Study Overview

Objective. To determine whether the administration of betamethasone to women who are likely to deliver in the late preterm period would decrease respiratory and other neonatal complications.

Design. Randomized controlled trial.

Setting and participants. Participants were women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation and a high probability of delivery in the late preterm period (which extends to 36 weeks 6 days) within the 17 university-based clinical centers participating in the Maternal Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Eligible women were randomly assigned in a 1:1 ratio to a course of 2 intramuscular injections of either 12 mg betamethasone or matching placebo administered 24 hours apart. After administration of the study medications, the women were treated clinically according to local practice, including discharge to home if delivery did not occur.

Main outcome measures. The primary outcome was a composite endpoint consisting of need for respiratory support, stillbirth, or neonatal death within 72 hours after delivery. Need for respiratory support was defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least 2 consecutive hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation. Secondary outcomes included 2 composite outcomes: (1) respiratory distress syndrome, transient tachypnea of the newborn, or apnea; and (2) respiratory distress syndrome, intraventricular hemorrhage, or necrotizing enterocolitis.

Main results. Among 24,133 women assessed for eligibility, 2831 women underwent randomization with 1429 assigned to the betamethasone group and 1402 to the placebo group. A total of 860 (60.2%) in the betamethasone group and 826 (58.9%) in the placebo group received the prespecified 2 doses of study medication. 1083 of the 1145 women (94.6%) who did not receive a second dose delivered before 24 hours. Two women in each study group were lost to follow-up, with outcome information available for 2827 neonates.

The rate of the primary outcome was lower in the betamethasone group (11.6%) than in the placebo group (14.4%), with a relative risk of 0.80% (95% CI 0.66 to 0.97; P = 0.02); the number needed to treat was 35 women to prevent 1 case of the primary outcome. In regard to secondary outcomes, the rate of the composite outcome of severe respiratory complications was also lower in the betamethasone group than in the placebo group (8.1% vs. 12.1%; relative risk 0.67; CI 0.53 to 0.84; P < 0.001). Of note, the betamethasone group had a higher incidence of neonatal hypoglycemia when compared to the placebo group (24.0% vs. 15.0%; relative risk 1.60; 95% CI 1.37 to 1.87; P < 0.001).

Conclusion. Administration of antenatal betamethasone in women at risk for late preterm delivery significantly decreased the rate of respiratory complications in newborns.

Commentary

Use of antenatal glucocorticoids for early preterm delivery has been a widely accepted practice, with strong evidence that glucocorticoids reduce adverse neonatal outcomes when administered to women who are likely to deliver before 34 weeks of gestation [1,2]. In addition, use of glucocorticoids at the time of elective cesarean delivery at term from the results of the Antenatal Steroids for Term Elective Caesarean Section (ASTECS) trial demonstrated reduction in the rate of admission to neonatal intensive care units for respiratory complications in the betamethasone group when comparing to placebo [3]. However, the use of glucocorticoids in the late preterm period to prevent adverse neonatal respiratory outcomes remained inconclusive after 2 smaller randomized trials [4,5].

In the current study, Gyamfi-Bannerman and colleagues addressed the issue of whether the use of glucocorticoids, specifically betamethasone, in the late preterm period may prevent adverse neonatal respiratory outcomes. While only 60.2% of the betamethasone group and 58.9% of the placebo group received the proposed 2 doses of study medication, administration of betamethasone decreased the need for substantial respiratory support during the first 72 hours after birth and other respiratory complications.

There were no clinically significant adverse neonatal effects except that the betamethasone cohort babies had a 60% increased relative risk of neonatal hypoglycemia. There were no reported adverse events related to the hypoglycemia, and infants with hypoglycemia were discharged on average 2 days earlier than those without, which suggests that the condition was self-limiting. The authors suggested monitoring neonatal blood glucose after betamethasone exposure in the late preterm period.  It will be important to answer questions about the long-term outcomes of this therapy, both benefits and risks, such as the potential reduction of chronic lung diseases or risk of developmental delay due to hypoglycemia [6].

Applications for Clinical Practice

This multicenter randomized controlled study provides strong evidence for administering antenatal glucocorticoids, such as betamethasone, in women at risk for late preterm delivery. Betamethasone administration significantly decreased the rate of respiratory complications in newborns, with the precaution to monitor for neonatal hypoglycemia.

 —Ka Ming Gordon Ngai, MD, MPH

Study Overview

Objective. To determine whether the administration of betamethasone to women who are likely to deliver in the late preterm period would decrease respiratory and other neonatal complications.

Design. Randomized controlled trial.

Setting and participants. Participants were women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation and a high probability of delivery in the late preterm period (which extends to 36 weeks 6 days) within the 17 university-based clinical centers participating in the Maternal Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Eligible women were randomly assigned in a 1:1 ratio to a course of 2 intramuscular injections of either 12 mg betamethasone or matching placebo administered 24 hours apart. After administration of the study medications, the women were treated clinically according to local practice, including discharge to home if delivery did not occur.

Main outcome measures. The primary outcome was a composite endpoint consisting of need for respiratory support, stillbirth, or neonatal death within 72 hours after delivery. Need for respiratory support was defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least 2 consecutive hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation. Secondary outcomes included 2 composite outcomes: (1) respiratory distress syndrome, transient tachypnea of the newborn, or apnea; and (2) respiratory distress syndrome, intraventricular hemorrhage, or necrotizing enterocolitis.

Main results. Among 24,133 women assessed for eligibility, 2831 women underwent randomization with 1429 assigned to the betamethasone group and 1402 to the placebo group. A total of 860 (60.2%) in the betamethasone group and 826 (58.9%) in the placebo group received the prespecified 2 doses of study medication. 1083 of the 1145 women (94.6%) who did not receive a second dose delivered before 24 hours. Two women in each study group were lost to follow-up, with outcome information available for 2827 neonates.

The rate of the primary outcome was lower in the betamethasone group (11.6%) than in the placebo group (14.4%), with a relative risk of 0.80% (95% CI 0.66 to 0.97; P = 0.02); the number needed to treat was 35 women to prevent 1 case of the primary outcome. In regard to secondary outcomes, the rate of the composite outcome of severe respiratory complications was also lower in the betamethasone group than in the placebo group (8.1% vs. 12.1%; relative risk 0.67; CI 0.53 to 0.84; P < 0.001). Of note, the betamethasone group had a higher incidence of neonatal hypoglycemia when compared to the placebo group (24.0% vs. 15.0%; relative risk 1.60; 95% CI 1.37 to 1.87; P < 0.001).

Conclusion. Administration of antenatal betamethasone in women at risk for late preterm delivery significantly decreased the rate of respiratory complications in newborns.

Commentary

Use of antenatal glucocorticoids for early preterm delivery has been a widely accepted practice, with strong evidence that glucocorticoids reduce adverse neonatal outcomes when administered to women who are likely to deliver before 34 weeks of gestation [1,2]. In addition, use of glucocorticoids at the time of elective cesarean delivery at term from the results of the Antenatal Steroids for Term Elective Caesarean Section (ASTECS) trial demonstrated reduction in the rate of admission to neonatal intensive care units for respiratory complications in the betamethasone group when comparing to placebo [3]. However, the use of glucocorticoids in the late preterm period to prevent adverse neonatal respiratory outcomes remained inconclusive after 2 smaller randomized trials [4,5].

In the current study, Gyamfi-Bannerman and colleagues addressed the issue of whether the use of glucocorticoids, specifically betamethasone, in the late preterm period may prevent adverse neonatal respiratory outcomes. While only 60.2% of the betamethasone group and 58.9% of the placebo group received the proposed 2 doses of study medication, administration of betamethasone decreased the need for substantial respiratory support during the first 72 hours after birth and other respiratory complications.

There were no clinically significant adverse neonatal effects except that the betamethasone cohort babies had a 60% increased relative risk of neonatal hypoglycemia. There were no reported adverse events related to the hypoglycemia, and infants with hypoglycemia were discharged on average 2 days earlier than those without, which suggests that the condition was self-limiting. The authors suggested monitoring neonatal blood glucose after betamethasone exposure in the late preterm period.  It will be important to answer questions about the long-term outcomes of this therapy, both benefits and risks, such as the potential reduction of chronic lung diseases or risk of developmental delay due to hypoglycemia [6].

Applications for Clinical Practice

This multicenter randomized controlled study provides strong evidence for administering antenatal glucocorticoids, such as betamethasone, in women at risk for late preterm delivery. Betamethasone administration significantly decreased the rate of respiratory complications in newborns, with the precaution to monitor for neonatal hypoglycemia.

 —Ka Ming Gordon Ngai, MD, MPH

Study Overview

Objective. To determine whether the administration of betamethasone to women who are likely to deliver in the late preterm period would decrease respiratory and other neonatal complications.

Design. Randomized controlled trial.

Setting and participants. Participants were women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation and a high probability of delivery in the late preterm period (which extends to 36 weeks 6 days) within the 17 university-based clinical centers participating in the Maternal Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Eligible women were randomly assigned in a 1:1 ratio to a course of 2 intramuscular injections of either 12 mg betamethasone or matching placebo administered 24 hours apart. After administration of the study medications, the women were treated clinically according to local practice, including discharge to home if delivery did not occur.

Main outcome measures. The primary outcome was a composite endpoint consisting of need for respiratory support, stillbirth, or neonatal death within 72 hours after delivery. Need for respiratory support was defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least 2 consecutive hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation. Secondary outcomes included 2 composite outcomes: (1) respiratory distress syndrome, transient tachypnea of the newborn, or apnea; and (2) respiratory distress syndrome, intraventricular hemorrhage, or necrotizing enterocolitis.

Main results. Among 24,133 women assessed for eligibility, 2831 women underwent randomization with 1429 assigned to the betamethasone group and 1402 to the placebo group. A total of 860 (60.2%) in the betamethasone group and 826 (58.9%) in the placebo group received the prespecified 2 doses of study medication. 1083 of the 1145 women (94.6%) who did not receive a second dose delivered before 24 hours. Two women in each study group were lost to follow-up, with outcome information available for 2827 neonates.

The rate of the primary outcome was lower in the betamethasone group (11.6%) than in the placebo group (14.4%), with a relative risk of 0.80% (95% CI 0.66 to 0.97; P = 0.02); the number needed to treat was 35 women to prevent 1 case of the primary outcome. In regard to secondary outcomes, the rate of the composite outcome of severe respiratory complications was also lower in the betamethasone group than in the placebo group (8.1% vs. 12.1%; relative risk 0.67; CI 0.53 to 0.84; P < 0.001). Of note, the betamethasone group had a higher incidence of neonatal hypoglycemia when compared to the placebo group (24.0% vs. 15.0%; relative risk 1.60; 95% CI 1.37 to 1.87; P < 0.001).

Conclusion. Administration of antenatal betamethasone in women at risk for late preterm delivery significantly decreased the rate of respiratory complications in newborns.

Commentary

Use of antenatal glucocorticoids for early preterm delivery has been a widely accepted practice, with strong evidence that glucocorticoids reduce adverse neonatal outcomes when administered to women who are likely to deliver before 34 weeks of gestation [1,2]. In addition, use of glucocorticoids at the time of elective cesarean delivery at term from the results of the Antenatal Steroids for Term Elective Caesarean Section (ASTECS) trial demonstrated reduction in the rate of admission to neonatal intensive care units for respiratory complications in the betamethasone group when comparing to placebo [3]. However, the use of glucocorticoids in the late preterm period to prevent adverse neonatal respiratory outcomes remained inconclusive after 2 smaller randomized trials [4,5].

In the current study, Gyamfi-Bannerman and colleagues addressed the issue of whether the use of glucocorticoids, specifically betamethasone, in the late preterm period may prevent adverse neonatal respiratory outcomes. While only 60.2% of the betamethasone group and 58.9% of the placebo group received the proposed 2 doses of study medication, administration of betamethasone decreased the need for substantial respiratory support during the first 72 hours after birth and other respiratory complications.

There were no clinically significant adverse neonatal effects except that the betamethasone cohort babies had a 60% increased relative risk of neonatal hypoglycemia. There were no reported adverse events related to the hypoglycemia, and infants with hypoglycemia were discharged on average 2 days earlier than those without, which suggests that the condition was self-limiting. The authors suggested monitoring neonatal blood glucose after betamethasone exposure in the late preterm period.  It will be important to answer questions about the long-term outcomes of this therapy, both benefits and risks, such as the potential reduction of chronic lung diseases or risk of developmental delay due to hypoglycemia [6].

Applications for Clinical Practice

This multicenter randomized controlled study provides strong evidence for administering antenatal glucocorticoids, such as betamethasone, in women at risk for late preterm delivery. Betamethasone administration significantly decreased the rate of respiratory complications in newborns, with the precaution to monitor for neonatal hypoglycemia.

 —Ka Ming Gordon Ngai, MD, MPH

Can’t we just be friends? This is the disquieting question we ask someone when we want to set boundaries. It is meant to define expectation, level of trust and intimacy in a relationship.

We are capable of forming an astonishing variety of relationships with others. We form deep emotional connections with romantic partners, close family, and dear friends. We create more superficial ties with colleagues, distant family, and professionals. Understanding the nature of our relationships is important. There are reasons why professors should not engage in romantic relationships with their students: mixing relationships can lead to confusion and destroy trust. The risk for misunderstanding and harm to one or both parties increases as the intensity of the relationship increases. Can a professor who has a personal relationship with a student be objective? Does the student really want to be kissed or is she feigning interest for a better grade?

The stakes are even higher for us physicians. Forming inappropriate relationships with patients can result in the loss of your medical license. This seems obvious to most of us, but when we examine the appropriateness of other nonprofessional connections, it becomes less clear.

What if you have an intimate but nonsexual relationship with a patient? What about having a family member or close friend as a patient? Most medical ethicists say that any relationship other than the straightforward, professional doctor/patient one is improper. This strict definition exists primarily to protect our patients but also to help us. The highest levels of quality and service can only come from the sterile yet compassionate trust that occurs only in doctor/patient connections.

As a male dermatologist, something as seemingly innocuous as my following a female patient on Instagram puts our professional relationship at risk. If a patient views you as a friend as well as a doctor, would he hesitate to divulge things that are important to his health but inappropriate for a friend to know? Moreover, if I have such knowledge, won’t that impair the trust we share as friends? Such conundrums might hinder your ability to care for your patients and limit the quality of service they receive.

Social media have added many more levels to the already complex ways we can relate to our patients. There are Facebook friends, Snapchat buddies, and Twitter followers. Most of these are diminishingly shallow in terms of the depth and seriousness of the relationship, but they can be misconstrued. In most instances, keep it simple: I’m your doctor. You’re my patient.

When patients ask me to friend them, as they sometime do, I remind them: I’m not your brother or your son. I am not your friend. You pay me to provide a service, yet what I give cannot be bought. I work for you when I’m home. I worry about you when I drive to the office. Someday, I may save your life.

I’m your doctor. No, we cannot be Facebook friends.

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego, and a volunteer clinical assistant professor at the University of California, San Diego. He is @dermdoc on Twitter.

Can’t we just be friends? This is the disquieting question we ask someone when we want to set boundaries. It is meant to define expectation, level of trust and intimacy in a relationship.

We are capable of forming an astonishing variety of relationships with others. We form deep emotional connections with romantic partners, close family, and dear friends. We create more superficial ties with colleagues, distant family, and professionals. Understanding the nature of our relationships is important. There are reasons why professors should not engage in romantic relationships with their students: mixing relationships can lead to confusion and destroy trust. The risk for misunderstanding and harm to one or both parties increases as the intensity of the relationship increases. Can a professor who has a personal relationship with a student be objective? Does the student really want to be kissed or is she feigning interest for a better grade?

The stakes are even higher for us physicians. Forming inappropriate relationships with patients can result in the loss of your medical license. This seems obvious to most of us, but when we examine the appropriateness of other nonprofessional connections, it becomes less clear.

What if you have an intimate but nonsexual relationship with a patient? What about having a family member or close friend as a patient? Most medical ethicists say that any relationship other than the straightforward, professional doctor/patient one is improper. This strict definition exists primarily to protect our patients but also to help us. The highest levels of quality and service can only come from the sterile yet compassionate trust that occurs only in doctor/patient connections.

As a male dermatologist, something as seemingly innocuous as my following a female patient on Instagram puts our professional relationship at risk. If a patient views you as a friend as well as a doctor, would he hesitate to divulge things that are important to his health but inappropriate for a friend to know? Moreover, if I have such knowledge, won’t that impair the trust we share as friends? Such conundrums might hinder your ability to care for your patients and limit the quality of service they receive.

Social media have added many more levels to the already complex ways we can relate to our patients. There are Facebook friends, Snapchat buddies, and Twitter followers. Most of these are diminishingly shallow in terms of the depth and seriousness of the relationship, but they can be misconstrued. In most instances, keep it simple: I’m your doctor. You’re my patient.

When patients ask me to friend them, as they sometime do, I remind them: I’m not your brother or your son. I am not your friend. You pay me to provide a service, yet what I give cannot be bought. I work for you when I’m home. I worry about you when I drive to the office. Someday, I may save your life.

I’m your doctor. No, we cannot be Facebook friends.

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego, and a volunteer clinical assistant professor at the University of California, San Diego. He is @dermdoc on Twitter.

Can’t we just be friends? This is the disquieting question we ask someone when we want to set boundaries. It is meant to define expectation, level of trust and intimacy in a relationship.

We are capable of forming an astonishing variety of relationships with others. We form deep emotional connections with romantic partners, close family, and dear friends. We create more superficial ties with colleagues, distant family, and professionals. Understanding the nature of our relationships is important. There are reasons why professors should not engage in romantic relationships with their students: mixing relationships can lead to confusion and destroy trust. The risk for misunderstanding and harm to one or both parties increases as the intensity of the relationship increases. Can a professor who has a personal relationship with a student be objective? Does the student really want to be kissed or is she feigning interest for a better grade?

The stakes are even higher for us physicians. Forming inappropriate relationships with patients can result in the loss of your medical license. This seems obvious to most of us, but when we examine the appropriateness of other nonprofessional connections, it becomes less clear.

What if you have an intimate but nonsexual relationship with a patient? What about having a family member or close friend as a patient? Most medical ethicists say that any relationship other than the straightforward, professional doctor/patient one is improper. This strict definition exists primarily to protect our patients but also to help us. The highest levels of quality and service can only come from the sterile yet compassionate trust that occurs only in doctor/patient connections.

As a male dermatologist, something as seemingly innocuous as my following a female patient on Instagram puts our professional relationship at risk. If a patient views you as a friend as well as a doctor, would he hesitate to divulge things that are important to his health but inappropriate for a friend to know? Moreover, if I have such knowledge, won’t that impair the trust we share as friends? Such conundrums might hinder your ability to care for your patients and limit the quality of service they receive.

Social media have added many more levels to the already complex ways we can relate to our patients. There are Facebook friends, Snapchat buddies, and Twitter followers. Most of these are diminishingly shallow in terms of the depth and seriousness of the relationship, but they can be misconstrued. In most instances, keep it simple: I’m your doctor. You’re my patient.

When patients ask me to friend them, as they sometime do, I remind them: I’m not your brother or your son. I am not your friend. You pay me to provide a service, yet what I give cannot be bought. I work for you when I’m home. I worry about you when I drive to the office. Someday, I may save your life.

I’m your doctor. No, we cannot be Facebook friends.

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego, and a volunteer clinical assistant professor at the University of California, San Diego. He is @dermdoc on Twitter.

Question: When a doctor could not find a dislodged biopsy guide wire, he abandoned his search after informing the patient of his intention to retrieve it at a later date. Two months later, he was successful in locating and removing the foreign body, but the patient alleged she suffered pain and anxiety in the interim. She filed a negligence lawsuit and, based on the “obvious” nature of her injuries, called no expert witness to testify on her behalf.

Which of the following choices is best?

A. Expert testimony is always needed to establish the applicable standard of care in medical negligence lawsuits.

B. Although a plaintiff is not qualified to expound on medical matters, he/she can offer evidence from learned treatises and medical texts.

C. The jury is the one who determines whether a plaintiff can invoke either the res ipsa loquitur doctrine or the “common knowledge” rule to obviate the need for an expert witness.

D. This patient will likely win her case.

E. All are incorrect.

Answer: E. It is well-established law that the question of negligence must be decided by reference to relevant medical standards of care for which the plaintiff carries the burden of proving through expert medical testimony. Only a professional, duly qualified by the court as an expert witness, is allowed to offer medical testimony – whereas the plaintiff typically will be disqualified from playing this role because of the complexity of issues involved.

However, under either the doctrine of res ipsa loquitur (“the thing speaks for itself”) or the “common knowledge” rule, a court (i.e., the judge) may allow the jury to infer negligence in the absence of expert testimony.

The res doctrine is invoked where there is only circumstantial but no direct evidence, and three conditions are met: 1) The injury would not have occurred in the absence of someone’s negligence; 2) the plaintiff was not at fault; and 3) the defendant had total control of the instrumentality that led to the injury.

The closely related “common knowledge” rule relies on the everyday knowledge and experience of the layperson to identify plain and obvious negligent conduct, which then allows the judge to waive the expert requirement.

The two principles are frequently used interchangeably, ultimately favoring the plaintiff by dispensing with the difficult and expensive task of securing a qualified expert willing to testify against a doctor defendant.

The best example of res in action is the surgeon who inadvertently leaves behind a sponge or instrument inside a body cavity. Other successfully litigated examples include a cardiac arrest in the operating room, hypoxia in the recovery room, burns to the buttock, gangrene after the accidental injection of penicillin into an artery, air trapped subcutaneously from a displaced needle, and a pierced eyeball during a procedure.

A particularly well-known example is Ybarra v. Spangard, in which the patient developed shoulder injuries during an appendectomy.¹ The Supreme Court of California felt it was appropriate to place the burden on the operating room defendants to explain how the patient, unconscious under general anesthesia throughout the procedure, sustained the shoulder injury.

The scenario provided in the opening question is taken from a 2013 New York case, James v. Wormuth, in which the plaintiff relied on the res doctrine.² The defendant doctor had left a guide wire in the plaintiff’s chest following a biopsy and was unable to locate it after a 20-minute search. However, he was able to retrieve the wire 2 months later under C-arm imaging.

The plaintiff sued the doctor for pain and anxiety, but did not call any expert witness, relying instead on the “foreign object” basis for invoking the res doctrine. The lower court ruled for the doctor, and the court of appeals affirmed.

It reasoned that the object was left behind deliberately, not unintentionally, and that under the circumstances of the case, an expert witness was needed to set out the applicable standard of care, without which a jury could not determine whether the doctor’s professional judgment breached the requisite standard. The court also ruled that the plaintiff failed to satisfy the “exclusive control” requirement of the res doctrine, because several other individuals participated to an extent in the medical procedure.

Hawaii’s case of Barbee v. Queen’s Medical Center is illustrative of the “common knowledge” rule.³ Mr. Barbee, age 75 years, underwent laparoscopic nephrectomy for a malignancy. Massive bleeding complicated his postoperative course, the hemoglobin falling into the 3 range, and he required emergent reoperation. Over the next 18 months, the patient progressively deteriorated, eventually requiring dialysis and dying from a stroke and intestinal volvulus.

Notwithstanding an initial jury verdict in favor of the plaintiff’s children, awarding each of the three children $365,000, the defendants filed a so-called JNOV motion (current term is “judgment as a matter of law”) to negate the jury verdict, on the basis that the plaintiffs failed to present competent expert testimony at trial to prove causation.

The plaintiffs countered that the cause of death was within the realm of common knowledge, thus no expert was necessary. They asserted that “any lay person can easily grasp the concept that a person dies from losing so much blood that multiple organs fail to perform their functions.” Mr. Barbee’s death thus was not “of such a technical nature that lay persons are incompetent to draw their own conclusions from facts presented without aid.”

Hawaii’s Intermediate Court of Appeals disagreed with the plaintiffs, holding that although “Hawaii does recognize a ‘common knowledge’ exception to the requirement that a plaintiff must introduce expert medical testimony on causation … this exception is rare in application.” The court asserted that the causal link between any alleged negligence and Mr. Barbee’s death 17 months later is not within the realm of common knowledge.

It reasoned that the long-term effects of internal bleeding are not so widely known as to be analogous to leaving a sponge within a patient or removing the wrong limb during an amputation. Moreover, Mr. Barbee had a long history of preexisting conditions, including hypertension, diabetes, and cancer. He also suffered numerous and serious postoperative medical conditions, including a stroke and surgery to remove part of his intestine, which had become gangrenous.

Thus, the role that preexisting conditions and/or the subsequent complications of this type played in Mr. Barbee’s death was not within the knowledge of the average layperson.

The “common knowledge” rule is aligned with, though not identical to, the res doctrine, but courts are known to conflate the two legal principles, often using them interchangeably.⁴

Strictly speaking, the “common knowledge” waiver comes into play where direct evidence of negligent conduct lies within the realm of everyday lay knowledge that the physician had deviated from common practice. It may or may not address the causation issue.

On the other hand, res is successfully invoked when, despite no direct evidence of negligence and causation, the circumstances surrounding the injury are such that the plaintiff’s case can go to the jury without expert testimony.

References

1. Ybarra v. Spangard, 154 P.2d 687 (Cal. 1944).

2. James v. Wormuth, 997 N.E.2d 133 (N.Y. 2013).

3. Barbee v. Queen’s Medical Center, 119 Haw 136 (2008).

4. Spinner, Amanda E. Common Ignorance: Medical Malpractice Law and the Misconceived Application of the “Common Knowledge” and “Res Ipsa Loquitur” Doctrines.” Touro Law Review: Vol. 31: No. 3, Article 15. Available at http://digitalcommons.tourolaw.edu/lawreview/vol31/iss3/15.

Dr. Tan is professor emeritus of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at [email protected].

Question: When a doctor could not find a dislodged biopsy guide wire, he abandoned his search after informing the patient of his intention to retrieve it at a later date. Two months later, he was successful in locating and removing the foreign body, but the patient alleged she suffered pain and anxiety in the interim. She filed a negligence lawsuit and, based on the “obvious” nature of her injuries, called no expert witness to testify on her behalf.

Which of the following choices is best?

A. Expert testimony is always needed to establish the applicable standard of care in medical negligence lawsuits.

B. Although a plaintiff is not qualified to expound on medical matters, he/she can offer evidence from learned treatises and medical texts.

C. The jury is the one who determines whether a plaintiff can invoke either the res ipsa loquitur doctrine or the “common knowledge” rule to obviate the need for an expert witness.

D. This patient will likely win her case.

E. All are incorrect.

Answer: E. It is well-established law that the question of negligence must be decided by reference to relevant medical standards of care for which the plaintiff carries the burden of proving through expert medical testimony. Only a professional, duly qualified by the court as an expert witness, is allowed to offer medical testimony – whereas the plaintiff typically will be disqualified from playing this role because of the complexity of issues involved.

However, under either the doctrine of res ipsa loquitur (“the thing speaks for itself”) or the “common knowledge” rule, a court (i.e., the judge) may allow the jury to infer negligence in the absence of expert testimony.

The res doctrine is invoked where there is only circumstantial but no direct evidence, and three conditions are met: 1) The injury would not have occurred in the absence of someone’s negligence; 2) the plaintiff was not at fault; and 3) the defendant had total control of the instrumentality that led to the injury.

The closely related “common knowledge” rule relies on the everyday knowledge and experience of the layperson to identify plain and obvious negligent conduct, which then allows the judge to waive the expert requirement.

The two principles are frequently used interchangeably, ultimately favoring the plaintiff by dispensing with the difficult and expensive task of securing a qualified expert willing to testify against a doctor defendant.

The best example of res in action is the surgeon who inadvertently leaves behind a sponge or instrument inside a body cavity. Other successfully litigated examples include a cardiac arrest in the operating room, hypoxia in the recovery room, burns to the buttock, gangrene after the accidental injection of penicillin into an artery, air trapped subcutaneously from a displaced needle, and a pierced eyeball during a procedure.

A particularly well-known example is Ybarra v. Spangard, in which the patient developed shoulder injuries during an appendectomy.¹ The Supreme Court of California felt it was appropriate to place the burden on the operating room defendants to explain how the patient, unconscious under general anesthesia throughout the procedure, sustained the shoulder injury.

The scenario provided in the opening question is taken from a 2013 New York case, James v. Wormuth, in which the plaintiff relied on the res doctrine.² The defendant doctor had left a guide wire in the plaintiff’s chest following a biopsy and was unable to locate it after a 20-minute search. However, he was able to retrieve the wire 2 months later under C-arm imaging.

The plaintiff sued the doctor for pain and anxiety, but did not call any expert witness, relying instead on the “foreign object” basis for invoking the res doctrine. The lower court ruled for the doctor, and the court of appeals affirmed.

It reasoned that the object was left behind deliberately, not unintentionally, and that under the circumstances of the case, an expert witness was needed to set out the applicable standard of care, without which a jury could not determine whether the doctor’s professional judgment breached the requisite standard. The court also ruled that the plaintiff failed to satisfy the “exclusive control” requirement of the res doctrine, because several other individuals participated to an extent in the medical procedure.

Hawaii’s case of Barbee v. Queen’s Medical Center is illustrative of the “common knowledge” rule.³ Mr. Barbee, age 75 years, underwent laparoscopic nephrectomy for a malignancy. Massive bleeding complicated his postoperative course, the hemoglobin falling into the 3 range, and he required emergent reoperation. Over the next 18 months, the patient progressively deteriorated, eventually requiring dialysis and dying from a stroke and intestinal volvulus.

Notwithstanding an initial jury verdict in favor of the plaintiff’s children, awarding each of the three children $365,000, the defendants filed a so-called JNOV motion (current term is “judgment as a matter of law”) to negate the jury verdict, on the basis that the plaintiffs failed to present competent expert testimony at trial to prove causation.

The plaintiffs countered that the cause of death was within the realm of common knowledge, thus no expert was necessary. They asserted that “any lay person can easily grasp the concept that a person dies from losing so much blood that multiple organs fail to perform their functions.” Mr. Barbee’s death thus was not “of such a technical nature that lay persons are incompetent to draw their own conclusions from facts presented without aid.”

Hawaii’s Intermediate Court of Appeals disagreed with the plaintiffs, holding that although “Hawaii does recognize a ‘common knowledge’ exception to the requirement that a plaintiff must introduce expert medical testimony on causation … this exception is rare in application.” The court asserted that the causal link between any alleged negligence and Mr. Barbee’s death 17 months later is not within the realm of common knowledge.

It reasoned that the long-term effects of internal bleeding are not so widely known as to be analogous to leaving a sponge within a patient or removing the wrong limb during an amputation. Moreover, Mr. Barbee had a long history of preexisting conditions, including hypertension, diabetes, and cancer. He also suffered numerous and serious postoperative medical conditions, including a stroke and surgery to remove part of his intestine, which had become gangrenous.

Thus, the role that preexisting conditions and/or the subsequent complications of this type played in Mr. Barbee’s death was not within the knowledge of the average layperson.

The “common knowledge” rule is aligned with, though not identical to, the res doctrine, but courts are known to conflate the two legal principles, often using them interchangeably.⁴

Strictly speaking, the “common knowledge” waiver comes into play where direct evidence of negligent conduct lies within the realm of everyday lay knowledge that the physician had deviated from common practice. It may or may not address the causation issue.

On the other hand, res is successfully invoked when, despite no direct evidence of negligence and causation, the circumstances surrounding the injury are such that the plaintiff’s case can go to the jury without expert testimony.

References

1. Ybarra v. Spangard, 154 P.2d 687 (Cal. 1944).

2. James v. Wormuth, 997 N.E.2d 133 (N.Y. 2013).

3. Barbee v. Queen’s Medical Center, 119 Haw 136 (2008).

4. Spinner, Amanda E. Common Ignorance: Medical Malpractice Law and the Misconceived Application of the “Common Knowledge” and “Res Ipsa Loquitur” Doctrines.” Touro Law Review: Vol. 31: No. 3, Article 15. Available at http://digitalcommons.tourolaw.edu/lawreview/vol31/iss3/15.

Dr. Tan is professor emeritus of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at [email protected].

Question: When a doctor could not find a dislodged biopsy guide wire, he abandoned his search after informing the patient of his intention to retrieve it at a later date. Two months later, he was successful in locating and removing the foreign body, but the patient alleged she suffered pain and anxiety in the interim. She filed a negligence lawsuit and, based on the “obvious” nature of her injuries, called no expert witness to testify on her behalf.

Which of the following choices is best?

A. Expert testimony is always needed to establish the applicable standard of care in medical negligence lawsuits.

B. Although a plaintiff is not qualified to expound on medical matters, he/she can offer evidence from learned treatises and medical texts.

C. The jury is the one who determines whether a plaintiff can invoke either the res ipsa loquitur doctrine or the “common knowledge” rule to obviate the need for an expert witness.

D. This patient will likely win her case.

E. All are incorrect.

Answer: E. It is well-established law that the question of negligence must be decided by reference to relevant medical standards of care for which the plaintiff carries the burden of proving through expert medical testimony. Only a professional, duly qualified by the court as an expert witness, is allowed to offer medical testimony – whereas the plaintiff typically will be disqualified from playing this role because of the complexity of issues involved.

However, under either the doctrine of res ipsa loquitur (“the thing speaks for itself”) or the “common knowledge” rule, a court (i.e., the judge) may allow the jury to infer negligence in the absence of expert testimony.

The res doctrine is invoked where there is only circumstantial but no direct evidence, and three conditions are met: 1) The injury would not have occurred in the absence of someone’s negligence; 2) the plaintiff was not at fault; and 3) the defendant had total control of the instrumentality that led to the injury.

The closely related “common knowledge” rule relies on the everyday knowledge and experience of the layperson to identify plain and obvious negligent conduct, which then allows the judge to waive the expert requirement.

The two principles are frequently used interchangeably, ultimately favoring the plaintiff by dispensing with the difficult and expensive task of securing a qualified expert willing to testify against a doctor defendant.

The best example of res in action is the surgeon who inadvertently leaves behind a sponge or instrument inside a body cavity. Other successfully litigated examples include a cardiac arrest in the operating room, hypoxia in the recovery room, burns to the buttock, gangrene after the accidental injection of penicillin into an artery, air trapped subcutaneously from a displaced needle, and a pierced eyeball during a procedure.

A particularly well-known example is Ybarra v. Spangard, in which the patient developed shoulder injuries during an appendectomy.¹ The Supreme Court of California felt it was appropriate to place the burden on the operating room defendants to explain how the patient, unconscious under general anesthesia throughout the procedure, sustained the shoulder injury.

The scenario provided in the opening question is taken from a 2013 New York case, James v. Wormuth, in which the plaintiff relied on the res doctrine.² The defendant doctor had left a guide wire in the plaintiff’s chest following a biopsy and was unable to locate it after a 20-minute search. However, he was able to retrieve the wire 2 months later under C-arm imaging.

The plaintiff sued the doctor for pain and anxiety, but did not call any expert witness, relying instead on the “foreign object” basis for invoking the res doctrine. The lower court ruled for the doctor, and the court of appeals affirmed.

It reasoned that the object was left behind deliberately, not unintentionally, and that under the circumstances of the case, an expert witness was needed to set out the applicable standard of care, without which a jury could not determine whether the doctor’s professional judgment breached the requisite standard. The court also ruled that the plaintiff failed to satisfy the “exclusive control” requirement of the res doctrine, because several other individuals participated to an extent in the medical procedure.

Hawaii’s case of Barbee v. Queen’s Medical Center is illustrative of the “common knowledge” rule.³ Mr. Barbee, age 75 years, underwent laparoscopic nephrectomy for a malignancy. Massive bleeding complicated his postoperative course, the hemoglobin falling into the 3 range, and he required emergent reoperation. Over the next 18 months, the patient progressively deteriorated, eventually requiring dialysis and dying from a stroke and intestinal volvulus.

Notwithstanding an initial jury verdict in favor of the plaintiff’s children, awarding each of the three children $365,000, the defendants filed a so-called JNOV motion (current term is “judgment as a matter of law”) to negate the jury verdict, on the basis that the plaintiffs failed to present competent expert testimony at trial to prove causation.

The plaintiffs countered that the cause of death was within the realm of common knowledge, thus no expert was necessary. They asserted that “any lay person can easily grasp the concept that a person dies from losing so much blood that multiple organs fail to perform their functions.” Mr. Barbee’s death thus was not “of such a technical nature that lay persons are incompetent to draw their own conclusions from facts presented without aid.”

Hawaii’s Intermediate Court of Appeals disagreed with the plaintiffs, holding that although “Hawaii does recognize a ‘common knowledge’ exception to the requirement that a plaintiff must introduce expert medical testimony on causation … this exception is rare in application.” The court asserted that the causal link between any alleged negligence and Mr. Barbee’s death 17 months later is not within the realm of common knowledge.

It reasoned that the long-term effects of internal bleeding are not so widely known as to be analogous to leaving a sponge within a patient or removing the wrong limb during an amputation. Moreover, Mr. Barbee had a long history of preexisting conditions, including hypertension, diabetes, and cancer. He also suffered numerous and serious postoperative medical conditions, including a stroke and surgery to remove part of his intestine, which had become gangrenous.

Thus, the role that preexisting conditions and/or the subsequent complications of this type played in Mr. Barbee’s death was not within the knowledge of the average layperson.

The “common knowledge” rule is aligned with, though not identical to, the res doctrine, but courts are known to conflate the two legal principles, often using them interchangeably.⁴

Strictly speaking, the “common knowledge” waiver comes into play where direct evidence of negligent conduct lies within the realm of everyday lay knowledge that the physician had deviated from common practice. It may or may not address the causation issue.

On the other hand, res is successfully invoked when, despite no direct evidence of negligence and causation, the circumstances surrounding the injury are such that the plaintiff’s case can go to the jury without expert testimony.

References

1. Ybarra v. Spangard, 154 P.2d 687 (Cal. 1944).

2. James v. Wormuth, 997 N.E.2d 133 (N.Y. 2013).

3. Barbee v. Queen’s Medical Center, 119 Haw 136 (2008).

4. Spinner, Amanda E. Common Ignorance: Medical Malpractice Law and the Misconceived Application of the “Common Knowledge” and “Res Ipsa Loquitur” Doctrines.” Touro Law Review: Vol. 31: No. 3, Article 15. Available at http://digitalcommons.tourolaw.edu/lawreview/vol31/iss3/15.

Dr. Tan is professor emeritus of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at [email protected].

Monoclonal antibodies

Photo by Linda Bartlett

NEW ORLEANS—A small study suggests that treatment with lenalidomide and dexamethasone (len-dex) prompts an increase in cancer stem cells (CSCs) for patients with newly diagnosed multiple myeloma (MM).

However, adding an anti-CD19 monoclonal antibody (mAb) to the regimen can reduce CSCs.

Most patients who received the mAb, MEDI-551, experienced a decrease in CSCs, but the cells rebounded after the patients stopped receiving  MEDI-551.

And those patients who did not see a decrease in CSCs progressed. However, some patients are still in response and remain on treatment with len-dex.

The investigators believe these early results suggest prolonged treatment with len-dex and MED-551 may be safe and clinically beneficial for MM patients.

The results were presented at the 2016 AACR Annual Meeting (abstract CT102).

The study included 17 patients with newly diagnosed MM. They had a median age of 65 (range, 34-73). Most had ISS stage I (n=11), 2 had stage II, and 4 had stage III. Seven patients had t(4;14).

“We chose to carry out this clinical trial in newly diagnosed patients because our original data showed that CD19 was almost always expressed by myeloma stem cells in these patients, whereas we don’t know if that is the case in more advanced patients,” said investigator William Matsui, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland.

The patients received 28-day cycles of len-dex (len at 25 mg PO, days 1-21, and dex at 40 mg PO, weekly). Patients received MEDI-551 (at 4 mg/kg IV) in cycle 3 (day 1, 8) and cycle 4 (day 1). Responding patients continued on len-dex.

The investigators measured MM CSCs by quantifying the growth of MM colonies (CFU-MM) from marrow aspirates at baseline and at the end of cycles 2 and 4.

The team quantified peripheral blood CSCs by flow cytometry (CD19+CD27+ALDH+) at baseline and the end of cycles 2, 4, 5, and 7.

“We wanted to see if these 2 assays gave similar results, and, in this clinical trial, they were almost identical,” said investigator Carol Ann Huff, MD, also of Johns Hopkins.

“Since it is much easier to draw blood than bone marrow from our patients, we think that we can primarily use blood to track multiple myeloma stem cells in the future.”

Response

Two patients did not receive MEDI-551 due to progressive disease and noncompliance. So the investigators assessed responses in 15 patients.

After cycle 2 (len-dex alone), there were 3 very good partial responses (VGPRs), 10 partial responses (PRs), 1 molecular response, and 1 case of stable disease.

After cycle 4 (len-dex plus MEDI-551), there were 6 VGPRs, 8 PRs, and 1 molecular response.

Ten patients who completed treatment with MED-551 remain on len-dex. At the end of cycle 7, there was 1 complete response, 8 VGPRs, and 1 PR.

CFU-MM

When compared to baseline, bone-marrow-derived CFU-MM increased a median of 2.5-fold (range, 0.4-7.4) after cycle 2 but decreased a median of 0.48-fold (range, 0.14-0.85) in 14 patients after cycle 4.

The investigators compared these results to 5 newly diagnosed MM patients who only received standard treatment with len-dex.

In these patients, CFU-MM increased a median of 9.3-fold (range, 4-14) at a median of 4 months (range, 2-4). This is in spite of the fact that all of these patients had a PR or better.

Circulating CSCs

Compared to baseline, circulating MM CSCs increased a median of 1.6-fold (range, 0.4-8.6) in 14 patients after cycle 2 but decreased a median of 0.6-fold (range, 0.01-7.4) in 13 patients after cycle 4.

At the end of cycle 5, MM CSCs had increased in 4 of the 10 patients who were still on len-dex. By the end of cycle 7, MM CSCs had increased in 8 of the patients.

Circulating MM CSCs increased by the end of cycle 4 in 2 patients, and both had progressed by end of cycle 7.

Safety and next steps

The investigators said there were no serious adverse events in this trial, but 2 patients experienced grade 2 infusion reactions after the first MEDI-551 dose.

The team plans to conduct further studies to assess the long-term impact of MED-551 in MM patients and determine how the mAb might work in combination with other treatments, particularly transplant.

“In other studies at Johns Hopkins, we have found that antibody therapies can work much better after a bone marrow transplant, especially allogeneic transplants,” Dr Matsui said.

Funding and drugs for this study were provided by MedImmune Inc., the developers of MEDI-551. Drs Huff and Matsui served as a paid scientific advisory board member and a consultant to MedImmune Inc., respectively.

Monoclonal antibodies

Photo by Linda Bartlett

NEW ORLEANS—A small study suggests that treatment with lenalidomide and dexamethasone (len-dex) prompts an increase in cancer stem cells (CSCs) for patients with newly diagnosed multiple myeloma (MM).

However, adding an anti-CD19 monoclonal antibody (mAb) to the regimen can reduce CSCs.

Most patients who received the mAb, MEDI-551, experienced a decrease in CSCs, but the cells rebounded after the patients stopped receiving  MEDI-551.

And those patients who did not see a decrease in CSCs progressed. However, some patients are still in response and remain on treatment with len-dex.

The investigators believe these early results suggest prolonged treatment with len-dex and MED-551 may be safe and clinically beneficial for MM patients.

The results were presented at the 2016 AACR Annual Meeting (abstract CT102).

The study included 17 patients with newly diagnosed MM. They had a median age of 65 (range, 34-73). Most had ISS stage I (n=11), 2 had stage II, and 4 had stage III. Seven patients had t(4;14).

“We chose to carry out this clinical trial in newly diagnosed patients because our original data showed that CD19 was almost always expressed by myeloma stem cells in these patients, whereas we don’t know if that is the case in more advanced patients,” said investigator William Matsui, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland.

The patients received 28-day cycles of len-dex (len at 25 mg PO, days 1-21, and dex at 40 mg PO, weekly). Patients received MEDI-551 (at 4 mg/kg IV) in cycle 3 (day 1, 8) and cycle 4 (day 1). Responding patients continued on len-dex.

The investigators measured MM CSCs by quantifying the growth of MM colonies (CFU-MM) from marrow aspirates at baseline and at the end of cycles 2 and 4.

The team quantified peripheral blood CSCs by flow cytometry (CD19+CD27+ALDH+) at baseline and the end of cycles 2, 4, 5, and 7.

“We wanted to see if these 2 assays gave similar results, and, in this clinical trial, they were almost identical,” said investigator Carol Ann Huff, MD, also of Johns Hopkins.

“Since it is much easier to draw blood than bone marrow from our patients, we think that we can primarily use blood to track multiple myeloma stem cells in the future.”

Response

Two patients did not receive MEDI-551 due to progressive disease and noncompliance. So the investigators assessed responses in 15 patients.

After cycle 2 (len-dex alone), there were 3 very good partial responses (VGPRs), 10 partial responses (PRs), 1 molecular response, and 1 case of stable disease.

After cycle 4 (len-dex plus MEDI-551), there were 6 VGPRs, 8 PRs, and 1 molecular response.

Ten patients who completed treatment with MED-551 remain on len-dex. At the end of cycle 7, there was 1 complete response, 8 VGPRs, and 1 PR.

CFU-MM

When compared to baseline, bone-marrow-derived CFU-MM increased a median of 2.5-fold (range, 0.4-7.4) after cycle 2 but decreased a median of 0.48-fold (range, 0.14-0.85) in 14 patients after cycle 4.

The investigators compared these results to 5 newly diagnosed MM patients who only received standard treatment with len-dex.

In these patients, CFU-MM increased a median of 9.3-fold (range, 4-14) at a median of 4 months (range, 2-4). This is in spite of the fact that all of these patients had a PR or better.

Circulating CSCs

Compared to baseline, circulating MM CSCs increased a median of 1.6-fold (range, 0.4-8.6) in 14 patients after cycle 2 but decreased a median of 0.6-fold (range, 0.01-7.4) in 13 patients after cycle 4.

At the end of cycle 5, MM CSCs had increased in 4 of the 10 patients who were still on len-dex. By the end of cycle 7, MM CSCs had increased in 8 of the patients.

Circulating MM CSCs increased by the end of cycle 4 in 2 patients, and both had progressed by end of cycle 7.

Safety and next steps

The investigators said there were no serious adverse events in this trial, but 2 patients experienced grade 2 infusion reactions after the first MEDI-551 dose.

The team plans to conduct further studies to assess the long-term impact of MED-551 in MM patients and determine how the mAb might work in combination with other treatments, particularly transplant.

“In other studies at Johns Hopkins, we have found that antibody therapies can work much better after a bone marrow transplant, especially allogeneic transplants,” Dr Matsui said.

Funding and drugs for this study were provided by MedImmune Inc., the developers of MEDI-551. Drs Huff and Matsui served as a paid scientific advisory board member and a consultant to MedImmune Inc., respectively.

Monoclonal antibodies

Photo by Linda Bartlett

NEW ORLEANS—A small study suggests that treatment with lenalidomide and dexamethasone (len-dex) prompts an increase in cancer stem cells (CSCs) for patients with newly diagnosed multiple myeloma (MM).

However, adding an anti-CD19 monoclonal antibody (mAb) to the regimen can reduce CSCs.

Most patients who received the mAb, MEDI-551, experienced a decrease in CSCs, but the cells rebounded after the patients stopped receiving  MEDI-551.

And those patients who did not see a decrease in CSCs progressed. However, some patients are still in response and remain on treatment with len-dex.

The investigators believe these early results suggest prolonged treatment with len-dex and MED-551 may be safe and clinically beneficial for MM patients.

The results were presented at the 2016 AACR Annual Meeting (abstract CT102).

The study included 17 patients with newly diagnosed MM. They had a median age of 65 (range, 34-73). Most had ISS stage I (n=11), 2 had stage II, and 4 had stage III. Seven patients had t(4;14).

“We chose to carry out this clinical trial in newly diagnosed patients because our original data showed that CD19 was almost always expressed by myeloma stem cells in these patients, whereas we don’t know if that is the case in more advanced patients,” said investigator William Matsui, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland.

The patients received 28-day cycles of len-dex (len at 25 mg PO, days 1-21, and dex at 40 mg PO, weekly). Patients received MEDI-551 (at 4 mg/kg IV) in cycle 3 (day 1, 8) and cycle 4 (day 1). Responding patients continued on len-dex.

The investigators measured MM CSCs by quantifying the growth of MM colonies (CFU-MM) from marrow aspirates at baseline and at the end of cycles 2 and 4.

The team quantified peripheral blood CSCs by flow cytometry (CD19+CD27+ALDH+) at baseline and the end of cycles 2, 4, 5, and 7.

“We wanted to see if these 2 assays gave similar results, and, in this clinical trial, they were almost identical,” said investigator Carol Ann Huff, MD, also of Johns Hopkins.

“Since it is much easier to draw blood than bone marrow from our patients, we think that we can primarily use blood to track multiple myeloma stem cells in the future.”

Response

Two patients did not receive MEDI-551 due to progressive disease and noncompliance. So the investigators assessed responses in 15 patients.

After cycle 2 (len-dex alone), there were 3 very good partial responses (VGPRs), 10 partial responses (PRs), 1 molecular response, and 1 case of stable disease.

After cycle 4 (len-dex plus MEDI-551), there were 6 VGPRs, 8 PRs, and 1 molecular response.

Ten patients who completed treatment with MED-551 remain on len-dex. At the end of cycle 7, there was 1 complete response, 8 VGPRs, and 1 PR.

CFU-MM

When compared to baseline, bone-marrow-derived CFU-MM increased a median of 2.5-fold (range, 0.4-7.4) after cycle 2 but decreased a median of 0.48-fold (range, 0.14-0.85) in 14 patients after cycle 4.

The investigators compared these results to 5 newly diagnosed MM patients who only received standard treatment with len-dex.

In these patients, CFU-MM increased a median of 9.3-fold (range, 4-14) at a median of 4 months (range, 2-4). This is in spite of the fact that all of these patients had a PR or better.

Circulating CSCs

Compared to baseline, circulating MM CSCs increased a median of 1.6-fold (range, 0.4-8.6) in 14 patients after cycle 2 but decreased a median of 0.6-fold (range, 0.01-7.4) in 13 patients after cycle 4.

At the end of cycle 5, MM CSCs had increased in 4 of the 10 patients who were still on len-dex. By the end of cycle 7, MM CSCs had increased in 8 of the patients.

Circulating MM CSCs increased by the end of cycle 4 in 2 patients, and both had progressed by end of cycle 7.

Safety and next steps

The investigators said there were no serious adverse events in this trial, but 2 patients experienced grade 2 infusion reactions after the first MEDI-551 dose.

The team plans to conduct further studies to assess the long-term impact of MED-551 in MM patients and determine how the mAb might work in combination with other treatments, particularly transplant.

“In other studies at Johns Hopkins, we have found that antibody therapies can work much better after a bone marrow transplant, especially allogeneic transplants,” Dr Matsui said.

Funding and drugs for this study were provided by MedImmune Inc., the developers of MEDI-551. Drs Huff and Matsui served as a paid scientific advisory board member and a consultant to MedImmune Inc., respectively.

Now with 15,000 members and growing, SHM continues to change the face of medicine—one patient at a time. We recently spoke with Dr. Glauber about her path to hospital medicine and why she believes in its continued growth and success during these times of unprecedented change.

Question: What steered you toward a career in hospital medicine?

Answer: Believe it or not, I did not enter medical school at New York Medical College with dreams of becoming a hospitalist. I first became aware of hospital medicine as a career path during my internal medicine residency at Loyola University School of Medicine in Maywood, Ill. I had some great hospitalist mentors during residency who clearly enjoyed their careers.

As I completed my training, hospital medicine was the clear choice for me. I wanted to manage patients with a variety of diagnoses and wasn’t ready to limit myself to any one subspecialty. I had always found diagnosis and management of acutely ill hospitalized patients to be the most interesting part of medicine, and I thoroughly enjoy working in the hospital environment. The field of hospital medicine was rapidly evolving, and I was curious to see where I could go with it. After four years, I can say with confidence that it has been a great experience.

Q: What do you see as the most rewarding part of your job?

A: Although my experiences practicing hospital medicine have been rewarding in a variety of ways, in the end, it’s pretty simple: I get satisfaction from helping my patients heal and helping them through the experience of hospitalization. It may take days, or it may take months to accomplish, and it is often the result of a cumulative effort of numerous hospitalists, consultants, and the entire hospital staff. But the reward for me is seeing my patient sitting in a chair, dressed in their street clothes, and waiting for their ride to come pick them up.

Q: Why do you think hospital medicine is the fastest-growing specialty in medicine? How can this momentum be sustained moving forward?

A: The growth of hospital medicine reflects the changing landscape of medicine nationwide. Hospitalist jobs are available because hospitals recognize the benefits of having us on hand to provide efficient and quality care to the patients. In terms of career choices, it is appealing to those coming straight out of residency, more experienced physicians practicing outpatient medicine, and even subspecialists who are looking for a career change. It is a satisfying and interesting job, which by nature benefits from unconventional work schedules. I think this flexibility is a big draw as well, in addition to the rewarding career.

Q: Why were you intrigued to join SHM and also attend Hospital Medicine 2016 (HM16)?

A: I think joining SHM is probably long overdue! I have been practicing for four years and feel that it’s time to take stock of my strengths and weaknesses as a hospitalist and try to improve. Through SHM, I can stay up to date on relevant medical topics, including everything from antibiotic resistance to glycemic control, as well as learn how to be a better hospitalist through the experience and research of colleagues. Attending HM16 seemed like a great way to get started, learn some new things, and network with hospitalists around the country.

Q: As a new member to SHM, what do you hope to gain from your membership?

A: I hope to hone my skills as a hospitalist and keep my finger on the pulse of hospital medicine. Keeping abreast of recent developments in medical knowledge and patient management is crucial to providing excellent patient care. There are also many other aspects of our day-to-day practice—for example, documentation and billing—that we weren’t taught how to manage in medical school. By joining SHM, I expect to benefit from the advice and experience of other hospitalists to improve my performance in these areas—and probably more I’ll learn about along the way.

Brett Radler is SHM’s communications coordinator.

Now with 15,000 members and growing, SHM continues to change the face of medicine—one patient at a time. We recently spoke with Dr. Glauber about her path to hospital medicine and why she believes in its continued growth and success during these times of unprecedented change.

Question: What steered you toward a career in hospital medicine?

Answer: Believe it or not, I did not enter medical school at New York Medical College with dreams of becoming a hospitalist. I first became aware of hospital medicine as a career path during my internal medicine residency at Loyola University School of Medicine in Maywood, Ill. I had some great hospitalist mentors during residency who clearly enjoyed their careers.

As I completed my training, hospital medicine was the clear choice for me. I wanted to manage patients with a variety of diagnoses and wasn’t ready to limit myself to any one subspecialty. I had always found diagnosis and management of acutely ill hospitalized patients to be the most interesting part of medicine, and I thoroughly enjoy working in the hospital environment. The field of hospital medicine was rapidly evolving, and I was curious to see where I could go with it. After four years, I can say with confidence that it has been a great experience.

Q: What do you see as the most rewarding part of your job?

A: Although my experiences practicing hospital medicine have been rewarding in a variety of ways, in the end, it’s pretty simple: I get satisfaction from helping my patients heal and helping them through the experience of hospitalization. It may take days, or it may take months to accomplish, and it is often the result of a cumulative effort of numerous hospitalists, consultants, and the entire hospital staff. But the reward for me is seeing my patient sitting in a chair, dressed in their street clothes, and waiting for their ride to come pick them up.

Q: Why do you think hospital medicine is the fastest-growing specialty in medicine? How can this momentum be sustained moving forward?

A: The growth of hospital medicine reflects the changing landscape of medicine nationwide. Hospitalist jobs are available because hospitals recognize the benefits of having us on hand to provide efficient and quality care to the patients. In terms of career choices, it is appealing to those coming straight out of residency, more experienced physicians practicing outpatient medicine, and even subspecialists who are looking for a career change. It is a satisfying and interesting job, which by nature benefits from unconventional work schedules. I think this flexibility is a big draw as well, in addition to the rewarding career.

Q: Why were you intrigued to join SHM and also attend Hospital Medicine 2016 (HM16)?

A: I think joining SHM is probably long overdue! I have been practicing for four years and feel that it’s time to take stock of my strengths and weaknesses as a hospitalist and try to improve. Through SHM, I can stay up to date on relevant medical topics, including everything from antibiotic resistance to glycemic control, as well as learn how to be a better hospitalist through the experience and research of colleagues. Attending HM16 seemed like a great way to get started, learn some new things, and network with hospitalists around the country.

Q: As a new member to SHM, what do you hope to gain from your membership?

A: I hope to hone my skills as a hospitalist and keep my finger on the pulse of hospital medicine. Keeping abreast of recent developments in medical knowledge and patient management is crucial to providing excellent patient care. There are also many other aspects of our day-to-day practice—for example, documentation and billing—that we weren’t taught how to manage in medical school. By joining SHM, I expect to benefit from the advice and experience of other hospitalists to improve my performance in these areas—and probably more I’ll learn about along the way.

Brett Radler is SHM’s communications coordinator.

Now with 15,000 members and growing, SHM continues to change the face of medicine—one patient at a time. We recently spoke with Dr. Glauber about her path to hospital medicine and why she believes in its continued growth and success during these times of unprecedented change.

Question: What steered you toward a career in hospital medicine?

Answer: Believe it or not, I did not enter medical school at New York Medical College with dreams of becoming a hospitalist. I first became aware of hospital medicine as a career path during my internal medicine residency at Loyola University School of Medicine in Maywood, Ill. I had some great hospitalist mentors during residency who clearly enjoyed their careers.

As I completed my training, hospital medicine was the clear choice for me. I wanted to manage patients with a variety of diagnoses and wasn’t ready to limit myself to any one subspecialty. I had always found diagnosis and management of acutely ill hospitalized patients to be the most interesting part of medicine, and I thoroughly enjoy working in the hospital environment. The field of hospital medicine was rapidly evolving, and I was curious to see where I could go with it. After four years, I can say with confidence that it has been a great experience.

Q: What do you see as the most rewarding part of your job?

A: Although my experiences practicing hospital medicine have been rewarding in a variety of ways, in the end, it’s pretty simple: I get satisfaction from helping my patients heal and helping them through the experience of hospitalization. It may take days, or it may take months to accomplish, and it is often the result of a cumulative effort of numerous hospitalists, consultants, and the entire hospital staff. But the reward for me is seeing my patient sitting in a chair, dressed in their street clothes, and waiting for their ride to come pick them up.

Q: Why do you think hospital medicine is the fastest-growing specialty in medicine? How can this momentum be sustained moving forward?

A: The growth of hospital medicine reflects the changing landscape of medicine nationwide. Hospitalist jobs are available because hospitals recognize the benefits of having us on hand to provide efficient and quality care to the patients. In terms of career choices, it is appealing to those coming straight out of residency, more experienced physicians practicing outpatient medicine, and even subspecialists who are looking for a career change. It is a satisfying and interesting job, which by nature benefits from unconventional work schedules. I think this flexibility is a big draw as well, in addition to the rewarding career.

Q: Why were you intrigued to join SHM and also attend Hospital Medicine 2016 (HM16)?

A: I think joining SHM is probably long overdue! I have been practicing for four years and feel that it’s time to take stock of my strengths and weaknesses as a hospitalist and try to improve. Through SHM, I can stay up to date on relevant medical topics, including everything from antibiotic resistance to glycemic control, as well as learn how to be a better hospitalist through the experience and research of colleagues. Attending HM16 seemed like a great way to get started, learn some new things, and network with hospitalists around the country.

Q: As a new member to SHM, what do you hope to gain from your membership?

A: I hope to hone my skills as a hospitalist and keep my finger on the pulse of hospital medicine. Keeping abreast of recent developments in medical knowledge and patient management is crucial to providing excellent patient care. There are also many other aspects of our day-to-day practice—for example, documentation and billing—that we weren’t taught how to manage in medical school. By joining SHM, I expect to benefit from the advice and experience of other hospitalists to improve my performance in these areas—and probably more I’ll learn about along the way.

Brett Radler is SHM’s communications coordinator.

N. Abel, MD, Alabama

A. Aboutalib, California

A. Afzal, MD, FACP, California

J. Allison, California

K. Anand, MD, California

K. Andruchow, APN, California

A. Anter, DO, California

M. Aresery, MD, California

L. Atkins, MD, California

N. Bassi, MD, PhD, California

H. Briggs, MD, PhD, California

E. Burgh, California

C. Caulfield, MD, California

P. C. Mohan, MD, California

D. Chau, MD, California

D. DeVere, MD, California

O. Dimitrijevic, MD, Colorado

P. Dodson, MD, Delaware

A. Domaoal, Florida

J. Dzundza, MD, Florida

A. Ellis, FNP, Florida

R. Erickson, Florida

A. Falescky, MD, Florida

W. Folad, MD, Georgia

K. Forb, Georgia

B. Fromkin, APN, Idaho

N. Gabriel, MD, Idaho

K. Gausewitz, Illinois

B. George, MD, Illinois

G. Goldman, MD, Kansas

A. Gonzalez, Kansas

G. Goyal, Kansas

W. Griffo, MD, Kentucky

D. Grygla, DO, MPH, FAAFP, Louisiana

B. Hammond, Louisiana

H. Haque, Louisiana

G. Harris, MD, Massachusetts

J. Harris, DO, Massachusetts

J. Hasan-Jones, FACHE, Massachusetts

L. Hsu, MD, Michigan

C. Janish, Michigan

S. Jindal, MD, Michigan

M. Johl, Minnesota

T. John, Missouri

D. Julka, MD, Missouri

O. Kamalu, MD, North Carolina

N. Kapadia, MD, New Jersey

K. Kaye, New Jersey

M. Keating, New Jersey

L. Kendall, New Jersey

M. L. Kerlin, New Jersey

T. Khan, New Jersey

A. Kim, APN, New Jersey

R. Klett, New Jersey

K. Knox, New Jersey

M. Kraynyak, MD, New Jersey

C. Larion, ACNP, New Jersey

D. Leforce, New Jersey

C. Leon, New Jersey

X. Li, MD, New Jersey

C. Maturo, DO, New Jersey

L. McGann, New York

R. Mercado Garcia, New York

J. Mikulca, PharmD, New York

M. Minock, APN, New York

Z. Moyenda, MD, MBA, New York

G. Nanna, USA, New York

I. Nasir, New York

D. Nestler, APN, New York

H. Nurse Bey, MD, New York

B. Oran, New York

N. Patel, MD, New York

V. Paulson, MD, New York

R. Porter, PA, Ohio

P. Prabhakar, Ohio

R. Quansah, MD, Ohio

F. Qureshi, MD, Ohio

M. Rahman, Ohio

R. Rajeshwar, Ohio

E. Randal, Ohio

A. Ray, Ohio

R. Regidor, Oklahoma

R. Reyes, MD, Oregon

T. Richardson, NP, Oregon

L. Rivera-Crespo, Oregon

T. Rothwell, PA, Oregon

E. Sacolick, MD, Pennsylvania

D. Sakai, Pennsylvania

M. Sapon-Amoah, FNP, Pennsylvania

M. M. Scoulos-Hanson, Pennsylvania

K. Seger, Pennsylvania

K. Shah, MD, Pennsylvania

S. Shah, MD, Pennsylvania

K. Shaukat, MD, Pennsylvania

J. Shipe-Spotloe, MS, PA-C, Pennsylvania

S. Sim, South Carolina

M. N. Simon, MD, MMM, CPE, South Carolina

A. Singh, South Carolina

S. Singh-Patel, DO, South Carolina

A. Srikanth, MBBS, South Carolina

R. Stanhiser, MD, Tennessee

J. Steinberg, MD, PhD, ACLS, Texas

L. Taylor, PA-C, Texas

E. Taylor, MD, Texas

L. Theaker, Texas

M. Thieman, Texas

J. Tong, Texas

L. Tuazon, MD, FACP, Texas

S. Tummalapalli, Utah

A. Ufferman, MD, Washington

N. Van Groningen, Washington

D. Vaughn, MD, Washington

K. Vo, Washington

T. Washko, MD, Wisconson

T. Waters, DO, West Virginia

L. Weisberger, USA, West Virginia

K. Welch, West Virginia

A. Whitehead, West Virginia

A. Yoon, MD, West Virginia

M. A. Yu, West Virginia

A. Yuen, DO, West Virginia

N. Abel, MD, Alabama

A. Aboutalib, California

A. Afzal, MD, FACP, California

J. Allison, California

K. Anand, MD, California

K. Andruchow, APN, California

A. Anter, DO, California

M. Aresery, MD, California

L. Atkins, MD, California

N. Bassi, MD, PhD, California

H. Briggs, MD, PhD, California

E. Burgh, California

C. Caulfield, MD, California

P. C. Mohan, MD, California

D. Chau, MD, California

D. DeVere, MD, California

O. Dimitrijevic, MD, Colorado

P. Dodson, MD, Delaware

A. Domaoal, Florida

J. Dzundza, MD, Florida

A. Ellis, FNP, Florida

R. Erickson, Florida

A. Falescky, MD, Florida

W. Folad, MD, Georgia

K. Forb, Georgia

B. Fromkin, APN, Idaho

N. Gabriel, MD, Idaho

K. Gausewitz, Illinois

B. George, MD, Illinois

G. Goldman, MD, Kansas

A. Gonzalez, Kansas

G. Goyal, Kansas

W. Griffo, MD, Kentucky

D. Grygla, DO, MPH, FAAFP, Louisiana

B. Hammond, Louisiana

H. Haque, Louisiana

G. Harris, MD, Massachusetts

J. Harris, DO, Massachusetts

J. Hasan-Jones, FACHE, Massachusetts

L. Hsu, MD, Michigan

C. Janish, Michigan

S. Jindal, MD, Michigan

M. Johl, Minnesota

T. John, Missouri

D. Julka, MD, Missouri

O. Kamalu, MD, North Carolina

N. Kapadia, MD, New Jersey

K. Kaye, New Jersey

M. Keating, New Jersey

L. Kendall, New Jersey

M. L. Kerlin, New Jersey

T. Khan, New Jersey

A. Kim, APN, New Jersey

R. Klett, New Jersey

K. Knox, New Jersey

M. Kraynyak, MD, New Jersey

C. Larion, ACNP, New Jersey

D. Leforce, New Jersey

C. Leon, New Jersey

X. Li, MD, New Jersey

C. Maturo, DO, New Jersey

L. McGann, New York

R. Mercado Garcia, New York

J. Mikulca, PharmD, New York

M. Minock, APN, New York

Z. Moyenda, MD, MBA, New York

G. Nanna, USA, New York

I. Nasir, New York

D. Nestler, APN, New York

H. Nurse Bey, MD, New York

B. Oran, New York

N. Patel, MD, New York

V. Paulson, MD, New York

R. Porter, PA, Ohio

P. Prabhakar, Ohio

R. Quansah, MD, Ohio

F. Qureshi, MD, Ohio

M. Rahman, Ohio

R. Rajeshwar, Ohio

E. Randal, Ohio

A. Ray, Ohio

R. Regidor, Oklahoma

R. Reyes, MD, Oregon

T. Richardson, NP, Oregon

L. Rivera-Crespo, Oregon

T. Rothwell, PA, Oregon

E. Sacolick, MD, Pennsylvania

D. Sakai, Pennsylvania

M. Sapon-Amoah, FNP, Pennsylvania

M. M. Scoulos-Hanson, Pennsylvania

K. Seger, Pennsylvania

K. Shah, MD, Pennsylvania

S. Shah, MD, Pennsylvania

K. Shaukat, MD, Pennsylvania

J. Shipe-Spotloe, MS, PA-C, Pennsylvania

S. Sim, South Carolina

M. N. Simon, MD, MMM, CPE, South Carolina

A. Singh, South Carolina

S. Singh-Patel, DO, South Carolina

A. Srikanth, MBBS, South Carolina

R. Stanhiser, MD, Tennessee

J. Steinberg, MD, PhD, ACLS, Texas

L. Taylor, PA-C, Texas

E. Taylor, MD, Texas

L. Theaker, Texas

M. Thieman, Texas

J. Tong, Texas

L. Tuazon, MD, FACP, Texas

S. Tummalapalli, Utah

A. Ufferman, MD, Washington

N. Van Groningen, Washington

D. Vaughn, MD, Washington

K. Vo, Washington

T. Washko, MD, Wisconson

T. Waters, DO, West Virginia

L. Weisberger, USA, West Virginia

K. Welch, West Virginia

A. Whitehead, West Virginia

A. Yoon, MD, West Virginia

M. A. Yu, West Virginia

A. Yuen, DO, West Virginia

N. Abel, MD, Alabama

A. Aboutalib, California

A. Afzal, MD, FACP, California

J. Allison, California

K. Anand, MD, California

K. Andruchow, APN, California

A. Anter, DO, California

M. Aresery, MD, California

L. Atkins, MD, California

N. Bassi, MD, PhD, California

H. Briggs, MD, PhD, California

E. Burgh, California

C. Caulfield, MD, California

P. C. Mohan, MD, California

D. Chau, MD, California

D. DeVere, MD, California

O. Dimitrijevic, MD, Colorado

P. Dodson, MD, Delaware

A. Domaoal, Florida

J. Dzundza, MD, Florida

A. Ellis, FNP, Florida

R. Erickson, Florida

A. Falescky, MD, Florida

W. Folad, MD, Georgia

K. Forb, Georgia

B. Fromkin, APN, Idaho

N. Gabriel, MD, Idaho

K. Gausewitz, Illinois

B. George, MD, Illinois

G. Goldman, MD, Kansas

A. Gonzalez, Kansas

G. Goyal, Kansas

W. Griffo, MD, Kentucky

D. Grygla, DO, MPH, FAAFP, Louisiana

B. Hammond, Louisiana

H. Haque, Louisiana

G. Harris, MD, Massachusetts

J. Harris, DO, Massachusetts

J. Hasan-Jones, FACHE, Massachusetts

L. Hsu, MD, Michigan

C. Janish, Michigan

S. Jindal, MD, Michigan

M. Johl, Minnesota

T. John, Missouri

D. Julka, MD, Missouri

O. Kamalu, MD, North Carolina

N. Kapadia, MD, New Jersey

K. Kaye, New Jersey

M. Keating, New Jersey

L. Kendall, New Jersey

M. L. Kerlin, New Jersey

T. Khan, New Jersey

A. Kim, APN, New Jersey

R. Klett, New Jersey

K. Knox, New Jersey

M. Kraynyak, MD, New Jersey

C. Larion, ACNP, New Jersey

D. Leforce, New Jersey

C. Leon, New Jersey

X. Li, MD, New Jersey

C. Maturo, DO, New Jersey

L. McGann, New York

R. Mercado Garcia, New York

J. Mikulca, PharmD, New York

M. Minock, APN, New York

Z. Moyenda, MD, MBA, New York

G. Nanna, USA, New York

I. Nasir, New York

D. Nestler, APN, New York

H. Nurse Bey, MD, New York

B. Oran, New York

N. Patel, MD, New York

V. Paulson, MD, New York

R. Porter, PA, Ohio

P. Prabhakar, Ohio

R. Quansah, MD, Ohio

F. Qureshi, MD, Ohio

M. Rahman, Ohio

R. Rajeshwar, Ohio

E. Randal, Ohio

A. Ray, Ohio

R. Regidor, Oklahoma

R. Reyes, MD, Oregon

T. Richardson, NP, Oregon

L. Rivera-Crespo, Oregon

T. Rothwell, PA, Oregon

E. Sacolick, MD, Pennsylvania

D. Sakai, Pennsylvania

M. Sapon-Amoah, FNP, Pennsylvania

M. M. Scoulos-Hanson, Pennsylvania

K. Seger, Pennsylvania

K. Shah, MD, Pennsylvania

S. Shah, MD, Pennsylvania

K. Shaukat, MD, Pennsylvania

J. Shipe-Spotloe, MS, PA-C, Pennsylvania

S. Sim, South Carolina

M. N. Simon, MD, MMM, CPE, South Carolina

A. Singh, South Carolina

S. Singh-Patel, DO, South Carolina

A. Srikanth, MBBS, South Carolina

R. Stanhiser, MD, Tennessee

J. Steinberg, MD, PhD, ACLS, Texas

L. Taylor, PA-C, Texas

E. Taylor, MD, Texas

L. Theaker, Texas

M. Thieman, Texas

J. Tong, Texas

L. Tuazon, MD, FACP, Texas

S. Tummalapalli, Utah

A. Ufferman, MD, Washington

N. Van Groningen, Washington

D. Vaughn, MD, Washington

K. Vo, Washington

T. Washko, MD, Wisconson

T. Waters, DO, West Virginia

L. Weisberger, USA, West Virginia

K. Welch, West Virginia

A. Whitehead, West Virginia

A. Yoon, MD, West Virginia

M. A. Yu, West Virginia

A. Yuen, DO, West Virginia

(Reuters Health) - When it comes to urgent medical problems like ankle injuries or suspected strep, virtual MDs may be no match for the real thing, a new U.S. study suggests.

Researchers enlisted 67 volunteers to test out how well eight popular virtual visit companies diagnosed these problems and four other common medical issues - sore throat, sinus infection, low back pain, and urinary tract infection.

About one in four patients got the wrong diagnosis or none at all from the virtual visits, the study found. What's more, virtual doctors followed standard protocols for diagnosing and treating these problems only 54% of the time.

"One of the more surprising findings of the study was the universally low rate of testing when it was needed," said lead researcher Dr. Adam Schoenfeld, of the University of California, San Francisco.

"We don't know why, but it may reflect the challenges of ordering or following up on tests performed near where the patient lives but far from where the doctor is, or concern about the costs to the patient of additional testing," Schoenfeld added by email.

Virtual visits using videoconferences, phone calls and web chats are becoming a more common way for patients to seek urgent care because it can save the inconvenience of a clinic visit or provide access to care when people can't get an appointment with their regular doctor.

Some insurers are starting to pay for virtual visits in certain situations, making this option more viable for patients who worry about costs.

For the current study, Schoenfeld and colleagues trained volunteers to act as if they had common acute medical problems and then sent them to virtual doctors provided by companies including Ameridoc, Amwell, Consult a Doctor, Doctor on Demand, MDAligne, MDLIVE, MeMD and NowClinic.

Altogether, the volunteers completed 599 virtual visits in 2013 and 2014.

The companies varied in how well they followed treatment guidelines, with standard care given anywhere from 34 to 66% of the time across the eight websites, the researchers report in JAMA Internal Medicine April 4.

Mode of communication - such as web chat or videoconference - didn't appear to influence how often treatment guidelines were

followed.

Virtual doctors got complete histories and did thorough exams anywhere from 52% to 82% of the time.   Virtual visits resulted in correct diagnoses anywhere from 65% to 94% of the time.

Often, virtual doctors failed to order urine tests needed to assess urinary tract infections, or to request images needed to diagnoses ankle pain, for example, and antibiotics were often prescribed inappropriately.

One limitation of the study is that the researchers only looked at virtual visits, so they couldn't compare these online doctors' visits to what might have happened with in-person clinical exams.

Still, it's possible that at least some of the variation in quality of care was the result of the remote visits, said Dr. Jeffrey Linder, a researcher at Brigham and Women's Hospital and Harvard Medical School who co-authored an editorial accompanying the study.

"There is a built-in barrier to getting testing, which led to worse care for ankle pain and recurrent urinary tract infections - for which the doctors should have ordered a test - and better care for low back pain - for which doctors should not have ordered a test," Linder said by email.

In an ideal world, patients would be able to have occasional virtual visits with their primary care providers, who know their medical histories, said Dr. David Levine, co-author of the editorial and also a researcher at Brigham and Women's and Harvard.

Although virtual urgent care and in-person urgent care have not been compared head-to-head, virtual urgent care has its downsides - indirect physical exam, difficult access to testing, and unclear follow-up," Levine said by email. "While the quality of care is not perfect anywhere, a patient's primary care doctor should be a person's first point of contact."

(Reuters Health) - When it comes to urgent medical problems like ankle injuries or suspected strep, virtual MDs may be no match for the real thing, a new U.S. study suggests.

Researchers enlisted 67 volunteers to test out how well eight popular virtual visit companies diagnosed these problems and four other common medical issues - sore throat, sinus infection, low back pain, and urinary tract infection.

About one in four patients got the wrong diagnosis or none at all from the virtual visits, the study found. What's more, virtual doctors followed standard protocols for diagnosing and treating these problems only 54% of the time.

"One of the more surprising findings of the study was the universally low rate of testing when it was needed," said lead researcher Dr. Adam Schoenfeld, of the University of California, San Francisco.

"We don't know why, but it may reflect the challenges of ordering or following up on tests performed near where the patient lives but far from where the doctor is, or concern about the costs to the patient of additional testing," Schoenfeld added by email.

Virtual visits using videoconferences, phone calls and web chats are becoming a more common way for patients to seek urgent care because it can save the inconvenience of a clinic visit or provide access to care when people can't get an appointment with their regular doctor.

Some insurers are starting to pay for virtual visits in certain situations, making this option more viable for patients who worry about costs.

For the current study, Schoenfeld and colleagues trained volunteers to act as if they had common acute medical problems and then sent them to virtual doctors provided by companies including Ameridoc, Amwell, Consult a Doctor, Doctor on Demand, MDAligne, MDLIVE, MeMD and NowClinic.

Altogether, the volunteers completed 599 virtual visits in 2013 and 2014.

The companies varied in how well they followed treatment guidelines, with standard care given anywhere from 34 to 66% of the time across the eight websites, the researchers report in JAMA Internal Medicine April 4.

Mode of communication - such as web chat or videoconference - didn't appear to influence how often treatment guidelines were

followed.

Virtual doctors got complete histories and did thorough exams anywhere from 52% to 82% of the time.   Virtual visits resulted in correct diagnoses anywhere from 65% to 94% of the time.

Often, virtual doctors failed to order urine tests needed to assess urinary tract infections, or to request images needed to diagnoses ankle pain, for example, and antibiotics were often prescribed inappropriately.

One limitation of the study is that the researchers only looked at virtual visits, so they couldn't compare these online doctors' visits to what might have happened with in-person clinical exams.

Still, it's possible that at least some of the variation in quality of care was the result of the remote visits, said Dr. Jeffrey Linder, a researcher at Brigham and Women's Hospital and Harvard Medical School who co-authored an editorial accompanying the study.

"There is a built-in barrier to getting testing, which led to worse care for ankle pain and recurrent urinary tract infections - for which the doctors should have ordered a test - and better care for low back pain - for which doctors should not have ordered a test," Linder said by email.

In an ideal world, patients would be able to have occasional virtual visits with their primary care providers, who know their medical histories, said Dr. David Levine, co-author of the editorial and also a researcher at Brigham and Women's and Harvard.

Although virtual urgent care and in-person urgent care have not been compared head-to-head, virtual urgent care has its downsides - indirect physical exam, difficult access to testing, and unclear follow-up," Levine said by email. "While the quality of care is not perfect anywhere, a patient's primary care doctor should be a person's first point of contact."

(Reuters Health) - When it comes to urgent medical problems like ankle injuries or suspected strep, virtual MDs may be no match for the real thing, a new U.S. study suggests.

Researchers enlisted 67 volunteers to test out how well eight popular virtual visit companies diagnosed these problems and four other common medical issues - sore throat, sinus infection, low back pain, and urinary tract infection.

About one in four patients got the wrong diagnosis or none at all from the virtual visits, the study found. What's more, virtual doctors followed standard protocols for diagnosing and treating these problems only 54% of the time.

"One of the more surprising findings of the study was the universally low rate of testing when it was needed," said lead researcher Dr. Adam Schoenfeld, of the University of California, San Francisco.

"We don't know why, but it may reflect the challenges of ordering or following up on tests performed near where the patient lives but far from where the doctor is, or concern about the costs to the patient of additional testing," Schoenfeld added by email.

Virtual visits using videoconferences, phone calls and web chats are becoming a more common way for patients to seek urgent care because it can save the inconvenience of a clinic visit or provide access to care when people can't get an appointment with their regular doctor.

Some insurers are starting to pay for virtual visits in certain situations, making this option more viable for patients who worry about costs.

For the current study, Schoenfeld and colleagues trained volunteers to act as if they had common acute medical problems and then sent them to virtual doctors provided by companies including Ameridoc, Amwell, Consult a Doctor, Doctor on Demand, MDAligne, MDLIVE, MeMD and NowClinic.

Altogether, the volunteers completed 599 virtual visits in 2013 and 2014.

The companies varied in how well they followed treatment guidelines, with standard care given anywhere from 34 to 66% of the time across the eight websites, the researchers report in JAMA Internal Medicine April 4.

Mode of communication - such as web chat or videoconference - didn't appear to influence how often treatment guidelines were

followed.

Virtual doctors got complete histories and did thorough exams anywhere from 52% to 82% of the time.   Virtual visits resulted in correct diagnoses anywhere from 65% to 94% of the time.

Often, virtual doctors failed to order urine tests needed to assess urinary tract infections, or to request images needed to diagnoses ankle pain, for example, and antibiotics were often prescribed inappropriately.

One limitation of the study is that the researchers only looked at virtual visits, so they couldn't compare these online doctors' visits to what might have happened with in-person clinical exams.

Still, it's possible that at least some of the variation in quality of care was the result of the remote visits, said Dr. Jeffrey Linder, a researcher at Brigham and Women's Hospital and Harvard Medical School who co-authored an editorial accompanying the study.

"There is a built-in barrier to getting testing, which led to worse care for ankle pain and recurrent urinary tract infections - for which the doctors should have ordered a test - and better care for low back pain - for which doctors should not have ordered a test," Linder said by email.

In an ideal world, patients would be able to have occasional virtual visits with their primary care providers, who know their medical histories, said Dr. David Levine, co-author of the editorial and also a researcher at Brigham and Women's and Harvard.

Although virtual urgent care and in-person urgent care have not been compared head-to-head, virtual urgent care has its downsides - indirect physical exam, difficult access to testing, and unclear follow-up," Levine said by email. "While the quality of care is not perfect anywhere, a patient's primary care doctor should be a person's first point of contact."

Lab mice

Photo by Aaron Logan

NEW ORLEANS—Preclinical data suggest IMMU-114, a humanized anti-HLA-DR IgG4 antibody, is active against acute and chronic leukemias.

In a mouse model of chronic lymphocytic leukemia (CLL), IMMU-114 significantly prolonged survival when compared to rituximab.

IMMU-114 also produced a significant survival benefit in a mouse model of acute lymphoblastic leukemia (ALL) that is refractory to doxorubicin.

These results were presented at the 2016 AACR Annual Meeting (abstract 587). The research was carried out by employees of Immunomedics, Inc., the company developing IMMU-114.

The researchers generated a mouse model of human CLL by growing the cell line JVM-3 in SCID mice. The team noted that this model has similar HLA-DR and CD20 expression.

So they compared the efficacy of IMMU-114 and the anti-CD20 antibody rituximab in these mice and found that, at all doses tested, IMMU-114 significantly improved the median survival time (MST).

When both drugs were given at 50 µg, the MST was 42 days with IMMU-114 and 19 days with rituximab (P<0.0001).

When both drugs were given at 100 µg, the MSTs were 54 days and 18 days, respectively (P=0.017). And when both drugs were given at 200 µg, the MSTs were 46 days and 18 days, respectively (P<0.0001).

In control mice that received only saline, the MST was 14 days.

In in vitro experiments with the cell line JVM-3, IMMU-114 and the BTK inhibitor ibrutinib exhibited synergy fighting against the CLL cells. When given with the PI3K inhibitor idelalisib, IMMU-114 produced an additive effect.

In a doxorubicin-refractory mouse model of ALL (MN 60), IMMU-114 provided a significant survival benefit over doxorubicin and saline controls.

The MSTs were 21 days with saline, 23 days with doxorubicin, 39 days with IMMU-114 at 25 µg (P<0.0001), and 42.5 days with IMMU-114 at 50 µg (P<0.0001).

The researchers said IMMU-114 was well tolerated in these experiments, as evidenced by no significant weight loss in the mice.

Lab mice

Photo by Aaron Logan

NEW ORLEANS—Preclinical data suggest IMMU-114, a humanized anti-HLA-DR IgG4 antibody, is active against acute and chronic leukemias.

In a mouse model of chronic lymphocytic leukemia (CLL), IMMU-114 significantly prolonged survival when compared to rituximab.

IMMU-114 also produced a significant survival benefit in a mouse model of acute lymphoblastic leukemia (ALL) that is refractory to doxorubicin.

These results were presented at the 2016 AACR Annual Meeting (abstract 587). The research was carried out by employees of Immunomedics, Inc., the company developing IMMU-114.

The researchers generated a mouse model of human CLL by growing the cell line JVM-3 in SCID mice. The team noted that this model has similar HLA-DR and CD20 expression.

So they compared the efficacy of IMMU-114 and the anti-CD20 antibody rituximab in these mice and found that, at all doses tested, IMMU-114 significantly improved the median survival time (MST).

When both drugs were given at 50 µg, the MST was 42 days with IMMU-114 and 19 days with rituximab (P<0.0001).

When both drugs were given at 100 µg, the MSTs were 54 days and 18 days, respectively (P=0.017). And when both drugs were given at 200 µg, the MSTs were 46 days and 18 days, respectively (P<0.0001).

In control mice that received only saline, the MST was 14 days.

In in vitro experiments with the cell line JVM-3, IMMU-114 and the BTK inhibitor ibrutinib exhibited synergy fighting against the CLL cells. When given with the PI3K inhibitor idelalisib, IMMU-114 produced an additive effect.

In a doxorubicin-refractory mouse model of ALL (MN 60), IMMU-114 provided a significant survival benefit over doxorubicin and saline controls.

The MSTs were 21 days with saline, 23 days with doxorubicin, 39 days with IMMU-114 at 25 µg (P<0.0001), and 42.5 days with IMMU-114 at 50 µg (P<0.0001).

The researchers said IMMU-114 was well tolerated in these experiments, as evidenced by no significant weight loss in the mice.

Lab mice

Photo by Aaron Logan

NEW ORLEANS—Preclinical data suggest IMMU-114, a humanized anti-HLA-DR IgG4 antibody, is active against acute and chronic leukemias.

In a mouse model of chronic lymphocytic leukemia (CLL), IMMU-114 significantly prolonged survival when compared to rituximab.

IMMU-114 also produced a significant survival benefit in a mouse model of acute lymphoblastic leukemia (ALL) that is refractory to doxorubicin.

These results were presented at the 2016 AACR Annual Meeting (abstract 587). The research was carried out by employees of Immunomedics, Inc., the company developing IMMU-114.

The researchers generated a mouse model of human CLL by growing the cell line JVM-3 in SCID mice. The team noted that this model has similar HLA-DR and CD20 expression.

So they compared the efficacy of IMMU-114 and the anti-CD20 antibody rituximab in these mice and found that, at all doses tested, IMMU-114 significantly improved the median survival time (MST).

When both drugs were given at 50 µg, the MST was 42 days with IMMU-114 and 19 days with rituximab (P<0.0001).

When both drugs were given at 100 µg, the MSTs were 54 days and 18 days, respectively (P=0.017). And when both drugs were given at 200 µg, the MSTs were 46 days and 18 days, respectively (P<0.0001).

In control mice that received only saline, the MST was 14 days.

In in vitro experiments with the cell line JVM-3, IMMU-114 and the BTK inhibitor ibrutinib exhibited synergy fighting against the CLL cells. When given with the PI3K inhibitor idelalisib, IMMU-114 produced an additive effect.

In a doxorubicin-refractory mouse model of ALL (MN 60), IMMU-114 provided a significant survival benefit over doxorubicin and saline controls.

The MSTs were 21 days with saline, 23 days with doxorubicin, 39 days with IMMU-114 at 25 µg (P<0.0001), and 42.5 days with IMMU-114 at 50 µg (P<0.0001).

The researchers said IMMU-114 was well tolerated in these experiments, as evidenced by no significant weight loss in the mice.

CML cells

Image from UC San Diego

Scientists say they have developed a model that can be used to calculate the proportion of cancer stem cells (CSCs) present over the course of treatment.

The model is designed to enable estimation of CSC fractions from longitudinal measurements of tumor burden.

The scientists tested the model in patients with chronic myeloid leukemia (CML) and found evidence to suggest the proportion of CSCs increases

substantially during extended treatment.

The team believes the model could eventually be used to help doctors predict tumor development and help them select suitable treatments for cancer patients.

“Cancer stem cells not only promote the growth of a tumor, they can also be resistant to radiotherapy and chemotherapy,” said Philipp Altrock, PhD, of the Dana Farber Cancer Institute in Boston, Massachusetts.

“If we can estimate the number of cancer stem cells at diagnosis and over the course of treatment, the treatment can be tailored accordingly.”

Dr Altrock and his colleagues discussed this possibility in Cancer Research.

The team first explained that their model incorporates tumor dynamics and tumor burden information. They said tumor expansion and regression curves can be leveraged to estimate the proportion of CSCs in individual patients at baseline and during therapy.

To test their model, the scientists used 2 independent cohorts of CML patients. The team evaluated the growth and decline of CML over the course of treatment with the tyrosine kinase inhibitor imatinib.

Based on the change of disease burden during treatment, the model calculated the proportion of CSCs.

Results suggested the proportion of CSCs in CML patients increases 100-fold after a year of treatment with imatinib. And that proportion continues to increase up to 1000-fold after 5 years of treatment.

The scientists noted that this model is parameter-free, so it can be applied to different types of cancer. However, they said further development is required before the model can be used in clinical practice.

CML cells

Image from UC San Diego

Scientists say they have developed a model that can be used to calculate the proportion of cancer stem cells (CSCs) present over the course of treatment.

The model is designed to enable estimation of CSC fractions from longitudinal measurements of tumor burden.

The scientists tested the model in patients with chronic myeloid leukemia (CML) and found evidence to suggest the proportion of CSCs increases

substantially during extended treatment.

The team believes the model could eventually be used to help doctors predict tumor development and help them select suitable treatments for cancer patients.

“Cancer stem cells not only promote the growth of a tumor, they can also be resistant to radiotherapy and chemotherapy,” said Philipp Altrock, PhD, of the Dana Farber Cancer Institute in Boston, Massachusetts.

“If we can estimate the number of cancer stem cells at diagnosis and over the course of treatment, the treatment can be tailored accordingly.”

Dr Altrock and his colleagues discussed this possibility in Cancer Research.

The team first explained that their model incorporates tumor dynamics and tumor burden information. They said tumor expansion and regression curves can be leveraged to estimate the proportion of CSCs in individual patients at baseline and during therapy.

To test their model, the scientists used 2 independent cohorts of CML patients. The team evaluated the growth and decline of CML over the course of treatment with the tyrosine kinase inhibitor imatinib.

Based on the change of disease burden during treatment, the model calculated the proportion of CSCs.

Results suggested the proportion of CSCs in CML patients increases 100-fold after a year of treatment with imatinib. And that proportion continues to increase up to 1000-fold after 5 years of treatment.

The scientists noted that this model is parameter-free, so it can be applied to different types of cancer. However, they said further development is required before the model can be used in clinical practice.

CML cells

Image from UC San Diego

Scientists say they have developed a model that can be used to calculate the proportion of cancer stem cells (CSCs) present over the course of treatment.

The model is designed to enable estimation of CSC fractions from longitudinal measurements of tumor burden.

The scientists tested the model in patients with chronic myeloid leukemia (CML) and found evidence to suggest the proportion of CSCs increases

substantially during extended treatment.

The team believes the model could eventually be used to help doctors predict tumor development and help them select suitable treatments for cancer patients.

“Cancer stem cells not only promote the growth of a tumor, they can also be resistant to radiotherapy and chemotherapy,” said Philipp Altrock, PhD, of the Dana Farber Cancer Institute in Boston, Massachusetts.

“If we can estimate the number of cancer stem cells at diagnosis and over the course of treatment, the treatment can be tailored accordingly.”

Dr Altrock and his colleagues discussed this possibility in Cancer Research.

The team first explained that their model incorporates tumor dynamics and tumor burden information. They said tumor expansion and regression curves can be leveraged to estimate the proportion of CSCs in individual patients at baseline and during therapy.

To test their model, the scientists used 2 independent cohorts of CML patients. The team evaluated the growth and decline of CML over the course of treatment with the tyrosine kinase inhibitor imatinib.

Based on the change of disease burden during treatment, the model calculated the proportion of CSCs.

Results suggested the proportion of CSCs in CML patients increases 100-fold after a year of treatment with imatinib. And that proportion continues to increase up to 1000-fold after 5 years of treatment.

The scientists noted that this model is parameter-free, so it can be applied to different types of cancer. However, they said further development is required before the model can be used in clinical practice.

Pembrolizumab (Keytruda)

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for pembrolizumab (Keytruda) to treat patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life threatening conditions, which have shown encouraging early clinical results demonstrating substantial improvement on a clinically significant endpoint over available therapies.

The breakthrough designation for pembrolizumab in cHL is based on data from the phase 1b KEYNOTE-013 trial and the phase 2 KEYNOTE-087 trial.

Findings from the KEYNOTE-013 study were presented at ASH 2014 (in patients with cHL) and ASH 2015 (in primary mediastinal large B-cell lymphoma).

Data from KEYNOTE-087 will be presented at an upcoming medical meeting, according to Merck, the company developing pembrolizumab.

Pembrolizumab also has breakthrough designation from the FDA as a treatment for advanced melanoma, advanced non-small cell lung cancer, and advanced colorectal cancer.

The drug is already FDA-approved to treat melanoma and non-small cell lung cancer. Pembrolizumab is administered at a dose of 2 mg/kg as an intravenous infusion over 30 minutes every 3 weeks for the approved indications.

Pembrolizumab (Keytruda)

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for pembrolizumab (Keytruda) to treat patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life threatening conditions, which have shown encouraging early clinical results demonstrating substantial improvement on a clinically significant endpoint over available therapies.

The breakthrough designation for pembrolizumab in cHL is based on data from the phase 1b KEYNOTE-013 trial and the phase 2 KEYNOTE-087 trial.

Findings from the KEYNOTE-013 study were presented at ASH 2014 (in patients with cHL) and ASH 2015 (in primary mediastinal large B-cell lymphoma).

Data from KEYNOTE-087 will be presented at an upcoming medical meeting, according to Merck, the company developing pembrolizumab.

Pembrolizumab also has breakthrough designation from the FDA as a treatment for advanced melanoma, advanced non-small cell lung cancer, and advanced colorectal cancer.

The drug is already FDA-approved to treat melanoma and non-small cell lung cancer. Pembrolizumab is administered at a dose of 2 mg/kg as an intravenous infusion over 30 minutes every 3 weeks for the approved indications.

Pembrolizumab (Keytruda)

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for pembrolizumab (Keytruda) to treat patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life threatening conditions, which have shown encouraging early clinical results demonstrating substantial improvement on a clinically significant endpoint over available therapies.

The breakthrough designation for pembrolizumab in cHL is based on data from the phase 1b KEYNOTE-013 trial and the phase 2 KEYNOTE-087 trial.

Findings from the KEYNOTE-013 study were presented at ASH 2014 (in patients with cHL) and ASH 2015 (in primary mediastinal large B-cell lymphoma).

Data from KEYNOTE-087 will be presented at an upcoming medical meeting, according to Merck, the company developing pembrolizumab.

Pembrolizumab also has breakthrough designation from the FDA as a treatment for advanced melanoma, advanced non-small cell lung cancer, and advanced colorectal cancer.

The drug is already FDA-approved to treat melanoma and non-small cell lung cancer. Pembrolizumab is administered at a dose of 2 mg/kg as an intravenous infusion over 30 minutes every 3 weeks for the approved indications.