

If a woman is diagnosed with VTE, she is often advised to stop hormone therapy, even while receiving anticoagulant therapy, because she is thought to have an increased risk of VTE recurrence.

However, this practice is based on the known association between hormone therapy and increased clotting risk in the absence of anticoagulants. The safety of the concurrent use of these medications had not been previously explored.

“While it has been common practice among healthcare providers to avoid prescribing hormone therapy and anticoagulants at the same time, there has been no evidence to support this decision,” said study author Ida Martinelli, MD, of the A. Bianchi Bonomi Hemophilia and Thrombosis Center in Milan, Italy.

“We conducted this study to address the fear felt by both the physician and patient when making the decision to stop or continue hormone therapy in this setting.”

The researchers compared the incidences of recurrent VTE and abnormal uterine bleeding in 1888 women who received anticoagulants with or without concurrent hormone therapy.

The team analyzed data from the EINSTEIN DVT and PE study, which was performed to evaluate the safety and efficacy of 2 anticoagulants—the direct oral anticoagulant rivaroxaban and the current standard of care, a low-molecular-weight heparin (enoxaparin) followed by a vitamin K antagonist (VKA).

Women of child-bearing potential were advised to use adequate methods of contraception to avoid birth defects.

Of all the women in the study, 475 used hormone therapy during the analysis period. Medications used included estrogen-only pills, combined estrogen-progestogen contraceptives, and progestin-only contraceptives.

Participants were questioned about symptoms or signs of recurrent VTE and bleeding, including uterine bleeding, during each follow-up visit.

Seven recurrent VTEs occurred while patients were using hormone therapy, while 38 events occurred during a period when patients were not using hormone therapy.

Based on this analysis, the researchers concluded that women on anticoagulants and hormone therapy experienced recurrent VTE at a rate of 3.7% per year. In contrast, those not on hormone therapy had a recurrence rate of 4.7% per year.

The incidence of abnormal uterine bleeding in patients on hormonal therapy was 22.5%, compared to 21.4% for women not on hormone therapy.

According to the study authors, the similar incidence of VTE and abnormal uterine bleeding in women who did and did not receive hormone therapy suggest that combined use of these therapies is safe.

The study also showed that abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA. The bleeding rate was estimated at 29.8% per year for patients on rivaroxaban and 15.5% per year in the enoxaparin/VKA group.

The researchers said this outcome suggests the need for further studies on rivaroxaban, which may be preferred for its convenience over enoxaparin/VKA.

“For the first time, we demonstrate that women suffering from blood clots can safely take hormone-containing contraceptives or hormone replacement therapy with anticoagulants, providing women the freedom to choose the method of birth control and other hormone-containing medications they prefer,” Dr Martinelli said.

“While further investigation is needed to evaluate the inconvenience of abnormal uterine bleeding with rivaroxaban and the other direct oral anticoagulants, these results dispel former misconceptions and should allow clinicians to confidently treat their patients who take blood thinners and hormones concurrently.”

Birth control pills

A study published in Blood indicates that women on anticoagulants can take estrogen-containing contraception or hormone replacement therapy

without an increased risk of venous thromboembolism (VTE) or uterine bleeding.

If a woman is diagnosed with VTE, she is often advised to stop hormone therapy, even while receiving anticoagulant therapy, because she is thought to have an increased risk of VTE recurrence.

However, this practice is based on the known association between hormone therapy and increased clotting risk in the absence of anticoagulants. The safety of the concurrent use of these medications had not been previously explored.

“While it has been common practice among healthcare providers to avoid prescribing hormone therapy and anticoagulants at the same time, there has been no evidence to support this decision,” said study author Ida Martinelli, MD, of the A. Bianchi Bonomi Hemophilia and Thrombosis Center in Milan, Italy.

“We conducted this study to address the fear felt by both the physician and patient when making the decision to stop or continue hormone therapy in this setting.”

The researchers compared the incidences of recurrent VTE and abnormal uterine bleeding in 1888 women who received anticoagulants with or without concurrent hormone therapy.

The team analyzed data from the EINSTEIN DVT and PE study, which was performed to evaluate the safety and efficacy of 2 anticoagulants—the direct oral anticoagulant rivaroxaban and the current standard of care, a low-molecular-weight heparin (enoxaparin) followed by a vitamin K antagonist (VKA).

Women of child-bearing potential were advised to use adequate methods of contraception to avoid birth defects.

Of all the women in the study, 475 used hormone therapy during the analysis period. Medications used included estrogen-only pills, combined estrogen-progestogen contraceptives, and progestin-only contraceptives.

Participants were questioned about symptoms or signs of recurrent VTE and bleeding, including uterine bleeding, during each follow-up visit.

Seven recurrent VTEs occurred while patients were using hormone therapy, while 38 events occurred during a period when patients were not using hormone therapy.

Based on this analysis, the researchers concluded that women on anticoagulants and hormone therapy experienced recurrent VTE at a rate of 3.7% per year. In contrast, those not on hormone therapy had a recurrence rate of 4.7% per year.

The incidence of abnormal uterine bleeding in patients on hormonal therapy was 22.5%, compared to 21.4% for women not on hormone therapy.

According to the study authors, the similar incidence of VTE and abnormal uterine bleeding in women who did and did not receive hormone therapy suggest that combined use of these therapies is safe.

The study also showed that abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA. The bleeding rate was estimated at 29.8% per year for patients on rivaroxaban and 15.5% per year in the enoxaparin/VKA group.

The researchers said this outcome suggests the need for further studies on rivaroxaban, which may be preferred for its convenience over enoxaparin/VKA.

“For the first time, we demonstrate that women suffering from blood clots can safely take hormone-containing contraceptives or hormone replacement therapy with anticoagulants, providing women the freedom to choose the method of birth control and other hormone-containing medications they prefer,” Dr Martinelli said.

“While further investigation is needed to evaluate the inconvenience of abnormal uterine bleeding with rivaroxaban and the other direct oral anticoagulants, these results dispel former misconceptions and should allow clinicians to confidently treat their patients who take blood thinners and hormones concurrently.”

Birth control pills

A study published in Blood indicates that women on anticoagulants can take estrogen-containing contraception or hormone replacement therapy

without an increased risk of venous thromboembolism (VTE) or uterine bleeding.

If a woman is diagnosed with VTE, she is often advised to stop hormone therapy, even while receiving anticoagulant therapy, because she is thought to have an increased risk of VTE recurrence.

However, this practice is based on the known association between hormone therapy and increased clotting risk in the absence of anticoagulants. The safety of the concurrent use of these medications had not been previously explored.

“While it has been common practice among healthcare providers to avoid prescribing hormone therapy and anticoagulants at the same time, there has been no evidence to support this decision,” said study author Ida Martinelli, MD, of the A. Bianchi Bonomi Hemophilia and Thrombosis Center in Milan, Italy.

“We conducted this study to address the fear felt by both the physician and patient when making the decision to stop or continue hormone therapy in this setting.”

The researchers compared the incidences of recurrent VTE and abnormal uterine bleeding in 1888 women who received anticoagulants with or without concurrent hormone therapy.

The team analyzed data from the EINSTEIN DVT and PE study, which was performed to evaluate the safety and efficacy of 2 anticoagulants—the direct oral anticoagulant rivaroxaban and the current standard of care, a low-molecular-weight heparin (enoxaparin) followed by a vitamin K antagonist (VKA).

Women of child-bearing potential were advised to use adequate methods of contraception to avoid birth defects.

Of all the women in the study, 475 used hormone therapy during the analysis period. Medications used included estrogen-only pills, combined estrogen-progestogen contraceptives, and progestin-only contraceptives.

Participants were questioned about symptoms or signs of recurrent VTE and bleeding, including uterine bleeding, during each follow-up visit.

Seven recurrent VTEs occurred while patients were using hormone therapy, while 38 events occurred during a period when patients were not using hormone therapy.

Based on this analysis, the researchers concluded that women on anticoagulants and hormone therapy experienced recurrent VTE at a rate of 3.7% per year. In contrast, those not on hormone therapy had a recurrence rate of 4.7% per year.

The incidence of abnormal uterine bleeding in patients on hormonal therapy was 22.5%, compared to 21.4% for women not on hormone therapy.

According to the study authors, the similar incidence of VTE and abnormal uterine bleeding in women who did and did not receive hormone therapy suggest that combined use of these therapies is safe.

The study also showed that abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA. The bleeding rate was estimated at 29.8% per year for patients on rivaroxaban and 15.5% per year in the enoxaparin/VKA group.

The researchers said this outcome suggests the need for further studies on rivaroxaban, which may be preferred for its convenience over enoxaparin/VKA.

“For the first time, we demonstrate that women suffering from blood clots can safely take hormone-containing contraceptives or hormone replacement therapy with anticoagulants, providing women the freedom to choose the method of birth control and other hormone-containing medications they prefer,” Dr Martinelli said.

“While further investigation is needed to evaluate the inconvenience of abnormal uterine bleeding with rivaroxaban and the other direct oral anticoagulants, these results dispel former misconceptions and should allow clinicians to confidently treat their patients who take blood thinners and hormones concurrently.”

Clinical question: What are best practices for evaluating patients with suspected acute pulmonary embolism (PE)?

Background: Use of CT in the evaluation of PE has increased across all clinical settings without improving mortality. Contrast CT carries the risks of radiation exposure, contrast-induced nephropathy, and incidental findings that require further investigation. The authors highlight evidence-based strategies for evaluation of PE, focusing on delivering high-value care.

Study design: Clinical guideline.

Setting: Literature review of studies across all adult clinical settings.

Synopsis: The clinical guidelines committee of the American College of Physicians conducted a literature search surrounding evaluation of suspected acute PE. From their review, they concluded:

• Pretest probability should initially be determined based on validated prediction tools (Wells score, Revised Geneva);
• In patients found to have low pretest probability and meeting the pulmonary embolism rule-out criteria (PERC), clinicians can forego d-dimer testing;
• In those with intermediate pretest probability or those with low pre-test probability who do not pass PERC, d-dimer measurement should be obtained;
• The d-dimer threshold should be age adjusted and imaging should not be pursued in patients whose d-dimer level falls below this cutoff, while those with positive d-dimers should receive CT pulmonary angiography (CTPA); and
• Patients with high pretest probability should undergo CTPA (or V/Q scan if CTPA is contraindicated) without d-dimer testing.

Bottom line: In suspected acute PE, first determine pretest probability using Wells and Revised Geneva, and then use this probability in conjunction with the PERC and d-dimer (as indicated) to guide decisions about imaging.

Citation: Raja AS, Greenberg JO, Qaseem A, Denberg TD, Fitterman N, Schuur JD. Evaluation of patients with suspected acute pulmonary embolism: best practice advice from the clinical guidelines committee of the American College of Physicians. Ann Intern Med. 2015;163(9):701-711.

Clinical question: What are best practices for evaluating patients with suspected acute pulmonary embolism (PE)?

Background: Use of CT in the evaluation of PE has increased across all clinical settings without improving mortality. Contrast CT carries the risks of radiation exposure, contrast-induced nephropathy, and incidental findings that require further investigation. The authors highlight evidence-based strategies for evaluation of PE, focusing on delivering high-value care.

Study design: Clinical guideline.

Setting: Literature review of studies across all adult clinical settings.

Synopsis: The clinical guidelines committee of the American College of Physicians conducted a literature search surrounding evaluation of suspected acute PE. From their review, they concluded:

• Pretest probability should initially be determined based on validated prediction tools (Wells score, Revised Geneva);
• In patients found to have low pretest probability and meeting the pulmonary embolism rule-out criteria (PERC), clinicians can forego d-dimer testing;
• In those with intermediate pretest probability or those with low pre-test probability who do not pass PERC, d-dimer measurement should be obtained;
• The d-dimer threshold should be age adjusted and imaging should not be pursued in patients whose d-dimer level falls below this cutoff, while those with positive d-dimers should receive CT pulmonary angiography (CTPA); and
• Patients with high pretest probability should undergo CTPA (or V/Q scan if CTPA is contraindicated) without d-dimer testing.

Bottom line: In suspected acute PE, first determine pretest probability using Wells and Revised Geneva, and then use this probability in conjunction with the PERC and d-dimer (as indicated) to guide decisions about imaging.

Citation: Raja AS, Greenberg JO, Qaseem A, Denberg TD, Fitterman N, Schuur JD. Evaluation of patients with suspected acute pulmonary embolism: best practice advice from the clinical guidelines committee of the American College of Physicians. Ann Intern Med. 2015;163(9):701-711.

Clinical question: What are best practices for evaluating patients with suspected acute pulmonary embolism (PE)?

Background: Use of CT in the evaluation of PE has increased across all clinical settings without improving mortality. Contrast CT carries the risks of radiation exposure, contrast-induced nephropathy, and incidental findings that require further investigation. The authors highlight evidence-based strategies for evaluation of PE, focusing on delivering high-value care.

Study design: Clinical guideline.

Setting: Literature review of studies across all adult clinical settings.

Synopsis: The clinical guidelines committee of the American College of Physicians conducted a literature search surrounding evaluation of suspected acute PE. From their review, they concluded:

• Pretest probability should initially be determined based on validated prediction tools (Wells score, Revised Geneva);
• In patients found to have low pretest probability and meeting the pulmonary embolism rule-out criteria (PERC), clinicians can forego d-dimer testing;
• In those with intermediate pretest probability or those with low pre-test probability who do not pass PERC, d-dimer measurement should be obtained;
• The d-dimer threshold should be age adjusted and imaging should not be pursued in patients whose d-dimer level falls below this cutoff, while those with positive d-dimers should receive CT pulmonary angiography (CTPA); and
• Patients with high pretest probability should undergo CTPA (or V/Q scan if CTPA is contraindicated) without d-dimer testing.

Bottom line: In suspected acute PE, first determine pretest probability using Wells and Revised Geneva, and then use this probability in conjunction with the PERC and d-dimer (as indicated) to guide decisions about imaging.

Citation: Raja AS, Greenberg JO, Qaseem A, Denberg TD, Fitterman N, Schuur JD. Evaluation of patients with suspected acute pulmonary embolism: best practice advice from the clinical guidelines committee of the American College of Physicians. Ann Intern Med. 2015;163(9):701-711.

Clinical question: Does time to consult after admission change the effect palliative care consultation has on cost of care?

Background: Studies have shown that early palliative care involvement improves quality of life and survival among cancer patients while reducing the cost of care. Little is known about the optimal timing of palliative care consultation and its effect on cost.

Study design: Prospective, observational study.

Setting: Multi-site, high-volume, tertiary care hospitals with established palliative care teams.

Synopsis: Clinical and cost data were collected for 969 adult patients with advanced cancer admitted to the five participating hospitals. Among those, 256 patients received palliative care consultation and 713 received usual care. Subsamples were created based on time to consultation after admission.

The study found that earlier consultation yielded larger effects on cost savings. There was a 24% reduction in total cost if consultation occurred within two days (95% CI, -$3,438 to -$1,122; P<0.001), with estimated savings of $2,280. For consultation within six days of admission, there was a $1,312 savings (95% CI, -$2,568 to -$ 1,122; P<0.04), consistent with a 14% reduction in total cost.

There are notable limitations to this study. Half of eligible patients were excluded due to incomplete data collection, resulting in a small sample size. Further, these results can be generalized only to inpatients with advanced cancer.

Bottom line: Reducing the time to consultation with palliative care increases cost savings. In advanced cancer patients, a 24% reduction in total costs was realized for consultation within two days following admission.

Citation: May P, Garrido MM, Cassel JB, et al. Prospective cohort study of hospital palliative care teams for inpatients with advanced cancer: earlier consultation is associated with larger cost-saving effect. J Clin Oncol. 2015;33(25):2745-2752.

Clinical question: Does time to consult after admission change the effect palliative care consultation has on cost of care?

Background: Studies have shown that early palliative care involvement improves quality of life and survival among cancer patients while reducing the cost of care. Little is known about the optimal timing of palliative care consultation and its effect on cost.

Study design: Prospective, observational study.

Setting: Multi-site, high-volume, tertiary care hospitals with established palliative care teams.

Synopsis: Clinical and cost data were collected for 969 adult patients with advanced cancer admitted to the five participating hospitals. Among those, 256 patients received palliative care consultation and 713 received usual care. Subsamples were created based on time to consultation after admission.

The study found that earlier consultation yielded larger effects on cost savings. There was a 24% reduction in total cost if consultation occurred within two days (95% CI, -$3,438 to -$1,122; P<0.001), with estimated savings of $2,280. For consultation within six days of admission, there was a $1,312 savings (95% CI, -$2,568 to -$ 1,122; P<0.04), consistent with a 14% reduction in total cost.

There are notable limitations to this study. Half of eligible patients were excluded due to incomplete data collection, resulting in a small sample size. Further, these results can be generalized only to inpatients with advanced cancer.

Bottom line: Reducing the time to consultation with palliative care increases cost savings. In advanced cancer patients, a 24% reduction in total costs was realized for consultation within two days following admission.

Citation: May P, Garrido MM, Cassel JB, et al. Prospective cohort study of hospital palliative care teams for inpatients with advanced cancer: earlier consultation is associated with larger cost-saving effect. J Clin Oncol. 2015;33(25):2745-2752.

Clinical question: Does time to consult after admission change the effect palliative care consultation has on cost of care?

Background: Studies have shown that early palliative care involvement improves quality of life and survival among cancer patients while reducing the cost of care. Little is known about the optimal timing of palliative care consultation and its effect on cost.

Study design: Prospective, observational study.

Setting: Multi-site, high-volume, tertiary care hospitals with established palliative care teams.

Synopsis: Clinical and cost data were collected for 969 adult patients with advanced cancer admitted to the five participating hospitals. Among those, 256 patients received palliative care consultation and 713 received usual care. Subsamples were created based on time to consultation after admission.

The study found that earlier consultation yielded larger effects on cost savings. There was a 24% reduction in total cost if consultation occurred within two days (95% CI, -$3,438 to -$1,122; P<0.001), with estimated savings of $2,280. For consultation within six days of admission, there was a $1,312 savings (95% CI, -$2,568 to -$ 1,122; P<0.04), consistent with a 14% reduction in total cost.

There are notable limitations to this study. Half of eligible patients were excluded due to incomplete data collection, resulting in a small sample size. Further, these results can be generalized only to inpatients with advanced cancer.

Bottom line: Reducing the time to consultation with palliative care increases cost savings. In advanced cancer patients, a 24% reduction in total costs was realized for consultation within two days following admission.

Citation: May P, Garrido MM, Cassel JB, et al. Prospective cohort study of hospital palliative care teams for inpatients with advanced cancer: earlier consultation is associated with larger cost-saving effect. J Clin Oncol. 2015;33(25):2745-2752.

On the heels of last year’s repeal of the sustainable growth rate (SGR) formula, 2016 promises to be a year of significant changes for the healthcare system. These changes will require providers to focus not just on the immediate pressures and requirements coming from Medicare, of which there are many, but also to look down the road to how things will change in the coming years.

The final year of reporting on quality measures for the Physician Quality Reporting System (PQRS) is 2016, with performance impacting Medicare payments in 2018. Reporting on quality measures doesn’t end there, however. The Medicare Access and CHIP Reauthorization Act (MACRA) repealed the SGR and created two new pathways for pay-for-performance for physicians and most other providers: the Merit-based Incentive Payment System (MIPS) and alternative payment models. After this year, reporting quality measures becomes one component of the MIPS, a program similar to hospital value-based purchasing, but designed for providers.

Quality measures are here to stay. They form the backbone for evaluating whether healthcare is of value. Under the MIPS, quality measures are combined with cost measures, meaningful use, and clinical performance improvement activities to create an aggregate score for providers. That score will be used to determine payment adjustments for providers starting in 2019.

Also in 2016, the Centers for Medicare and Medicaid Services (CMS) will lay the foundation for the MIPS. It is a completely new program, and although it will build on elements of existing programs like PQRS, meaningful use, and the physician value-based payment modifier, its structure and ramifications are ultimately unknown. CMS has indicated its intention to issue the regulatory backbone of MIPS in just a few months. These regulations will be the new reality of Medicare’s fee-for-service for the foreseeable future.

The ramifications of MIPS cannot be understated. It will apply an adjustment based on performance on all Medicare Part B payments. That adjustment starts at +/- 4.0% in 2019 and rises to +/- 9.0% by 2022, a number that is not as far off as it seems based on how these programs operate.

SHM expects many of the current PQRS policies to be continued under MIPS, which means, unfortunately, that many of the challenges facing hospitalists will continue. Hospitalists do not have many measures to report on; most measures are developed for outpatient practices, are simply not reflective of the variability of hospitalist practice, and, even if specified for inpatient reporting, are not clinically relevant.

To meet the needs of hospitalists, SHM will advocate strongly for CMS to develop more flexible and relevant reporting options. We will work to ensure that hospitalists are not structurally disadvantaged by the policies set in place.

Given these upcoming changes, it is as important as ever for you to stay engaged and informed about the policy changes coming down the road. It might be just the start of the year, but already there’s a lot of critical work to do. To get involved and remain apprised of the changes, join SHM’s grassroots network at www.hospitalmedicine.org/grassroots. TH

Joshua Lapps is SHM’s government relations manager.

On the heels of last year’s repeal of the sustainable growth rate (SGR) formula, 2016 promises to be a year of significant changes for the healthcare system. These changes will require providers to focus not just on the immediate pressures and requirements coming from Medicare, of which there are many, but also to look down the road to how things will change in the coming years.

The final year of reporting on quality measures for the Physician Quality Reporting System (PQRS) is 2016, with performance impacting Medicare payments in 2018. Reporting on quality measures doesn’t end there, however. The Medicare Access and CHIP Reauthorization Act (MACRA) repealed the SGR and created two new pathways for pay-for-performance for physicians and most other providers: the Merit-based Incentive Payment System (MIPS) and alternative payment models. After this year, reporting quality measures becomes one component of the MIPS, a program similar to hospital value-based purchasing, but designed for providers.

Quality measures are here to stay. They form the backbone for evaluating whether healthcare is of value. Under the MIPS, quality measures are combined with cost measures, meaningful use, and clinical performance improvement activities to create an aggregate score for providers. That score will be used to determine payment adjustments for providers starting in 2019.

Also in 2016, the Centers for Medicare and Medicaid Services (CMS) will lay the foundation for the MIPS. It is a completely new program, and although it will build on elements of existing programs like PQRS, meaningful use, and the physician value-based payment modifier, its structure and ramifications are ultimately unknown. CMS has indicated its intention to issue the regulatory backbone of MIPS in just a few months. These regulations will be the new reality of Medicare’s fee-for-service for the foreseeable future.

The ramifications of MIPS cannot be understated. It will apply an adjustment based on performance on all Medicare Part B payments. That adjustment starts at +/- 4.0% in 2019 and rises to +/- 9.0% by 2022, a number that is not as far off as it seems based on how these programs operate.

SHM expects many of the current PQRS policies to be continued under MIPS, which means, unfortunately, that many of the challenges facing hospitalists will continue. Hospitalists do not have many measures to report on; most measures are developed for outpatient practices, are simply not reflective of the variability of hospitalist practice, and, even if specified for inpatient reporting, are not clinically relevant.

To meet the needs of hospitalists, SHM will advocate strongly for CMS to develop more flexible and relevant reporting options. We will work to ensure that hospitalists are not structurally disadvantaged by the policies set in place.

Given these upcoming changes, it is as important as ever for you to stay engaged and informed about the policy changes coming down the road. It might be just the start of the year, but already there’s a lot of critical work to do. To get involved and remain apprised of the changes, join SHM’s grassroots network at www.hospitalmedicine.org/grassroots. TH

Joshua Lapps is SHM’s government relations manager.

On the heels of last year’s repeal of the sustainable growth rate (SGR) formula, 2016 promises to be a year of significant changes for the healthcare system. These changes will require providers to focus not just on the immediate pressures and requirements coming from Medicare, of which there are many, but also to look down the road to how things will change in the coming years.

The final year of reporting on quality measures for the Physician Quality Reporting System (PQRS) is 2016, with performance impacting Medicare payments in 2018. Reporting on quality measures doesn’t end there, however. The Medicare Access and CHIP Reauthorization Act (MACRA) repealed the SGR and created two new pathways for pay-for-performance for physicians and most other providers: the Merit-based Incentive Payment System (MIPS) and alternative payment models. After this year, reporting quality measures becomes one component of the MIPS, a program similar to hospital value-based purchasing, but designed for providers.

Quality measures are here to stay. They form the backbone for evaluating whether healthcare is of value. Under the MIPS, quality measures are combined with cost measures, meaningful use, and clinical performance improvement activities to create an aggregate score for providers. That score will be used to determine payment adjustments for providers starting in 2019.

Also in 2016, the Centers for Medicare and Medicaid Services (CMS) will lay the foundation for the MIPS. It is a completely new program, and although it will build on elements of existing programs like PQRS, meaningful use, and the physician value-based payment modifier, its structure and ramifications are ultimately unknown. CMS has indicated its intention to issue the regulatory backbone of MIPS in just a few months. These regulations will be the new reality of Medicare’s fee-for-service for the foreseeable future.

The ramifications of MIPS cannot be understated. It will apply an adjustment based on performance on all Medicare Part B payments. That adjustment starts at +/- 4.0% in 2019 and rises to +/- 9.0% by 2022, a number that is not as far off as it seems based on how these programs operate.

SHM expects many of the current PQRS policies to be continued under MIPS, which means, unfortunately, that many of the challenges facing hospitalists will continue. Hospitalists do not have many measures to report on; most measures are developed for outpatient practices, are simply not reflective of the variability of hospitalist practice, and, even if specified for inpatient reporting, are not clinically relevant.

To meet the needs of hospitalists, SHM will advocate strongly for CMS to develop more flexible and relevant reporting options. We will work to ensure that hospitalists are not structurally disadvantaged by the policies set in place.

Given these upcoming changes, it is as important as ever for you to stay engaged and informed about the policy changes coming down the road. It might be just the start of the year, but already there’s a lot of critical work to do. To get involved and remain apprised of the changes, join SHM’s grassroots network at www.hospitalmedicine.org/grassroots. TH

Joshua Lapps is SHM’s government relations manager.

S. Godfrey, Alabama

W. Mohamed, MD, Alabama

S. Paladugu, MBBS, Alabama

E. Razzouk, Alabama

S. Bommena, MD, Arizona

L. Ledbetter, NP, Arizona

R. Nambusi, MD, Arkansas

S. Asarch, California

J. Barber, California

M. Bikhchandani, California

B. Boesch, DO, California

C. Brown, California

A. Bui, California

E. Collier, California

L. Demyan, California

S. Dowlatshahi, California

M. Edmunds, California

A. Eniasivam, MD, California

Z. Fernandez, California

S. George, MD, California

E. Granflor, ACNP, MSN, RN, California

V. Guitierrez, California

M. Incze, California

B. Jones-Linares, California

S. Judon, California

L. Khuu, MD, California

T. Kim, MD, California

A. Lakhanpal, California

B. Lee, California

E. Li, California

E. Liaw, California

V. Lieu, California

S. Lim, California

B. Lin, California

B. Lizarraga, California

J. Martinez-Cuellar, MD, California

M. Militante-Miller, DO, California

H. Montoya, California

D. Moon, California

L. Mukdad, California

N. Nardoni, California

K. Nguyen, California

B. Ramirez, California

R. Ramos, California

A. Reyes, California

W. Schlesinger, California

B. Scott, California

S. Singh, DO, California

C. Su, California

A. Tavakoli, California

O. Viramontes, California

J. Wassei, MD, California

R. Weiss, MD, California

J. Yuan, MD, California

W. Zellalem, DO, California

Y. Zheng, California

P. Filipowski, MD, Colorado

T. Guns, BHA, Colorado

A. Koch, DO, Colorado

N. Matthews, MD, Colorado

G. McGuire, MD, Colorado

M. Prakash, MBBS, Colorado

L. Stiff, MD, Colorado

J. Garcia, MD, Connecticut

L. Haut, Connecticut

O. Aly, MD, Washington, D.C.

C. Cole, MBA, Washington, D.C.

K. Allen, DO, Florida

S. Andrews, ANP, MS, Florida

G. Clayton, MD, Florida

P. Dubon, MD, Florida

S. Jadonath, MD, Florida

F. Keen, FACP, MD, Florida

A. Khanna, MD, Florida

J. Morrison, MD, PhD, Florida

K. Myint, MBBS, Florida

C. Riccard, MD, Florida

P. Russoniello, ARNP, RN, Florida

L. Staat, ARNP, Florida

K. Tamar, FACS, Florida

R. Torres, MD, Florida

M. Klimenko, MD, Georgia

S. Kommidi, MD, Georgia

H. Patel, MD, Georgia

T. Agni, Illinois

O. Al-Heeti, MD, Illinois

M. Allen, Illinois

C. Brines, Illinois

C. Campbell, Illinois

J. Cho, Illinois

A. Cordasco, Illinois

K. Cramer, Illinois

K. Crawford, Illinois

L. Crawford, Illinois

J. Dale, Illinois

R. Davidov, Illinois

O. Doolittle, Illinois

A. Fuller, Illinois

L. Garland, MD, Illinois

S. Godbois, Illinois

E. Gonzales, Illinois

S. Gupta, MD, Illinois

R. Hameeduddin, DO, Illinois

K. Hayes, Illinois

C. Hill, Illinois

M. Jackson, Illinois

S. Jackson, Illinois

H. Jang, Illinois

M. Keegan, Illinois

E. Kimmie, Illinois

T. Lombardo, Illinois

S. McGowan, Illinois

M. Megaly, Illinois

A. Morker, Illinois

L. Moyar, Illinois

V. Patel, Illinois

C. Pena, Illinois

C. Pinotti, Illinois

W. Poisson, Illinois

K. Puleo, Illinois

R. Schmidgall, Illinois

B. Segel, MD, Illinois

S. Teshale, MD, Illinois

N. Velasquez, Illinois

S. Yeom, Illinois

M. Deb Roy, MD, Indiana

N. Delecaris, MD, Indiana

J. Gilbert, MD, Indiana

M. Ali, Iowa

S. Patel, MD, Kentucky

H. Shah, DO, Kentucky

S. Abraham, MD, Louisiana

M. Bergstedt, MD, Louisiana

J. Burtch, Louisiana

S. Chaney, MD, Louisiana

P. Karam, Louisiana

D. Kim, Louisiana

J. Leong, Louisiana

A. Sheeder, MD, Louisiana

C. Yeh, Louisiana

M. Cunanan-Bush, Maryland

K. Gottlieb, MD, MBA, MS, Maryland

T. Halley, FAAP, Maryland

E. Sholder, PA-C, Maryland

S. Sumner, DO, Maryland

A. Diranian, PA-C, Massachusetts

M. Hunt, DO, Massachusetts

S. Sasidharan, Massachusetts

A. Abdulrazzak, MD, FACP, Michigan

M. Antonishen, Michigan

A. Dhaliwal, MD, Michigan

A. Drummond, MD, Michigan

K. Fitzgerald, MD, Michigan

J. Greenberg, MD, Michigan

C. Lang, MD, Michigan

S. McGinnis, DO, Michigan

L. McMann, Michigan

A. Uwaje, FACP, MD, Michigan

E. Wisniewski, MSN, RN, Michigan

J. Benson, DO, Minnesota

V. Chaudhary, MD, Minnesota

T. Wood, Minnesota

C. Yarke, MD, Minnesota

D. Phillippi, MD, Mississippi

D. Loa, Missouri

J. Loa, Missouri

N. Patel, MD, Missouri

E. Sauer, Missouri

K. Tompkins, MD, FAAP, Missouri

J. Price, FAAFP, Montana

J. Codjoe, MD, New Jersey

I. Khan, MD, New Jersey

E. Merrill, MD, New Jersey

S. Park, DO, New Jersey

T. Ronan, MD, New Mexico

N. Varvaresou, ACNP, New Mexico

E. Ahn, MD, New York

S. Anandan, New York

D. Buff, MD, New York

B. Kranitzky, MD, New York

E. Levine, MHS, MD, New York

J. Noworyta, PA-C, New York

M. Padial, New York

J. Tucker, PA-C, New York

A. Vien, New York

J. DeCoster, MD, MPH, North Carolina

P. Gambrell, NP-C, North Carolina

D. Shah, NP, North Carolina

L. Tlhabano, MD, North Carolina

O. Aduroja, MD, Ohio

A. Ahsan, MD, Ohio

A. Belagavi, Ohio

R. Carletti, Ohio

C. Cox, RN, BSN, Ohio

G. Farkas, Ohio

M. Lileas, MD, DO, FACP, Ohio

A. Lopez, MD, Ohio

S. Mall, Ohio

A. Moren, MD, Ohio

B. Sanaullah, MD, MBBS, Ohio

A. Singh, MBBS, MD, Ohio

A. Thakur, MBBS, Ohio

T. Klimenko, ACNP, Oklahoma

L. Van Dyke, ACNP, Oklahoma

K. Gandhi, Oregon

R. Petersen, Oregon

J. Pruett, MD, Oregon

C. Cobb, MSN, NP, CRNP, FNP-C, Pennsylvania

J. Hickland, Pennsylvania

O. Kufile, MD, Pennsylvania

E. McCullough, MPH, PA-C, Pennsylvania

M. McFall, Pennsylvania

S. Nazir, Pennsylvania

A. Puri, MD, Pennsylvania

W. Romeo, MS, Pennsylvania

J. Gelzhiser, MD, Rhode Island

S. Kim, BA, Rhode Island

K. Cooley, South Carolina

J. Katchman, South Carolina

T. Phillips, South Carolina

J. Oakley, PA, South Dakota

J. Douglass, DO, Tennessee

B. Herron, Tennessee

M. McCain, LPN, FNP, Tennessee

K. Zaman, MD, Tennessee

R. Desai, DO, Texas

P. LeGros, Texas

O. Nguyen, MS, Texas

S. Papineni, MD, Texas

B. Rhinehart, PA-C, Texas

C. Szych, MD, Texas

D. Allred, APRN, Utah

G. Price, Utah

K. Leonard, MD, FAAP, Vermont

D. Rand, DO, Vermont

G. Cabrera, MD, MBA, Virginia

M. Stanton, PA-C, Virginia

J. Voss, Virginia

J. Cameron, MD, Washington

K. Chaganur, MBBS, Washington

G. Dalmacion, MD, Washington

M. Lo, Washington

M. Mahal, BS, MD, Washington

D. Newton, MD, Washington

H. Bertelson, Wisconsin

E. Kitchin, MD, Wisconsin

S. Patel, MD, Wisconsin

E. Yanke, MD, Wisconsin

S. Negrete, BSC, CCFP, MD, Canada

C. Chu, MBBS, MRCP, China

J. Chan, China

N. Pillai, MBBS, MACP, Malaysia

J. Gonzalez Moreno, MD, Mexico

S. Godfrey, Alabama

W. Mohamed, MD, Alabama

S. Paladugu, MBBS, Alabama

E. Razzouk, Alabama

S. Bommena, MD, Arizona

L. Ledbetter, NP, Arizona

R. Nambusi, MD, Arkansas

S. Asarch, California

J. Barber, California

M. Bikhchandani, California

B. Boesch, DO, California

C. Brown, California

A. Bui, California

E. Collier, California

L. Demyan, California

S. Dowlatshahi, California

M. Edmunds, California

A. Eniasivam, MD, California

Z. Fernandez, California

S. George, MD, California

E. Granflor, ACNP, MSN, RN, California

V. Guitierrez, California

M. Incze, California

B. Jones-Linares, California

S. Judon, California

L. Khuu, MD, California

T. Kim, MD, California

A. Lakhanpal, California

B. Lee, California

E. Li, California

E. Liaw, California

V. Lieu, California

S. Lim, California

B. Lin, California

B. Lizarraga, California

J. Martinez-Cuellar, MD, California

M. Militante-Miller, DO, California

H. Montoya, California

D. Moon, California

L. Mukdad, California

N. Nardoni, California

K. Nguyen, California

B. Ramirez, California

R. Ramos, California

A. Reyes, California

W. Schlesinger, California

B. Scott, California

S. Singh, DO, California

C. Su, California

A. Tavakoli, California

O. Viramontes, California

J. Wassei, MD, California

R. Weiss, MD, California

J. Yuan, MD, California

W. Zellalem, DO, California

Y. Zheng, California

P. Filipowski, MD, Colorado

T. Guns, BHA, Colorado

A. Koch, DO, Colorado

N. Matthews, MD, Colorado

G. McGuire, MD, Colorado

M. Prakash, MBBS, Colorado

L. Stiff, MD, Colorado

J. Garcia, MD, Connecticut

L. Haut, Connecticut

O. Aly, MD, Washington, D.C.

C. Cole, MBA, Washington, D.C.

K. Allen, DO, Florida

S. Andrews, ANP, MS, Florida

G. Clayton, MD, Florida

P. Dubon, MD, Florida

S. Jadonath, MD, Florida

F. Keen, FACP, MD, Florida

A. Khanna, MD, Florida

J. Morrison, MD, PhD, Florida

K. Myint, MBBS, Florida

C. Riccard, MD, Florida

P. Russoniello, ARNP, RN, Florida

L. Staat, ARNP, Florida

K. Tamar, FACS, Florida

R. Torres, MD, Florida

M. Klimenko, MD, Georgia

S. Kommidi, MD, Georgia

H. Patel, MD, Georgia

T. Agni, Illinois

O. Al-Heeti, MD, Illinois

M. Allen, Illinois

C. Brines, Illinois

C. Campbell, Illinois

J. Cho, Illinois

A. Cordasco, Illinois

K. Cramer, Illinois

K. Crawford, Illinois

L. Crawford, Illinois

J. Dale, Illinois

R. Davidov, Illinois

O. Doolittle, Illinois

A. Fuller, Illinois

L. Garland, MD, Illinois

S. Godbois, Illinois

E. Gonzales, Illinois

S. Gupta, MD, Illinois

R. Hameeduddin, DO, Illinois

K. Hayes, Illinois

C. Hill, Illinois

M. Jackson, Illinois

S. Jackson, Illinois

H. Jang, Illinois

M. Keegan, Illinois

E. Kimmie, Illinois

T. Lombardo, Illinois

S. McGowan, Illinois

M. Megaly, Illinois

A. Morker, Illinois

L. Moyar, Illinois

V. Patel, Illinois

C. Pena, Illinois

C. Pinotti, Illinois

W. Poisson, Illinois

K. Puleo, Illinois

R. Schmidgall, Illinois

B. Segel, MD, Illinois

S. Teshale, MD, Illinois

N. Velasquez, Illinois

S. Yeom, Illinois

M. Deb Roy, MD, Indiana

N. Delecaris, MD, Indiana

J. Gilbert, MD, Indiana

M. Ali, Iowa

S. Patel, MD, Kentucky

H. Shah, DO, Kentucky

S. Abraham, MD, Louisiana

M. Bergstedt, MD, Louisiana

J. Burtch, Louisiana

S. Chaney, MD, Louisiana

P. Karam, Louisiana

D. Kim, Louisiana

J. Leong, Louisiana

A. Sheeder, MD, Louisiana

C. Yeh, Louisiana

M. Cunanan-Bush, Maryland

K. Gottlieb, MD, MBA, MS, Maryland

T. Halley, FAAP, Maryland

E. Sholder, PA-C, Maryland

S. Sumner, DO, Maryland

A. Diranian, PA-C, Massachusetts

M. Hunt, DO, Massachusetts

S. Sasidharan, Massachusetts

A. Abdulrazzak, MD, FACP, Michigan

M. Antonishen, Michigan

A. Dhaliwal, MD, Michigan

A. Drummond, MD, Michigan

K. Fitzgerald, MD, Michigan

J. Greenberg, MD, Michigan

C. Lang, MD, Michigan

S. McGinnis, DO, Michigan

L. McMann, Michigan

A. Uwaje, FACP, MD, Michigan

E. Wisniewski, MSN, RN, Michigan

J. Benson, DO, Minnesota

V. Chaudhary, MD, Minnesota

T. Wood, Minnesota

C. Yarke, MD, Minnesota

D. Phillippi, MD, Mississippi

D. Loa, Missouri

J. Loa, Missouri

N. Patel, MD, Missouri

E. Sauer, Missouri

K. Tompkins, MD, FAAP, Missouri

J. Price, FAAFP, Montana

J. Codjoe, MD, New Jersey

I. Khan, MD, New Jersey

E. Merrill, MD, New Jersey

S. Park, DO, New Jersey

T. Ronan, MD, New Mexico

N. Varvaresou, ACNP, New Mexico

E. Ahn, MD, New York

S. Anandan, New York

D. Buff, MD, New York

B. Kranitzky, MD, New York

E. Levine, MHS, MD, New York

J. Noworyta, PA-C, New York

M. Padial, New York

J. Tucker, PA-C, New York

A. Vien, New York

J. DeCoster, MD, MPH, North Carolina

P. Gambrell, NP-C, North Carolina

D. Shah, NP, North Carolina

L. Tlhabano, MD, North Carolina

O. Aduroja, MD, Ohio

A. Ahsan, MD, Ohio

A. Belagavi, Ohio

R. Carletti, Ohio

C. Cox, RN, BSN, Ohio

G. Farkas, Ohio

M. Lileas, MD, DO, FACP, Ohio

A. Lopez, MD, Ohio

S. Mall, Ohio

A. Moren, MD, Ohio

B. Sanaullah, MD, MBBS, Ohio

A. Singh, MBBS, MD, Ohio

A. Thakur, MBBS, Ohio

T. Klimenko, ACNP, Oklahoma

L. Van Dyke, ACNP, Oklahoma

K. Gandhi, Oregon

R. Petersen, Oregon

J. Pruett, MD, Oregon

C. Cobb, MSN, NP, CRNP, FNP-C, Pennsylvania

J. Hickland, Pennsylvania

O. Kufile, MD, Pennsylvania

E. McCullough, MPH, PA-C, Pennsylvania

M. McFall, Pennsylvania

S. Nazir, Pennsylvania

A. Puri, MD, Pennsylvania

W. Romeo, MS, Pennsylvania

J. Gelzhiser, MD, Rhode Island

S. Kim, BA, Rhode Island

K. Cooley, South Carolina

J. Katchman, South Carolina

T. Phillips, South Carolina

J. Oakley, PA, South Dakota

J. Douglass, DO, Tennessee

B. Herron, Tennessee

M. McCain, LPN, FNP, Tennessee

K. Zaman, MD, Tennessee

R. Desai, DO, Texas

P. LeGros, Texas

O. Nguyen, MS, Texas

S. Papineni, MD, Texas

B. Rhinehart, PA-C, Texas

C. Szych, MD, Texas

D. Allred, APRN, Utah

G. Price, Utah

K. Leonard, MD, FAAP, Vermont

D. Rand, DO, Vermont

G. Cabrera, MD, MBA, Virginia

M. Stanton, PA-C, Virginia

J. Voss, Virginia

J. Cameron, MD, Washington

K. Chaganur, MBBS, Washington

G. Dalmacion, MD, Washington

M. Lo, Washington

M. Mahal, BS, MD, Washington

D. Newton, MD, Washington

H. Bertelson, Wisconsin

E. Kitchin, MD, Wisconsin

S. Patel, MD, Wisconsin

E. Yanke, MD, Wisconsin

S. Negrete, BSC, CCFP, MD, Canada

C. Chu, MBBS, MRCP, China

J. Chan, China

N. Pillai, MBBS, MACP, Malaysia

J. Gonzalez Moreno, MD, Mexico

S. Godfrey, Alabama

W. Mohamed, MD, Alabama

S. Paladugu, MBBS, Alabama

E. Razzouk, Alabama

S. Bommena, MD, Arizona

L. Ledbetter, NP, Arizona

R. Nambusi, MD, Arkansas

S. Asarch, California

J. Barber, California

M. Bikhchandani, California

B. Boesch, DO, California

C. Brown, California

A. Bui, California

E. Collier, California

L. Demyan, California

S. Dowlatshahi, California

M. Edmunds, California

A. Eniasivam, MD, California

Z. Fernandez, California

S. George, MD, California

E. Granflor, ACNP, MSN, RN, California

V. Guitierrez, California

M. Incze, California

B. Jones-Linares, California

S. Judon, California

L. Khuu, MD, California

T. Kim, MD, California

A. Lakhanpal, California

B. Lee, California

E. Li, California

E. Liaw, California

V. Lieu, California

S. Lim, California

B. Lin, California

B. Lizarraga, California

J. Martinez-Cuellar, MD, California

M. Militante-Miller, DO, California

H. Montoya, California

D. Moon, California

L. Mukdad, California

N. Nardoni, California

K. Nguyen, California

B. Ramirez, California

R. Ramos, California

A. Reyes, California

W. Schlesinger, California

B. Scott, California

S. Singh, DO, California

C. Su, California

A. Tavakoli, California

O. Viramontes, California

J. Wassei, MD, California

R. Weiss, MD, California

J. Yuan, MD, California

W. Zellalem, DO, California

Y. Zheng, California

P. Filipowski, MD, Colorado

T. Guns, BHA, Colorado

A. Koch, DO, Colorado

N. Matthews, MD, Colorado

G. McGuire, MD, Colorado

M. Prakash, MBBS, Colorado

L. Stiff, MD, Colorado

J. Garcia, MD, Connecticut

L. Haut, Connecticut

O. Aly, MD, Washington, D.C.

C. Cole, MBA, Washington, D.C.

K. Allen, DO, Florida

S. Andrews, ANP, MS, Florida

G. Clayton, MD, Florida

P. Dubon, MD, Florida

S. Jadonath, MD, Florida

F. Keen, FACP, MD, Florida

A. Khanna, MD, Florida

J. Morrison, MD, PhD, Florida

K. Myint, MBBS, Florida

C. Riccard, MD, Florida

P. Russoniello, ARNP, RN, Florida

L. Staat, ARNP, Florida

K. Tamar, FACS, Florida

R. Torres, MD, Florida

M. Klimenko, MD, Georgia

S. Kommidi, MD, Georgia

H. Patel, MD, Georgia

T. Agni, Illinois

O. Al-Heeti, MD, Illinois

M. Allen, Illinois

C. Brines, Illinois

C. Campbell, Illinois

J. Cho, Illinois

A. Cordasco, Illinois

K. Cramer, Illinois

K. Crawford, Illinois

L. Crawford, Illinois

J. Dale, Illinois

R. Davidov, Illinois

O. Doolittle, Illinois

A. Fuller, Illinois

L. Garland, MD, Illinois

S. Godbois, Illinois

E. Gonzales, Illinois

S. Gupta, MD, Illinois

R. Hameeduddin, DO, Illinois

K. Hayes, Illinois

C. Hill, Illinois

M. Jackson, Illinois

S. Jackson, Illinois

H. Jang, Illinois

M. Keegan, Illinois

E. Kimmie, Illinois

T. Lombardo, Illinois

S. McGowan, Illinois

M. Megaly, Illinois

A. Morker, Illinois

L. Moyar, Illinois

V. Patel, Illinois

C. Pena, Illinois

C. Pinotti, Illinois

W. Poisson, Illinois

K. Puleo, Illinois

R. Schmidgall, Illinois

B. Segel, MD, Illinois

S. Teshale, MD, Illinois

N. Velasquez, Illinois

S. Yeom, Illinois

M. Deb Roy, MD, Indiana

N. Delecaris, MD, Indiana

J. Gilbert, MD, Indiana

M. Ali, Iowa

S. Patel, MD, Kentucky

H. Shah, DO, Kentucky

S. Abraham, MD, Louisiana

M. Bergstedt, MD, Louisiana

J. Burtch, Louisiana

S. Chaney, MD, Louisiana

P. Karam, Louisiana

D. Kim, Louisiana

J. Leong, Louisiana

A. Sheeder, MD, Louisiana

C. Yeh, Louisiana

M. Cunanan-Bush, Maryland

K. Gottlieb, MD, MBA, MS, Maryland

T. Halley, FAAP, Maryland

E. Sholder, PA-C, Maryland

S. Sumner, DO, Maryland

A. Diranian, PA-C, Massachusetts

M. Hunt, DO, Massachusetts

S. Sasidharan, Massachusetts

A. Abdulrazzak, MD, FACP, Michigan

M. Antonishen, Michigan

A. Dhaliwal, MD, Michigan

A. Drummond, MD, Michigan

K. Fitzgerald, MD, Michigan

J. Greenberg, MD, Michigan

C. Lang, MD, Michigan

S. McGinnis, DO, Michigan

L. McMann, Michigan

A. Uwaje, FACP, MD, Michigan

E. Wisniewski, MSN, RN, Michigan

J. Benson, DO, Minnesota

V. Chaudhary, MD, Minnesota

T. Wood, Minnesota

C. Yarke, MD, Minnesota

D. Phillippi, MD, Mississippi

D. Loa, Missouri

J. Loa, Missouri

N. Patel, MD, Missouri

E. Sauer, Missouri

K. Tompkins, MD, FAAP, Missouri

J. Price, FAAFP, Montana

J. Codjoe, MD, New Jersey

I. Khan, MD, New Jersey

E. Merrill, MD, New Jersey

S. Park, DO, New Jersey

T. Ronan, MD, New Mexico

N. Varvaresou, ACNP, New Mexico

E. Ahn, MD, New York

S. Anandan, New York

D. Buff, MD, New York

B. Kranitzky, MD, New York

E. Levine, MHS, MD, New York

J. Noworyta, PA-C, New York

M. Padial, New York

J. Tucker, PA-C, New York

A. Vien, New York

J. DeCoster, MD, MPH, North Carolina

P. Gambrell, NP-C, North Carolina

D. Shah, NP, North Carolina

L. Tlhabano, MD, North Carolina

O. Aduroja, MD, Ohio

A. Ahsan, MD, Ohio

A. Belagavi, Ohio

R. Carletti, Ohio

C. Cox, RN, BSN, Ohio

G. Farkas, Ohio

M. Lileas, MD, DO, FACP, Ohio

A. Lopez, MD, Ohio

S. Mall, Ohio

A. Moren, MD, Ohio

B. Sanaullah, MD, MBBS, Ohio

A. Singh, MBBS, MD, Ohio

A. Thakur, MBBS, Ohio

T. Klimenko, ACNP, Oklahoma

L. Van Dyke, ACNP, Oklahoma

K. Gandhi, Oregon

R. Petersen, Oregon

J. Pruett, MD, Oregon

C. Cobb, MSN, NP, CRNP, FNP-C, Pennsylvania

J. Hickland, Pennsylvania

O. Kufile, MD, Pennsylvania

E. McCullough, MPH, PA-C, Pennsylvania

M. McFall, Pennsylvania

S. Nazir, Pennsylvania

A. Puri, MD, Pennsylvania

W. Romeo, MS, Pennsylvania

J. Gelzhiser, MD, Rhode Island

S. Kim, BA, Rhode Island

K. Cooley, South Carolina

J. Katchman, South Carolina

T. Phillips, South Carolina

J. Oakley, PA, South Dakota

J. Douglass, DO, Tennessee

B. Herron, Tennessee

M. McCain, LPN, FNP, Tennessee

K. Zaman, MD, Tennessee

R. Desai, DO, Texas

P. LeGros, Texas

O. Nguyen, MS, Texas

S. Papineni, MD, Texas

B. Rhinehart, PA-C, Texas

C. Szych, MD, Texas

D. Allred, APRN, Utah

G. Price, Utah

K. Leonard, MD, FAAP, Vermont

D. Rand, DO, Vermont

G. Cabrera, MD, MBA, Virginia

M. Stanton, PA-C, Virginia

J. Voss, Virginia

J. Cameron, MD, Washington

K. Chaganur, MBBS, Washington

G. Dalmacion, MD, Washington

M. Lo, Washington

M. Mahal, BS, MD, Washington

D. Newton, MD, Washington

H. Bertelson, Wisconsin

E. Kitchin, MD, Wisconsin

S. Patel, MD, Wisconsin

E. Yanke, MD, Wisconsin

S. Negrete, BSC, CCFP, MD, Canada

C. Chu, MBBS, MRCP, China

J. Chan, China

N. Pillai, MBBS, MACP, Malaysia

J. Gonzalez Moreno, MD, Mexico

Vials of drug

Photo by Bill Branson

Results of the phase 3 ENDEAVOR trial suggest combination carfilzomib and dexamethasone prolongs progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (MM), when compared to bortezomib plus dexamethasone.

The median PFS was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm.

It is not clear whether this translates to an improvement in overall survival, as those data are not yet mature.

Treatment discontinuation due to adverse events (AEs) and on-study deaths were comparable between the treatment arms, although there were several AEs that occurred more frequently in the carfilzomib arm than the bortezomib arm.

These results were published in The Lancet Oncology. The trial was funded by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen.

Patient treatment and characteristics

The ENDEAVOR trial included 929 patients with relapsed/refractory MM who had received 1 to 3 prior therapeutic regimens. They were randomized to receive carfilzomib in combination with low-dose dexamethasone (n=464) or bortezomib with low-dose dexamethasone (n=465) until progression.

Patients received carfilzomib as a 30-minute infusion on days 1, 2, 8, 9, 15, and 16 of 28-day treatment cycles, along with 20 mg of dexamethasone. For cycle 1 only, carfilzomib was administered at 20 mg/m² on days 1 and 2, followed by escalation to 56 mg/m² from day 8. Patients who tolerated 56 mg/m² in cycle 1 were kept at this dose for subsequent cycles.

Patients who received bortezomib (1.3 mg/m²) with low-dose dexamethasone (20 mg) were given bortezomib subcutaneously or intravenously at the discretion of the investigator. More than 75% of the patients received bortezomib subcutaneously.

Baseline characteristics were generally balanced between the treatment arms. Both arms had a median age of 65 (overall range, 30-89), and about half were male. Three-quarters of patients in both arms were white, a little over 10% were Asian, 2% were black, and about 10% did not report race/ethnicity.

A majority of patients in both arms (more than 90%) had an ECOG score of 0 or 1. Most patients (more than 60%) had standard-risk cytogenetics.

The median number of prior treatment regimens was 2 in both arms. Patients in both arms had received prior lenalidomide (38% in both arms), thalidomide (45% in the carfilzomib arm and 53% in the bortezomib arm), bortezomib (54% in both arms), and carfilzomib (<1% in both arms).

Results

The median PFS in the carfilzomib arm was roughly double that of the bortezomib arm—18.7 months and 9.4 months, respectively. The hazard ratio was 0.53 (P<0.0001).

Overall survival data are not mature and are still being monitored.

The overall response rate was 77% in the carfilzomib arm and 63% in the bortezomib arm (P<0.0001). The duration of response was 21.3 months and 10.4 months, respectively.

The proportion of patients achieving a very good partial response or better was 54.3% in the carfilzomib arm and 29% in the bortezomib arm (P<0.0001). The complete response rates were 13% and 6%, respectively (P<0.001).

Treatment discontinuation due to AEs and on-study deaths were comparable between the arms. There were 75 deaths in the carfilzomib arm and 88 deaths in the bortezomib arm.

Of the 263 patients in the carfilzomib arm who discontinued treatment, 65 did so because of AEs. Of the 351 patients in the bortezomib arm who discontinued treatment, 73 did so because of AEs.

A number of known AEs were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including any-grade dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).

Rates of grade 3 or higher AEs were 73% in the carfilzomib arm and 67% in the bortezomib arm. Grade 3 or higher AEs of interest in the carfilzomib and bortezomib arms, respectively, were hypertension (9% vs 3%), dyspnea (5% vs 2%), cardiac failure (5% vs 2%), acute renal failure (4% vs 3%), ischemic heart disease (2% vs 2%), and pulmonary hypertension (0.6% vs 0.2%).

Vials of drug

Photo by Bill Branson

Results of the phase 3 ENDEAVOR trial suggest combination carfilzomib and dexamethasone prolongs progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (MM), when compared to bortezomib plus dexamethasone.

The median PFS was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm.

It is not clear whether this translates to an improvement in overall survival, as those data are not yet mature.

Treatment discontinuation due to adverse events (AEs) and on-study deaths were comparable between the treatment arms, although there were several AEs that occurred more frequently in the carfilzomib arm than the bortezomib arm.

These results were published in The Lancet Oncology. The trial was funded by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen.

Patient treatment and characteristics

The ENDEAVOR trial included 929 patients with relapsed/refractory MM who had received 1 to 3 prior therapeutic regimens. They were randomized to receive carfilzomib in combination with low-dose dexamethasone (n=464) or bortezomib with low-dose dexamethasone (n=465) until progression.

Patients received carfilzomib as a 30-minute infusion on days 1, 2, 8, 9, 15, and 16 of 28-day treatment cycles, along with 20 mg of dexamethasone. For cycle 1 only, carfilzomib was administered at 20 mg/m² on days 1 and 2, followed by escalation to 56 mg/m² from day 8. Patients who tolerated 56 mg/m² in cycle 1 were kept at this dose for subsequent cycles.

Patients who received bortezomib (1.3 mg/m²) with low-dose dexamethasone (20 mg) were given bortezomib subcutaneously or intravenously at the discretion of the investigator. More than 75% of the patients received bortezomib subcutaneously.

Baseline characteristics were generally balanced between the treatment arms. Both arms had a median age of 65 (overall range, 30-89), and about half were male. Three-quarters of patients in both arms were white, a little over 10% were Asian, 2% were black, and about 10% did not report race/ethnicity.

A majority of patients in both arms (more than 90%) had an ECOG score of 0 or 1. Most patients (more than 60%) had standard-risk cytogenetics.

The median number of prior treatment regimens was 2 in both arms. Patients in both arms had received prior lenalidomide (38% in both arms), thalidomide (45% in the carfilzomib arm and 53% in the bortezomib arm), bortezomib (54% in both arms), and carfilzomib (<1% in both arms).

Results

The median PFS in the carfilzomib arm was roughly double that of the bortezomib arm—18.7 months and 9.4 months, respectively. The hazard ratio was 0.53 (P<0.0001).

Overall survival data are not mature and are still being monitored.

The overall response rate was 77% in the carfilzomib arm and 63% in the bortezomib arm (P<0.0001). The duration of response was 21.3 months and 10.4 months, respectively.

The proportion of patients achieving a very good partial response or better was 54.3% in the carfilzomib arm and 29% in the bortezomib arm (P<0.0001). The complete response rates were 13% and 6%, respectively (P<0.001).

Treatment discontinuation due to AEs and on-study deaths were comparable between the arms. There were 75 deaths in the carfilzomib arm and 88 deaths in the bortezomib arm.

Of the 263 patients in the carfilzomib arm who discontinued treatment, 65 did so because of AEs. Of the 351 patients in the bortezomib arm who discontinued treatment, 73 did so because of AEs.

A number of known AEs were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including any-grade dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).

Rates of grade 3 or higher AEs were 73% in the carfilzomib arm and 67% in the bortezomib arm. Grade 3 or higher AEs of interest in the carfilzomib and bortezomib arms, respectively, were hypertension (9% vs 3%), dyspnea (5% vs 2%), cardiac failure (5% vs 2%), acute renal failure (4% vs 3%), ischemic heart disease (2% vs 2%), and pulmonary hypertension (0.6% vs 0.2%).

Vials of drug

Photo by Bill Branson

Results of the phase 3 ENDEAVOR trial suggest combination carfilzomib and dexamethasone prolongs progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (MM), when compared to bortezomib plus dexamethasone.

The median PFS was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm.

It is not clear whether this translates to an improvement in overall survival, as those data are not yet mature.

Treatment discontinuation due to adverse events (AEs) and on-study deaths were comparable between the treatment arms, although there were several AEs that occurred more frequently in the carfilzomib arm than the bortezomib arm.

These results were published in The Lancet Oncology. The trial was funded by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen.

Patient treatment and characteristics

The ENDEAVOR trial included 929 patients with relapsed/refractory MM who had received 1 to 3 prior therapeutic regimens. They were randomized to receive carfilzomib in combination with low-dose dexamethasone (n=464) or bortezomib with low-dose dexamethasone (n=465) until progression.

Patients received carfilzomib as a 30-minute infusion on days 1, 2, 8, 9, 15, and 16 of 28-day treatment cycles, along with 20 mg of dexamethasone. For cycle 1 only, carfilzomib was administered at 20 mg/m² on days 1 and 2, followed by escalation to 56 mg/m² from day 8. Patients who tolerated 56 mg/m² in cycle 1 were kept at this dose for subsequent cycles.

Patients who received bortezomib (1.3 mg/m²) with low-dose dexamethasone (20 mg) were given bortezomib subcutaneously or intravenously at the discretion of the investigator. More than 75% of the patients received bortezomib subcutaneously.

Baseline characteristics were generally balanced between the treatment arms. Both arms had a median age of 65 (overall range, 30-89), and about half were male. Three-quarters of patients in both arms were white, a little over 10% were Asian, 2% were black, and about 10% did not report race/ethnicity.

A majority of patients in both arms (more than 90%) had an ECOG score of 0 or 1. Most patients (more than 60%) had standard-risk cytogenetics.

The median number of prior treatment regimens was 2 in both arms. Patients in both arms had received prior lenalidomide (38% in both arms), thalidomide (45% in the carfilzomib arm and 53% in the bortezomib arm), bortezomib (54% in both arms), and carfilzomib (<1% in both arms).

Results

The median PFS in the carfilzomib arm was roughly double that of the bortezomib arm—18.7 months and 9.4 months, respectively. The hazard ratio was 0.53 (P<0.0001).

Overall survival data are not mature and are still being monitored.

The overall response rate was 77% in the carfilzomib arm and 63% in the bortezomib arm (P<0.0001). The duration of response was 21.3 months and 10.4 months, respectively.

The proportion of patients achieving a very good partial response or better was 54.3% in the carfilzomib arm and 29% in the bortezomib arm (P<0.0001). The complete response rates were 13% and 6%, respectively (P<0.001).

Treatment discontinuation due to AEs and on-study deaths were comparable between the arms. There were 75 deaths in the carfilzomib arm and 88 deaths in the bortezomib arm.

Of the 263 patients in the carfilzomib arm who discontinued treatment, 65 did so because of AEs. Of the 351 patients in the bortezomib arm who discontinued treatment, 73 did so because of AEs.

A number of known AEs were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including any-grade dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).

Rates of grade 3 or higher AEs were 73% in the carfilzomib arm and 67% in the bortezomib arm. Grade 3 or higher AEs of interest in the carfilzomib and bortezomib arms, respectively, were hypertension (9% vs 3%), dyspnea (5% vs 2%), cardiac failure (5% vs 2%), acute renal failure (4% vs 3%), ischemic heart disease (2% vs 2%), and pulmonary hypertension (0.6% vs 0.2%).

In high-risk patients, blood pressure lowering is associated with significant reductions in vascular events for a range of comorbidities and baseline blood pressures, said the authors of a meta-analysis of 123 randomized controlled trials published in the last 50 years.

Each 10–mm Hg reduction in systolic blood pressure was associated with a 20% reduction in major cardiovascular disease events (95% confidence interval, 0.77-0.83), a 17% reduction in coronary heart disease (95% CI, 0.78-0.88), a 27% reduction in stroke (95% CI, 0.68-0.77), and a 28% reduction in heart failure (95% CI, 0.67-0.78), based on the meta-analysis published Dec. 23 by the Lancet.

©crossstudio/ThinkStock

The exception was a lack of overall benefit of blood pressure lowering for renal failure events, a finding consistent with a previous meta-analysis of moderate versus intensive blood pressure reduction.

“Lowering of blood pressure into what has been regarded the normotensive range should therefore be routinely considered for the prevention of cardiovascular disease among those deemed to be of sufficient absolute risk,” wrote Dena Ettehad of the George Institute for Global Health, Oxford, and coauthors.

“Revision is urgently needed to recent blood pressure lowering guidelines that have relaxed the blood pressure lowering thresholds,” they added.

The researchers conducted a meta-analysis of blood pressure lowering treatment, involving a total of 613,815 participants and a minimum of 1,000 patient-years of follow-up in each study arm.

The analysis indicated that a 10–mm Hg reduction in systolic blood pressure achieved an overall 13% reduction in all-cause mortality (95% CI, 0.84-0.91) but had no significant impact on the risk of renal failure events.

These effects remained similar even when the effects were compared between strata of mean baseline systolic blood pressure, baseline coronary heart disease, or baseline cardiovascular disease (Lancet 2015 Dec 23. doi: 10.1016/S0140-6736(15)01225-8).

“In stratified analyses, we saw no strong evidence that proportional effects were diminished in trials that included people with lower baseline systolic blood pressure (less than 130 mm Hg), and major cardiovascular events were clearly reduced in high-risk patients with various baseline comorbidities,” the investigators wrote.

“Both of these major findings – the efficacy of blood pressure lowering below 130 mm Hg and the similar proportional effects in high-risk populations – are consistent with and extend the findings of the SPRINT trial,” they said.

The authors did note greater proportional reductions in the risk of stroke in populations without a history of cerebrovascular disease, compared with those with a history.

Populations without diabetes had significantly greater proportional reductions in risk, compared with those with diabetes, while populations without chronic kidney disease had greater proportional reductions in the risk of major cardiovascular disease events, compared with those with chronic kidney disease.

The five classes of antihypertensives were generally as effective as each other in reducing the risk of major outcomes.

The authors noted that, while there were small but significant differences between drug classes for outcomes, these effects may have been the result of differences in control regimens or the concurrent use of multiple drug classes in many trials.

Two authors were supported by the National Institute of Health Research, one by the Clarendon Fund, and one by the Rhodes Trust. The George Institute is supported by the Oxford Martin School. Two authors declared grants from Servier, and one also declared investments for the development of a polypill. No other conflicts of interest were declared.

In high-risk patients, blood pressure lowering is associated with significant reductions in vascular events for a range of comorbidities and baseline blood pressures, said the authors of a meta-analysis of 123 randomized controlled trials published in the last 50 years.

Each 10–mm Hg reduction in systolic blood pressure was associated with a 20% reduction in major cardiovascular disease events (95% confidence interval, 0.77-0.83), a 17% reduction in coronary heart disease (95% CI, 0.78-0.88), a 27% reduction in stroke (95% CI, 0.68-0.77), and a 28% reduction in heart failure (95% CI, 0.67-0.78), based on the meta-analysis published Dec. 23 by the Lancet.

©crossstudio/ThinkStock

The exception was a lack of overall benefit of blood pressure lowering for renal failure events, a finding consistent with a previous meta-analysis of moderate versus intensive blood pressure reduction.

“Lowering of blood pressure into what has been regarded the normotensive range should therefore be routinely considered for the prevention of cardiovascular disease among those deemed to be of sufficient absolute risk,” wrote Dena Ettehad of the George Institute for Global Health, Oxford, and coauthors.

“Revision is urgently needed to recent blood pressure lowering guidelines that have relaxed the blood pressure lowering thresholds,” they added.

The researchers conducted a meta-analysis of blood pressure lowering treatment, involving a total of 613,815 participants and a minimum of 1,000 patient-years of follow-up in each study arm.

The analysis indicated that a 10–mm Hg reduction in systolic blood pressure achieved an overall 13% reduction in all-cause mortality (95% CI, 0.84-0.91) but had no significant impact on the risk of renal failure events.

These effects remained similar even when the effects were compared between strata of mean baseline systolic blood pressure, baseline coronary heart disease, or baseline cardiovascular disease (Lancet 2015 Dec 23. doi: 10.1016/S0140-6736(15)01225-8).

“In stratified analyses, we saw no strong evidence that proportional effects were diminished in trials that included people with lower baseline systolic blood pressure (less than 130 mm Hg), and major cardiovascular events were clearly reduced in high-risk patients with various baseline comorbidities,” the investigators wrote.

“Both of these major findings – the efficacy of blood pressure lowering below 130 mm Hg and the similar proportional effects in high-risk populations – are consistent with and extend the findings of the SPRINT trial,” they said.

The authors did note greater proportional reductions in the risk of stroke in populations without a history of cerebrovascular disease, compared with those with a history.

Populations without diabetes had significantly greater proportional reductions in risk, compared with those with diabetes, while populations without chronic kidney disease had greater proportional reductions in the risk of major cardiovascular disease events, compared with those with chronic kidney disease.

The five classes of antihypertensives were generally as effective as each other in reducing the risk of major outcomes.

The authors noted that, while there were small but significant differences between drug classes for outcomes, these effects may have been the result of differences in control regimens or the concurrent use of multiple drug classes in many trials.

Two authors were supported by the National Institute of Health Research, one by the Clarendon Fund, and one by the Rhodes Trust. The George Institute is supported by the Oxford Martin School. Two authors declared grants from Servier, and one also declared investments for the development of a polypill. No other conflicts of interest were declared.

In high-risk patients, blood pressure lowering is associated with significant reductions in vascular events for a range of comorbidities and baseline blood pressures, said the authors of a meta-analysis of 123 randomized controlled trials published in the last 50 years.

Each 10–mm Hg reduction in systolic blood pressure was associated with a 20% reduction in major cardiovascular disease events (95% confidence interval, 0.77-0.83), a 17% reduction in coronary heart disease (95% CI, 0.78-0.88), a 27% reduction in stroke (95% CI, 0.68-0.77), and a 28% reduction in heart failure (95% CI, 0.67-0.78), based on the meta-analysis published Dec. 23 by the Lancet.

©crossstudio/ThinkStock

The exception was a lack of overall benefit of blood pressure lowering for renal failure events, a finding consistent with a previous meta-analysis of moderate versus intensive blood pressure reduction.

“Lowering of blood pressure into what has been regarded the normotensive range should therefore be routinely considered for the prevention of cardiovascular disease among those deemed to be of sufficient absolute risk,” wrote Dena Ettehad of the George Institute for Global Health, Oxford, and coauthors.

“Revision is urgently needed to recent blood pressure lowering guidelines that have relaxed the blood pressure lowering thresholds,” they added.

The researchers conducted a meta-analysis of blood pressure lowering treatment, involving a total of 613,815 participants and a minimum of 1,000 patient-years of follow-up in each study arm.

The analysis indicated that a 10–mm Hg reduction in systolic blood pressure achieved an overall 13% reduction in all-cause mortality (95% CI, 0.84-0.91) but had no significant impact on the risk of renal failure events.

These effects remained similar even when the effects were compared between strata of mean baseline systolic blood pressure, baseline coronary heart disease, or baseline cardiovascular disease (Lancet 2015 Dec 23. doi: 10.1016/S0140-6736(15)01225-8).

“In stratified analyses, we saw no strong evidence that proportional effects were diminished in trials that included people with lower baseline systolic blood pressure (less than 130 mm Hg), and major cardiovascular events were clearly reduced in high-risk patients with various baseline comorbidities,” the investigators wrote.

“Both of these major findings – the efficacy of blood pressure lowering below 130 mm Hg and the similar proportional effects in high-risk populations – are consistent with and extend the findings of the SPRINT trial,” they said.

The authors did note greater proportional reductions in the risk of stroke in populations without a history of cerebrovascular disease, compared with those with a history.

Populations without diabetes had significantly greater proportional reductions in risk, compared with those with diabetes, while populations without chronic kidney disease had greater proportional reductions in the risk of major cardiovascular disease events, compared with those with chronic kidney disease.

The five classes of antihypertensives were generally as effective as each other in reducing the risk of major outcomes.

The authors noted that, while there were small but significant differences between drug classes for outcomes, these effects may have been the result of differences in control regimens or the concurrent use of multiple drug classes in many trials.

Two authors were supported by the National Institute of Health Research, one by the Clarendon Fund, and one by the Rhodes Trust. The George Institute is supported by the Oxford Martin School. Two authors declared grants from Servier, and one also declared investments for the development of a polypill. No other conflicts of interest were declared.

Secukinumab, an interleukin 17-A inhibitor approved for the treatment of moderate to severe psoriasis, significantly reduced the signs and symptoms of ankylosing spondylitis in two phase III trials, researchers reported Dec. 23 in the New England Journal of Medicine.

The results of the double-blind MEASURE 1 and MEASURE 2 trials extend the positive results of the phase II study, according to Dr. Dominique Baeten of the Academic Medical Center at the University of Amsterdam and his colleagues (N Engl J Med. 2015 Dec 23. doi: 10.1056/NEJMoa1505066).

“Although head-to-head trials would be required to fully assess the efficacy and safety of secukinumab versus TNF-inhibitors, the [20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria] response rates achieved with secukinumab at week 16 in our studies were similar to those reported in phase III studies of anti-TNF agents in which most of the patients had not received previous anti-TNF therapy (response rates of 58% to 64% at weeks 12 to 24), even though 30% to 40% of the patients in our studies had had no response to previous anti-TNF treatment,” the authors wrote.

“Thus, secukinumab not only is effective in patients who have not received TNF agents previously but also may be effective in patients in whom previous anti-TNF treatment failed,” they added.

In MEASURE 1, 371 patients received intravenous secukinumab (10 mg/kg of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8.

The study’s primary endpoint of ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively, (P less than .001 for both comparisons with placebo).

In MEASURE 2, 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4.

At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg.

In this trial, ASAS20 rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P less than .001 for the 150-mg dose and P = .10 for the 75-mg dose).

The researchers noted that the ineffectiveness of the 75-mg dose in MEASURE 2 suggests that the efficacy of secukinumab at the 75-mg dose in MEASURE 1 may have been due to the greater exposure at week 16 as a result of the intravenous loading regimen, not to the 75-mg subcutaneous maintenance dose.

The safety profile of secukinumab in the present studies was consistent with previous studies of secukinumab for ankylosing spondylitis and moderate-to-severe plaque psoriasis, Dr. Baeten and his associates said.

During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients.

Overall, the results suggest that interleukin-17A plays a role in the pathogenesis of ankylosing spondylitis, and they validate inhibition of this cytokine as a potential therapeutic approach, the study authors concluded.

The study was sponsored by Novartis Pharma. Dr. Baeten has received a grant from Novartis to study the impact of IL-17A blockade in experimental models of spondyloarthritis. He also has been a consultant for Novartis for the design and conduct of the secukinumab program in ankylosing spondylitis and psoriatic arthritis.

Secukinumab, an interleukin 17-A inhibitor approved for the treatment of moderate to severe psoriasis, significantly reduced the signs and symptoms of ankylosing spondylitis in two phase III trials, researchers reported Dec. 23 in the New England Journal of Medicine.

The results of the double-blind MEASURE 1 and MEASURE 2 trials extend the positive results of the phase II study, according to Dr. Dominique Baeten of the Academic Medical Center at the University of Amsterdam and his colleagues (N Engl J Med. 2015 Dec 23. doi: 10.1056/NEJMoa1505066).

“Although head-to-head trials would be required to fully assess the efficacy and safety of secukinumab versus TNF-inhibitors, the [20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria] response rates achieved with secukinumab at week 16 in our studies were similar to those reported in phase III studies of anti-TNF agents in which most of the patients had not received previous anti-TNF therapy (response rates of 58% to 64% at weeks 12 to 24), even though 30% to 40% of the patients in our studies had had no response to previous anti-TNF treatment,” the authors wrote.

“Thus, secukinumab not only is effective in patients who have not received TNF agents previously but also may be effective in patients in whom previous anti-TNF treatment failed,” they added.

In MEASURE 1, 371 patients received intravenous secukinumab (10 mg/kg of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8.

The study’s primary endpoint of ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively, (P less than .001 for both comparisons with placebo).

In MEASURE 2, 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4.

At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg.

In this trial, ASAS20 rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P less than .001 for the 150-mg dose and P = .10 for the 75-mg dose).

The researchers noted that the ineffectiveness of the 75-mg dose in MEASURE 2 suggests that the efficacy of secukinumab at the 75-mg dose in MEASURE 1 may have been due to the greater exposure at week 16 as a result of the intravenous loading regimen, not to the 75-mg subcutaneous maintenance dose.

The safety profile of secukinumab in the present studies was consistent with previous studies of secukinumab for ankylosing spondylitis and moderate-to-severe plaque psoriasis, Dr. Baeten and his associates said.

During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients.

Overall, the results suggest that interleukin-17A plays a role in the pathogenesis of ankylosing spondylitis, and they validate inhibition of this cytokine as a potential therapeutic approach, the study authors concluded.

The study was sponsored by Novartis Pharma. Dr. Baeten has received a grant from Novartis to study the impact of IL-17A blockade in experimental models of spondyloarthritis. He also has been a consultant for Novartis for the design and conduct of the secukinumab program in ankylosing spondylitis and psoriatic arthritis.

Secukinumab, an interleukin 17-A inhibitor approved for the treatment of moderate to severe psoriasis, significantly reduced the signs and symptoms of ankylosing spondylitis in two phase III trials, researchers reported Dec. 23 in the New England Journal of Medicine.

The results of the double-blind MEASURE 1 and MEASURE 2 trials extend the positive results of the phase II study, according to Dr. Dominique Baeten of the Academic Medical Center at the University of Amsterdam and his colleagues (N Engl J Med. 2015 Dec 23. doi: 10.1056/NEJMoa1505066).

“Although head-to-head trials would be required to fully assess the efficacy and safety of secukinumab versus TNF-inhibitors, the [20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria] response rates achieved with secukinumab at week 16 in our studies were similar to those reported in phase III studies of anti-TNF agents in which most of the patients had not received previous anti-TNF therapy (response rates of 58% to 64% at weeks 12 to 24), even though 30% to 40% of the patients in our studies had had no response to previous anti-TNF treatment,” the authors wrote.

“Thus, secukinumab not only is effective in patients who have not received TNF agents previously but also may be effective in patients in whom previous anti-TNF treatment failed,” they added.

In MEASURE 1, 371 patients received intravenous secukinumab (10 mg/kg of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8.

The study’s primary endpoint of ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively, (P less than .001 for both comparisons with placebo).

In MEASURE 2, 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4.

At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg.

In this trial, ASAS20 rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P less than .001 for the 150-mg dose and P = .10 for the 75-mg dose).

The researchers noted that the ineffectiveness of the 75-mg dose in MEASURE 2 suggests that the efficacy of secukinumab at the 75-mg dose in MEASURE 1 may have been due to the greater exposure at week 16 as a result of the intravenous loading regimen, not to the 75-mg subcutaneous maintenance dose.

The safety profile of secukinumab in the present studies was consistent with previous studies of secukinumab for ankylosing spondylitis and moderate-to-severe plaque psoriasis, Dr. Baeten and his associates said.

During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients.

Overall, the results suggest that interleukin-17A plays a role in the pathogenesis of ankylosing spondylitis, and they validate inhibition of this cytokine as a potential therapeutic approach, the study authors concluded.

The study was sponsored by Novartis Pharma. Dr. Baeten has received a grant from Novartis to study the impact of IL-17A blockade in experimental models of spondyloarthritis. He also has been a consultant for Novartis for the design and conduct of the secukinumab program in ankylosing spondylitis and psoriatic arthritis.