The Quality Institute of the Ohio Hospital Association (OHA) recently launched its fifth regional quality collaborative in the state, bringing together hospital administrators, physicians, and other clinicians to tackle statewide goals of reducing infections, readmissions, and adverse events while increasing patient satisfaction. A hospitalist involved in the initiative says it sets an example for other states to follow.

"Hospitalists are on the front lines of quality," says Craig Cairns, MD, MPH, a hospitalist and vice president of medical affairs at Licking Memorial Health Systems in Newark, Ohio. "But it helps to get a statewide or regional group together to share problems and potential solutions."

Licking Memorial, for example, participates in OHA's statewide quality initiatives, including one on physician handwashing and STAAR (State Action on Avoidable Rehospitalizations), a multistate care-transitions initiative developed by the Institute for Healthcare Improvement.

Licking has set a goal of reducing its readmission rate to 10.5%, Dr. Cairns says. "Trying to get the patient back to the primary medical home as quickly as possible can be difficult," he adds. "We work with support people at medical offices to try to ensure a spot for our patients going home."

Because one of the risk factors for preventable rehospitalizations is heart failure, Licking also recently instituted a heart-failure clinic, staffed by two hospital cardiologists.

The first of the regional collaborations started in the Dayton area in 1998, according to David Engler, PhD, vice president of OHA's Quality Institute. The collaborative has posted a 36% reduction in heart-attack mortality over the past three years, the equivalent of 52 lives saved.

"We were brought in to help them on a specific issue: a higher-than-expected acute myocardial infarction mortality rate," Dr. Engler says. "We held collaborative meetings, developed risk management models, and began to track data across sites." Peer-review protocols developed by OHA make it possible to share quality data among the participating hospitals, with participants agreeing not to use these for marketing or competitive advantage.

A total of 133 hospitals participate in one of OHA's regional or statewide quality collaborations.

The Quality Institute of the Ohio Hospital Association (OHA) recently launched its fifth regional quality collaborative in the state, bringing together hospital administrators, physicians, and other clinicians to tackle statewide goals of reducing infections, readmissions, and adverse events while increasing patient satisfaction. A hospitalist involved in the initiative says it sets an example for other states to follow.

"Hospitalists are on the front lines of quality," says Craig Cairns, MD, MPH, a hospitalist and vice president of medical affairs at Licking Memorial Health Systems in Newark, Ohio. "But it helps to get a statewide or regional group together to share problems and potential solutions."

Licking Memorial, for example, participates in OHA's statewide quality initiatives, including one on physician handwashing and STAAR (State Action on Avoidable Rehospitalizations), a multistate care-transitions initiative developed by the Institute for Healthcare Improvement.

Licking has set a goal of reducing its readmission rate to 10.5%, Dr. Cairns says. "Trying to get the patient back to the primary medical home as quickly as possible can be difficult," he adds. "We work with support people at medical offices to try to ensure a spot for our patients going home."

Because one of the risk factors for preventable rehospitalizations is heart failure, Licking also recently instituted a heart-failure clinic, staffed by two hospital cardiologists.

The first of the regional collaborations started in the Dayton area in 1998, according to David Engler, PhD, vice president of OHA's Quality Institute. The collaborative has posted a 36% reduction in heart-attack mortality over the past three years, the equivalent of 52 lives saved.

"We were brought in to help them on a specific issue: a higher-than-expected acute myocardial infarction mortality rate," Dr. Engler says. "We held collaborative meetings, developed risk management models, and began to track data across sites." Peer-review protocols developed by OHA make it possible to share quality data among the participating hospitals, with participants agreeing not to use these for marketing or competitive advantage.

A total of 133 hospitals participate in one of OHA's regional or statewide quality collaborations.

The Quality Institute of the Ohio Hospital Association (OHA) recently launched its fifth regional quality collaborative in the state, bringing together hospital administrators, physicians, and other clinicians to tackle statewide goals of reducing infections, readmissions, and adverse events while increasing patient satisfaction. A hospitalist involved in the initiative says it sets an example for other states to follow.

"Hospitalists are on the front lines of quality," says Craig Cairns, MD, MPH, a hospitalist and vice president of medical affairs at Licking Memorial Health Systems in Newark, Ohio. "But it helps to get a statewide or regional group together to share problems and potential solutions."

Licking Memorial, for example, participates in OHA's statewide quality initiatives, including one on physician handwashing and STAAR (State Action on Avoidable Rehospitalizations), a multistate care-transitions initiative developed by the Institute for Healthcare Improvement.

Licking has set a goal of reducing its readmission rate to 10.5%, Dr. Cairns says. "Trying to get the patient back to the primary medical home as quickly as possible can be difficult," he adds. "We work with support people at medical offices to try to ensure a spot for our patients going home."

Because one of the risk factors for preventable rehospitalizations is heart failure, Licking also recently instituted a heart-failure clinic, staffed by two hospital cardiologists.

The first of the regional collaborations started in the Dayton area in 1998, according to David Engler, PhD, vice president of OHA's Quality Institute. The collaborative has posted a 36% reduction in heart-attack mortality over the past three years, the equivalent of 52 lives saved.

"We were brought in to help them on a specific issue: a higher-than-expected acute myocardial infarction mortality rate," Dr. Engler says. "We held collaborative meetings, developed risk management models, and began to track data across sites." Peer-review protocols developed by OHA make it possible to share quality data among the participating hospitals, with participants agreeing not to use these for marketing or competitive advantage.

A total of 133 hospitals participate in one of OHA's regional or statewide quality collaborations.

BOCA RATON, FLA. – Coexisting subspecialty fellowship programs have at most only minimal adverse impact on general surgery residency training operative volumes, according to a national study sponsored by the American Board of Surgery.

The analysis also demonstrated that fellowship-bound general surgery residents tend to select additional cases in their chosen future subspecialty, thereby in effect creating a self-directed early tracking program, Dr. John B. Hanks said at the annual meeting of the American Surgical Association.

The American Board of Surgery (ABS) conducted the study in response to concerns that because 80% of general surgery residents pursue fellowship training, an insufficient number of cases could be available for resident training. But the national data indicate that this is not a problem, according to Dr. Hanks, professor and chief of general surgery at the University of Virginia, Charlottesville.

The study entailed detailed analysis of the operative logs of 976 applicants to the 2009 ABS qualifying exam. The applicants came from 246 general surgery residency programs. In all, 97 of these residency programs coexisted with a vascular surgery fellowship program, 35 with a colorectal surgery fellowship program, 80 with a minimally invasive surgery training program, and 12 with an endocrine surgery fellowship program. The investigators scrutinized case volumes for predefined key operations in the areas of vascular, colorectal, endocrine, and minimally invasive surgery (MIS).

Residents bound for fellowships in vascular, colorectal, and endocrine surgery performed significantly more total cases in each of those areas than did general surgery residents who were not bound for fellowships. For example, operative logs for the 90 vascular surgery fellowship–bound residents showed a mean experience of 165 vascular cases, compared with 123 cases for the other general surgery residents. And residents headed for colorectal surgery fellowships had a mean of 204 colorectal surgery cases, compared with 163 for all other general surgery residents.

In contrast, residents who were headed for an MIS fellowship and those who were not averaged a similar number of minimally invasive operations.

With regard to the effect of coexisting fellowship programs on general surgery residents’ operative experience in those specific areas, there was a negative impact only for MIS. Residents in general surgery training programs with a coexisting MIS fellowship averaged about 10% fewer MIS cases than did residents in institutions without a fellowship.

"That difference reaches statistical significance, although the practical significance of this effect may be open for debate," Dr. Hanks observed.

The situation was different for residents at institutions with coexisting colorectal or vascular surgery fellowships; those fellowships had no impact on general surgery residents’ case volumes in those specialty-specific areas. And the presence of a coexisting endocrine surgery fellowship was actually associated with a significant increase in endocrine surgery case volumes for all residents, he continued.

Discussant Dr. Layton F. Rikkers cautioned that the ABS study describes national trends using broad strokes, and the data don’t necessarily apply to any individual residency program.

"As an example, the only fellowship we developed at the University of Wisconsin, Madison, during the time I was chairman there was a vascular surgery fellowship," said Dr. Rikkers, professor of surgery at the university and past president of the ABS. "The year prior to developing the fellowship, our residents were in the 93rd percentile nationally with respect to vascular surgery cases done. Over the many years since that fellowship was established, our residents are in the 10th to 20th percentile for vascular surgery cases."

Dr. Hanks declared having no financial conflict of interest.

BOCA RATON, FLA. – Coexisting subspecialty fellowship programs have at most only minimal adverse impact on general surgery residency training operative volumes, according to a national study sponsored by the American Board of Surgery.

The analysis also demonstrated that fellowship-bound general surgery residents tend to select additional cases in their chosen future subspecialty, thereby in effect creating a self-directed early tracking program, Dr. John B. Hanks said at the annual meeting of the American Surgical Association.

The American Board of Surgery (ABS) conducted the study in response to concerns that because 80% of general surgery residents pursue fellowship training, an insufficient number of cases could be available for resident training. But the national data indicate that this is not a problem, according to Dr. Hanks, professor and chief of general surgery at the University of Virginia, Charlottesville.

The study entailed detailed analysis of the operative logs of 976 applicants to the 2009 ABS qualifying exam. The applicants came from 246 general surgery residency programs. In all, 97 of these residency programs coexisted with a vascular surgery fellowship program, 35 with a colorectal surgery fellowship program, 80 with a minimally invasive surgery training program, and 12 with an endocrine surgery fellowship program. The investigators scrutinized case volumes for predefined key operations in the areas of vascular, colorectal, endocrine, and minimally invasive surgery (MIS).

Residents bound for fellowships in vascular, colorectal, and endocrine surgery performed significantly more total cases in each of those areas than did general surgery residents who were not bound for fellowships. For example, operative logs for the 90 vascular surgery fellowship–bound residents showed a mean experience of 165 vascular cases, compared with 123 cases for the other general surgery residents. And residents headed for colorectal surgery fellowships had a mean of 204 colorectal surgery cases, compared with 163 for all other general surgery residents.

In contrast, residents who were headed for an MIS fellowship and those who were not averaged a similar number of minimally invasive operations.

With regard to the effect of coexisting fellowship programs on general surgery residents’ operative experience in those specific areas, there was a negative impact only for MIS. Residents in general surgery training programs with a coexisting MIS fellowship averaged about 10% fewer MIS cases than did residents in institutions without a fellowship.

"That difference reaches statistical significance, although the practical significance of this effect may be open for debate," Dr. Hanks observed.

The situation was different for residents at institutions with coexisting colorectal or vascular surgery fellowships; those fellowships had no impact on general surgery residents’ case volumes in those specialty-specific areas. And the presence of a coexisting endocrine surgery fellowship was actually associated with a significant increase in endocrine surgery case volumes for all residents, he continued.

Discussant Dr. Layton F. Rikkers cautioned that the ABS study describes national trends using broad strokes, and the data don’t necessarily apply to any individual residency program.

"As an example, the only fellowship we developed at the University of Wisconsin, Madison, during the time I was chairman there was a vascular surgery fellowship," said Dr. Rikkers, professor of surgery at the university and past president of the ABS. "The year prior to developing the fellowship, our residents were in the 93rd percentile nationally with respect to vascular surgery cases done. Over the many years since that fellowship was established, our residents are in the 10th to 20th percentile for vascular surgery cases."

Dr. Hanks declared having no financial conflict of interest.

BOCA RATON, FLA. – Coexisting subspecialty fellowship programs have at most only minimal adverse impact on general surgery residency training operative volumes, according to a national study sponsored by the American Board of Surgery.

The analysis also demonstrated that fellowship-bound general surgery residents tend to select additional cases in their chosen future subspecialty, thereby in effect creating a self-directed early tracking program, Dr. John B. Hanks said at the annual meeting of the American Surgical Association.

The American Board of Surgery (ABS) conducted the study in response to concerns that because 80% of general surgery residents pursue fellowship training, an insufficient number of cases could be available for resident training. But the national data indicate that this is not a problem, according to Dr. Hanks, professor and chief of general surgery at the University of Virginia, Charlottesville.

The study entailed detailed analysis of the operative logs of 976 applicants to the 2009 ABS qualifying exam. The applicants came from 246 general surgery residency programs. In all, 97 of these residency programs coexisted with a vascular surgery fellowship program, 35 with a colorectal surgery fellowship program, 80 with a minimally invasive surgery training program, and 12 with an endocrine surgery fellowship program. The investigators scrutinized case volumes for predefined key operations in the areas of vascular, colorectal, endocrine, and minimally invasive surgery (MIS).

Residents bound for fellowships in vascular, colorectal, and endocrine surgery performed significantly more total cases in each of those areas than did general surgery residents who were not bound for fellowships. For example, operative logs for the 90 vascular surgery fellowship–bound residents showed a mean experience of 165 vascular cases, compared with 123 cases for the other general surgery residents. And residents headed for colorectal surgery fellowships had a mean of 204 colorectal surgery cases, compared with 163 for all other general surgery residents.

In contrast, residents who were headed for an MIS fellowship and those who were not averaged a similar number of minimally invasive operations.

With regard to the effect of coexisting fellowship programs on general surgery residents’ operative experience in those specific areas, there was a negative impact only for MIS. Residents in general surgery training programs with a coexisting MIS fellowship averaged about 10% fewer MIS cases than did residents in institutions without a fellowship.

"That difference reaches statistical significance, although the practical significance of this effect may be open for debate," Dr. Hanks observed.

The situation was different for residents at institutions with coexisting colorectal or vascular surgery fellowships; those fellowships had no impact on general surgery residents’ case volumes in those specialty-specific areas. And the presence of a coexisting endocrine surgery fellowship was actually associated with a significant increase in endocrine surgery case volumes for all residents, he continued.

Discussant Dr. Layton F. Rikkers cautioned that the ABS study describes national trends using broad strokes, and the data don’t necessarily apply to any individual residency program.

"As an example, the only fellowship we developed at the University of Wisconsin, Madison, during the time I was chairman there was a vascular surgery fellowship," said Dr. Rikkers, professor of surgery at the university and past president of the ABS. "The year prior to developing the fellowship, our residents were in the 93rd percentile nationally with respect to vascular surgery cases done. Over the many years since that fellowship was established, our residents are in the 10th to 20th percentile for vascular surgery cases."

Dr. Hanks declared having no financial conflict of interest.

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Two new drug therapies to treat chronic hepatitis C (HCV) are the first new options for hospitalists in 20 years. But freedom of choice doesn't come cheap.

Telaprevir, from Vertex Pharmaceuticals, will cost $49,200 for a 12-week regimen, while boceprevir, from Merck & Co., will cost from $26,400 to $48,000 for regimens of 24 and 48 weeks, respectively, Reuters reports. Telaprevir will go by the brand name Incivek, while boceprevir is known as Victrelis.

"The price is expensive," but financial support for some patients is expected early on, says Satya Chelamkuri, MD, a hospitalist with Cogent Healthcare at Allegiance Health in Jackson, Mich. "When the generic comes out, it will be a great help to patients with hepatitis C. Cost is a worry, but with help from pharmaceutical companies, the majority of the patients who need it will hopefully get the treatment."

Still, Dr. Chelamkuri expects the drugs to appear relatively quickly on hospital formularies, in large part because of the efficacy they showed in trials. The standard treatment for years, a cocktail of peginterferon-alpha and ribavirin, has a roughly 50% response rate. Both of the new treatments, which have been formally approved by the FDA in the past six weeks, boost the cure rates to a range of 66% to 80% by working in tandem with the current therapy.

"A less than 50% [response rate] for the previous regime and around 70% for the new regime. That’s a considerable difference," Dr. Chelamkuri says.

Two new drug therapies to treat chronic hepatitis C (HCV) are the first new options for hospitalists in 20 years. But freedom of choice doesn't come cheap.

Telaprevir, from Vertex Pharmaceuticals, will cost $49,200 for a 12-week regimen, while boceprevir, from Merck & Co., will cost from $26,400 to $48,000 for regimens of 24 and 48 weeks, respectively, Reuters reports. Telaprevir will go by the brand name Incivek, while boceprevir is known as Victrelis.

"The price is expensive," but financial support for some patients is expected early on, says Satya Chelamkuri, MD, a hospitalist with Cogent Healthcare at Allegiance Health in Jackson, Mich. "When the generic comes out, it will be a great help to patients with hepatitis C. Cost is a worry, but with help from pharmaceutical companies, the majority of the patients who need it will hopefully get the treatment."

Still, Dr. Chelamkuri expects the drugs to appear relatively quickly on hospital formularies, in large part because of the efficacy they showed in trials. The standard treatment for years, a cocktail of peginterferon-alpha and ribavirin, has a roughly 50% response rate. Both of the new treatments, which have been formally approved by the FDA in the past six weeks, boost the cure rates to a range of 66% to 80% by working in tandem with the current therapy.

"A less than 50% [response rate] for the previous regime and around 70% for the new regime. That’s a considerable difference," Dr. Chelamkuri says.

Two new drug therapies to treat chronic hepatitis C (HCV) are the first new options for hospitalists in 20 years. But freedom of choice doesn't come cheap.

Telaprevir, from Vertex Pharmaceuticals, will cost $49,200 for a 12-week regimen, while boceprevir, from Merck & Co., will cost from $26,400 to $48,000 for regimens of 24 and 48 weeks, respectively, Reuters reports. Telaprevir will go by the brand name Incivek, while boceprevir is known as Victrelis.

"The price is expensive," but financial support for some patients is expected early on, says Satya Chelamkuri, MD, a hospitalist with Cogent Healthcare at Allegiance Health in Jackson, Mich. "When the generic comes out, it will be a great help to patients with hepatitis C. Cost is a worry, but with help from pharmaceutical companies, the majority of the patients who need it will hopefully get the treatment."

Still, Dr. Chelamkuri expects the drugs to appear relatively quickly on hospital formularies, in large part because of the efficacy they showed in trials. The standard treatment for years, a cocktail of peginterferon-alpha and ribavirin, has a roughly 50% response rate. Both of the new treatments, which have been formally approved by the FDA in the past six weeks, boost the cure rates to a range of 66% to 80% by working in tandem with the current therapy.

"A less than 50% [response rate] for the previous regime and around 70% for the new regime. That’s a considerable difference," Dr. Chelamkuri says.

Clinical question: Does the mortality rate differ between patients treated perioperatively with atenolol versus metoprolol?

Background: Perioperative beta-blockers have been shown to reduce mortality in patients with significant cardiac risk factors. Different beta-blockers have been used in the studies demonstrating benefit, and it is uncertain which beta-blocker is the preferred agent. The purpose of this study was to compare the perioperative benefits of metoprolol versus atenolol.

Study design: Retrospective cohort study.

Setting: San Francisco Veterans Affairs Medical Center.

Synopsis: Computerized records of patients who underwent surgery from 1996 to 2008 were extracted into a database, and patients who received inpatient beta-blockers after surgery were included. Of these patients, 3,787 received beta-blockade exclusively with either atenolol (n=1,011) or metoprolol (n=2,776) during hospitalization. Perioperative risk reduction was better with atenolol versus metoprolol. Mortality rates were 1% versus 3% at 30 days (P=0.0008), and 7% versus 13% at one year (P=<0.0001) with atenolol and metoprolol, respectively. Similar results were found in the analysis of 1,871 patients who were on their respective beta-blocker as an outpatient before surgery.

Because the metoprolol group had higher prevalence of risk factors, such as coronary artery disease, peripheral vascular disease, and congestive heart failure, a propensity-matched analysis was performed to remove differences in risk factors between the groups. After propensity matching, the metoprolol group still had statistically significant higher mortality at 30 days and one year, even though causality cannot be established in this retrospective study.

Bottom line: Atenolol was associated with fewer cases of perioperative mortality compared with metoprolol in patients with cardiac risk factors or established cardiovascular disease.

Citation: Wallace AW, Au S, Cason BA. Perioperative ß-blockade: atenolol is associated with reduced mortality when compared to metoprolol. Anesthesiology. 2011;114:824-836.

For more physician reviews of HM-related research, visit our website.

Clinical question: Does the mortality rate differ between patients treated perioperatively with atenolol versus metoprolol?

Background: Perioperative beta-blockers have been shown to reduce mortality in patients with significant cardiac risk factors. Different beta-blockers have been used in the studies demonstrating benefit, and it is uncertain which beta-blocker is the preferred agent. The purpose of this study was to compare the perioperative benefits of metoprolol versus atenolol.

Study design: Retrospective cohort study.

Setting: San Francisco Veterans Affairs Medical Center.

Synopsis: Computerized records of patients who underwent surgery from 1996 to 2008 were extracted into a database, and patients who received inpatient beta-blockers after surgery were included. Of these patients, 3,787 received beta-blockade exclusively with either atenolol (n=1,011) or metoprolol (n=2,776) during hospitalization. Perioperative risk reduction was better with atenolol versus metoprolol. Mortality rates were 1% versus 3% at 30 days (P=0.0008), and 7% versus 13% at one year (P=<0.0001) with atenolol and metoprolol, respectively. Similar results were found in the analysis of 1,871 patients who were on their respective beta-blocker as an outpatient before surgery.

Because the metoprolol group had higher prevalence of risk factors, such as coronary artery disease, peripheral vascular disease, and congestive heart failure, a propensity-matched analysis was performed to remove differences in risk factors between the groups. After propensity matching, the metoprolol group still had statistically significant higher mortality at 30 days and one year, even though causality cannot be established in this retrospective study.

Bottom line: Atenolol was associated with fewer cases of perioperative mortality compared with metoprolol in patients with cardiac risk factors or established cardiovascular disease.

Citation: Wallace AW, Au S, Cason BA. Perioperative ß-blockade: atenolol is associated with reduced mortality when compared to metoprolol. Anesthesiology. 2011;114:824-836.

For more physician reviews of HM-related research, visit our website.

Clinical question: Does the mortality rate differ between patients treated perioperatively with atenolol versus metoprolol?

Background: Perioperative beta-blockers have been shown to reduce mortality in patients with significant cardiac risk factors. Different beta-blockers have been used in the studies demonstrating benefit, and it is uncertain which beta-blocker is the preferred agent. The purpose of this study was to compare the perioperative benefits of metoprolol versus atenolol.

Study design: Retrospective cohort study.

Setting: San Francisco Veterans Affairs Medical Center.

Synopsis: Computerized records of patients who underwent surgery from 1996 to 2008 were extracted into a database, and patients who received inpatient beta-blockers after surgery were included. Of these patients, 3,787 received beta-blockade exclusively with either atenolol (n=1,011) or metoprolol (n=2,776) during hospitalization. Perioperative risk reduction was better with atenolol versus metoprolol. Mortality rates were 1% versus 3% at 30 days (P=0.0008), and 7% versus 13% at one year (P=<0.0001) with atenolol and metoprolol, respectively. Similar results were found in the analysis of 1,871 patients who were on their respective beta-blocker as an outpatient before surgery.

Because the metoprolol group had higher prevalence of risk factors, such as coronary artery disease, peripheral vascular disease, and congestive heart failure, a propensity-matched analysis was performed to remove differences in risk factors between the groups. After propensity matching, the metoprolol group still had statistically significant higher mortality at 30 days and one year, even though causality cannot be established in this retrospective study.

Bottom line: Atenolol was associated with fewer cases of perioperative mortality compared with metoprolol in patients with cardiac risk factors or established cardiovascular disease.

Citation: Wallace AW, Au S, Cason BA. Perioperative ß-blockade: atenolol is associated with reduced mortality when compared to metoprolol. Anesthesiology. 2011;114:824-836.

For more physician reviews of HM-related research, visit our website.

The Food and Drug Administration unveiled on June 21 the final nine warning images that will appear on every package of cigarettes by 2012 – graphic photos and drawings intended to educate and even deter consumers from buying cigarettes.

The images, set to debut in stores this September, are required by the 2009 Tobacco Control Act, according to FDA spokesman Jeffrey Ventura, who added that these are the first changes to cigarette pack warnings in 25 years. By Oct. 22, 2012, cigarette manufacturers will no longer be able to distribute cigarettes for sale in the United States unless they display these warnings.

Courtesy of Food and Drug Administration

The law required the warnings to cover the top half of the front and back of cigarette packs and 20% of cigarette advertisements, and they must contain color graphics depicting the negative health consequences of smoking.

"This is something Congress wanted to happen and mandated that the FDA carry out," Mr. Ventura said in an interview. Based on a study of 18,000 smokers conducted for the FDA by RTI International, federal officials said they firmly believe that visually communicating smoking’s harm will deter cigarette consumption over the long run.

The images include photos of tobacco-diseased lungs beside healthy lungs, a corpse in casket, a man exhaling smoke though a tracheostomy, and lip cancer. There are also several cartoons and photos of mothers blowing smoke into infants’ faces. One positive image shows a burly man exposing a T-shirt saying, "I Quit."

Blunt statements accompany each image, intended to drive home the messages that cigarette smoke not only directly harms the smoker, but the smokers’ children and people in close proximity.

"The introduction of these warnings is expected to have a significant public health impact by decreasing the number of smokers, resulting in lives saved, increased life expectancy, and improved health status," FDA officials said in a press statement.

Mr. Ventura said the images were selected after the consumer study involving smokers aged 15-50 years. After viewing each of the images, subjects rated their emotional and cognitive responses, their ability to recall the images, and their opinions on whether the pictures could alter their beliefs about the danger of smoking and the desire to buy tobacco products and quitting tobacco.

Young people responded most strongly to a cartoon image depicting tobacco addiction – a cigarette being injected into an arm vein as well as a puppet controlled by strings.

Adults, on the other hand, responded most strongly to photos showing the direct effects of cancer on their bodies – the man with the tracheostomy and a woman smoking in the pouring rain, trying to shield her cigarette with a folded newspaper. Adults also reacted more strongly than did young people to images depicting harm to young children.

The study did conclude, however, that none of the images were significantly related to an increased likelihood of quitting smoking within the next 30 days, or the likelihood of smoking a year after viewing the images. Thus, the report noted, the campaign is more likely to exert a long-term behavioral impact than any immediate effects.

Courtesy of Food and Drug Administration

"Eliciting strong emotional and cognitive reactions to the graphic cigarette warning label enhances recall and processing of the health warning, which helps ensure that the warning is better processed, understood, and remembered," the study said. "As attitudes and beliefs change, they eventually lead to changes in intentions to quit or start smoking and then later to lower smoking initiation and successful cessation. The time scale on which this behavior change process occurs is largely unknown in the context of the impact of exposure to graphic warning labels on smoking behaviors, but the effects on behavior change are unlikely to be immediate or short-term.

Nevertheless, groups promoting antitobacco messages – including the American Heart Association – strongly believe that the warnings will enhance consumer education and change behavior.

"Undoubtedly, the new graphic health warnings will heighten awareness about the dangers of smoking and, more importantly, encourage smokers to quit and discourage smoking initiation," an AHA press statement read. "We’re confident that the new labels will move us closer to our goal of making the nation 100% smoke free."

Tobacco-Free Kids, a group dedicated to educating children and teens about the dangers of smoking, also issued a statement of support, but with a moderated view on the campaign’s possible impact. The group also called on political leaders to financially commit to "waging war" against tobacco.

"The warnings and other FDA regulations are powerful tools, but they are a complement – not a replacement – to other federal and state strategies to reduce tobacco use," Matthew L. Meyers, the group’s president, said in the statement. "To win the fight against tobacco, elected leaders must also fund and implement public education campaigns, expand health care coverage for therapies to help smokers quit, increase tobacco taxes, and enact strong smoke-free laws in every state."

The Food and Drug Administration unveiled on June 21 the final nine warning images that will appear on every package of cigarettes by 2012 – graphic photos and drawings intended to educate and even deter consumers from buying cigarettes.

The images, set to debut in stores this September, are required by the 2009 Tobacco Control Act, according to FDA spokesman Jeffrey Ventura, who added that these are the first changes to cigarette pack warnings in 25 years. By Oct. 22, 2012, cigarette manufacturers will no longer be able to distribute cigarettes for sale in the United States unless they display these warnings.

Courtesy of Food and Drug Administration

The law required the warnings to cover the top half of the front and back of cigarette packs and 20% of cigarette advertisements, and they must contain color graphics depicting the negative health consequences of smoking.

"This is something Congress wanted to happen and mandated that the FDA carry out," Mr. Ventura said in an interview. Based on a study of 18,000 smokers conducted for the FDA by RTI International, federal officials said they firmly believe that visually communicating smoking’s harm will deter cigarette consumption over the long run.

The images include photos of tobacco-diseased lungs beside healthy lungs, a corpse in casket, a man exhaling smoke though a tracheostomy, and lip cancer. There are also several cartoons and photos of mothers blowing smoke into infants’ faces. One positive image shows a burly man exposing a T-shirt saying, "I Quit."

Blunt statements accompany each image, intended to drive home the messages that cigarette smoke not only directly harms the smoker, but the smokers’ children and people in close proximity.

"The introduction of these warnings is expected to have a significant public health impact by decreasing the number of smokers, resulting in lives saved, increased life expectancy, and improved health status," FDA officials said in a press statement.

Mr. Ventura said the images were selected after the consumer study involving smokers aged 15-50 years. After viewing each of the images, subjects rated their emotional and cognitive responses, their ability to recall the images, and their opinions on whether the pictures could alter their beliefs about the danger of smoking and the desire to buy tobacco products and quitting tobacco.

Young people responded most strongly to a cartoon image depicting tobacco addiction – a cigarette being injected into an arm vein as well as a puppet controlled by strings.

Adults, on the other hand, responded most strongly to photos showing the direct effects of cancer on their bodies – the man with the tracheostomy and a woman smoking in the pouring rain, trying to shield her cigarette with a folded newspaper. Adults also reacted more strongly than did young people to images depicting harm to young children.

The study did conclude, however, that none of the images were significantly related to an increased likelihood of quitting smoking within the next 30 days, or the likelihood of smoking a year after viewing the images. Thus, the report noted, the campaign is more likely to exert a long-term behavioral impact than any immediate effects.

Courtesy of Food and Drug Administration

"Eliciting strong emotional and cognitive reactions to the graphic cigarette warning label enhances recall and processing of the health warning, which helps ensure that the warning is better processed, understood, and remembered," the study said. "As attitudes and beliefs change, they eventually lead to changes in intentions to quit or start smoking and then later to lower smoking initiation and successful cessation. The time scale on which this behavior change process occurs is largely unknown in the context of the impact of exposure to graphic warning labels on smoking behaviors, but the effects on behavior change are unlikely to be immediate or short-term.

Nevertheless, groups promoting antitobacco messages – including the American Heart Association – strongly believe that the warnings will enhance consumer education and change behavior.

"Undoubtedly, the new graphic health warnings will heighten awareness about the dangers of smoking and, more importantly, encourage smokers to quit and discourage smoking initiation," an AHA press statement read. "We’re confident that the new labels will move us closer to our goal of making the nation 100% smoke free."

Tobacco-Free Kids, a group dedicated to educating children and teens about the dangers of smoking, also issued a statement of support, but with a moderated view on the campaign’s possible impact. The group also called on political leaders to financially commit to "waging war" against tobacco.

"The warnings and other FDA regulations are powerful tools, but they are a complement – not a replacement – to other federal and state strategies to reduce tobacco use," Matthew L. Meyers, the group’s president, said in the statement. "To win the fight against tobacco, elected leaders must also fund and implement public education campaigns, expand health care coverage for therapies to help smokers quit, increase tobacco taxes, and enact strong smoke-free laws in every state."

The Food and Drug Administration unveiled on June 21 the final nine warning images that will appear on every package of cigarettes by 2012 – graphic photos and drawings intended to educate and even deter consumers from buying cigarettes.

The images, set to debut in stores this September, are required by the 2009 Tobacco Control Act, according to FDA spokesman Jeffrey Ventura, who added that these are the first changes to cigarette pack warnings in 25 years. By Oct. 22, 2012, cigarette manufacturers will no longer be able to distribute cigarettes for sale in the United States unless they display these warnings.

Courtesy of Food and Drug Administration

The law required the warnings to cover the top half of the front and back of cigarette packs and 20% of cigarette advertisements, and they must contain color graphics depicting the negative health consequences of smoking.

"This is something Congress wanted to happen and mandated that the FDA carry out," Mr. Ventura said in an interview. Based on a study of 18,000 smokers conducted for the FDA by RTI International, federal officials said they firmly believe that visually communicating smoking’s harm will deter cigarette consumption over the long run.

The images include photos of tobacco-diseased lungs beside healthy lungs, a corpse in casket, a man exhaling smoke though a tracheostomy, and lip cancer. There are also several cartoons and photos of mothers blowing smoke into infants’ faces. One positive image shows a burly man exposing a T-shirt saying, "I Quit."

Blunt statements accompany each image, intended to drive home the messages that cigarette smoke not only directly harms the smoker, but the smokers’ children and people in close proximity.

"The introduction of these warnings is expected to have a significant public health impact by decreasing the number of smokers, resulting in lives saved, increased life expectancy, and improved health status," FDA officials said in a press statement.

Mr. Ventura said the images were selected after the consumer study involving smokers aged 15-50 years. After viewing each of the images, subjects rated their emotional and cognitive responses, their ability to recall the images, and their opinions on whether the pictures could alter their beliefs about the danger of smoking and the desire to buy tobacco products and quitting tobacco.

Young people responded most strongly to a cartoon image depicting tobacco addiction – a cigarette being injected into an arm vein as well as a puppet controlled by strings.

Adults, on the other hand, responded most strongly to photos showing the direct effects of cancer on their bodies – the man with the tracheostomy and a woman smoking in the pouring rain, trying to shield her cigarette with a folded newspaper. Adults also reacted more strongly than did young people to images depicting harm to young children.

The study did conclude, however, that none of the images were significantly related to an increased likelihood of quitting smoking within the next 30 days, or the likelihood of smoking a year after viewing the images. Thus, the report noted, the campaign is more likely to exert a long-term behavioral impact than any immediate effects.

Courtesy of Food and Drug Administration

"Eliciting strong emotional and cognitive reactions to the graphic cigarette warning label enhances recall and processing of the health warning, which helps ensure that the warning is better processed, understood, and remembered," the study said. "As attitudes and beliefs change, they eventually lead to changes in intentions to quit or start smoking and then later to lower smoking initiation and successful cessation. The time scale on which this behavior change process occurs is largely unknown in the context of the impact of exposure to graphic warning labels on smoking behaviors, but the effects on behavior change are unlikely to be immediate or short-term.

Nevertheless, groups promoting antitobacco messages – including the American Heart Association – strongly believe that the warnings will enhance consumer education and change behavior.

"Undoubtedly, the new graphic health warnings will heighten awareness about the dangers of smoking and, more importantly, encourage smokers to quit and discourage smoking initiation," an AHA press statement read. "We’re confident that the new labels will move us closer to our goal of making the nation 100% smoke free."

Tobacco-Free Kids, a group dedicated to educating children and teens about the dangers of smoking, also issued a statement of support, but with a moderated view on the campaign’s possible impact. The group also called on political leaders to financially commit to "waging war" against tobacco.

"The warnings and other FDA regulations are powerful tools, but they are a complement – not a replacement – to other federal and state strategies to reduce tobacco use," Matthew L. Meyers, the group’s president, said in the statement. "To win the fight against tobacco, elected leaders must also fund and implement public education campaigns, expand health care coverage for therapies to help smokers quit, increase tobacco taxes, and enact strong smoke-free laws in every state."

CHICAGO – That lenalidomide can improve overall and progression-free survival rates in multiple myeloma patients is evident, but whether the drug also increases their risk of second primary cancers is debatable.

Of three studies looking at the question, only one found an association between secondary primary malignancies and lenalidomide (Revlimid) in first-line therapy, investigators reported at the American Society of Clinical Oncology annual meeting.

And even then the risk was low – far less than the risk of death from multiple myeloma without a lenalidomide-containing regimen, said Dr. Antonio P. Palumbo of the University of Torino (Italy) and the Italian Multiple Myeloma Study Group.

Two other studies – one with 6-year follow-up data on continuous lenalidomide in first-line therapy and the other on lenalidomide in relapsed/refractory disease – failed to spot a signal for second cancer risk.

"I think it’s fair to say that currently we lack clear answers due to small numbers and study limitations," said Dr. C. Ola Landgren of the National Cancer Institute, the invited discussant for all three papers.

"I think we need to put both benefits and risks into the algorithms when we think about these things. ... I also think despite the fact that we don’t have clear data, we always have to discuss these things with our patients, and we as doctors have to stay updated as more information emerges," he said.

Three randomized clinical trials stirred the debate by reporting in separate presentations at the 2010 annual meeting of the American Society of Hematology that they saw more hematologic malignancies in lenalidomide treatment arms than in control groups (McCarthy, P.L. et al, abstract 37; Attal, M. et al, abstract 310; Palumbo, A. et al, abstract 622).

Despite these reports, 25 years after a multiple myeloma diagnosis, the cumulative incidence of all second cancers is about 8%, whereas the cumulative probability of death from competing causes is more than 90%, suggesting that any risk of a second malignancy is far outweighed by the risk of multiple myeloma and its sequelae, Dr. Landgren pointed out.

First-Line Therapy: Italian Experience

In the first of the three studies presented at ASCO 2011, Dr. Palumbo’s group looked at second-cancer rates among patients randomly assigned to first-line therapy with either melphalan and prednisone alone, or to melphalan, prednisone, and lenalidomide with or without lenalidomide maintenance in the international MM-015 trial.

They found that at a median follow-up of 30 months, 12 of 150 (8%) patients on melphalan-prednisone plus lenalidomide with maintenance (MPR-R) developed an invasive second primary malignancy, compared with 9 of 152 patients (5.9%) on the same combination without lenalidomide maintenance (MPR), and 4 of 153 (2.6%) patients on melphalan and prednisone only.

Hematologic malignancies accounted for 7 of the 12 new cancers among patients treated with MPR-R, 5 of 9 on MPR, and 1 of 4 on MP. Solid tumors accounted for the remaining invasive cancers in each group. In addition, one patient on MPR-R, four on MPR, and five on MP developed nonmelanoma skin cancers.

In an additional analysis of 9 pooled experimental studies, the investigators found that among 1,788 patients followed for more than 1 year, the risk of dying of myeloma was greater than 40% out to 7 years compared with about a 2% risk of developing a second hematologic malignancy, and a 3% risk of developing a solid tumor.

Among patients receiving lenalidomide and an alkylating agent, the risk of developing any malignancy was around 7%, and the risk of dying of myeloma was about 27%. The risk of a second malignancy was lower – about 2% out to 6 years– among those patients who did not receive lenalidomide, but their risk of dying of myeloma was about 45%, Dr. Palumbo said.

He also pointed out that in the general population, the risk of a second primary malignancy among 65- to 74-year-olds is around 2% per 100 patient-years, and that the risk doubles among people 85 and older.

First-Line Therapy: BiRD Regimen

In the second study, Dr. Adriana Rossi and her colleagues at Cornell University, New York, and New York–Presbyterian Hospital examined the incidence of second primary cancers in 68 transplant-eligible patients receiving lenalidomide in first-line therapy as part of the BiRD regimen (clarithromycin [Biaxin], lenalidomide, and dexamethasone).

There were five solid tumors (two colon, one metastatic melanoma, one pancreas, and one prostate), but no hematologic malignancies. The melanoma was diagnosed 8 months after the primary myeloma diagnosis; the other cases occurred 25-53 months after the initial myeloma diagnosis (median, 31.2 months). The authors found no association between second primary cancers and a specific multiple myeloma chromosomal abnormality, prior malignancy, transplant status, study status, or sex.

The incidence rate of second primary malignancy was similar to that of all primary cancers reported among people 65 and older in the U.S. Surveillance, Epidemiology, and End Results (SEER) data set spanning 2003-2007, they noted.

"Routine screening and prevention measures should continue as medically indicated for all patients, including examination for skin cancers, and as survival in patients with multiple myeloma continues to improve, so will our understanding of their risk of development of second primary malignancies," she said.

Relapsed/Refractory Disease

The third trial looked at the risk of new primary cancers in patients receiving lenalidomide and dexamethasone for relapsed/refractory disease.

Dr. Meletios Dimopoulos of the University of Athens and colleagues in the international MM-009/010 trials performed a pooled analysis comparing the incidence of second primary cancers in 704 patients who received dexamethasone with either lenalidomide or placebo, and compared them with standard incidence rates.

They found that there were no differences in incidence rates of invasive second primary malignancies between patients in the lenalidomide plus dexamethasone arm or dexamethasone-only arms, and that the incidence rates of second primary cancers in general were low and similar to the background rate among people of similar age in the general population.

Additionally, patients who received lenalidomide and dexamethasone had significantly better overall survival (median, 38 months) despite the fact that about half of all patients in the placebo/dexamathesaone arm (median, 31.6 months) were crossed over to lenalidomide-based therapy (P = .045).

"The overall benefit-risk ratio of the use of lenalidomide in the relapsed/refractory setting remains strongly positive," said the presenter of the abstract, Dr. Ruben Niesvizky of Cornell University.

Lenalidomide is not approved as first-line therapy in the United States. Dr. Palumbo’s study was supported by the Fondazione Neoplasie Sangue Onlus. Dr. Rossi’s and Dr. Dimopoulos’s studies were funded by Celgene. Dr. Palumbo has received honoraria and served as a consultant to Celgene and other companies. Dr. Rossi said she had no relevant financial relationships to disclose. Dr. Dimopoulos disclosed receiving honoraria from Celgene. Dr. Niesvizky said he had received honoraria and research funding from Celgene; he also served in a consulting/advisory role for Celgene and other companies.

CHICAGO – That lenalidomide can improve overall and progression-free survival rates in multiple myeloma patients is evident, but whether the drug also increases their risk of second primary cancers is debatable.

Of three studies looking at the question, only one found an association between secondary primary malignancies and lenalidomide (Revlimid) in first-line therapy, investigators reported at the American Society of Clinical Oncology annual meeting.

And even then the risk was low – far less than the risk of death from multiple myeloma without a lenalidomide-containing regimen, said Dr. Antonio P. Palumbo of the University of Torino (Italy) and the Italian Multiple Myeloma Study Group.

Two other studies – one with 6-year follow-up data on continuous lenalidomide in first-line therapy and the other on lenalidomide in relapsed/refractory disease – failed to spot a signal for second cancer risk.

"I think it’s fair to say that currently we lack clear answers due to small numbers and study limitations," said Dr. C. Ola Landgren of the National Cancer Institute, the invited discussant for all three papers.

"I think we need to put both benefits and risks into the algorithms when we think about these things. ... I also think despite the fact that we don’t have clear data, we always have to discuss these things with our patients, and we as doctors have to stay updated as more information emerges," he said.

Three randomized clinical trials stirred the debate by reporting in separate presentations at the 2010 annual meeting of the American Society of Hematology that they saw more hematologic malignancies in lenalidomide treatment arms than in control groups (McCarthy, P.L. et al, abstract 37; Attal, M. et al, abstract 310; Palumbo, A. et al, abstract 622).

Despite these reports, 25 years after a multiple myeloma diagnosis, the cumulative incidence of all second cancers is about 8%, whereas the cumulative probability of death from competing causes is more than 90%, suggesting that any risk of a second malignancy is far outweighed by the risk of multiple myeloma and its sequelae, Dr. Landgren pointed out.

First-Line Therapy: Italian Experience

In the first of the three studies presented at ASCO 2011, Dr. Palumbo’s group looked at second-cancer rates among patients randomly assigned to first-line therapy with either melphalan and prednisone alone, or to melphalan, prednisone, and lenalidomide with or without lenalidomide maintenance in the international MM-015 trial.

They found that at a median follow-up of 30 months, 12 of 150 (8%) patients on melphalan-prednisone plus lenalidomide with maintenance (MPR-R) developed an invasive second primary malignancy, compared with 9 of 152 patients (5.9%) on the same combination without lenalidomide maintenance (MPR), and 4 of 153 (2.6%) patients on melphalan and prednisone only.

Hematologic malignancies accounted for 7 of the 12 new cancers among patients treated with MPR-R, 5 of 9 on MPR, and 1 of 4 on MP. Solid tumors accounted for the remaining invasive cancers in each group. In addition, one patient on MPR-R, four on MPR, and five on MP developed nonmelanoma skin cancers.

In an additional analysis of 9 pooled experimental studies, the investigators found that among 1,788 patients followed for more than 1 year, the risk of dying of myeloma was greater than 40% out to 7 years compared with about a 2% risk of developing a second hematologic malignancy, and a 3% risk of developing a solid tumor.

Among patients receiving lenalidomide and an alkylating agent, the risk of developing any malignancy was around 7%, and the risk of dying of myeloma was about 27%. The risk of a second malignancy was lower – about 2% out to 6 years– among those patients who did not receive lenalidomide, but their risk of dying of myeloma was about 45%, Dr. Palumbo said.

He also pointed out that in the general population, the risk of a second primary malignancy among 65- to 74-year-olds is around 2% per 100 patient-years, and that the risk doubles among people 85 and older.

First-Line Therapy: BiRD Regimen

In the second study, Dr. Adriana Rossi and her colleagues at Cornell University, New York, and New York–Presbyterian Hospital examined the incidence of second primary cancers in 68 transplant-eligible patients receiving lenalidomide in first-line therapy as part of the BiRD regimen (clarithromycin [Biaxin], lenalidomide, and dexamethasone).

There were five solid tumors (two colon, one metastatic melanoma, one pancreas, and one prostate), but no hematologic malignancies. The melanoma was diagnosed 8 months after the primary myeloma diagnosis; the other cases occurred 25-53 months after the initial myeloma diagnosis (median, 31.2 months). The authors found no association between second primary cancers and a specific multiple myeloma chromosomal abnormality, prior malignancy, transplant status, study status, or sex.

The incidence rate of second primary malignancy was similar to that of all primary cancers reported among people 65 and older in the U.S. Surveillance, Epidemiology, and End Results (SEER) data set spanning 2003-2007, they noted.

"Routine screening and prevention measures should continue as medically indicated for all patients, including examination for skin cancers, and as survival in patients with multiple myeloma continues to improve, so will our understanding of their risk of development of second primary malignancies," she said.

Relapsed/Refractory Disease

The third trial looked at the risk of new primary cancers in patients receiving lenalidomide and dexamethasone for relapsed/refractory disease.

Dr. Meletios Dimopoulos of the University of Athens and colleagues in the international MM-009/010 trials performed a pooled analysis comparing the incidence of second primary cancers in 704 patients who received dexamethasone with either lenalidomide or placebo, and compared them with standard incidence rates.

They found that there were no differences in incidence rates of invasive second primary malignancies between patients in the lenalidomide plus dexamethasone arm or dexamethasone-only arms, and that the incidence rates of second primary cancers in general were low and similar to the background rate among people of similar age in the general population.

Additionally, patients who received lenalidomide and dexamethasone had significantly better overall survival (median, 38 months) despite the fact that about half of all patients in the placebo/dexamathesaone arm (median, 31.6 months) were crossed over to lenalidomide-based therapy (P = .045).

"The overall benefit-risk ratio of the use of lenalidomide in the relapsed/refractory setting remains strongly positive," said the presenter of the abstract, Dr. Ruben Niesvizky of Cornell University.

Lenalidomide is not approved as first-line therapy in the United States. Dr. Palumbo’s study was supported by the Fondazione Neoplasie Sangue Onlus. Dr. Rossi’s and Dr. Dimopoulos’s studies were funded by Celgene. Dr. Palumbo has received honoraria and served as a consultant to Celgene and other companies. Dr. Rossi said she had no relevant financial relationships to disclose. Dr. Dimopoulos disclosed receiving honoraria from Celgene. Dr. Niesvizky said he had received honoraria and research funding from Celgene; he also served in a consulting/advisory role for Celgene and other companies.

CHICAGO – That lenalidomide can improve overall and progression-free survival rates in multiple myeloma patients is evident, but whether the drug also increases their risk of second primary cancers is debatable.

Of three studies looking at the question, only one found an association between secondary primary malignancies and lenalidomide (Revlimid) in first-line therapy, investigators reported at the American Society of Clinical Oncology annual meeting.

And even then the risk was low – far less than the risk of death from multiple myeloma without a lenalidomide-containing regimen, said Dr. Antonio P. Palumbo of the University of Torino (Italy) and the Italian Multiple Myeloma Study Group.

Two other studies – one with 6-year follow-up data on continuous lenalidomide in first-line therapy and the other on lenalidomide in relapsed/refractory disease – failed to spot a signal for second cancer risk.

"I think it’s fair to say that currently we lack clear answers due to small numbers and study limitations," said Dr. C. Ola Landgren of the National Cancer Institute, the invited discussant for all three papers.

"I think we need to put both benefits and risks into the algorithms when we think about these things. ... I also think despite the fact that we don’t have clear data, we always have to discuss these things with our patients, and we as doctors have to stay updated as more information emerges," he said.

Three randomized clinical trials stirred the debate by reporting in separate presentations at the 2010 annual meeting of the American Society of Hematology that they saw more hematologic malignancies in lenalidomide treatment arms than in control groups (McCarthy, P.L. et al, abstract 37; Attal, M. et al, abstract 310; Palumbo, A. et al, abstract 622).

Despite these reports, 25 years after a multiple myeloma diagnosis, the cumulative incidence of all second cancers is about 8%, whereas the cumulative probability of death from competing causes is more than 90%, suggesting that any risk of a second malignancy is far outweighed by the risk of multiple myeloma and its sequelae, Dr. Landgren pointed out.

First-Line Therapy: Italian Experience

In the first of the three studies presented at ASCO 2011, Dr. Palumbo’s group looked at second-cancer rates among patients randomly assigned to first-line therapy with either melphalan and prednisone alone, or to melphalan, prednisone, and lenalidomide with or without lenalidomide maintenance in the international MM-015 trial.

They found that at a median follow-up of 30 months, 12 of 150 (8%) patients on melphalan-prednisone plus lenalidomide with maintenance (MPR-R) developed an invasive second primary malignancy, compared with 9 of 152 patients (5.9%) on the same combination without lenalidomide maintenance (MPR), and 4 of 153 (2.6%) patients on melphalan and prednisone only.

Hematologic malignancies accounted for 7 of the 12 new cancers among patients treated with MPR-R, 5 of 9 on MPR, and 1 of 4 on MP. Solid tumors accounted for the remaining invasive cancers in each group. In addition, one patient on MPR-R, four on MPR, and five on MP developed nonmelanoma skin cancers.

In an additional analysis of 9 pooled experimental studies, the investigators found that among 1,788 patients followed for more than 1 year, the risk of dying of myeloma was greater than 40% out to 7 years compared with about a 2% risk of developing a second hematologic malignancy, and a 3% risk of developing a solid tumor.

Among patients receiving lenalidomide and an alkylating agent, the risk of developing any malignancy was around 7%, and the risk of dying of myeloma was about 27%. The risk of a second malignancy was lower – about 2% out to 6 years– among those patients who did not receive lenalidomide, but their risk of dying of myeloma was about 45%, Dr. Palumbo said.

He also pointed out that in the general population, the risk of a second primary malignancy among 65- to 74-year-olds is around 2% per 100 patient-years, and that the risk doubles among people 85 and older.

First-Line Therapy: BiRD Regimen

In the second study, Dr. Adriana Rossi and her colleagues at Cornell University, New York, and New York–Presbyterian Hospital examined the incidence of second primary cancers in 68 transplant-eligible patients receiving lenalidomide in first-line therapy as part of the BiRD regimen (clarithromycin [Biaxin], lenalidomide, and dexamethasone).

There were five solid tumors (two colon, one metastatic melanoma, one pancreas, and one prostate), but no hematologic malignancies. The melanoma was diagnosed 8 months after the primary myeloma diagnosis; the other cases occurred 25-53 months after the initial myeloma diagnosis (median, 31.2 months). The authors found no association between second primary cancers and a specific multiple myeloma chromosomal abnormality, prior malignancy, transplant status, study status, or sex.

The incidence rate of second primary malignancy was similar to that of all primary cancers reported among people 65 and older in the U.S. Surveillance, Epidemiology, and End Results (SEER) data set spanning 2003-2007, they noted.

"Routine screening and prevention measures should continue as medically indicated for all patients, including examination for skin cancers, and as survival in patients with multiple myeloma continues to improve, so will our understanding of their risk of development of second primary malignancies," she said.

Relapsed/Refractory Disease

The third trial looked at the risk of new primary cancers in patients receiving lenalidomide and dexamethasone for relapsed/refractory disease.

Dr. Meletios Dimopoulos of the University of Athens and colleagues in the international MM-009/010 trials performed a pooled analysis comparing the incidence of second primary cancers in 704 patients who received dexamethasone with either lenalidomide or placebo, and compared them with standard incidence rates.

They found that there were no differences in incidence rates of invasive second primary malignancies between patients in the lenalidomide plus dexamethasone arm or dexamethasone-only arms, and that the incidence rates of second primary cancers in general were low and similar to the background rate among people of similar age in the general population.

Additionally, patients who received lenalidomide and dexamethasone had significantly better overall survival (median, 38 months) despite the fact that about half of all patients in the placebo/dexamathesaone arm (median, 31.6 months) were crossed over to lenalidomide-based therapy (P = .045).

"The overall benefit-risk ratio of the use of lenalidomide in the relapsed/refractory setting remains strongly positive," said the presenter of the abstract, Dr. Ruben Niesvizky of Cornell University.

Lenalidomide is not approved as first-line therapy in the United States. Dr. Palumbo’s study was supported by the Fondazione Neoplasie Sangue Onlus. Dr. Rossi’s and Dr. Dimopoulos’s studies were funded by Celgene. Dr. Palumbo has received honoraria and served as a consultant to Celgene and other companies. Dr. Rossi said she had no relevant financial relationships to disclose. Dr. Dimopoulos disclosed receiving honoraria from Celgene. Dr. Niesvizky said he had received honoraria and research funding from Celgene; he also served in a consulting/advisory role for Celgene and other companies.

LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.

First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).

Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.

Rituximab is not licensed for the treatment of MCL in Europe or the United States.

"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.

"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.

Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).

The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m²) was given as a single dose every 2 months until disease progression.

The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.

Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.

The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.

Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.

Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)

Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.

"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."

Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.

LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.

First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).

Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.

Rituximab is not licensed for the treatment of MCL in Europe or the United States.

"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.

"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.

Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).

The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m²) was given as a single dose every 2 months until disease progression.

The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.

Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.

The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.

Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.

Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)

Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.

"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."

Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.

LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.

First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).

Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.

Rituximab is not licensed for the treatment of MCL in Europe or the United States.

"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.

"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.

Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).

The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m²) was given as a single dose every 2 months until disease progression.

The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.

Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.

The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.

Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.

Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)

Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.

"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."

Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.

LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.

First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).

Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.

Rituximab is not licensed for the treatment of MCL in Europe or the United States.

"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.

"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.

Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).

The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m²) was given as a single dose every 2 months until disease progression.

The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.

Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.

The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.

Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.

Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)

Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.

"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."

Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.

LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.

First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).

Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.

Rituximab is not licensed for the treatment of MCL in Europe or the United States.

"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.

"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.

Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).

The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m²) was given as a single dose every 2 months until disease progression.

The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.

Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.

The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.

Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.

Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)

Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.

"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."

Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.

LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.

First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).

Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.

Rituximab is not licensed for the treatment of MCL in Europe or the United States.

"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.

"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.

Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).

The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m²) was given as a single dose every 2 months until disease progression.

The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.

Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.

The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.

Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.

Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)

Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.

"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."

Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.

CHICAGO – It doesn’t seem to matter whether patients with newly diagnosed, diffuse large B-cell lymphoma receive a standard chemotherapy regimen in a dose-dense fashion every 14 days for six cycles, or every 21 days for eight cycles, said investigators in a multinational trial that was presented at the annual meeting of the American Society of Clinical Oncology.

There were no significant differences in the primary outcome of overall survival or the secondary outcome of failure-free survival among 1,080 patients who were randomly assigned to the two R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens, reported Dr. David Cunningham of the Royal Marsden Hospital in London, on behalf of colleagues in the U.K. National Cancer Research Institute’s lymphoma clinical study group.

Half the population received R-CHOP every 3 weeks for eight cycles (R-CHOP-21), and the other half was assigned to R-CHOP every 2 weeks for six cycles, followed by two additional rituximab infusions (R-CHOP-14).

Dr. Cunningham highlighted the following findings:

• The 2-year overall survival rates were 81% in the R-CHOP-21 arm, and 83% in the R-CHOP-14 arm (log rank P = .70).

• Overall response rates (a combination of complete responses [CR], complete unconfirmed responses [CRu], and partial responses [PR]) were 88% in R-CHOP-21 and 90% in R-CHOP-14 (P = .11).

• Rates of combined CR/CRu were 63% and 58%, respectively (P = .15).

• The 2-year failure-free survival rates were identical, at 75% in each group.

Toxicities were also generally similar between the treatment groups, except for a lower incidence of neutropenia in the R-CHOP-14 arm, which reflected primary prophylaxis with granulocyte-colony-stimulating factor (G-CSF) in that group.

There were no differences in failure-free survival between the treatment arms when patients were stratified by age, sex, disease stage, bulky disease, B symptoms, prognostic score, IPI (International Prognostic Index) score, cell proliferation (as measured by the MIB-1 monoclonal antibody), or diffuse large B-cell lymphoma (DLBCL) phenotype.

"We couldn’t actually identify any of the subsets or subgroups that benefited from one or the other treatment," Dr. Cunningham said.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, commented that the study "compared some questions that have been burning in our minds for a long time," calling it a "very robust analysis of a very important study."

Summing up this study and three other abstracts that looked at alternative therapies for DLBCL, Dr. Vose said that R-CHOP-21 is still the standard of care for young patients with low, low/intermediate, or high/intermediate IPI scores, although R-CHOP-14 plus two rituximab infusions or R-CHOEP (R-CHOP plus etoposide) are acceptable alternatives. For young patients with high IPI, R-CHOP-21 followed by consolidation autologous transplant should be offered. For older patients, R-CHOP-21 for eight cycles is equivalent to R-CHOP-14 for six cycles plus two rituximab infusions.

The trial began recruiting after a 2004 German study showed that a dose-dense regimen of six cycles of CHOP-14 improved 5-year overall survival in patients older than 60 years by 13%, compared with six cycles of CHOP-21 (Blood 2004;104:634-41).

Since that publication, however, the addition of rituximab to six or eight cycles of CHOP or similar chemotherapy regimens was shown to improve overall survival of DLBCL by 10%-16% in two trials. Those findings raised interest in whether CHOP-14 might still be superior to CHOP-21 in patients who also receive rituximab, and whether such an effect would be seen across all age groups, Dr. Cunningham said.

He reported the final results of the trial, which involved 1,080 adults who had newly diagnosed CD20-positive DLBCL and were recruited from 119 sites. The patients were stratified by IPI score, age (60 years and younger, or older than 60), and treatment center.

In all, 23% of patients on R-CHOP-21 and 22% on R-CHOP-14 had died by the time of the final study analysis. DLBCL was the leading cause of death in both arms. Other causes included treatment-related toxicity, cardiac causes (all cardiac deaths occurred 3-15 months after completion of therapy), secondary malignancy, and other/unknown causes.

In her discussion, Dr. Vose pointed out that R-CHOP-14, which requires G-CSF support after every cycle, costs about $31,308, compared with $29,247 for R-CHOP-21, in which G-CSF is used only to treat (but not to prevent) neutropenia or febrile neutropenia. In the trial, G-CSF was used in 38% of R-CHOP-21 cycles, compared with 100% of R-CHOP-14 cycles.

In addition, R-CHOP every 21 days for six cycles (not eight) is generally considered to be the standard of care in the United States, she noted; a direct comparison of this shorter regimen with R-CHOP-14 would have been welcome, she said.

The trial was funded by the U.K. National Cancer Research Institute. The authors had no relevant financial disclosures.

CHICAGO – It doesn’t seem to matter whether patients with newly diagnosed, diffuse large B-cell lymphoma receive a standard chemotherapy regimen in a dose-dense fashion every 14 days for six cycles, or every 21 days for eight cycles, said investigators in a multinational trial that was presented at the annual meeting of the American Society of Clinical Oncology.

There were no significant differences in the primary outcome of overall survival or the secondary outcome of failure-free survival among 1,080 patients who were randomly assigned to the two R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens, reported Dr. David Cunningham of the Royal Marsden Hospital in London, on behalf of colleagues in the U.K. National Cancer Research Institute’s lymphoma clinical study group.

Half the population received R-CHOP every 3 weeks for eight cycles (R-CHOP-21), and the other half was assigned to R-CHOP every 2 weeks for six cycles, followed by two additional rituximab infusions (R-CHOP-14).

Dr. Cunningham highlighted the following findings:

• The 2-year overall survival rates were 81% in the R-CHOP-21 arm, and 83% in the R-CHOP-14 arm (log rank P = .70).

• Overall response rates (a combination of complete responses [CR], complete unconfirmed responses [CRu], and partial responses [PR]) were 88% in R-CHOP-21 and 90% in R-CHOP-14 (P = .11).

• Rates of combined CR/CRu were 63% and 58%, respectively (P = .15).

• The 2-year failure-free survival rates were identical, at 75% in each group.

Toxicities were also generally similar between the treatment groups, except for a lower incidence of neutropenia in the R-CHOP-14 arm, which reflected primary prophylaxis with granulocyte-colony-stimulating factor (G-CSF) in that group.

There were no differences in failure-free survival between the treatment arms when patients were stratified by age, sex, disease stage, bulky disease, B symptoms, prognostic score, IPI (International Prognostic Index) score, cell proliferation (as measured by the MIB-1 monoclonal antibody), or diffuse large B-cell lymphoma (DLBCL) phenotype.

"We couldn’t actually identify any of the subsets or subgroups that benefited from one or the other treatment," Dr. Cunningham said.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, commented that the study "compared some questions that have been burning in our minds for a long time," calling it a "very robust analysis of a very important study."

Summing up this study and three other abstracts that looked at alternative therapies for DLBCL, Dr. Vose said that R-CHOP-21 is still the standard of care for young patients with low, low/intermediate, or high/intermediate IPI scores, although R-CHOP-14 plus two rituximab infusions or R-CHOEP (R-CHOP plus etoposide) are acceptable alternatives. For young patients with high IPI, R-CHOP-21 followed by consolidation autologous transplant should be offered. For older patients, R-CHOP-21 for eight cycles is equivalent to R-CHOP-14 for six cycles plus two rituximab infusions.

The trial began recruiting after a 2004 German study showed that a dose-dense regimen of six cycles of CHOP-14 improved 5-year overall survival in patients older than 60 years by 13%, compared with six cycles of CHOP-21 (Blood 2004;104:634-41).

Since that publication, however, the addition of rituximab to six or eight cycles of CHOP or similar chemotherapy regimens was shown to improve overall survival of DLBCL by 10%-16% in two trials. Those findings raised interest in whether CHOP-14 might still be superior to CHOP-21 in patients who also receive rituximab, and whether such an effect would be seen across all age groups, Dr. Cunningham said.

He reported the final results of the trial, which involved 1,080 adults who had newly diagnosed CD20-positive DLBCL and were recruited from 119 sites. The patients were stratified by IPI score, age (60 years and younger, or older than 60), and treatment center.

In all, 23% of patients on R-CHOP-21 and 22% on R-CHOP-14 had died by the time of the final study analysis. DLBCL was the leading cause of death in both arms. Other causes included treatment-related toxicity, cardiac causes (all cardiac deaths occurred 3-15 months after completion of therapy), secondary malignancy, and other/unknown causes.

In her discussion, Dr. Vose pointed out that R-CHOP-14, which requires G-CSF support after every cycle, costs about $31,308, compared with $29,247 for R-CHOP-21, in which G-CSF is used only to treat (but not to prevent) neutropenia or febrile neutropenia. In the trial, G-CSF was used in 38% of R-CHOP-21 cycles, compared with 100% of R-CHOP-14 cycles.

In addition, R-CHOP every 21 days for six cycles (not eight) is generally considered to be the standard of care in the United States, she noted; a direct comparison of this shorter regimen with R-CHOP-14 would have been welcome, she said.

The trial was funded by the U.K. National Cancer Research Institute. The authors had no relevant financial disclosures.

CHICAGO – It doesn’t seem to matter whether patients with newly diagnosed, diffuse large B-cell lymphoma receive a standard chemotherapy regimen in a dose-dense fashion every 14 days for six cycles, or every 21 days for eight cycles, said investigators in a multinational trial that was presented at the annual meeting of the American Society of Clinical Oncology.

There were no significant differences in the primary outcome of overall survival or the secondary outcome of failure-free survival among 1,080 patients who were randomly assigned to the two R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens, reported Dr. David Cunningham of the Royal Marsden Hospital in London, on behalf of colleagues in the U.K. National Cancer Research Institute’s lymphoma clinical study group.

Half the population received R-CHOP every 3 weeks for eight cycles (R-CHOP-21), and the other half was assigned to R-CHOP every 2 weeks for six cycles, followed by two additional rituximab infusions (R-CHOP-14).

Dr. Cunningham highlighted the following findings:

• The 2-year overall survival rates were 81% in the R-CHOP-21 arm, and 83% in the R-CHOP-14 arm (log rank P = .70).

• Overall response rates (a combination of complete responses [CR], complete unconfirmed responses [CRu], and partial responses [PR]) were 88% in R-CHOP-21 and 90% in R-CHOP-14 (P = .11).

• Rates of combined CR/CRu were 63% and 58%, respectively (P = .15).

• The 2-year failure-free survival rates were identical, at 75% in each group.

Toxicities were also generally similar between the treatment groups, except for a lower incidence of neutropenia in the R-CHOP-14 arm, which reflected primary prophylaxis with granulocyte-colony-stimulating factor (G-CSF) in that group.

There were no differences in failure-free survival between the treatment arms when patients were stratified by age, sex, disease stage, bulky disease, B symptoms, prognostic score, IPI (International Prognostic Index) score, cell proliferation (as measured by the MIB-1 monoclonal antibody), or diffuse large B-cell lymphoma (DLBCL) phenotype.

"We couldn’t actually identify any of the subsets or subgroups that benefited from one or the other treatment," Dr. Cunningham said.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, commented that the study "compared some questions that have been burning in our minds for a long time," calling it a "very robust analysis of a very important study."

Summing up this study and three other abstracts that looked at alternative therapies for DLBCL, Dr. Vose said that R-CHOP-21 is still the standard of care for young patients with low, low/intermediate, or high/intermediate IPI scores, although R-CHOP-14 plus two rituximab infusions or R-CHOEP (R-CHOP plus etoposide) are acceptable alternatives. For young patients with high IPI, R-CHOP-21 followed by consolidation autologous transplant should be offered. For older patients, R-CHOP-21 for eight cycles is equivalent to R-CHOP-14 for six cycles plus two rituximab infusions.

The trial began recruiting after a 2004 German study showed that a dose-dense regimen of six cycles of CHOP-14 improved 5-year overall survival in patients older than 60 years by 13%, compared with six cycles of CHOP-21 (Blood 2004;104:634-41).

Since that publication, however, the addition of rituximab to six or eight cycles of CHOP or similar chemotherapy regimens was shown to improve overall survival of DLBCL by 10%-16% in two trials. Those findings raised interest in whether CHOP-14 might still be superior to CHOP-21 in patients who also receive rituximab, and whether such an effect would be seen across all age groups, Dr. Cunningham said.

He reported the final results of the trial, which involved 1,080 adults who had newly diagnosed CD20-positive DLBCL and were recruited from 119 sites. The patients were stratified by IPI score, age (60 years and younger, or older than 60), and treatment center.

In all, 23% of patients on R-CHOP-21 and 22% on R-CHOP-14 had died by the time of the final study analysis. DLBCL was the leading cause of death in both arms. Other causes included treatment-related toxicity, cardiac causes (all cardiac deaths occurred 3-15 months after completion of therapy), secondary malignancy, and other/unknown causes.

In her discussion, Dr. Vose pointed out that R-CHOP-14, which requires G-CSF support after every cycle, costs about $31,308, compared with $29,247 for R-CHOP-21, in which G-CSF is used only to treat (but not to prevent) neutropenia or febrile neutropenia. In the trial, G-CSF was used in 38% of R-CHOP-21 cycles, compared with 100% of R-CHOP-14 cycles.

In addition, R-CHOP every 21 days for six cycles (not eight) is generally considered to be the standard of care in the United States, she noted; a direct comparison of this shorter regimen with R-CHOP-14 would have been welcome, she said.

The trial was funded by the U.K. National Cancer Research Institute. The authors had no relevant financial disclosures.