PHILADELPHIA – Although overt hepatic encephalopathy was reduced in patients taking rifaximin with baseline Child-Pugh class A, B, or C, there was no significant difference in the reduction based on the level of hepatic impairment, according to a recent presentation at the annual meeting of the American College of Gastroenterology.

Jeff Craven/MDedge News

Steven L. Flamm, MD, from Northwestern University, Chicago, and his colleagues examined results from a previous randomized, double-blinded trial of 140 patients receiving twice-daily rifaximin at 550 mg for 6 months in which the results showed rifaximin successfully maintained remission of hepatic encephalopathy (HE), compared with 159 patients receiving placebo.

“This pivotal study was published in March of 2010, but one of the post hoc assessments that was not performed was looking at various different phases of hepatic impairment as dictated by [Child-Pugh] class and each of those responses to this product,” Dr. Flamm said in his presentation.

Patients in the study were included if they had a Model For End-Stage Liver Disease score of 25 or less and two or more overt HE within 6 months (Conn score 1 or less) but were currently in remission. The researchers allowed the use of concomitant lactulose during the study period, which was used in 94.1% of rifaximin and 91.2% of placebo patients.

In the post hoc analysis, Dr. Flamm and his colleagues divided rifaximin and placebo patients into Child-Pugh class A (46 patients vs. 56 patients), class B (65 patients vs. 72 patients), and class C (17 patients vs. 14 patients) groups. For rifaximin and placebo patients, the mean age was 57.3 years and 57.2 years in the class A group, 54.4 years and 57.0 years in the class B group, and 56.1 years and 57.6 years in the class C group, respectively.

Overall, 8 of 46 rifaximin patients (17.4%) in the Child-Pugh class A and 15 of 65 rifaximin patients (23.1%) in the class B groups experienced an overt HE event during the 6-month study period, compared with 26 of 56 patients in the class A (46.4%) and 32 of 72 patients (44.4%) in the class B placebo groups; 5 of 17 rifaximin patients (29.4%) in the Child-Pugh class C group experienced their first overt HE event, compared with 9 of 14 (64.3%) patients in the placebo group.

With regard to first HE-related hospitalization, 5 of 46 patients (10.9%) in the rifaximin Child-Pugh class A group, 8 of 65 rifaximin patients (12.3%) in the class B group, and 4 of 17 rifaximin patients (23.5%) in the class C group experienced hospitalization because of HE, compared with 15 of 56 patients (23.2%) in the Child-Pugh class A group, 15 of 72 patients (20.8%) in the class B group, and 5 of 14 patients (35.7%) in the class C placebo group. The researchers noted lactulose use in the majority of patient cases in the study “provided further benefit” in reducing overt HE events.

“Although numeric differences were observed favoring rifaximin for the incidence of HE-related hospitalizations, a risk reduction versus placebo could not be firmly established, and presumably this was largely due to a lack of adequate power because of small sample size,” Dr. Flamm said.

This study and its analysis were supported by Salix Pharmaceuticals. Dr. Flamm and other coauthors report advisory committee membership, board membership, employment, or consultancy with AbbVie, Bristol-Myers Squibb, Gilead Sciences, Intercept Pharmaceuticals, Merck and Salix Pharmaceuticals. One coauthor reported no relevant conflicts of interest.

SOURCE: Flamm SL et al ACG 2018, Presentation 58.

PHILADELPHIA – Although overt hepatic encephalopathy was reduced in patients taking rifaximin with baseline Child-Pugh class A, B, or C, there was no significant difference in the reduction based on the level of hepatic impairment, according to a recent presentation at the annual meeting of the American College of Gastroenterology.

Jeff Craven/MDedge News

Steven L. Flamm, MD, from Northwestern University, Chicago, and his colleagues examined results from a previous randomized, double-blinded trial of 140 patients receiving twice-daily rifaximin at 550 mg for 6 months in which the results showed rifaximin successfully maintained remission of hepatic encephalopathy (HE), compared with 159 patients receiving placebo.

“This pivotal study was published in March of 2010, but one of the post hoc assessments that was not performed was looking at various different phases of hepatic impairment as dictated by [Child-Pugh] class and each of those responses to this product,” Dr. Flamm said in his presentation.

Patients in the study were included if they had a Model For End-Stage Liver Disease score of 25 or less and two or more overt HE within 6 months (Conn score 1 or less) but were currently in remission. The researchers allowed the use of concomitant lactulose during the study period, which was used in 94.1% of rifaximin and 91.2% of placebo patients.

In the post hoc analysis, Dr. Flamm and his colleagues divided rifaximin and placebo patients into Child-Pugh class A (46 patients vs. 56 patients), class B (65 patients vs. 72 patients), and class C (17 patients vs. 14 patients) groups. For rifaximin and placebo patients, the mean age was 57.3 years and 57.2 years in the class A group, 54.4 years and 57.0 years in the class B group, and 56.1 years and 57.6 years in the class C group, respectively.

Overall, 8 of 46 rifaximin patients (17.4%) in the Child-Pugh class A and 15 of 65 rifaximin patients (23.1%) in the class B groups experienced an overt HE event during the 6-month study period, compared with 26 of 56 patients in the class A (46.4%) and 32 of 72 patients (44.4%) in the class B placebo groups; 5 of 17 rifaximin patients (29.4%) in the Child-Pugh class C group experienced their first overt HE event, compared with 9 of 14 (64.3%) patients in the placebo group.

With regard to first HE-related hospitalization, 5 of 46 patients (10.9%) in the rifaximin Child-Pugh class A group, 8 of 65 rifaximin patients (12.3%) in the class B group, and 4 of 17 rifaximin patients (23.5%) in the class C group experienced hospitalization because of HE, compared with 15 of 56 patients (23.2%) in the Child-Pugh class A group, 15 of 72 patients (20.8%) in the class B group, and 5 of 14 patients (35.7%) in the class C placebo group. The researchers noted lactulose use in the majority of patient cases in the study “provided further benefit” in reducing overt HE events.

“Although numeric differences were observed favoring rifaximin for the incidence of HE-related hospitalizations, a risk reduction versus placebo could not be firmly established, and presumably this was largely due to a lack of adequate power because of small sample size,” Dr. Flamm said.

This study and its analysis were supported by Salix Pharmaceuticals. Dr. Flamm and other coauthors report advisory committee membership, board membership, employment, or consultancy with AbbVie, Bristol-Myers Squibb, Gilead Sciences, Intercept Pharmaceuticals, Merck and Salix Pharmaceuticals. One coauthor reported no relevant conflicts of interest.

SOURCE: Flamm SL et al ACG 2018, Presentation 58.

PHILADELPHIA – Although overt hepatic encephalopathy was reduced in patients taking rifaximin with baseline Child-Pugh class A, B, or C, there was no significant difference in the reduction based on the level of hepatic impairment, according to a recent presentation at the annual meeting of the American College of Gastroenterology.

Jeff Craven/MDedge News

Steven L. Flamm, MD, from Northwestern University, Chicago, and his colleagues examined results from a previous randomized, double-blinded trial of 140 patients receiving twice-daily rifaximin at 550 mg for 6 months in which the results showed rifaximin successfully maintained remission of hepatic encephalopathy (HE), compared with 159 patients receiving placebo.

“This pivotal study was published in March of 2010, but one of the post hoc assessments that was not performed was looking at various different phases of hepatic impairment as dictated by [Child-Pugh] class and each of those responses to this product,” Dr. Flamm said in his presentation.

Patients in the study were included if they had a Model For End-Stage Liver Disease score of 25 or less and two or more overt HE within 6 months (Conn score 1 or less) but were currently in remission. The researchers allowed the use of concomitant lactulose during the study period, which was used in 94.1% of rifaximin and 91.2% of placebo patients.

In the post hoc analysis, Dr. Flamm and his colleagues divided rifaximin and placebo patients into Child-Pugh class A (46 patients vs. 56 patients), class B (65 patients vs. 72 patients), and class C (17 patients vs. 14 patients) groups. For rifaximin and placebo patients, the mean age was 57.3 years and 57.2 years in the class A group, 54.4 years and 57.0 years in the class B group, and 56.1 years and 57.6 years in the class C group, respectively.

Overall, 8 of 46 rifaximin patients (17.4%) in the Child-Pugh class A and 15 of 65 rifaximin patients (23.1%) in the class B groups experienced an overt HE event during the 6-month study period, compared with 26 of 56 patients in the class A (46.4%) and 32 of 72 patients (44.4%) in the class B placebo groups; 5 of 17 rifaximin patients (29.4%) in the Child-Pugh class C group experienced their first overt HE event, compared with 9 of 14 (64.3%) patients in the placebo group.

With regard to first HE-related hospitalization, 5 of 46 patients (10.9%) in the rifaximin Child-Pugh class A group, 8 of 65 rifaximin patients (12.3%) in the class B group, and 4 of 17 rifaximin patients (23.5%) in the class C group experienced hospitalization because of HE, compared with 15 of 56 patients (23.2%) in the Child-Pugh class A group, 15 of 72 patients (20.8%) in the class B group, and 5 of 14 patients (35.7%) in the class C placebo group. The researchers noted lactulose use in the majority of patient cases in the study “provided further benefit” in reducing overt HE events.

“Although numeric differences were observed favoring rifaximin for the incidence of HE-related hospitalizations, a risk reduction versus placebo could not be firmly established, and presumably this was largely due to a lack of adequate power because of small sample size,” Dr. Flamm said.

This study and its analysis were supported by Salix Pharmaceuticals. Dr. Flamm and other coauthors report advisory committee membership, board membership, employment, or consultancy with AbbVie, Bristol-Myers Squibb, Gilead Sciences, Intercept Pharmaceuticals, Merck and Salix Pharmaceuticals. One coauthor reported no relevant conflicts of interest.

SOURCE: Flamm SL et al ACG 2018, Presentation 58.

The USPSTF recommends screening all women of reproductive age for intimate partner violence. Also today, drug overdose deaths are down since late 2017, the risk for stroke in the elderly after an acute MI extends to 12 weeks, and high-dose flu vaccine for patients with rheumatoid arthritis beats the standard dose.
Amazon Alexa
Apple Podcasts
Spotify

The USPSTF recommends screening all women of reproductive age for intimate partner violence. Also today, drug overdose deaths are down since late 2017, the risk for stroke in the elderly after an acute MI extends to 12 weeks, and high-dose flu vaccine for patients with rheumatoid arthritis beats the standard dose.
Amazon Alexa
Apple Podcasts
Spotify

The USPSTF recommends screening all women of reproductive age for intimate partner violence. Also today, drug overdose deaths are down since late 2017, the risk for stroke in the elderly after an acute MI extends to 12 weeks, and high-dose flu vaccine for patients with rheumatoid arthritis beats the standard dose.
Amazon Alexa
Apple Podcasts
Spotify

American Indian/Alaska Native (AI/AN) women face the same barriers as all low-income minority women face in accessing preventive care, but according to researchers from Rutgers University in New Jersey and University of Arizona, they also face “unique challenges and circumstances.” The researchers reviewed 18 studies to find out more about facilitators of, and barriers to, breast cancer screening.

Low-income women are more likely to be diagnosed at a later stage and to die of breast cancer, one study found. The factors are well known: cost, lack of a usual source of care, lack of insurance, distance from a facility, and lack of transportation.

However, the researchers of the meta-analysis say, “compounding these barriers,” AI/AN women expressed the belief that preventive care is not a priority, especially when it is their own preventive care. Moreover, some barriers that might be unique to the AI/AN women included concern with “manifest destiny”: the assumption that thinking or talking about breast cancer can cause it, for instance. One study examined “traditionality” and found women who could be seen as more traditional, defining themselves as living an “Indian way of life,” were less likely to be current with screening. Other women expressed mistrust in the technology of screening or spoke about perception of discrimination in the health care system.

Although this population has access to screening through IHS facilities, women who also have insurance (typically Medicaid) are more likely to get screened. Women in rural areas who lived near an IHS facility were more likely than were urban women to get mammograms. The researchers suggest this could be because rural women are more likely to be isolated from other mammogram facilities. Too, the IHS is “chronically underfunded,” the researchers note, likely a cause of the health disparities and limiting scope of services.

Their review made clear that efforts to intervene with AI/AN women to increase breast cancer screening have been limited, the researchers say. The intervention studies they reviewed “were not successful in improving screening rates or adherence.” The qualitative studies, on the other hand, suggest that women may be more responsive to locally supportive, targeted, and culturally appropriate interventions that respect traditionality yet encourage trust in the medical system.

American Indian/Alaska Native (AI/AN) women face the same barriers as all low-income minority women face in accessing preventive care, but according to researchers from Rutgers University in New Jersey and University of Arizona, they also face “unique challenges and circumstances.” The researchers reviewed 18 studies to find out more about facilitators of, and barriers to, breast cancer screening.

Low-income women are more likely to be diagnosed at a later stage and to die of breast cancer, one study found. The factors are well known: cost, lack of a usual source of care, lack of insurance, distance from a facility, and lack of transportation.

However, the researchers of the meta-analysis say, “compounding these barriers,” AI/AN women expressed the belief that preventive care is not a priority, especially when it is their own preventive care. Moreover, some barriers that might be unique to the AI/AN women included concern with “manifest destiny”: the assumption that thinking or talking about breast cancer can cause it, for instance. One study examined “traditionality” and found women who could be seen as more traditional, defining themselves as living an “Indian way of life,” were less likely to be current with screening. Other women expressed mistrust in the technology of screening or spoke about perception of discrimination in the health care system.

Although this population has access to screening through IHS facilities, women who also have insurance (typically Medicaid) are more likely to get screened. Women in rural areas who lived near an IHS facility were more likely than were urban women to get mammograms. The researchers suggest this could be because rural women are more likely to be isolated from other mammogram facilities. Too, the IHS is “chronically underfunded,” the researchers note, likely a cause of the health disparities and limiting scope of services.

Their review made clear that efforts to intervene with AI/AN women to increase breast cancer screening have been limited, the researchers say. The intervention studies they reviewed “were not successful in improving screening rates or adherence.” The qualitative studies, on the other hand, suggest that women may be more responsive to locally supportive, targeted, and culturally appropriate interventions that respect traditionality yet encourage trust in the medical system.

American Indian/Alaska Native (AI/AN) women face the same barriers as all low-income minority women face in accessing preventive care, but according to researchers from Rutgers University in New Jersey and University of Arizona, they also face “unique challenges and circumstances.” The researchers reviewed 18 studies to find out more about facilitators of, and barriers to, breast cancer screening.

Low-income women are more likely to be diagnosed at a later stage and to die of breast cancer, one study found. The factors are well known: cost, lack of a usual source of care, lack of insurance, distance from a facility, and lack of transportation.

However, the researchers of the meta-analysis say, “compounding these barriers,” AI/AN women expressed the belief that preventive care is not a priority, especially when it is their own preventive care. Moreover, some barriers that might be unique to the AI/AN women included concern with “manifest destiny”: the assumption that thinking or talking about breast cancer can cause it, for instance. One study examined “traditionality” and found women who could be seen as more traditional, defining themselves as living an “Indian way of life,” were less likely to be current with screening. Other women expressed mistrust in the technology of screening or spoke about perception of discrimination in the health care system.

Although this population has access to screening through IHS facilities, women who also have insurance (typically Medicaid) are more likely to get screened. Women in rural areas who lived near an IHS facility were more likely than were urban women to get mammograms. The researchers suggest this could be because rural women are more likely to be isolated from other mammogram facilities. Too, the IHS is “chronically underfunded,” the researchers note, likely a cause of the health disparities and limiting scope of services.

Their review made clear that efforts to intervene with AI/AN women to increase breast cancer screening have been limited, the researchers say. The intervention studies they reviewed “were not successful in improving screening rates or adherence.” The qualitative studies, on the other hand, suggest that women may be more responsive to locally supportive, targeted, and culturally appropriate interventions that respect traditionality yet encourage trust in the medical system.

Photo from Bayer

Health Canada has approved Jivi^® (antihemophilic factor [recombinant, B-domain deleted, PEGylated]) for use in patients with hemophilia A.

Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate developed by Bayer.

Health Canada has approved Jivi for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in previously treated hemophilia A patients age 12 and older.

Jivi is also approved for the control and prevention of episodic bleeding and for perioperative management of bleeding.

The recommended initial dosing for Jivi as prophylaxis is twice weekly, with the ability to dose every 5 days and further adjust dosing based on bleeding episodes.

Health Canada’s approval of Jivi is based on the PROTECT VIII trial. Results from this trial are available in the U.S. prescribing information for Jivi.

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A. In part B, Jivi was used for perioperative management of bleeding.

Efficacy

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

Photo from Bayer

Health Canada has approved Jivi^® (antihemophilic factor [recombinant, B-domain deleted, PEGylated]) for use in patients with hemophilia A.

Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate developed by Bayer.

Health Canada has approved Jivi for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in previously treated hemophilia A patients age 12 and older.

Jivi is also approved for the control and prevention of episodic bleeding and for perioperative management of bleeding.

The recommended initial dosing for Jivi as prophylaxis is twice weekly, with the ability to dose every 5 days and further adjust dosing based on bleeding episodes.

Health Canada’s approval of Jivi is based on the PROTECT VIII trial. Results from this trial are available in the U.S. prescribing information for Jivi.

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A. In part B, Jivi was used for perioperative management of bleeding.

Efficacy

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

Photo from Bayer

Health Canada has approved Jivi^® (antihemophilic factor [recombinant, B-domain deleted, PEGylated]) for use in patients with hemophilia A.

Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate developed by Bayer.

Health Canada has approved Jivi for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in previously treated hemophilia A patients age 12 and older.

Jivi is also approved for the control and prevention of episodic bleeding and for perioperative management of bleeding.

The recommended initial dosing for Jivi as prophylaxis is twice weekly, with the ability to dose every 5 days and further adjust dosing based on bleeding episodes.

Health Canada’s approval of Jivi is based on the PROTECT VIII trial. Results from this trial are available in the U.S. prescribing information for Jivi.

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A. In part B, Jivi was used for perioperative management of bleeding.

Efficacy

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

and Krystyn Van Vliet

Specially grown mesenchymal stromal cells (MSCs) can improve hematopoietic recovery, according to preclinical research published in Stem Cell Research and Therapy.

Researchers grew MSCs on a surface with mechanical properties similar to those of bone marrow, which prompted the MSCs to secrete growth factors that aid hematopoietic recovery.

When implanted in irradiated mice, these “mechanoprimed” MSCs sped recovery of all hematopoietic lineages and improved the animals’ survival.

“[MSCs] act like drug factories,” explained study author Krystyn Van Vliet, PhD, of the Massachusetts Institute of Technology in Cambridge.

“They can become tissue lineage cells, but they also pump out a lot of factors that change the environment that the hematopoietic stem cells are operating in.”

Dr. Van Vliet and her colleagues noted that MSCs play an important role in supporting, maintaining, and expanding hematopoietic stem and progenitor cells (HSPCs). However, in a given population of MSCs, usually only about 20% of the cells produce the factors needed to stimulate hematopoietic recovery.

In an earlier study, Dr. Van Vliet and her colleagues showed they could sort MSCs with a microfluidic device that can identify the 20% of cells that promote hematopoietic recovery.

However, the researchers wanted to improve on that by finding a way to stimulate an entire population of MSCs to produce the necessary factors. To do that, they first had to discover which factors were the most important.

Analyses in mice suggested eight factors were associated with improved survival after irradiation—IL-6, IL-8, BMP2, EGF, FGF1, RANTES, VEGF-A, and ANG-1.

Mechanopriming

Having identified factors associated with hematopoietic recovery, Dr. Van Vliet and her colleagues explored the idea of mechanopriming MSCs so they would produce more of these factors.

Over the past decade, researchers have shown that varying the mechanical properties of surfaces on which stem cells are grown can affect their differentiation into mature cell types. However, in this study, the researchers showed that mechanical properties can also affect the factors stem cells secrete before committing to a specific lineage.

For the growth surface, Dr. Van Vliet and her colleagues tested a polymer called polydimethylsiloxane (PDMS). The team varied the mechanical stiffness of the PDMS surface to see how this would affect the MSCs.

MSCs grown on the least stiff PDMS surface produced the greatest number of factors necessary to induce differentiation in HSPCs. These MSCs were able to promote hematopoiesis in an in vitro co-culture model with HSPCs.

Testing in mice

The researchers then tested the mechanoprimed MSCs by implanting them into irradiated mice.

The mechanoprimed MSCs quickly repopulated the animals’ blood cells and helped them recover more quickly than mice treated with MSCs grown on traditional glass surfaces.

Mice that received mechanoprimed MSCs also recovered faster than mice treated with factor-producing MSCs selected by the microfluidic sorting device.

Dr. Van Vliet’s lab is now performing more animal studies in hopes of developing a combination treatment of MSCs and HSPCs that could be tested in humans.

The current research was funded by the National Institutes of Health and the BioSystems and Micromechanics Interdisciplinary Research Group of the Singapore-MIT Alliance for Research and Technology through the Singapore National Research Foundation.

The researchers said they had no competing interests.

and Krystyn Van Vliet

Specially grown mesenchymal stromal cells (MSCs) can improve hematopoietic recovery, according to preclinical research published in Stem Cell Research and Therapy.

Researchers grew MSCs on a surface with mechanical properties similar to those of bone marrow, which prompted the MSCs to secrete growth factors that aid hematopoietic recovery.

When implanted in irradiated mice, these “mechanoprimed” MSCs sped recovery of all hematopoietic lineages and improved the animals’ survival.

“[MSCs] act like drug factories,” explained study author Krystyn Van Vliet, PhD, of the Massachusetts Institute of Technology in Cambridge.

“They can become tissue lineage cells, but they also pump out a lot of factors that change the environment that the hematopoietic stem cells are operating in.”

Dr. Van Vliet and her colleagues noted that MSCs play an important role in supporting, maintaining, and expanding hematopoietic stem and progenitor cells (HSPCs). However, in a given population of MSCs, usually only about 20% of the cells produce the factors needed to stimulate hematopoietic recovery.

In an earlier study, Dr. Van Vliet and her colleagues showed they could sort MSCs with a microfluidic device that can identify the 20% of cells that promote hematopoietic recovery.

However, the researchers wanted to improve on that by finding a way to stimulate an entire population of MSCs to produce the necessary factors. To do that, they first had to discover which factors were the most important.

Analyses in mice suggested eight factors were associated with improved survival after irradiation—IL-6, IL-8, BMP2, EGF, FGF1, RANTES, VEGF-A, and ANG-1.

Mechanopriming

Having identified factors associated with hematopoietic recovery, Dr. Van Vliet and her colleagues explored the idea of mechanopriming MSCs so they would produce more of these factors.

Over the past decade, researchers have shown that varying the mechanical properties of surfaces on which stem cells are grown can affect their differentiation into mature cell types. However, in this study, the researchers showed that mechanical properties can also affect the factors stem cells secrete before committing to a specific lineage.

For the growth surface, Dr. Van Vliet and her colleagues tested a polymer called polydimethylsiloxane (PDMS). The team varied the mechanical stiffness of the PDMS surface to see how this would affect the MSCs.

MSCs grown on the least stiff PDMS surface produced the greatest number of factors necessary to induce differentiation in HSPCs. These MSCs were able to promote hematopoiesis in an in vitro co-culture model with HSPCs.

Testing in mice

The researchers then tested the mechanoprimed MSCs by implanting them into irradiated mice.

The mechanoprimed MSCs quickly repopulated the animals’ blood cells and helped them recover more quickly than mice treated with MSCs grown on traditional glass surfaces.

Mice that received mechanoprimed MSCs also recovered faster than mice treated with factor-producing MSCs selected by the microfluidic sorting device.

Dr. Van Vliet’s lab is now performing more animal studies in hopes of developing a combination treatment of MSCs and HSPCs that could be tested in humans.

The current research was funded by the National Institutes of Health and the BioSystems and Micromechanics Interdisciplinary Research Group of the Singapore-MIT Alliance for Research and Technology through the Singapore National Research Foundation.

The researchers said they had no competing interests.

and Krystyn Van Vliet

Specially grown mesenchymal stromal cells (MSCs) can improve hematopoietic recovery, according to preclinical research published in Stem Cell Research and Therapy.

Researchers grew MSCs on a surface with mechanical properties similar to those of bone marrow, which prompted the MSCs to secrete growth factors that aid hematopoietic recovery.

When implanted in irradiated mice, these “mechanoprimed” MSCs sped recovery of all hematopoietic lineages and improved the animals’ survival.

“[MSCs] act like drug factories,” explained study author Krystyn Van Vliet, PhD, of the Massachusetts Institute of Technology in Cambridge.

“They can become tissue lineage cells, but they also pump out a lot of factors that change the environment that the hematopoietic stem cells are operating in.”

Dr. Van Vliet and her colleagues noted that MSCs play an important role in supporting, maintaining, and expanding hematopoietic stem and progenitor cells (HSPCs). However, in a given population of MSCs, usually only about 20% of the cells produce the factors needed to stimulate hematopoietic recovery.

In an earlier study, Dr. Van Vliet and her colleagues showed they could sort MSCs with a microfluidic device that can identify the 20% of cells that promote hematopoietic recovery.

However, the researchers wanted to improve on that by finding a way to stimulate an entire population of MSCs to produce the necessary factors. To do that, they first had to discover which factors were the most important.

Analyses in mice suggested eight factors were associated with improved survival after irradiation—IL-6, IL-8, BMP2, EGF, FGF1, RANTES, VEGF-A, and ANG-1.

Mechanopriming

Having identified factors associated with hematopoietic recovery, Dr. Van Vliet and her colleagues explored the idea of mechanopriming MSCs so they would produce more of these factors.

Over the past decade, researchers have shown that varying the mechanical properties of surfaces on which stem cells are grown can affect their differentiation into mature cell types. However, in this study, the researchers showed that mechanical properties can also affect the factors stem cells secrete before committing to a specific lineage.

For the growth surface, Dr. Van Vliet and her colleagues tested a polymer called polydimethylsiloxane (PDMS). The team varied the mechanical stiffness of the PDMS surface to see how this would affect the MSCs.

MSCs grown on the least stiff PDMS surface produced the greatest number of factors necessary to induce differentiation in HSPCs. These MSCs were able to promote hematopoiesis in an in vitro co-culture model with HSPCs.

Testing in mice

The researchers then tested the mechanoprimed MSCs by implanting them into irradiated mice.

The mechanoprimed MSCs quickly repopulated the animals’ blood cells and helped them recover more quickly than mice treated with MSCs grown on traditional glass surfaces.

Mice that received mechanoprimed MSCs also recovered faster than mice treated with factor-producing MSCs selected by the microfluidic sorting device.

Dr. Van Vliet’s lab is now performing more animal studies in hopes of developing a combination treatment of MSCs and HSPCs that could be tested in humans.

The current research was funded by the National Institutes of Health and the BioSystems and Micromechanics Interdisciplinary Research Group of the Singapore-MIT Alliance for Research and Technology through the Singapore National Research Foundation.

The researchers said they had no competing interests.

Photo by Rhoda Baer

Researchers say they may have determined why African Americans have a two- to three-fold increased risk of multiple myeloma (MM) compared to European Americans.

The team genotyped 881 MM samples from various racial groups and identified three gene subtypes—t(11;14), t(14;16), and t(14;20)—that explain the racial disparity.

They found that patients with African ancestry of 80% or more had a significantly higher occurrence of these subtypes compared to individuals with African ancestry less than 0.1%.

And these subtypes are driving the disparity in MM diagnoses between the populations.

The researchers state that previous attempts to explain the disparity relied on self-reported race rather than quantitatively measured genetic ancestry, which could result in bias.

“A major new aspect of this study is that we identified the ancestry of each patient through DNA sequencing, which allowed us to determine ancestry more accurately,” said study author Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.

He and his colleagues reported their findings in Blood Cancer Journal.

All 881 samples had abnormal plasma cell FISH, 851 had a normal chromosome study, and 30 had an abnormal study.

Median age for the entire group was 64 (range, 26–90), with 35.4% in the 60–69 age category. More samples were from men (n=478, 54.3%) than women (n=403, 45.7%).

Researchers observed no significant difference between men and women in the proportion of primary cytogenetic abnormalities.

Of the 881 samples, the median African ancestry was 2.3%, the median European ancestry was 64.7%, and Northern European ancestry was 26.6%.

Thirty percent of the entire cohort had less than 0.1% African ancestry, and 13.6% had 80% or greater African ancestry.

Using a logistic regression model, the researchers determined that a 10% increase in the percentage of African ancestry was associated with a 6% increase in the odds of detecting t(11;14), t(14;16), or t(14;20) (odds ratio=1.06, 95% CI: 1.02–1.11; P=0.05).

The researchers plotted the probability of observing these cytogenetic abnormalities with the percentage of African ancestry and found the differences were most striking in the extreme populations—individuals with ≥80.0% African ancestry and individuals with <0.1% African ancestry.

Upon further analysis, the team found a significantly higher prevalence of t(11;14), t(14;16),  and t(14;20) in the group of patients with the greatest proportion of African ancestry (P=0.008) compared to the European cohort.

The researchers said the differences only emerged in the highest (n=120 individuals) and lowest (n=235 individuals) cohorts. Most patients (n=526, 60%) were not included in these extreme populations because they had mixed ancestry.

The team observed no significant differences when the cutoff of African ancestry was greater than 50%.

“Our findings provide important information that will help us determine the mechanism by which myeloma is more common in African Americans, as well as help us in our quest to find out what causes myeloma in the first place,” Dr. Rajkumar said.

The research was supported by the National Cancer Institute of the National Institutes of Health and the Mayo Clinic Department of Laboratory Medicine and Pathology and Center for Individualized Medicine. One study author reported relationships with Celgene, Takeda, Prothena, Janssen, Pfizer, Alnylam, and GSK. Two authors reported relationships with the DNA Diagnostics Center.

Photo by Rhoda Baer

Researchers say they may have determined why African Americans have a two- to three-fold increased risk of multiple myeloma (MM) compared to European Americans.

The team genotyped 881 MM samples from various racial groups and identified three gene subtypes—t(11;14), t(14;16), and t(14;20)—that explain the racial disparity.

They found that patients with African ancestry of 80% or more had a significantly higher occurrence of these subtypes compared to individuals with African ancestry less than 0.1%.

And these subtypes are driving the disparity in MM diagnoses between the populations.

The researchers state that previous attempts to explain the disparity relied on self-reported race rather than quantitatively measured genetic ancestry, which could result in bias.

“A major new aspect of this study is that we identified the ancestry of each patient through DNA sequencing, which allowed us to determine ancestry more accurately,” said study author Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.

He and his colleagues reported their findings in Blood Cancer Journal.

All 881 samples had abnormal plasma cell FISH, 851 had a normal chromosome study, and 30 had an abnormal study.

Median age for the entire group was 64 (range, 26–90), with 35.4% in the 60–69 age category. More samples were from men (n=478, 54.3%) than women (n=403, 45.7%).

Researchers observed no significant difference between men and women in the proportion of primary cytogenetic abnormalities.

Of the 881 samples, the median African ancestry was 2.3%, the median European ancestry was 64.7%, and Northern European ancestry was 26.6%.

Thirty percent of the entire cohort had less than 0.1% African ancestry, and 13.6% had 80% or greater African ancestry.

Using a logistic regression model, the researchers determined that a 10% increase in the percentage of African ancestry was associated with a 6% increase in the odds of detecting t(11;14), t(14;16), or t(14;20) (odds ratio=1.06, 95% CI: 1.02–1.11; P=0.05).

The researchers plotted the probability of observing these cytogenetic abnormalities with the percentage of African ancestry and found the differences were most striking in the extreme populations—individuals with ≥80.0% African ancestry and individuals with <0.1% African ancestry.

Upon further analysis, the team found a significantly higher prevalence of t(11;14), t(14;16),  and t(14;20) in the group of patients with the greatest proportion of African ancestry (P=0.008) compared to the European cohort.

The researchers said the differences only emerged in the highest (n=120 individuals) and lowest (n=235 individuals) cohorts. Most patients (n=526, 60%) were not included in these extreme populations because they had mixed ancestry.

The team observed no significant differences when the cutoff of African ancestry was greater than 50%.

“Our findings provide important information that will help us determine the mechanism by which myeloma is more common in African Americans, as well as help us in our quest to find out what causes myeloma in the first place,” Dr. Rajkumar said.

The research was supported by the National Cancer Institute of the National Institutes of Health and the Mayo Clinic Department of Laboratory Medicine and Pathology and Center for Individualized Medicine. One study author reported relationships with Celgene, Takeda, Prothena, Janssen, Pfizer, Alnylam, and GSK. Two authors reported relationships with the DNA Diagnostics Center.

Photo by Rhoda Baer

Researchers say they may have determined why African Americans have a two- to three-fold increased risk of multiple myeloma (MM) compared to European Americans.

The team genotyped 881 MM samples from various racial groups and identified three gene subtypes—t(11;14), t(14;16), and t(14;20)—that explain the racial disparity.

They found that patients with African ancestry of 80% or more had a significantly higher occurrence of these subtypes compared to individuals with African ancestry less than 0.1%.

And these subtypes are driving the disparity in MM diagnoses between the populations.

The researchers state that previous attempts to explain the disparity relied on self-reported race rather than quantitatively measured genetic ancestry, which could result in bias.

“A major new aspect of this study is that we identified the ancestry of each patient through DNA sequencing, which allowed us to determine ancestry more accurately,” said study author Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.

He and his colleagues reported their findings in Blood Cancer Journal.

All 881 samples had abnormal plasma cell FISH, 851 had a normal chromosome study, and 30 had an abnormal study.

Median age for the entire group was 64 (range, 26–90), with 35.4% in the 60–69 age category. More samples were from men (n=478, 54.3%) than women (n=403, 45.7%).

Researchers observed no significant difference between men and women in the proportion of primary cytogenetic abnormalities.

Of the 881 samples, the median African ancestry was 2.3%, the median European ancestry was 64.7%, and Northern European ancestry was 26.6%.

Thirty percent of the entire cohort had less than 0.1% African ancestry, and 13.6% had 80% or greater African ancestry.

Using a logistic regression model, the researchers determined that a 10% increase in the percentage of African ancestry was associated with a 6% increase in the odds of detecting t(11;14), t(14;16), or t(14;20) (odds ratio=1.06, 95% CI: 1.02–1.11; P=0.05).

The researchers plotted the probability of observing these cytogenetic abnormalities with the percentage of African ancestry and found the differences were most striking in the extreme populations—individuals with ≥80.0% African ancestry and individuals with <0.1% African ancestry.

Upon further analysis, the team found a significantly higher prevalence of t(11;14), t(14;16),  and t(14;20) in the group of patients with the greatest proportion of African ancestry (P=0.008) compared to the European cohort.

The researchers said the differences only emerged in the highest (n=120 individuals) and lowest (n=235 individuals) cohorts. Most patients (n=526, 60%) were not included in these extreme populations because they had mixed ancestry.

The team observed no significant differences when the cutoff of African ancestry was greater than 50%.

“Our findings provide important information that will help us determine the mechanism by which myeloma is more common in African Americans, as well as help us in our quest to find out what causes myeloma in the first place,” Dr. Rajkumar said.

The research was supported by the National Cancer Institute of the National Institutes of Health and the Mayo Clinic Department of Laboratory Medicine and Pathology and Center for Individualized Medicine. One study author reported relationships with Celgene, Takeda, Prothena, Janssen, Pfizer, Alnylam, and GSK. Two authors reported relationships with the DNA Diagnostics Center.

Photo by Bill Branson

Final results of a phase 3 trial suggest bortezomib plus rituximab and chemotherapy can significantly improve overall survival (OS) in transplant-ineligible patients with newly diagnosed mantle cell lymphoma (MCL).

In the LYM-3002 trial, researchers compared bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

The median OS was significantly longer in patients who received VR-CAP than in those who received R-CHOP—90.7 months and 55.7 months, respectively.

This survival benefit was observed in patients with low- and intermediate-risk disease but not high-risk disease.

Tadeusz Robak, MD, of the Medical University of Lodz in Poland, and his colleagues reported these results in The Lancet Oncology alongside a related commentary.

The LYM-3002 trial began more than a decade ago, and initial results were published in 2015. At that time, the VR-CAP group showed a significant increase in progression-free survival compared with the R-CHOP group.

The final analysis of LYM-3002 included 268 of the original 487 MCL patients. Twenty-three percent of patients in the VR-CAP group (n=32) discontinued due to death, as did 40% of patients in the R-CHOP group (n=51). The main cause of death was progression—29% and 14%, respectively.

Among the 268 patients in the final analysis, 140 belonged to the VR-CAP group and 128 to the R-CHOP group. The patients’ median age was 66 (range, 26-83), 71% (n=190) were male, 74% (n=199) had stage IV disease, and 31% were classified as high risk based on the MCL-specific International Prognostic Index (MIPI).

About half of patients received therapies after the trial interventions (n=255, 52%)—43% (n=104) in the VR-CAP group and 62% (n=151) in the R-CHOP group. Most patients received subsequent antineoplastic therapy—77% (n=80) and 81% (n=123), respectively—and more than half received rituximab as second-line therapy—53% (n=55) and 59% (n=89), respectively.

Results

At a median follow-up of 82.0 months, the median OS was significantly longer in the VR-CAP group than in the R-CHOP group—90.7 months (95% CI, 71.4 to not estimable) and 55.7 months (95% CI, 47.2 to 68.9), respectively (hazard ratio [HR]=0.66 [95% CI, 0.51–0.85]; P=0.001).

The 4-year OS was 67.3% in the VR-CAP group and 54.3% in the R-CHOP group. The 6-year OS was 56.6% and 42.0%, respectively.

The researchers noted that VR-CAP was associated with significantly improved OS among patients in the low-risk and intermediate-risk MIPI categories but not in the high-risk category.

In the low-risk cohort, the median OS was 81.7 months in the R-CHOP group and not estimable in the VR-CAP group (HR=0.54 [95% CI, 0.30–0.95]; P≤0.05).

In the intermediate-risk cohort, the median OS was 62.2 months in the R-CHOP group and not estimable in the VR-CAP group (HR=0.55 [95% CI, 0.36–0.85]; P≤0.01).

In the high-risk cohort, the median OS was 37.1 months in the R-CHOP group and 30.4 months in the VR-CAP group (HR=1.02 [95% CI, 0.69–1.50]).

The researchers reported three new adverse events in the final analysis—grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group as well as grade 2 pneumonia in the R-CHOP group.

The team acknowledged that a key limitation of this study was that rituximab was not given as maintenance since it was not considered standard care at the time of study initiation.

Moving forward, Dr. Robak and his colleagues recommend that bortezomib be investigated in combination with newer targeted therapies in order to establish best practice for treating MCL.

The LYM-3002 study was sponsored by Janssen Research & Development. The study authors reported financial ties to Janssen, Celgene, Ipsen, Johnson & Johnson, Novartis, and other companies.

Photo by Bill Branson

Final results of a phase 3 trial suggest bortezomib plus rituximab and chemotherapy can significantly improve overall survival (OS) in transplant-ineligible patients with newly diagnosed mantle cell lymphoma (MCL).

In the LYM-3002 trial, researchers compared bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

The median OS was significantly longer in patients who received VR-CAP than in those who received R-CHOP—90.7 months and 55.7 months, respectively.

This survival benefit was observed in patients with low- and intermediate-risk disease but not high-risk disease.

Tadeusz Robak, MD, of the Medical University of Lodz in Poland, and his colleagues reported these results in The Lancet Oncology alongside a related commentary.

The LYM-3002 trial began more than a decade ago, and initial results were published in 2015. At that time, the VR-CAP group showed a significant increase in progression-free survival compared with the R-CHOP group.

The final analysis of LYM-3002 included 268 of the original 487 MCL patients. Twenty-three percent of patients in the VR-CAP group (n=32) discontinued due to death, as did 40% of patients in the R-CHOP group (n=51). The main cause of death was progression—29% and 14%, respectively.

Among the 268 patients in the final analysis, 140 belonged to the VR-CAP group and 128 to the R-CHOP group. The patients’ median age was 66 (range, 26-83), 71% (n=190) were male, 74% (n=199) had stage IV disease, and 31% were classified as high risk based on the MCL-specific International Prognostic Index (MIPI).

About half of patients received therapies after the trial interventions (n=255, 52%)—43% (n=104) in the VR-CAP group and 62% (n=151) in the R-CHOP group. Most patients received subsequent antineoplastic therapy—77% (n=80) and 81% (n=123), respectively—and more than half received rituximab as second-line therapy—53% (n=55) and 59% (n=89), respectively.

Results

At a median follow-up of 82.0 months, the median OS was significantly longer in the VR-CAP group than in the R-CHOP group—90.7 months (95% CI, 71.4 to not estimable) and 55.7 months (95% CI, 47.2 to 68.9), respectively (hazard ratio [HR]=0.66 [95% CI, 0.51–0.85]; P=0.001).

The 4-year OS was 67.3% in the VR-CAP group and 54.3% in the R-CHOP group. The 6-year OS was 56.6% and 42.0%, respectively.

The researchers noted that VR-CAP was associated with significantly improved OS among patients in the low-risk and intermediate-risk MIPI categories but not in the high-risk category.

In the low-risk cohort, the median OS was 81.7 months in the R-CHOP group and not estimable in the VR-CAP group (HR=0.54 [95% CI, 0.30–0.95]; P≤0.05).

In the intermediate-risk cohort, the median OS was 62.2 months in the R-CHOP group and not estimable in the VR-CAP group (HR=0.55 [95% CI, 0.36–0.85]; P≤0.01).

In the high-risk cohort, the median OS was 37.1 months in the R-CHOP group and 30.4 months in the VR-CAP group (HR=1.02 [95% CI, 0.69–1.50]).

The researchers reported three new adverse events in the final analysis—grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group as well as grade 2 pneumonia in the R-CHOP group.

The team acknowledged that a key limitation of this study was that rituximab was not given as maintenance since it was not considered standard care at the time of study initiation.

Moving forward, Dr. Robak and his colleagues recommend that bortezomib be investigated in combination with newer targeted therapies in order to establish best practice for treating MCL.

The LYM-3002 study was sponsored by Janssen Research & Development. The study authors reported financial ties to Janssen, Celgene, Ipsen, Johnson & Johnson, Novartis, and other companies.

Photo by Bill Branson

Final results of a phase 3 trial suggest bortezomib plus rituximab and chemotherapy can significantly improve overall survival (OS) in transplant-ineligible patients with newly diagnosed mantle cell lymphoma (MCL).

In the LYM-3002 trial, researchers compared bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

The median OS was significantly longer in patients who received VR-CAP than in those who received R-CHOP—90.7 months and 55.7 months, respectively.

This survival benefit was observed in patients with low- and intermediate-risk disease but not high-risk disease.

Tadeusz Robak, MD, of the Medical University of Lodz in Poland, and his colleagues reported these results in The Lancet Oncology alongside a related commentary.

The LYM-3002 trial began more than a decade ago, and initial results were published in 2015. At that time, the VR-CAP group showed a significant increase in progression-free survival compared with the R-CHOP group.

The final analysis of LYM-3002 included 268 of the original 487 MCL patients. Twenty-three percent of patients in the VR-CAP group (n=32) discontinued due to death, as did 40% of patients in the R-CHOP group (n=51). The main cause of death was progression—29% and 14%, respectively.

Among the 268 patients in the final analysis, 140 belonged to the VR-CAP group and 128 to the R-CHOP group. The patients’ median age was 66 (range, 26-83), 71% (n=190) were male, 74% (n=199) had stage IV disease, and 31% were classified as high risk based on the MCL-specific International Prognostic Index (MIPI).

About half of patients received therapies after the trial interventions (n=255, 52%)—43% (n=104) in the VR-CAP group and 62% (n=151) in the R-CHOP group. Most patients received subsequent antineoplastic therapy—77% (n=80) and 81% (n=123), respectively—and more than half received rituximab as second-line therapy—53% (n=55) and 59% (n=89), respectively.

Results

At a median follow-up of 82.0 months, the median OS was significantly longer in the VR-CAP group than in the R-CHOP group—90.7 months (95% CI, 71.4 to not estimable) and 55.7 months (95% CI, 47.2 to 68.9), respectively (hazard ratio [HR]=0.66 [95% CI, 0.51–0.85]; P=0.001).

The 4-year OS was 67.3% in the VR-CAP group and 54.3% in the R-CHOP group. The 6-year OS was 56.6% and 42.0%, respectively.

The researchers noted that VR-CAP was associated with significantly improved OS among patients in the low-risk and intermediate-risk MIPI categories but not in the high-risk category.

In the low-risk cohort, the median OS was 81.7 months in the R-CHOP group and not estimable in the VR-CAP group (HR=0.54 [95% CI, 0.30–0.95]; P≤0.05).

In the intermediate-risk cohort, the median OS was 62.2 months in the R-CHOP group and not estimable in the VR-CAP group (HR=0.55 [95% CI, 0.36–0.85]; P≤0.01).

In the high-risk cohort, the median OS was 37.1 months in the R-CHOP group and 30.4 months in the VR-CAP group (HR=1.02 [95% CI, 0.69–1.50]).

The researchers reported three new adverse events in the final analysis—grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group as well as grade 2 pneumonia in the R-CHOP group.

The team acknowledged that a key limitation of this study was that rituximab was not given as maintenance since it was not considered standard care at the time of study initiation.

Moving forward, Dr. Robak and his colleagues recommend that bortezomib be investigated in combination with newer targeted therapies in order to establish best practice for treating MCL.

The LYM-3002 study was sponsored by Janssen Research & Development. The study authors reported financial ties to Janssen, Celgene, Ipsen, Johnson & Johnson, Novartis, and other companies.

The FP suspected a basal cell carcinoma (BCC) or squamous cell carcinoma.

Informed consent was obtained, and the FP numbed the area with 1% lidocaine and epinephrine using a 30 gauge needle. The area was exquisitely tender, so a small needle was used and the anesthesia was injected slowly. (It is safe and recommended to use epinephrine for biopsy on or around the nose.) The physician performed a shave biopsy. (See the Watch & Learn video on “Shave biopsy.”)

The biopsy results confirmed an infiltrative BCC. The physician recognized this as a more aggressive BCC and its location at the nasolabial fold suggested that the patient was at an increased risk for recurrence. He communicated these risk factors to the patient, and she accepted a referral for Mohs surgery.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Basal cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:989-998.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP suspected a basal cell carcinoma (BCC) or squamous cell carcinoma.

Informed consent was obtained, and the FP numbed the area with 1% lidocaine and epinephrine using a 30 gauge needle. The area was exquisitely tender, so a small needle was used and the anesthesia was injected slowly. (It is safe and recommended to use epinephrine for biopsy on or around the nose.) The physician performed a shave biopsy. (See the Watch & Learn video on “Shave biopsy.”)

The biopsy results confirmed an infiltrative BCC. The physician recognized this as a more aggressive BCC and its location at the nasolabial fold suggested that the patient was at an increased risk for recurrence. He communicated these risk factors to the patient, and she accepted a referral for Mohs surgery.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Basal cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:989-998.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP suspected a basal cell carcinoma (BCC) or squamous cell carcinoma.

Informed consent was obtained, and the FP numbed the area with 1% lidocaine and epinephrine using a 30 gauge needle. The area was exquisitely tender, so a small needle was used and the anesthesia was injected slowly. (It is safe and recommended to use epinephrine for biopsy on or around the nose.) The physician performed a shave biopsy. (See the Watch & Learn video on “Shave biopsy.”)

The biopsy results confirmed an infiltrative BCC. The physician recognized this as a more aggressive BCC and its location at the nasolabial fold suggested that the patient was at an increased risk for recurrence. He communicated these risk factors to the patient, and she accepted a referral for Mohs surgery.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Basal cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:989-998.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

Moderate application of topical therapies directly prior to radiotherapy (RT) treatment sessions may be safe and might exhibit minimal effects on delivered treatment dose, investigators report.

The researchers found that although avoiding topical agents prior to radiation treatments was widespread, preclinical data indicate that there is no difference in the radiation dose on the skin with or without a 1- to 2-mm-thick layer of topical agent.

In an online survey, which queried 133 patients and 108 clinicians in relation to existing practices surrounding topical agent use, 83.4% of patients were informed to discontinue application of topical therapies directly before RT treatment sessions. In addition, 54.1% were told to clean and remove any enduring topical agents before treatment. Among clinicians, 91.4% reported to have received or given advice to stop application of topicals before obtaining RT treatment, Brian C. Baumann, MD, and his associates reported in JAMA Oncology.

However, in a preclinical study using a mouse- and tissue-equivalent phantom model to determine the dosimetric effects of concomitant topical agent use with daily RT treatments, Dr. Baumann, of Washington University in St. Louis, and his colleagues determined that when a topical agent was given prior to RT at a thickness below 2 mm, no changes were seen in radiation treatment dose, irrespective of depth, photon and electron energy level, or beam angle.

However, a proportionally thicker covering (3 mm or more) caused a bolus effect at the surface, which resulted in electron dose increases of 2%-5%, and photon increases of 15%-35%, when compared with controls.

Investigators measured radiation dose and photon beam intensity at various surface depths after applying two commonly used topical therapies, a healing ointment of 41% petrolatum or silver sulfadiazine cream 1%. The agents were administered using a thick (1-2 mm) application and proportionally thicker (3 mm or more) covering.

“Thin or moderately applied topical agents, even if applied just before RT, may have minimal influence on skin dose regardless of beam energy or beam incidence,” the investigators wrote. However, the findings do suggest that “applying very thick amounts of a topical agent before RT may increase the surface dose and should be avoided,” they said.

The authors reported that the study was funded by development funds from the University of Pennsylvania, Philadelphia. One of the coauthors, James M. Metz, MD, disclosed service on advisory boards for Ion Beam Applications and Varian Medical Systems for proton therapy; however, these roles were not relevant to this study.
 

SOURCE: Baumann BC et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4292.

Moderate application of topical therapies directly prior to radiotherapy (RT) treatment sessions may be safe and might exhibit minimal effects on delivered treatment dose, investigators report.

The researchers found that although avoiding topical agents prior to radiation treatments was widespread, preclinical data indicate that there is no difference in the radiation dose on the skin with or without a 1- to 2-mm-thick layer of topical agent.

In an online survey, which queried 133 patients and 108 clinicians in relation to existing practices surrounding topical agent use, 83.4% of patients were informed to discontinue application of topical therapies directly before RT treatment sessions. In addition, 54.1% were told to clean and remove any enduring topical agents before treatment. Among clinicians, 91.4% reported to have received or given advice to stop application of topicals before obtaining RT treatment, Brian C. Baumann, MD, and his associates reported in JAMA Oncology.

However, in a preclinical study using a mouse- and tissue-equivalent phantom model to determine the dosimetric effects of concomitant topical agent use with daily RT treatments, Dr. Baumann, of Washington University in St. Louis, and his colleagues determined that when a topical agent was given prior to RT at a thickness below 2 mm, no changes were seen in radiation treatment dose, irrespective of depth, photon and electron energy level, or beam angle.

However, a proportionally thicker covering (3 mm or more) caused a bolus effect at the surface, which resulted in electron dose increases of 2%-5%, and photon increases of 15%-35%, when compared with controls.

Investigators measured radiation dose and photon beam intensity at various surface depths after applying two commonly used topical therapies, a healing ointment of 41% petrolatum or silver sulfadiazine cream 1%. The agents were administered using a thick (1-2 mm) application and proportionally thicker (3 mm or more) covering.

“Thin or moderately applied topical agents, even if applied just before RT, may have minimal influence on skin dose regardless of beam energy or beam incidence,” the investigators wrote. However, the findings do suggest that “applying very thick amounts of a topical agent before RT may increase the surface dose and should be avoided,” they said.

The authors reported that the study was funded by development funds from the University of Pennsylvania, Philadelphia. One of the coauthors, James M. Metz, MD, disclosed service on advisory boards for Ion Beam Applications and Varian Medical Systems for proton therapy; however, these roles were not relevant to this study.
 

SOURCE: Baumann BC et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4292.

Moderate application of topical therapies directly prior to radiotherapy (RT) treatment sessions may be safe and might exhibit minimal effects on delivered treatment dose, investigators report.

The researchers found that although avoiding topical agents prior to radiation treatments was widespread, preclinical data indicate that there is no difference in the radiation dose on the skin with or without a 1- to 2-mm-thick layer of topical agent.

In an online survey, which queried 133 patients and 108 clinicians in relation to existing practices surrounding topical agent use, 83.4% of patients were informed to discontinue application of topical therapies directly before RT treatment sessions. In addition, 54.1% were told to clean and remove any enduring topical agents before treatment. Among clinicians, 91.4% reported to have received or given advice to stop application of topicals before obtaining RT treatment, Brian C. Baumann, MD, and his associates reported in JAMA Oncology.

However, in a preclinical study using a mouse- and tissue-equivalent phantom model to determine the dosimetric effects of concomitant topical agent use with daily RT treatments, Dr. Baumann, of Washington University in St. Louis, and his colleagues determined that when a topical agent was given prior to RT at a thickness below 2 mm, no changes were seen in radiation treatment dose, irrespective of depth, photon and electron energy level, or beam angle.

However, a proportionally thicker covering (3 mm or more) caused a bolus effect at the surface, which resulted in electron dose increases of 2%-5%, and photon increases of 15%-35%, when compared with controls.

Investigators measured radiation dose and photon beam intensity at various surface depths after applying two commonly used topical therapies, a healing ointment of 41% petrolatum or silver sulfadiazine cream 1%. The agents were administered using a thick (1-2 mm) application and proportionally thicker (3 mm or more) covering.

“Thin or moderately applied topical agents, even if applied just before RT, may have minimal influence on skin dose regardless of beam energy or beam incidence,” the investigators wrote. However, the findings do suggest that “applying very thick amounts of a topical agent before RT may increase the surface dose and should be avoided,” they said.

The authors reported that the study was funded by development funds from the University of Pennsylvania, Philadelphia. One of the coauthors, James M. Metz, MD, disclosed service on advisory boards for Ion Beam Applications and Varian Medical Systems for proton therapy; however, these roles were not relevant to this study.
 

SOURCE: Baumann BC et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4292.