Visit the Society of Gynecologic Surgeons online: sgsonline.org

Related articles:  

• Alternative options for visualizing ureteral patency during intraoperative cystoscopy
• Use of suprapubic Carter-Thomason needle to assist in cystoscopic excision of an intravesical foreign object
• Uterine artery ligation: Advanced techniques and considerations for the difficult laparoscopic hysterectomy
• Cervical injection of methylene blue for identification of sentinel lymph nodes in cervical cancer
• Misplaced hysteroscopic sterilization micro-insert in the peritoneal cavity: A corpus alienum
• Laparoscopic cystectomy for large, bilateral ovarian dermoids
• Small bowel surgery for the benign gynecologist

Visit the Society of Gynecologic Surgeons online: sgsonline.org

Related articles:  

• Alternative options for visualizing ureteral patency during intraoperative cystoscopy
• Use of suprapubic Carter-Thomason needle to assist in cystoscopic excision of an intravesical foreign object
• Uterine artery ligation: Advanced techniques and considerations for the difficult laparoscopic hysterectomy
• Cervical injection of methylene blue for identification of sentinel lymph nodes in cervical cancer
• Misplaced hysteroscopic sterilization micro-insert in the peritoneal cavity: A corpus alienum
• Laparoscopic cystectomy for large, bilateral ovarian dermoids
• Small bowel surgery for the benign gynecologist

Visit the Society of Gynecologic Surgeons online: sgsonline.org

Related articles:  

• Alternative options for visualizing ureteral patency during intraoperative cystoscopy
• Use of suprapubic Carter-Thomason needle to assist in cystoscopic excision of an intravesical foreign object
• Uterine artery ligation: Advanced techniques and considerations for the difficult laparoscopic hysterectomy
• Cervical injection of methylene blue for identification of sentinel lymph nodes in cervical cancer
• Misplaced hysteroscopic sterilization micro-insert in the peritoneal cavity: A corpus alienum
• Laparoscopic cystectomy for large, bilateral ovarian dermoids
• Small bowel surgery for the benign gynecologist

NEWPORT BEACH, CALIF. – While off-label use of spironolactone for treatment of acne is quite common, it should be prescribed with special caution, advised Julie C. Harper, MD.

“The vast majority of you write this for acne,” Dr. Harper, a dermatologist in private practice in Birmingham, Ala., said during a presentation on adult acne at the Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

NEWPORT BEACH, CALIF. – While off-label use of spironolactone for treatment of acne is quite common, it should be prescribed with special caution, advised Julie C. Harper, MD.

“The vast majority of you write this for acne,” Dr. Harper, a dermatologist in private practice in Birmingham, Ala., said during a presentation on adult acne at the Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

NEWPORT BEACH, CALIF. – While off-label use of spironolactone for treatment of acne is quite common, it should be prescribed with special caution, advised Julie C. Harper, MD.

“The vast majority of you write this for acne,” Dr. Harper, a dermatologist in private practice in Birmingham, Ala., said during a presentation on adult acne at the Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

SHM is now accepting submissions for the Hospital Medicine 2017 (HM17) Research, Innovations, and Clinical Vignettes (RIV) abstract and poster competition. Seize the opportunity to present your research, innovative ideas, and clinical stories to a national audience at HM17, May 1–4, 2017, in Las Vegas. Learn more by visiting www.hospitalmedicine2017.org.

SHM strongly recommends that you complete your submission well ahead of the deadline of Monday, December 5, 2016. New to SHM? Registration for HM17 includes a complimentary one-year SHM membership. Register online prior to March 6, 2017, to receive the best registration rates.

SHM is now accepting submissions for the Hospital Medicine 2017 (HM17) Research, Innovations, and Clinical Vignettes (RIV) abstract and poster competition. Seize the opportunity to present your research, innovative ideas, and clinical stories to a national audience at HM17, May 1–4, 2017, in Las Vegas. Learn more by visiting www.hospitalmedicine2017.org.

SHM strongly recommends that you complete your submission well ahead of the deadline of Monday, December 5, 2016. New to SHM? Registration for HM17 includes a complimentary one-year SHM membership. Register online prior to March 6, 2017, to receive the best registration rates.

SHM is now accepting submissions for the Hospital Medicine 2017 (HM17) Research, Innovations, and Clinical Vignettes (RIV) abstract and poster competition. Seize the opportunity to present your research, innovative ideas, and clinical stories to a national audience at HM17, May 1–4, 2017, in Las Vegas. Learn more by visiting www.hospitalmedicine2017.org.

SHM strongly recommends that you complete your submission well ahead of the deadline of Monday, December 5, 2016. New to SHM? Registration for HM17 includes a complimentary one-year SHM membership. Register online prior to March 6, 2017, to receive the best registration rates.

The regular decision application is open through November 30, with a decision on or before December 31, 2016. Learn how you can join other hospitalists who have earned this exclusive designation and recognition at www.hospitalmedicine.org/fellows.

The regular decision application is open through November 30, with a decision on or before December 31, 2016. Learn how you can join other hospitalists who have earned this exclusive designation and recognition at www.hospitalmedicine.org/fellows.

The regular decision application is open through November 30, with a decision on or before December 31, 2016. Learn how you can join other hospitalists who have earned this exclusive designation and recognition at www.hospitalmedicine.org/fellows.

Syringes filled with Zarxio

(filgrastim-sndz), the first

biosimilar approved in the US

© Sandoz Inc. 2015

WASHINGTON, DC—A survey of roughly 1200 US physicians has revealed gaps in their knowledge about biosimilars.

The results showed that some physicians had difficulty defining biosimilars, did not fully understand how the US Food and Drug Administration (FDA) approves biosimilars, and may not know how to prescribe biosimilars appropriately.

The results were published in Advances in Therapy and presented at the DIA Biosimilars 2016 conference.

The 19-question survey was created by the Biosimilars Forum and conducted by SERMO, a global social network organization for physicians, from November 20, 2015, to January 4, 2016.

Responses were obtained from 1201 US physicians across specialties that are high prescribers of biologics, including hematologist-oncologists, dermatologists, gastroenterologists, medical oncologists, nephrologists, and rheumatologists.

Knowledge gaps

The survey revealed 5 major knowledge gaps regarding biosimilars:

1. Defining biologics, biosimilars, and biosimilarity¹
2. Understanding the approval process and the FDA’s use of “totality of evidence” to evaluate biosimilars
3. Understanding that the safety profile of a biosimilar is expected to be the same as that of the originator biologic
4. Understanding how decisions are made by the FDA for extrapolation² of indications
5. Defining interchangeability³ and the related rules regarding pharmacy-level substitution.

“With 4 biosimilars approved by the FDA and more than 60 in development, the survey highlights the need for greater biosimilars education for physicians and healthcare professionals,” said study author Hillel Cohen, PhD, executive director of scientific affairs at Sandoz Inc.

“Education will help physicians and healthcare professionals have a better understanding and knowledge of biosimilars so that they feel comfortable about administering biosimilars to patients when appropriate.”

FDA approval

Most of the physicians surveyed did not clearly understand the concept of extrapolation as applied to biosimilars. Only 12% of survey respondents said they trust extrapolation of the studied biosimilar indication(s) as the basis to obtain approval of other licensed indications of the originator product.

Almost 60% of respondents correctly understood that, to be approved as “interchangeable” with the originator, a biosimilar must be shown to be safe and effective for back-and-forth switching, with no negative impacts to safety or efficacy.

However, almost 80% of respondents did not agree, or potentially did not realize, that an FDA designation of “interchangeable” may enable a pharmacist to switch between the originator biologic and biosimilar and vice versa.

A little more than half of physicians surveyed knew that, for a biosimilar to be approved, the FDA must find the biosimilar to be equally effective (62.3%) and safe (57.2%) when compared to the originator biologic.

Most physicians surveyed (74.5%) said they trust the FDA’s biosimilar approval decisions.

Biosimilar use

Fewer than half of the survey respondents (44.8%) believed that biosimilars will be safe and appropriate for use in existing patients as well as naïve patients.

Overall, respondents expressed a general agreement that switching an existing patient to a biosimilar may be appropriate, with 9 in 10 (91%) saying they would consider switching a patient from an originator biologic to a biosimilar as an effective alternative to the originator if it would help the patient have better access to his/her medications.

In addition, 82.2% of respondents believed biosimilars will expand treatment options and provide savings to patients and the healthcare system.

“The Biosimilars Forum launched the Partnership for Biosimilar Education and Access to provide evidence-based education for healthcare professionals, patients, and the public,” Dr Cohen said. “The forum will use the survey results to provide education on the key concepts of biosimilars as we advance our mission to encourage awareness, access, and adoption of these important medicines.”

The Biosimilars Forum intends to conduct a similar survey in 2 to 3 years with the same design in order to monitor trends in the awareness, knowledge, and perceptions of biosimilars over time.

1. A biosimilar medicine is a biologic that is highly similar to an FDA-approved biological medicine, known as an originator biologic. A biosimilar must (1) be highly similar to the originator biologic, notwithstanding minor differences in clinically inactive components, and (2) have no clinically meaningful differences in safety or effectiveness compared to the originator biologic. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

2. Extrapolation is the process by which a biosimilar may be approved for one or more indications for which its reference biological product is licensed but for which there was no head-to-head clinical comparison. This approval is based on the extrapolation of the totality of data obtained with the biosimilar molecule in direct comparison to the originator biologic. Every indication for which extrapolation is sought must be scientifically justified. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

3. An interchangeable biologic is a biosimilar that has been demonstrated to produce the same clinical result as its originator biologic in any given patient. In addition, for a product that is administered multiple times to an individual, the risk in terms of safety or diminished efficacy of alternating between use of the interchangeable biologic and its originator biologic is not greater than the risk of using the originator biologic alone. Designation of interchangeability requires additional supporting evidence, which will be further defined by the FDA. An interchangeable biologic may be substituted by a pharmacist for the originator biologic or vice-versa without the intervention of the healthcare professional who wrote the prescription. State laws govern the substitution process, and communication to the healthcare provider who wrote the prescription may be required after the product is dispensed. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

Syringes filled with Zarxio

(filgrastim-sndz), the first

biosimilar approved in the US

© Sandoz Inc. 2015

WASHINGTON, DC—A survey of roughly 1200 US physicians has revealed gaps in their knowledge about biosimilars.

The results showed that some physicians had difficulty defining biosimilars, did not fully understand how the US Food and Drug Administration (FDA) approves biosimilars, and may not know how to prescribe biosimilars appropriately.

The results were published in Advances in Therapy and presented at the DIA Biosimilars 2016 conference.

The 19-question survey was created by the Biosimilars Forum and conducted by SERMO, a global social network organization for physicians, from November 20, 2015, to January 4, 2016.

Responses were obtained from 1201 US physicians across specialties that are high prescribers of biologics, including hematologist-oncologists, dermatologists, gastroenterologists, medical oncologists, nephrologists, and rheumatologists.

Knowledge gaps

The survey revealed 5 major knowledge gaps regarding biosimilars:

1. Defining biologics, biosimilars, and biosimilarity¹
2. Understanding the approval process and the FDA’s use of “totality of evidence” to evaluate biosimilars
3. Understanding that the safety profile of a biosimilar is expected to be the same as that of the originator biologic
4. Understanding how decisions are made by the FDA for extrapolation² of indications
5. Defining interchangeability³ and the related rules regarding pharmacy-level substitution.

“With 4 biosimilars approved by the FDA and more than 60 in development, the survey highlights the need for greater biosimilars education for physicians and healthcare professionals,” said study author Hillel Cohen, PhD, executive director of scientific affairs at Sandoz Inc.

“Education will help physicians and healthcare professionals have a better understanding and knowledge of biosimilars so that they feel comfortable about administering biosimilars to patients when appropriate.”

FDA approval

Most of the physicians surveyed did not clearly understand the concept of extrapolation as applied to biosimilars. Only 12% of survey respondents said they trust extrapolation of the studied biosimilar indication(s) as the basis to obtain approval of other licensed indications of the originator product.

Almost 60% of respondents correctly understood that, to be approved as “interchangeable” with the originator, a biosimilar must be shown to be safe and effective for back-and-forth switching, with no negative impacts to safety or efficacy.

However, almost 80% of respondents did not agree, or potentially did not realize, that an FDA designation of “interchangeable” may enable a pharmacist to switch between the originator biologic and biosimilar and vice versa.

A little more than half of physicians surveyed knew that, for a biosimilar to be approved, the FDA must find the biosimilar to be equally effective (62.3%) and safe (57.2%) when compared to the originator biologic.

Most physicians surveyed (74.5%) said they trust the FDA’s biosimilar approval decisions.

Biosimilar use

Fewer than half of the survey respondents (44.8%) believed that biosimilars will be safe and appropriate for use in existing patients as well as naïve patients.

Overall, respondents expressed a general agreement that switching an existing patient to a biosimilar may be appropriate, with 9 in 10 (91%) saying they would consider switching a patient from an originator biologic to a biosimilar as an effective alternative to the originator if it would help the patient have better access to his/her medications.

In addition, 82.2% of respondents believed biosimilars will expand treatment options and provide savings to patients and the healthcare system.

“The Biosimilars Forum launched the Partnership for Biosimilar Education and Access to provide evidence-based education for healthcare professionals, patients, and the public,” Dr Cohen said. “The forum will use the survey results to provide education on the key concepts of biosimilars as we advance our mission to encourage awareness, access, and adoption of these important medicines.”

The Biosimilars Forum intends to conduct a similar survey in 2 to 3 years with the same design in order to monitor trends in the awareness, knowledge, and perceptions of biosimilars over time.

1. A biosimilar medicine is a biologic that is highly similar to an FDA-approved biological medicine, known as an originator biologic. A biosimilar must (1) be highly similar to the originator biologic, notwithstanding minor differences in clinically inactive components, and (2) have no clinically meaningful differences in safety or effectiveness compared to the originator biologic. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

2. Extrapolation is the process by which a biosimilar may be approved for one or more indications for which its reference biological product is licensed but for which there was no head-to-head clinical comparison. This approval is based on the extrapolation of the totality of data obtained with the biosimilar molecule in direct comparison to the originator biologic. Every indication for which extrapolation is sought must be scientifically justified. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

3. An interchangeable biologic is a biosimilar that has been demonstrated to produce the same clinical result as its originator biologic in any given patient. In addition, for a product that is administered multiple times to an individual, the risk in terms of safety or diminished efficacy of alternating between use of the interchangeable biologic and its originator biologic is not greater than the risk of using the originator biologic alone. Designation of interchangeability requires additional supporting evidence, which will be further defined by the FDA. An interchangeable biologic may be substituted by a pharmacist for the originator biologic or vice-versa without the intervention of the healthcare professional who wrote the prescription. State laws govern the substitution process, and communication to the healthcare provider who wrote the prescription may be required after the product is dispensed. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

Syringes filled with Zarxio

(filgrastim-sndz), the first

biosimilar approved in the US

© Sandoz Inc. 2015

WASHINGTON, DC—A survey of roughly 1200 US physicians has revealed gaps in their knowledge about biosimilars.

The results showed that some physicians had difficulty defining biosimilars, did not fully understand how the US Food and Drug Administration (FDA) approves biosimilars, and may not know how to prescribe biosimilars appropriately.

The results were published in Advances in Therapy and presented at the DIA Biosimilars 2016 conference.

The 19-question survey was created by the Biosimilars Forum and conducted by SERMO, a global social network organization for physicians, from November 20, 2015, to January 4, 2016.

Responses were obtained from 1201 US physicians across specialties that are high prescribers of biologics, including hematologist-oncologists, dermatologists, gastroenterologists, medical oncologists, nephrologists, and rheumatologists.

Knowledge gaps

The survey revealed 5 major knowledge gaps regarding biosimilars:

1. Defining biologics, biosimilars, and biosimilarity¹
2. Understanding the approval process and the FDA’s use of “totality of evidence” to evaluate biosimilars
3. Understanding that the safety profile of a biosimilar is expected to be the same as that of the originator biologic
4. Understanding how decisions are made by the FDA for extrapolation² of indications
5. Defining interchangeability³ and the related rules regarding pharmacy-level substitution.

“With 4 biosimilars approved by the FDA and more than 60 in development, the survey highlights the need for greater biosimilars education for physicians and healthcare professionals,” said study author Hillel Cohen, PhD, executive director of scientific affairs at Sandoz Inc.

“Education will help physicians and healthcare professionals have a better understanding and knowledge of biosimilars so that they feel comfortable about administering biosimilars to patients when appropriate.”

FDA approval

Most of the physicians surveyed did not clearly understand the concept of extrapolation as applied to biosimilars. Only 12% of survey respondents said they trust extrapolation of the studied biosimilar indication(s) as the basis to obtain approval of other licensed indications of the originator product.

Almost 60% of respondents correctly understood that, to be approved as “interchangeable” with the originator, a biosimilar must be shown to be safe and effective for back-and-forth switching, with no negative impacts to safety or efficacy.

However, almost 80% of respondents did not agree, or potentially did not realize, that an FDA designation of “interchangeable” may enable a pharmacist to switch between the originator biologic and biosimilar and vice versa.

A little more than half of physicians surveyed knew that, for a biosimilar to be approved, the FDA must find the biosimilar to be equally effective (62.3%) and safe (57.2%) when compared to the originator biologic.

Most physicians surveyed (74.5%) said they trust the FDA’s biosimilar approval decisions.

Biosimilar use

Fewer than half of the survey respondents (44.8%) believed that biosimilars will be safe and appropriate for use in existing patients as well as naïve patients.

Overall, respondents expressed a general agreement that switching an existing patient to a biosimilar may be appropriate, with 9 in 10 (91%) saying they would consider switching a patient from an originator biologic to a biosimilar as an effective alternative to the originator if it would help the patient have better access to his/her medications.

In addition, 82.2% of respondents believed biosimilars will expand treatment options and provide savings to patients and the healthcare system.

“The Biosimilars Forum launched the Partnership for Biosimilar Education and Access to provide evidence-based education for healthcare professionals, patients, and the public,” Dr Cohen said. “The forum will use the survey results to provide education on the key concepts of biosimilars as we advance our mission to encourage awareness, access, and adoption of these important medicines.”

The Biosimilars Forum intends to conduct a similar survey in 2 to 3 years with the same design in order to monitor trends in the awareness, knowledge, and perceptions of biosimilars over time.

1. A biosimilar medicine is a biologic that is highly similar to an FDA-approved biological medicine, known as an originator biologic. A biosimilar must (1) be highly similar to the originator biologic, notwithstanding minor differences in clinically inactive components, and (2) have no clinically meaningful differences in safety or effectiveness compared to the originator biologic. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

2. Extrapolation is the process by which a biosimilar may be approved for one or more indications for which its reference biological product is licensed but for which there was no head-to-head clinical comparison. This approval is based on the extrapolation of the totality of data obtained with the biosimilar molecule in direct comparison to the originator biologic. Every indication for which extrapolation is sought must be scientifically justified. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

3. An interchangeable biologic is a biosimilar that has been demonstrated to produce the same clinical result as its originator biologic in any given patient. In addition, for a product that is administered multiple times to an individual, the risk in terms of safety or diminished efficacy of alternating between use of the interchangeable biologic and its originator biologic is not greater than the risk of using the originator biologic alone. Designation of interchangeability requires additional supporting evidence, which will be further defined by the FDA. An interchangeable biologic may be substituted by a pharmacist for the originator biologic or vice-versa without the intervention of the healthcare professional who wrote the prescription. State laws govern the substitution process, and communication to the healthcare provider who wrote the prescription may be required after the product is dispensed. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

Man living in the Ecuadorian

Andes who suffers from

chronic mountain sickness

Photo courtesy of

UC San Diego Health

Findings from a study of people living at high altitude have implications for the treatment of red blood cell (RBC) disorders such as anemia and polycythemia, according to researchers.

To better understand why some people adapt well to life at high altitude while others don’t, the researchers studied RBCs derived from representatives of both groups who were living in the Andes Mountains.

The study revealed that high-altitude dwellers prone to chronic mountain sickness produce massive amounts of RBCs thanks to overproduction of the enzyme SENP1.

The researchers reported these findings in the Journal of Experimental Medicine.

“In addition to improving the health of millions of people around the world who live above 8000 feet, information on how Andeans have adapted—or not adapted—to high-altitude life might teach us how to speed up red blood cell production at lower altitudes, such as in anemia or when blood transfusions are needed rapidly,” said study author Gabriel Haddad, MD, of the University of California San Diego School of Medicine.

Dr Haddad and his colleagues noted that chronic mountain sickness affects approximately 20% of people who live at high altitudes, and a critical aspect of the condition is polycythemia.

Some extra RBCs can be beneficial in high-altitude, low-oxygen environments by helping to keep blood oxygenated. However, too many RBCs can increase the risk of heart attack and stroke, even in young adults.

For this study, the researchers collected skin cells from people living in the Andes Mountains—4 who were healthy and 5 who suffer from chronic mountain sickness—plus an additional 3 healthy people who live at sea level and served as controls.

To produce enough RBCs from each participant to study them in the lab, the researchers converted the skin cells into induced pluripotent stem cells (iPSCs).

Then, adding a cocktail of growth factors and other molecules, the team coaxed the iPSCs to differentiate into RBCs. Multiple samples were tested for each person, for a total of at least 24 iPSC lines.

The researchers exposed the RBCs to low-oxygen conditions that mimic high altitude—5% oxygen—for 3 weeks.

RBCs from healthy sea-level or high-altitude-dwelling donors increased a little or not at all. In contrast, RBC counts from high-altitude dwellers with chronic mountain sickness increased 60-fold.

This result led the researchers to question why people with chronic mountain sickness produce so many extra RBCs in response to low oxygen.

In a previous study, the team had compared the genomes of high-altitude dwellers with and without chronic mountain sickness. This revealed a gene that varied between the 2 groups—SENP1, which is increased in low-oxygen situations in people with chronic mountain sickness but not in healthy individuals.

In the current study, the researchers set out to determine if SENP1 plays a role in high-altitude adaptation.

The team inhibited the SENP1 gene in iPSCs from patients with chronic mountain sickness. As a result, excessive RBC production was reduced by more than 90%.

When the researchers added extra SENP1 to healthy, adapted highlander iPSCs, RBC production increased 30-fold, nearly recapitulating that seen in patients with chronic mountains sickness.

Further experiments revealed how SENP1 affects RBC production. Elevated levels of the enzyme in chronic mountain sickness boost levels of several other proteins that promote cell division and survival, including VEGF, GATA1, and Bcl-xL.

“We’re interested in determining the early steps in this process—how low oxygen triggers SENP1 in the first place,” said study author Priti Azad, PhD, of the University of California San Diego School of Medicine.

“We are also investigating how existing altitude sickness medications, such as Diamox, work and whether or not it’s through this same mechanism.”

Man living in the Ecuadorian

Andes who suffers from

chronic mountain sickness

Photo courtesy of

UC San Diego Health

Findings from a study of people living at high altitude have implications for the treatment of red blood cell (RBC) disorders such as anemia and polycythemia, according to researchers.

To better understand why some people adapt well to life at high altitude while others don’t, the researchers studied RBCs derived from representatives of both groups who were living in the Andes Mountains.

The study revealed that high-altitude dwellers prone to chronic mountain sickness produce massive amounts of RBCs thanks to overproduction of the enzyme SENP1.

The researchers reported these findings in the Journal of Experimental Medicine.

“In addition to improving the health of millions of people around the world who live above 8000 feet, information on how Andeans have adapted—or not adapted—to high-altitude life might teach us how to speed up red blood cell production at lower altitudes, such as in anemia or when blood transfusions are needed rapidly,” said study author Gabriel Haddad, MD, of the University of California San Diego School of Medicine.

Dr Haddad and his colleagues noted that chronic mountain sickness affects approximately 20% of people who live at high altitudes, and a critical aspect of the condition is polycythemia.

Some extra RBCs can be beneficial in high-altitude, low-oxygen environments by helping to keep blood oxygenated. However, too many RBCs can increase the risk of heart attack and stroke, even in young adults.

For this study, the researchers collected skin cells from people living in the Andes Mountains—4 who were healthy and 5 who suffer from chronic mountain sickness—plus an additional 3 healthy people who live at sea level and served as controls.

To produce enough RBCs from each participant to study them in the lab, the researchers converted the skin cells into induced pluripotent stem cells (iPSCs).

Then, adding a cocktail of growth factors and other molecules, the team coaxed the iPSCs to differentiate into RBCs. Multiple samples were tested for each person, for a total of at least 24 iPSC lines.

The researchers exposed the RBCs to low-oxygen conditions that mimic high altitude—5% oxygen—for 3 weeks.

RBCs from healthy sea-level or high-altitude-dwelling donors increased a little or not at all. In contrast, RBC counts from high-altitude dwellers with chronic mountain sickness increased 60-fold.

This result led the researchers to question why people with chronic mountain sickness produce so many extra RBCs in response to low oxygen.

In a previous study, the team had compared the genomes of high-altitude dwellers with and without chronic mountain sickness. This revealed a gene that varied between the 2 groups—SENP1, which is increased in low-oxygen situations in people with chronic mountain sickness but not in healthy individuals.

In the current study, the researchers set out to determine if SENP1 plays a role in high-altitude adaptation.

The team inhibited the SENP1 gene in iPSCs from patients with chronic mountain sickness. As a result, excessive RBC production was reduced by more than 90%.

When the researchers added extra SENP1 to healthy, adapted highlander iPSCs, RBC production increased 30-fold, nearly recapitulating that seen in patients with chronic mountains sickness.

Further experiments revealed how SENP1 affects RBC production. Elevated levels of the enzyme in chronic mountain sickness boost levels of several other proteins that promote cell division and survival, including VEGF, GATA1, and Bcl-xL.

“We’re interested in determining the early steps in this process—how low oxygen triggers SENP1 in the first place,” said study author Priti Azad, PhD, of the University of California San Diego School of Medicine.

“We are also investigating how existing altitude sickness medications, such as Diamox, work and whether or not it’s through this same mechanism.”

Man living in the Ecuadorian

Andes who suffers from

chronic mountain sickness

Photo courtesy of

UC San Diego Health

Findings from a study of people living at high altitude have implications for the treatment of red blood cell (RBC) disorders such as anemia and polycythemia, according to researchers.

To better understand why some people adapt well to life at high altitude while others don’t, the researchers studied RBCs derived from representatives of both groups who were living in the Andes Mountains.

The study revealed that high-altitude dwellers prone to chronic mountain sickness produce massive amounts of RBCs thanks to overproduction of the enzyme SENP1.

The researchers reported these findings in the Journal of Experimental Medicine.

“In addition to improving the health of millions of people around the world who live above 8000 feet, information on how Andeans have adapted—or not adapted—to high-altitude life might teach us how to speed up red blood cell production at lower altitudes, such as in anemia or when blood transfusions are needed rapidly,” said study author Gabriel Haddad, MD, of the University of California San Diego School of Medicine.

Dr Haddad and his colleagues noted that chronic mountain sickness affects approximately 20% of people who live at high altitudes, and a critical aspect of the condition is polycythemia.

Some extra RBCs can be beneficial in high-altitude, low-oxygen environments by helping to keep blood oxygenated. However, too many RBCs can increase the risk of heart attack and stroke, even in young adults.

For this study, the researchers collected skin cells from people living in the Andes Mountains—4 who were healthy and 5 who suffer from chronic mountain sickness—plus an additional 3 healthy people who live at sea level and served as controls.

To produce enough RBCs from each participant to study them in the lab, the researchers converted the skin cells into induced pluripotent stem cells (iPSCs).

Then, adding a cocktail of growth factors and other molecules, the team coaxed the iPSCs to differentiate into RBCs. Multiple samples were tested for each person, for a total of at least 24 iPSC lines.

The researchers exposed the RBCs to low-oxygen conditions that mimic high altitude—5% oxygen—for 3 weeks.

RBCs from healthy sea-level or high-altitude-dwelling donors increased a little or not at all. In contrast, RBC counts from high-altitude dwellers with chronic mountain sickness increased 60-fold.

This result led the researchers to question why people with chronic mountain sickness produce so many extra RBCs in response to low oxygen.

In a previous study, the team had compared the genomes of high-altitude dwellers with and without chronic mountain sickness. This revealed a gene that varied between the 2 groups—SENP1, which is increased in low-oxygen situations in people with chronic mountain sickness but not in healthy individuals.

In the current study, the researchers set out to determine if SENP1 plays a role in high-altitude adaptation.

The team inhibited the SENP1 gene in iPSCs from patients with chronic mountain sickness. As a result, excessive RBC production was reduced by more than 90%.

When the researchers added extra SENP1 to healthy, adapted highlander iPSCs, RBC production increased 30-fold, nearly recapitulating that seen in patients with chronic mountains sickness.

Further experiments revealed how SENP1 affects RBC production. Elevated levels of the enzyme in chronic mountain sickness boost levels of several other proteins that promote cell division and survival, including VEGF, GATA1, and Bcl-xL.

“We’re interested in determining the early steps in this process—how low oxygen triggers SENP1 in the first place,” said study author Priti Azad, PhD, of the University of California San Diego School of Medicine.

“We are also investigating how existing altitude sickness medications, such as Diamox, work and whether or not it’s through this same mechanism.”

CMV infection

NEW ORLEANS—The antiviral agent maribavir has shown activity against cytomegalovirus (CMV) in a phase 2 trial.

The trial included transplant recipients with a CMV infection that was resistant or refractory to prior treatment with (val)ganciclovir or foscarnet.

Sixty-seven percent of patients treated with varying doses of maribavir for up to 24 weeks had no detectable levels of CMV in their plasma within 6 weeks of starting treatment.

However, CMV infection did recur in some of these patients.

Dysgeusia was the most commonly reported treatment-emergent adverse event (AE), and one patient died of an AE that was considered possibly related to maribavir.

These results were presented at IDWeek 2016 (abstract 78). The study was sponsored by Shire.

“Cytomegalovirus infection that is resistant or refractory to standard therapy in transplant patients is associated with significant complications and high mortality,” said study investigator Genovefa Papanicolaou, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.

“The phase 2 findings support further research to confirm these results among patients who have limited options to combat the infection.”

Maribavir is a member of a class of drugs called benzimidazole ribosides. Maribavir is thought to inhibit viral DNA assembly and egress of viral capsids from the nucleus of infected cells. The drug has not been shown to affect the maturation of viral DNA or affect the viral DNA polymerase.

This phase 2 study of maribavir included 120 patients ages 12 and older with CMV infection (≥1000 DNA copies/mL of blood plasma) that was resistant or refractory to (val)ganciclovir or foscarnet.

Forty-seven of the patients had received a hematopoietic stem cell transplant, and 73 had a solid organ transplant. The patients’ median age was 55 (range, 18 to 74).

The patients were randomized to 1 of 3 twice-daily oral doses of maribavir—400 mg, 800 mg, or 1200 mg—for up to 24 weeks of treatment.

Efficacy

The study’s primary efficacy endpoint was the proportion of patients with confirmed undetectable plasma CMV DNA within 6 weeks of treatment.

Overall, 67% (80/120) of patients met the primary efficacy endpoint. This included 70% (n=28) of patients in the 400 mg group, 63% (n=25) in the 800 mg group, and 67% (n=27) in the 1200 mg group.

CMV infection recurred in 30 patients, including 7 in the 400 mg group, 11 in the 800 mg group, and 12 in the 1200 mg group.

Safety

The primary safety analysis was focused on the incidence of treatment-emergent AEs. The incidence was 78% (n=93) overall, including 78% (n=31) in the 400 mg group, 80% (n=32) in the 800 mg group, and 75% (n=30) in the 1200 mg group.

Twenty-seven percent of patients died due to any AE, 1 of which (multi-organ failure) was considered possibly related to maribavir.

Forty-one patients (34%) discontinued treatment with maribavir due to an AE, including 17 patients who discontinued due to CMV infection.

Dysgeusia was the most common treatment-emergent AE and led to treatment discontinuation in 1 patient. Dysgeusia occurred in 65% (n=78) of all patients, including 60% (n=24) in the 400 mg group, 63% (n=25) in the 800 mg group, and 73% (n=29) in the 1200 mg group.

Other treatment-emergent AEs (occurring in at least 20% of patients) for all doses included nausea, vomiting, CMV infection, diarrhea, fatigue, and anemia. Immunosuppressant drug level increases were reported as an AE in 10% of all patients.

CMV infection

NEW ORLEANS—The antiviral agent maribavir has shown activity against cytomegalovirus (CMV) in a phase 2 trial.

The trial included transplant recipients with a CMV infection that was resistant or refractory to prior treatment with (val)ganciclovir or foscarnet.

Sixty-seven percent of patients treated with varying doses of maribavir for up to 24 weeks had no detectable levels of CMV in their plasma within 6 weeks of starting treatment.

However, CMV infection did recur in some of these patients.

Dysgeusia was the most commonly reported treatment-emergent adverse event (AE), and one patient died of an AE that was considered possibly related to maribavir.

These results were presented at IDWeek 2016 (abstract 78). The study was sponsored by Shire.

“Cytomegalovirus infection that is resistant or refractory to standard therapy in transplant patients is associated with significant complications and high mortality,” said study investigator Genovefa Papanicolaou, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.

“The phase 2 findings support further research to confirm these results among patients who have limited options to combat the infection.”

Maribavir is a member of a class of drugs called benzimidazole ribosides. Maribavir is thought to inhibit viral DNA assembly and egress of viral capsids from the nucleus of infected cells. The drug has not been shown to affect the maturation of viral DNA or affect the viral DNA polymerase.

This phase 2 study of maribavir included 120 patients ages 12 and older with CMV infection (≥1000 DNA copies/mL of blood plasma) that was resistant or refractory to (val)ganciclovir or foscarnet.

Forty-seven of the patients had received a hematopoietic stem cell transplant, and 73 had a solid organ transplant. The patients’ median age was 55 (range, 18 to 74).

The patients were randomized to 1 of 3 twice-daily oral doses of maribavir—400 mg, 800 mg, or 1200 mg—for up to 24 weeks of treatment.

Efficacy

The study’s primary efficacy endpoint was the proportion of patients with confirmed undetectable plasma CMV DNA within 6 weeks of treatment.

Overall, 67% (80/120) of patients met the primary efficacy endpoint. This included 70% (n=28) of patients in the 400 mg group, 63% (n=25) in the 800 mg group, and 67% (n=27) in the 1200 mg group.

CMV infection recurred in 30 patients, including 7 in the 400 mg group, 11 in the 800 mg group, and 12 in the 1200 mg group.

Safety

The primary safety analysis was focused on the incidence of treatment-emergent AEs. The incidence was 78% (n=93) overall, including 78% (n=31) in the 400 mg group, 80% (n=32) in the 800 mg group, and 75% (n=30) in the 1200 mg group.

Twenty-seven percent of patients died due to any AE, 1 of which (multi-organ failure) was considered possibly related to maribavir.

Forty-one patients (34%) discontinued treatment with maribavir due to an AE, including 17 patients who discontinued due to CMV infection.

Dysgeusia was the most common treatment-emergent AE and led to treatment discontinuation in 1 patient. Dysgeusia occurred in 65% (n=78) of all patients, including 60% (n=24) in the 400 mg group, 63% (n=25) in the 800 mg group, and 73% (n=29) in the 1200 mg group.

Other treatment-emergent AEs (occurring in at least 20% of patients) for all doses included nausea, vomiting, CMV infection, diarrhea, fatigue, and anemia. Immunosuppressant drug level increases were reported as an AE in 10% of all patients.

CMV infection

NEW ORLEANS—The antiviral agent maribavir has shown activity against cytomegalovirus (CMV) in a phase 2 trial.

The trial included transplant recipients with a CMV infection that was resistant or refractory to prior treatment with (val)ganciclovir or foscarnet.

Sixty-seven percent of patients treated with varying doses of maribavir for up to 24 weeks had no detectable levels of CMV in their plasma within 6 weeks of starting treatment.

However, CMV infection did recur in some of these patients.

Dysgeusia was the most commonly reported treatment-emergent adverse event (AE), and one patient died of an AE that was considered possibly related to maribavir.

These results were presented at IDWeek 2016 (abstract 78). The study was sponsored by Shire.

“Cytomegalovirus infection that is resistant or refractory to standard therapy in transplant patients is associated with significant complications and high mortality,” said study investigator Genovefa Papanicolaou, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.

“The phase 2 findings support further research to confirm these results among patients who have limited options to combat the infection.”

Maribavir is a member of a class of drugs called benzimidazole ribosides. Maribavir is thought to inhibit viral DNA assembly and egress of viral capsids from the nucleus of infected cells. The drug has not been shown to affect the maturation of viral DNA or affect the viral DNA polymerase.

This phase 2 study of maribavir included 120 patients ages 12 and older with CMV infection (≥1000 DNA copies/mL of blood plasma) that was resistant or refractory to (val)ganciclovir or foscarnet.

Forty-seven of the patients had received a hematopoietic stem cell transplant, and 73 had a solid organ transplant. The patients’ median age was 55 (range, 18 to 74).

The patients were randomized to 1 of 3 twice-daily oral doses of maribavir—400 mg, 800 mg, or 1200 mg—for up to 24 weeks of treatment.

Efficacy

The study’s primary efficacy endpoint was the proportion of patients with confirmed undetectable plasma CMV DNA within 6 weeks of treatment.

Overall, 67% (80/120) of patients met the primary efficacy endpoint. This included 70% (n=28) of patients in the 400 mg group, 63% (n=25) in the 800 mg group, and 67% (n=27) in the 1200 mg group.

CMV infection recurred in 30 patients, including 7 in the 400 mg group, 11 in the 800 mg group, and 12 in the 1200 mg group.

Safety

The primary safety analysis was focused on the incidence of treatment-emergent AEs. The incidence was 78% (n=93) overall, including 78% (n=31) in the 400 mg group, 80% (n=32) in the 800 mg group, and 75% (n=30) in the 1200 mg group.

Twenty-seven percent of patients died due to any AE, 1 of which (multi-organ failure) was considered possibly related to maribavir.

Forty-one patients (34%) discontinued treatment with maribavir due to an AE, including 17 patients who discontinued due to CMV infection.

Dysgeusia was the most common treatment-emergent AE and led to treatment discontinuation in 1 patient. Dysgeusia occurred in 65% (n=78) of all patients, including 60% (n=24) in the 400 mg group, 63% (n=25) in the 800 mg group, and 73% (n=29) in the 1200 mg group.

Other treatment-emergent AEs (occurring in at least 20% of patients) for all doses included nausea, vomiting, CMV infection, diarrhea, fatigue, and anemia. Immunosuppressant drug level increases were reported as an AE in 10% of all patients.

Nivolumab (Opdivo)

Photo from Business Wire

COLOGNE—Results from the CheckMate -205 study suggest nivolumab can produce a high objective response rate (ORR) in patients with heavily pretreated classical Hodgkin lymphoma (cHL).

Investigators recently presented results from one of the cohorts in this phase 2 trial—cohort C—which included cHL patients who received nivolumab after undergoing autologous hematopoietic stem cell transplant (auto-HSCT) and receiving treatment with brentuximab vedotin (BV).

At a median follow-up of 8.8 months, the ORR, as assessed by an independent radiologic review committee (IRRC), was 73%.

The median progression-free survival (PFS) was 11.2 months, and the 6-month overall survival (OS) was 94%.

Investigators said the safety profile of nivolumab in this patient population was consistent with previously reported data in patients with cHL, and no new clinically meaningful safety signals were identified.

“These data from cohort C build on existing evidence supporting the benefit of Opdivo [nivolumab] in classical Hodgkin lymphoma patients who have relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin,” said investigator Andreas Engert, MD, of the University Hospital of Cologne in Germany.

“Results from cohort C indicated a benefit with Opdivo regardless of the order of prior treatment with autologous hematopoietic stem cell transplantation and brentuximab vedotin, providing important insights as we continue researching the potential role Opdivo could provide for heavily pretreated classical Hodgkin lymphoma patients.”

The results were presented at the 10th International Symposium on Hodgkin Lymphoma (abstract T022). Abstracts from this meeting have been published in haematologica.

The CheckMate -205 trial is sponsored by Bristol-Myers Squibb.

About the trial

CheckMate -205 is a multi-cohort study in which investigators are evaluating the safety and efficacy of nivolumab in adults with cHL.

Cohort A included cHL patients who had received auto-HSCT and were BV-naïve (n=63). Cohort B included cHL patients who had received auto-HSCT followed by BV (n=80).

Cohort C included cHL patients who had received BV before and/or after auto-HSCT (n=100).

The study also includes a cohort D, which is currently enrolling and evaluating nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Patients enrolled in this trial have received nivolumab at 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity. In cohort C, patients were also treated until investigator-assessed complete response (CR) lasting 1 year.

The study’s primary endpoint was ORR by IRRC assessment. Secondary and other exploratory endpoints included duration of response by IRRC assessment for CR rate and partial response rate, PFS by IRRC assessment, OS, and safety.

Response

The investigators presented results from cohort C (n=100), which included patients with cHL who had received BV before and/or after auto-HSCT.

At a median follow-up of 8.8 months, ORR per the IRRC was 73% (n=73) overall. The investigators said ORR was consistent across patient subgroups, regardless of the timing of prior BV relative to auto-HSCT.

The ORR was 70% (n=23) in patients who received BV only before auto-HSCT, 72% (n=41) in patients who received BV only after auto-HSCT, and 88% (n=7) in patients who received BV before and after auto-HSCT.

The CR rate was 17% (n=17) overall, 18.2% (n=6) in patients who received BV only before auto-HSCT, 12.3% (n=7) in patients who received BV only after auto-HSCT, and 38% (n=3) in patients who received BV before and after auto-HSCT.

Survival

The median PFS was 11.2 months (range, 8.5 months to not achieved) overall, 11.2 months (range, 8.5 months to not achieved) in patients who received BV only before auto-HSCT, 8.9 months (range, 8.3 months to not achieved) in patients who received BV only after auto-HSCT, and not achieved (range, 5.6 months to not achieved) in patients who received BV before and after auto-HSCT.

The 6-month OS was 93.9% overall, 97% in patients who received BV only before auto-HSCT, 91% in patients who received BV only after auto-HSCT, and 100% in patients who received BV before and after auto-HSCT.

Safety

Treatment-related adverse events (AEs) occurred in 68% of patients between the first dose and 30 days after the last dose of nivolumab. The most common treatment-related AEs were diarrhea, infusion-related reaction, and fatigue (11% each).

Grade 3/4 AEs occurred in 19% of patients. Serious treatment-related AEs were reported in 17% of patients, and treatment-related AEs leading to discontinuation occurred in 6% of patients.

At present, no treatment-related deaths have been reported.

Nivolumab (Opdivo)

Photo from Business Wire

COLOGNE—Results from the CheckMate -205 study suggest nivolumab can produce a high objective response rate (ORR) in patients with heavily pretreated classical Hodgkin lymphoma (cHL).

Investigators recently presented results from one of the cohorts in this phase 2 trial—cohort C—which included cHL patients who received nivolumab after undergoing autologous hematopoietic stem cell transplant (auto-HSCT) and receiving treatment with brentuximab vedotin (BV).

At a median follow-up of 8.8 months, the ORR, as assessed by an independent radiologic review committee (IRRC), was 73%.

The median progression-free survival (PFS) was 11.2 months, and the 6-month overall survival (OS) was 94%.

Investigators said the safety profile of nivolumab in this patient population was consistent with previously reported data in patients with cHL, and no new clinically meaningful safety signals were identified.

“These data from cohort C build on existing evidence supporting the benefit of Opdivo [nivolumab] in classical Hodgkin lymphoma patients who have relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin,” said investigator Andreas Engert, MD, of the University Hospital of Cologne in Germany.

“Results from cohort C indicated a benefit with Opdivo regardless of the order of prior treatment with autologous hematopoietic stem cell transplantation and brentuximab vedotin, providing important insights as we continue researching the potential role Opdivo could provide for heavily pretreated classical Hodgkin lymphoma patients.”

The results were presented at the 10th International Symposium on Hodgkin Lymphoma (abstract T022). Abstracts from this meeting have been published in haematologica.

The CheckMate -205 trial is sponsored by Bristol-Myers Squibb.

About the trial

CheckMate -205 is a multi-cohort study in which investigators are evaluating the safety and efficacy of nivolumab in adults with cHL.

Cohort A included cHL patients who had received auto-HSCT and were BV-naïve (n=63). Cohort B included cHL patients who had received auto-HSCT followed by BV (n=80).

Cohort C included cHL patients who had received BV before and/or after auto-HSCT (n=100).

The study also includes a cohort D, which is currently enrolling and evaluating nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Patients enrolled in this trial have received nivolumab at 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity. In cohort C, patients were also treated until investigator-assessed complete response (CR) lasting 1 year.

The study’s primary endpoint was ORR by IRRC assessment. Secondary and other exploratory endpoints included duration of response by IRRC assessment for CR rate and partial response rate, PFS by IRRC assessment, OS, and safety.

Response

The investigators presented results from cohort C (n=100), which included patients with cHL who had received BV before and/or after auto-HSCT.

At a median follow-up of 8.8 months, ORR per the IRRC was 73% (n=73) overall. The investigators said ORR was consistent across patient subgroups, regardless of the timing of prior BV relative to auto-HSCT.

The ORR was 70% (n=23) in patients who received BV only before auto-HSCT, 72% (n=41) in patients who received BV only after auto-HSCT, and 88% (n=7) in patients who received BV before and after auto-HSCT.

The CR rate was 17% (n=17) overall, 18.2% (n=6) in patients who received BV only before auto-HSCT, 12.3% (n=7) in patients who received BV only after auto-HSCT, and 38% (n=3) in patients who received BV before and after auto-HSCT.

Survival

The median PFS was 11.2 months (range, 8.5 months to not achieved) overall, 11.2 months (range, 8.5 months to not achieved) in patients who received BV only before auto-HSCT, 8.9 months (range, 8.3 months to not achieved) in patients who received BV only after auto-HSCT, and not achieved (range, 5.6 months to not achieved) in patients who received BV before and after auto-HSCT.

The 6-month OS was 93.9% overall, 97% in patients who received BV only before auto-HSCT, 91% in patients who received BV only after auto-HSCT, and 100% in patients who received BV before and after auto-HSCT.

Safety

Treatment-related adverse events (AEs) occurred in 68% of patients between the first dose and 30 days after the last dose of nivolumab. The most common treatment-related AEs were diarrhea, infusion-related reaction, and fatigue (11% each).

Grade 3/4 AEs occurred in 19% of patients. Serious treatment-related AEs were reported in 17% of patients, and treatment-related AEs leading to discontinuation occurred in 6% of patients.

At present, no treatment-related deaths have been reported.

Nivolumab (Opdivo)

Photo from Business Wire

COLOGNE—Results from the CheckMate -205 study suggest nivolumab can produce a high objective response rate (ORR) in patients with heavily pretreated classical Hodgkin lymphoma (cHL).

Investigators recently presented results from one of the cohorts in this phase 2 trial—cohort C—which included cHL patients who received nivolumab after undergoing autologous hematopoietic stem cell transplant (auto-HSCT) and receiving treatment with brentuximab vedotin (BV).

At a median follow-up of 8.8 months, the ORR, as assessed by an independent radiologic review committee (IRRC), was 73%.

The median progression-free survival (PFS) was 11.2 months, and the 6-month overall survival (OS) was 94%.

Investigators said the safety profile of nivolumab in this patient population was consistent with previously reported data in patients with cHL, and no new clinically meaningful safety signals were identified.

“These data from cohort C build on existing evidence supporting the benefit of Opdivo [nivolumab] in classical Hodgkin lymphoma patients who have relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin,” said investigator Andreas Engert, MD, of the University Hospital of Cologne in Germany.

“Results from cohort C indicated a benefit with Opdivo regardless of the order of prior treatment with autologous hematopoietic stem cell transplantation and brentuximab vedotin, providing important insights as we continue researching the potential role Opdivo could provide for heavily pretreated classical Hodgkin lymphoma patients.”

The results were presented at the 10th International Symposium on Hodgkin Lymphoma (abstract T022). Abstracts from this meeting have been published in haematologica.

The CheckMate -205 trial is sponsored by Bristol-Myers Squibb.

About the trial

CheckMate -205 is a multi-cohort study in which investigators are evaluating the safety and efficacy of nivolumab in adults with cHL.

Cohort A included cHL patients who had received auto-HSCT and were BV-naïve (n=63). Cohort B included cHL patients who had received auto-HSCT followed by BV (n=80).

Cohort C included cHL patients who had received BV before and/or after auto-HSCT (n=100).

The study also includes a cohort D, which is currently enrolling and evaluating nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Patients enrolled in this trial have received nivolumab at 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity. In cohort C, patients were also treated until investigator-assessed complete response (CR) lasting 1 year.

The study’s primary endpoint was ORR by IRRC assessment. Secondary and other exploratory endpoints included duration of response by IRRC assessment for CR rate and partial response rate, PFS by IRRC assessment, OS, and safety.

Response

The investigators presented results from cohort C (n=100), which included patients with cHL who had received BV before and/or after auto-HSCT.

At a median follow-up of 8.8 months, ORR per the IRRC was 73% (n=73) overall. The investigators said ORR was consistent across patient subgroups, regardless of the timing of prior BV relative to auto-HSCT.

The ORR was 70% (n=23) in patients who received BV only before auto-HSCT, 72% (n=41) in patients who received BV only after auto-HSCT, and 88% (n=7) in patients who received BV before and after auto-HSCT.

The CR rate was 17% (n=17) overall, 18.2% (n=6) in patients who received BV only before auto-HSCT, 12.3% (n=7) in patients who received BV only after auto-HSCT, and 38% (n=3) in patients who received BV before and after auto-HSCT.

Survival

The median PFS was 11.2 months (range, 8.5 months to not achieved) overall, 11.2 months (range, 8.5 months to not achieved) in patients who received BV only before auto-HSCT, 8.9 months (range, 8.3 months to not achieved) in patients who received BV only after auto-HSCT, and not achieved (range, 5.6 months to not achieved) in patients who received BV before and after auto-HSCT.

The 6-month OS was 93.9% overall, 97% in patients who received BV only before auto-HSCT, 91% in patients who received BV only after auto-HSCT, and 100% in patients who received BV before and after auto-HSCT.

Safety

Treatment-related adverse events (AEs) occurred in 68% of patients between the first dose and 30 days after the last dose of nivolumab. The most common treatment-related AEs were diarrhea, infusion-related reaction, and fatigue (11% each).

Grade 3/4 AEs occurred in 19% of patients. Serious treatment-related AEs were reported in 17% of patients, and treatment-related AEs leading to discontinuation occurred in 6% of patients.

At present, no treatment-related deaths have been reported.

Each year about 37,000 people get potentially deadly bloodstream infections related to dialysis. But those infections could be cut dramatically by implementing evidence-based recommendations, the CDC says. For several years, facilities that have followed CDC recommendations have successfully reduced bloodstream infections in dialysis patients. "Making evidence-based safety steps a routine part of patient care is a proven strategy to keep dialysis patients safe from bloodstream infections," said CDC Director Tom Frieden, MD, MPH.

Related: Needlesticks and Infections: Still Not Enough Information

The CDC is teaming up with a coalition of health care and patient advocacy organizations and other public health partners in the Making Dialysis Safer for Patients Coalition, an initiative to expand the use of the recommendations and tools to improve dialysis patient safety.

The coalition will promote the use of the CDC’s Core Interventions and provide facilities with resources, including patient and staff education materials with tips to prevent infection; protocols for dialysis facilities; dialysis audit tools and checklists on, for example, catheter care; and videos and DVDs on best practices.

Related: Hospital-Acquired Infections on the Decline

“Dialysis patients are particularly vulnerable to infections,” said Dr. Priti Patel, medical director of the coalition. “We want to get lifesaving tools into the right hands to make a real impact on patients’ lives.”

Each year about 37,000 people get potentially deadly bloodstream infections related to dialysis. But those infections could be cut dramatically by implementing evidence-based recommendations, the CDC says. For several years, facilities that have followed CDC recommendations have successfully reduced bloodstream infections in dialysis patients. "Making evidence-based safety steps a routine part of patient care is a proven strategy to keep dialysis patients safe from bloodstream infections," said CDC Director Tom Frieden, MD, MPH.

Related: Needlesticks and Infections: Still Not Enough Information

The CDC is teaming up with a coalition of health care and patient advocacy organizations and other public health partners in the Making Dialysis Safer for Patients Coalition, an initiative to expand the use of the recommendations and tools to improve dialysis patient safety.

The coalition will promote the use of the CDC’s Core Interventions and provide facilities with resources, including patient and staff education materials with tips to prevent infection; protocols for dialysis facilities; dialysis audit tools and checklists on, for example, catheter care; and videos and DVDs on best practices.

Related: Hospital-Acquired Infections on the Decline

“Dialysis patients are particularly vulnerable to infections,” said Dr. Priti Patel, medical director of the coalition. “We want to get lifesaving tools into the right hands to make a real impact on patients’ lives.”

Each year about 37,000 people get potentially deadly bloodstream infections related to dialysis. But those infections could be cut dramatically by implementing evidence-based recommendations, the CDC says. For several years, facilities that have followed CDC recommendations have successfully reduced bloodstream infections in dialysis patients. "Making evidence-based safety steps a routine part of patient care is a proven strategy to keep dialysis patients safe from bloodstream infections," said CDC Director Tom Frieden, MD, MPH.

Related: Needlesticks and Infections: Still Not Enough Information

The CDC is teaming up with a coalition of health care and patient advocacy organizations and other public health partners in the Making Dialysis Safer for Patients Coalition, an initiative to expand the use of the recommendations and tools to improve dialysis patient safety.

The coalition will promote the use of the CDC’s Core Interventions and provide facilities with resources, including patient and staff education materials with tips to prevent infection; protocols for dialysis facilities; dialysis audit tools and checklists on, for example, catheter care; and videos and DVDs on best practices.

Related: Hospital-Acquired Infections on the Decline

“Dialysis patients are particularly vulnerable to infections,” said Dr. Priti Patel, medical director of the coalition. “We want to get lifesaving tools into the right hands to make a real impact on patients’ lives.”

ANSWER

The radiograph does not demonstrate any evidence of acute chest or intrathoracic injury. Of note, it appears that the left humerus is dislocated anteriorly and inferiorly.

Dedicated shoulder radiographs were obtained, which confirmed the dislocation with no evidence of fracture. Orthopedics was consulted for evaluation and subsequent reduction.

ANSWER

The radiograph does not demonstrate any evidence of acute chest or intrathoracic injury. Of note, it appears that the left humerus is dislocated anteriorly and inferiorly.

Dedicated shoulder radiographs were obtained, which confirmed the dislocation with no evidence of fracture. Orthopedics was consulted for evaluation and subsequent reduction.

ANSWER

The radiograph does not demonstrate any evidence of acute chest or intrathoracic injury. Of note, it appears that the left humerus is dislocated anteriorly and inferiorly.

Dedicated shoulder radiographs were obtained, which confirmed the dislocation with no evidence of fracture. Orthopedics was consulted for evaluation and subsequent reduction.