Federal judges have blocked the Trump administration from weakening the Affordable Care Act’s contraceptive mandate. Too much sleep and too little sleep are linked to atherosclerosis, there is no drop in gout prevalence, but there isn’t an increase either, and back pain persists in one in five patients.

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Federal judges have blocked the Trump administration from weakening the Affordable Care Act’s contraceptive mandate. Too much sleep and too little sleep are linked to atherosclerosis, there is no drop in gout prevalence, but there isn’t an increase either, and back pain persists in one in five patients.

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Apple Podcasts

Google Podcasts

Spotify
 

Federal judges have blocked the Trump administration from weakening the Affordable Care Act’s contraceptive mandate. Too much sleep and too little sleep are linked to atherosclerosis, there is no drop in gout prevalence, but there isn’t an increase either, and back pain persists in one in five patients.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Disease-modifying therapies give patients with relapsing-remitting multiple sclerosis a lower risk of developing secondary progressive disease that may only be topped in specific patients with highly active disease by the use of nonmyeloablative hematopoietic stem cell transplantation, according to findings from two studies published online Jan. 15 in JAMA.

copyright Zerbor/Thinkstock

The first study found that interferon-beta, glatiramer acetate (Copaxone), fingolimod (Gilenya), natalizumab (Tysabri), and alemtuzumab (Lemtrada) are associated with a lower risk of conversion to secondary progressive MS, compared with no treatment. Initial treatment with the newer therapies provided a greater risk reduction, compared with initial treatment with interferon-beta or glatiramer acetate.

The second study, described as “the first randomized trial of HSCT [nonmyeloablative hematopoietic stem cell transplantation] in patients with relapsing-remitting MS,” suggests that HSCT prolongs the time to disease progression, compared with disease-modifying therapies (DMTs). It also suggests that HSCT can lead to clinical improvement.
 

DMTs reduced risk of conversion to secondary progressive MS

Few previous studies have examined the association between DMTs and the risk of conversion from relapsing-remitting MS to secondary progressive MS. Those that have analyzed this association have not used a validated definition of secondary progressive MS. J. William L. Brown, MD, of the University of Cambridge, England, and his colleagues used a validated definition of secondary progressive MS that was published in 2016 to investigate how DMTs affect the rate of conversion, compared with no treatment. The researchers also compared the risk reduction provided by fingolimod, alemtuzumab, or natalizumab with that provided by interferon-beta or glatiramer acetate.

Dr. Brown and his colleagues analyzed prospectively collected clinical data from an international observational cohort study called MSBase. Eligible participants had relapsing-remitting MS, the complete MSBase minimum data set, at least one Expanded Disability Status Scale (EDSS) score recorded within 6 months before baseline, and at least two EDSS scores recorded after baseline. Participants initiated a DMT or began clinical monitoring during 1988-2012. The population had a minimum follow-up duration of 4 years. Patients who stopped their initial therapy within 6 months and those participating in clinical trials were excluded.

The primary outcome was conversion to secondary progressive MS. Dr. Brown and his colleagues defined this outcome as an EDSS increase of 1 point for participants with a baseline EDSS score of 5.5 or less and as an increase of 0.5 points for participants with a baseline EDSS score higher than 5.5. This increase had to occur in the absence of relapses and be confirmed at a subsequent visit 3 or fewer months later. In addition, the increased EDSS score had to be 4 or more.

After excluding ineligible participants, the investigators matched 1,555 patients from 68 centers in 21 countries. Each therapy analyzed was associated with reduced risk of converting to secondary progressive MS, compared with no treatment. The hazard ratios for conversion were 0.71 for interferon-beta or glatiramer acetate, 0.37 for fingolimod, 0.61 for natalizumab, and 0.52 for alemtuzumab, compared with no treatment.

Treatment with interferon-beta or glatiramer acetate within 5 years of disease onset was associated with a reduced risk of conversion (HR, 0.77), compared with treatment later than 5 years after disease onset. Similarly, patients who escalated treatment from interferon-beta or glatiramer acetate to any of the other three DMTs within 5 years of disease onset had a significantly lower risk of conversion (HR, 0.76) than did those who escalated later. Furthermore, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a significantly reduced risk of conversion (HR, 0.66), compared with initial treatment with interferon-beta or glatiramer acetate.

One of the study’s limitations is its observational design, which precludes the determination of causality, Dr. Brown and his colleagues said. In addition, functional score subcomponents of the EDSS were unavailable, which prevented the researchers from using the definition of secondary progressive MS with the best combination of sensitivity, specificity, and accuracy. Some analyses were limited by small numbers of patients, and the study did not evaluate the risks associated with DMTs. Nevertheless, “these findings, considered along with these therapies’ risks, may help inform decisions about DMT selection,” the authors concluded.

Financial support for this study was provided by the National Health and Medical Research Council of Australia and the University of Melbourne. Dr. Brown received a Next Generation Fellowship funded by the Grand Charity of the Freemasons and an MSBase 2017 Fellowship. Alemtuzumab studies conducted in Cambridge were supported by the National Institute for Health Research Cambridge Biomedical Research Centre and the MS Society UK.
 

HSCT delayed disease progression

In a previous case series, Richard K. Burt, MD, of Northwestern University in Chicago, and his colleagues found that patients with relapsing-remitting MS who underwent nonmyeloablative HSCT had neurologic improvement and a 70% likelihood of having a 4-year period of disease remission. Dr. Burt and his colleagues undertook the MS international stem cell transplant trial to compare the effects of nonmyeloablative HSCT with those of continued DMT treatment on disease progression in participants with highly active relapsing-remitting MS.

The researchers enrolled 110 participants at four international centers into their open-label trial. Eligible participants had two or more clinical relapses or one relapse and at least one gadolinium-enhancing lesion at a separate time within the previous 12 months, despite DMT treatment. The investigators also required participants to have an EDSS score between 2.0 and 6.0. Patients with primary or secondary progressive MS were excluded.

Dr. Burt and his colleagues randomized participants to receive HSCT or an approved DMT that was more effective or in a different class than the one they were receiving at baseline. Ocrelizumab (Ocrevus) was not administered during the study because it had not yet been approved. The investigators excluded alemtuzumab because of its association with persistent lymphopenia and autoimmune disorders. After 1 year of treatment, patients receiving a DMT who had disability progression could cross over to the HSCT arm. Patients randomized to HSCT stopped taking their usual DMT.

Time to disease progression was the study’s primary endpoint. The investigators defined disease progression as an increase in EDSS score of at least 1 point on two evaluations 6 months apart after at least 1 year of treatment. The increase was required to result from MS. The neurologist who recorded participants’ EDSS evaluations was blinded to treatment group assignment.

The researchers randomized 55 patients to each study arm. Approximately 66% of participants were women, and the sample’s mean age was 36 years. There were no significant baseline differences between groups on demographic, clinical, or imaging characteristics. Three patients in the HSCT group were withdrawn from the study, and four in the DMT group were lost to follow-up after seeking HSCT at outside facilities.

Three patients in the HSCT group and 34 patients in the DMT group had disease progression. Mean follow-up duration was 2.8 years. The investigators could not calculate the median time to progression in the HSCT group because too few events occurred. Median time to progression was 24 months in the DMT group (HR, 0.07). During the first year, mean EDSS scores decreased (indicating improvement) from 3.38 to 2.36 in the HSCT group. Mean EDSS scores increased from 3.31 to 3.98 in the DMT group. No participants died, and no patients who received HSCT-developed nonhematopoietic grade 4 toxicities.

“To our knowledge, this is the first randomized trial of HSCT in patients with relapsing-remitting MS,” Dr. Burt and his colleagues said. Although observational studies have found similar EDSS improvements following HSCT, “this degree of improvement has not been demonstrated in pharmaceutical trials even with more intensive DMT such as alemtuzumab,” they concluded.

The Danhakl Family Foundation, the Cumming Foundation, the McNamara Purcell Foundation, Morgan Stanley, and the National Institute for Health Research Sheffield Clinical Research Facility provided financial support for this study. No pharmaceutical companies supported the study.

[email protected]

SOURCEs: Brown JWL et al. JAMA. 2019;321(2):175-87. doi: 10.1001/jama.2018.20588.; and Burt RK et al. JAMA. 2019;321(2):165-74. doi: 10.1001/jama.2018.18743.

Disease-modifying therapies give patients with relapsing-remitting multiple sclerosis a lower risk of developing secondary progressive disease that may only be topped in specific patients with highly active disease by the use of nonmyeloablative hematopoietic stem cell transplantation, according to findings from two studies published online Jan. 15 in JAMA.

copyright Zerbor/Thinkstock

The first study found that interferon-beta, glatiramer acetate (Copaxone), fingolimod (Gilenya), natalizumab (Tysabri), and alemtuzumab (Lemtrada) are associated with a lower risk of conversion to secondary progressive MS, compared with no treatment. Initial treatment with the newer therapies provided a greater risk reduction, compared with initial treatment with interferon-beta or glatiramer acetate.

The second study, described as “the first randomized trial of HSCT [nonmyeloablative hematopoietic stem cell transplantation] in patients with relapsing-remitting MS,” suggests that HSCT prolongs the time to disease progression, compared with disease-modifying therapies (DMTs). It also suggests that HSCT can lead to clinical improvement.
 

DMTs reduced risk of conversion to secondary progressive MS

Few previous studies have examined the association between DMTs and the risk of conversion from relapsing-remitting MS to secondary progressive MS. Those that have analyzed this association have not used a validated definition of secondary progressive MS. J. William L. Brown, MD, of the University of Cambridge, England, and his colleagues used a validated definition of secondary progressive MS that was published in 2016 to investigate how DMTs affect the rate of conversion, compared with no treatment. The researchers also compared the risk reduction provided by fingolimod, alemtuzumab, or natalizumab with that provided by interferon-beta or glatiramer acetate.

Dr. Brown and his colleagues analyzed prospectively collected clinical data from an international observational cohort study called MSBase. Eligible participants had relapsing-remitting MS, the complete MSBase minimum data set, at least one Expanded Disability Status Scale (EDSS) score recorded within 6 months before baseline, and at least two EDSS scores recorded after baseline. Participants initiated a DMT or began clinical monitoring during 1988-2012. The population had a minimum follow-up duration of 4 years. Patients who stopped their initial therapy within 6 months and those participating in clinical trials were excluded.

The primary outcome was conversion to secondary progressive MS. Dr. Brown and his colleagues defined this outcome as an EDSS increase of 1 point for participants with a baseline EDSS score of 5.5 or less and as an increase of 0.5 points for participants with a baseline EDSS score higher than 5.5. This increase had to occur in the absence of relapses and be confirmed at a subsequent visit 3 or fewer months later. In addition, the increased EDSS score had to be 4 or more.

After excluding ineligible participants, the investigators matched 1,555 patients from 68 centers in 21 countries. Each therapy analyzed was associated with reduced risk of converting to secondary progressive MS, compared with no treatment. The hazard ratios for conversion were 0.71 for interferon-beta or glatiramer acetate, 0.37 for fingolimod, 0.61 for natalizumab, and 0.52 for alemtuzumab, compared with no treatment.

Treatment with interferon-beta or glatiramer acetate within 5 years of disease onset was associated with a reduced risk of conversion (HR, 0.77), compared with treatment later than 5 years after disease onset. Similarly, patients who escalated treatment from interferon-beta or glatiramer acetate to any of the other three DMTs within 5 years of disease onset had a significantly lower risk of conversion (HR, 0.76) than did those who escalated later. Furthermore, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a significantly reduced risk of conversion (HR, 0.66), compared with initial treatment with interferon-beta or glatiramer acetate.

One of the study’s limitations is its observational design, which precludes the determination of causality, Dr. Brown and his colleagues said. In addition, functional score subcomponents of the EDSS were unavailable, which prevented the researchers from using the definition of secondary progressive MS with the best combination of sensitivity, specificity, and accuracy. Some analyses were limited by small numbers of patients, and the study did not evaluate the risks associated with DMTs. Nevertheless, “these findings, considered along with these therapies’ risks, may help inform decisions about DMT selection,” the authors concluded.

Financial support for this study was provided by the National Health and Medical Research Council of Australia and the University of Melbourne. Dr. Brown received a Next Generation Fellowship funded by the Grand Charity of the Freemasons and an MSBase 2017 Fellowship. Alemtuzumab studies conducted in Cambridge were supported by the National Institute for Health Research Cambridge Biomedical Research Centre and the MS Society UK.
 

HSCT delayed disease progression

In a previous case series, Richard K. Burt, MD, of Northwestern University in Chicago, and his colleagues found that patients with relapsing-remitting MS who underwent nonmyeloablative HSCT had neurologic improvement and a 70% likelihood of having a 4-year period of disease remission. Dr. Burt and his colleagues undertook the MS international stem cell transplant trial to compare the effects of nonmyeloablative HSCT with those of continued DMT treatment on disease progression in participants with highly active relapsing-remitting MS.

The researchers enrolled 110 participants at four international centers into their open-label trial. Eligible participants had two or more clinical relapses or one relapse and at least one gadolinium-enhancing lesion at a separate time within the previous 12 months, despite DMT treatment. The investigators also required participants to have an EDSS score between 2.0 and 6.0. Patients with primary or secondary progressive MS were excluded.

Dr. Burt and his colleagues randomized participants to receive HSCT or an approved DMT that was more effective or in a different class than the one they were receiving at baseline. Ocrelizumab (Ocrevus) was not administered during the study because it had not yet been approved. The investigators excluded alemtuzumab because of its association with persistent lymphopenia and autoimmune disorders. After 1 year of treatment, patients receiving a DMT who had disability progression could cross over to the HSCT arm. Patients randomized to HSCT stopped taking their usual DMT.

Time to disease progression was the study’s primary endpoint. The investigators defined disease progression as an increase in EDSS score of at least 1 point on two evaluations 6 months apart after at least 1 year of treatment. The increase was required to result from MS. The neurologist who recorded participants’ EDSS evaluations was blinded to treatment group assignment.

The researchers randomized 55 patients to each study arm. Approximately 66% of participants were women, and the sample’s mean age was 36 years. There were no significant baseline differences between groups on demographic, clinical, or imaging characteristics. Three patients in the HSCT group were withdrawn from the study, and four in the DMT group were lost to follow-up after seeking HSCT at outside facilities.

Three patients in the HSCT group and 34 patients in the DMT group had disease progression. Mean follow-up duration was 2.8 years. The investigators could not calculate the median time to progression in the HSCT group because too few events occurred. Median time to progression was 24 months in the DMT group (HR, 0.07). During the first year, mean EDSS scores decreased (indicating improvement) from 3.38 to 2.36 in the HSCT group. Mean EDSS scores increased from 3.31 to 3.98 in the DMT group. No participants died, and no patients who received HSCT-developed nonhematopoietic grade 4 toxicities.

“To our knowledge, this is the first randomized trial of HSCT in patients with relapsing-remitting MS,” Dr. Burt and his colleagues said. Although observational studies have found similar EDSS improvements following HSCT, “this degree of improvement has not been demonstrated in pharmaceutical trials even with more intensive DMT such as alemtuzumab,” they concluded.

The Danhakl Family Foundation, the Cumming Foundation, the McNamara Purcell Foundation, Morgan Stanley, and the National Institute for Health Research Sheffield Clinical Research Facility provided financial support for this study. No pharmaceutical companies supported the study.

[email protected]

SOURCEs: Brown JWL et al. JAMA. 2019;321(2):175-87. doi: 10.1001/jama.2018.20588.; and Burt RK et al. JAMA. 2019;321(2):165-74. doi: 10.1001/jama.2018.18743.

Disease-modifying therapies give patients with relapsing-remitting multiple sclerosis a lower risk of developing secondary progressive disease that may only be topped in specific patients with highly active disease by the use of nonmyeloablative hematopoietic stem cell transplantation, according to findings from two studies published online Jan. 15 in JAMA.

copyright Zerbor/Thinkstock

The first study found that interferon-beta, glatiramer acetate (Copaxone), fingolimod (Gilenya), natalizumab (Tysabri), and alemtuzumab (Lemtrada) are associated with a lower risk of conversion to secondary progressive MS, compared with no treatment. Initial treatment with the newer therapies provided a greater risk reduction, compared with initial treatment with interferon-beta or glatiramer acetate.

The second study, described as “the first randomized trial of HSCT [nonmyeloablative hematopoietic stem cell transplantation] in patients with relapsing-remitting MS,” suggests that HSCT prolongs the time to disease progression, compared with disease-modifying therapies (DMTs). It also suggests that HSCT can lead to clinical improvement.
 

DMTs reduced risk of conversion to secondary progressive MS

Few previous studies have examined the association between DMTs and the risk of conversion from relapsing-remitting MS to secondary progressive MS. Those that have analyzed this association have not used a validated definition of secondary progressive MS. J. William L. Brown, MD, of the University of Cambridge, England, and his colleagues used a validated definition of secondary progressive MS that was published in 2016 to investigate how DMTs affect the rate of conversion, compared with no treatment. The researchers also compared the risk reduction provided by fingolimod, alemtuzumab, or natalizumab with that provided by interferon-beta or glatiramer acetate.

Dr. Brown and his colleagues analyzed prospectively collected clinical data from an international observational cohort study called MSBase. Eligible participants had relapsing-remitting MS, the complete MSBase minimum data set, at least one Expanded Disability Status Scale (EDSS) score recorded within 6 months before baseline, and at least two EDSS scores recorded after baseline. Participants initiated a DMT or began clinical monitoring during 1988-2012. The population had a minimum follow-up duration of 4 years. Patients who stopped their initial therapy within 6 months and those participating in clinical trials were excluded.

The primary outcome was conversion to secondary progressive MS. Dr. Brown and his colleagues defined this outcome as an EDSS increase of 1 point for participants with a baseline EDSS score of 5.5 or less and as an increase of 0.5 points for participants with a baseline EDSS score higher than 5.5. This increase had to occur in the absence of relapses and be confirmed at a subsequent visit 3 or fewer months later. In addition, the increased EDSS score had to be 4 or more.

After excluding ineligible participants, the investigators matched 1,555 patients from 68 centers in 21 countries. Each therapy analyzed was associated with reduced risk of converting to secondary progressive MS, compared with no treatment. The hazard ratios for conversion were 0.71 for interferon-beta or glatiramer acetate, 0.37 for fingolimod, 0.61 for natalizumab, and 0.52 for alemtuzumab, compared with no treatment.

Treatment with interferon-beta or glatiramer acetate within 5 years of disease onset was associated with a reduced risk of conversion (HR, 0.77), compared with treatment later than 5 years after disease onset. Similarly, patients who escalated treatment from interferon-beta or glatiramer acetate to any of the other three DMTs within 5 years of disease onset had a significantly lower risk of conversion (HR, 0.76) than did those who escalated later. Furthermore, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a significantly reduced risk of conversion (HR, 0.66), compared with initial treatment with interferon-beta or glatiramer acetate.

One of the study’s limitations is its observational design, which precludes the determination of causality, Dr. Brown and his colleagues said. In addition, functional score subcomponents of the EDSS were unavailable, which prevented the researchers from using the definition of secondary progressive MS with the best combination of sensitivity, specificity, and accuracy. Some analyses were limited by small numbers of patients, and the study did not evaluate the risks associated with DMTs. Nevertheless, “these findings, considered along with these therapies’ risks, may help inform decisions about DMT selection,” the authors concluded.

Financial support for this study was provided by the National Health and Medical Research Council of Australia and the University of Melbourne. Dr. Brown received a Next Generation Fellowship funded by the Grand Charity of the Freemasons and an MSBase 2017 Fellowship. Alemtuzumab studies conducted in Cambridge were supported by the National Institute for Health Research Cambridge Biomedical Research Centre and the MS Society UK.
 

HSCT delayed disease progression

In a previous case series, Richard K. Burt, MD, of Northwestern University in Chicago, and his colleagues found that patients with relapsing-remitting MS who underwent nonmyeloablative HSCT had neurologic improvement and a 70% likelihood of having a 4-year period of disease remission. Dr. Burt and his colleagues undertook the MS international stem cell transplant trial to compare the effects of nonmyeloablative HSCT with those of continued DMT treatment on disease progression in participants with highly active relapsing-remitting MS.

The researchers enrolled 110 participants at four international centers into their open-label trial. Eligible participants had two or more clinical relapses or one relapse and at least one gadolinium-enhancing lesion at a separate time within the previous 12 months, despite DMT treatment. The investigators also required participants to have an EDSS score between 2.0 and 6.0. Patients with primary or secondary progressive MS were excluded.

Dr. Burt and his colleagues randomized participants to receive HSCT or an approved DMT that was more effective or in a different class than the one they were receiving at baseline. Ocrelizumab (Ocrevus) was not administered during the study because it had not yet been approved. The investigators excluded alemtuzumab because of its association with persistent lymphopenia and autoimmune disorders. After 1 year of treatment, patients receiving a DMT who had disability progression could cross over to the HSCT arm. Patients randomized to HSCT stopped taking their usual DMT.

Time to disease progression was the study’s primary endpoint. The investigators defined disease progression as an increase in EDSS score of at least 1 point on two evaluations 6 months apart after at least 1 year of treatment. The increase was required to result from MS. The neurologist who recorded participants’ EDSS evaluations was blinded to treatment group assignment.

The researchers randomized 55 patients to each study arm. Approximately 66% of participants were women, and the sample’s mean age was 36 years. There were no significant baseline differences between groups on demographic, clinical, or imaging characteristics. Three patients in the HSCT group were withdrawn from the study, and four in the DMT group were lost to follow-up after seeking HSCT at outside facilities.

Three patients in the HSCT group and 34 patients in the DMT group had disease progression. Mean follow-up duration was 2.8 years. The investigators could not calculate the median time to progression in the HSCT group because too few events occurred. Median time to progression was 24 months in the DMT group (HR, 0.07). During the first year, mean EDSS scores decreased (indicating improvement) from 3.38 to 2.36 in the HSCT group. Mean EDSS scores increased from 3.31 to 3.98 in the DMT group. No participants died, and no patients who received HSCT-developed nonhematopoietic grade 4 toxicities.

“To our knowledge, this is the first randomized trial of HSCT in patients with relapsing-remitting MS,” Dr. Burt and his colleagues said. Although observational studies have found similar EDSS improvements following HSCT, “this degree of improvement has not been demonstrated in pharmaceutical trials even with more intensive DMT such as alemtuzumab,” they concluded.

The Danhakl Family Foundation, the Cumming Foundation, the McNamara Purcell Foundation, Morgan Stanley, and the National Institute for Health Research Sheffield Clinical Research Facility provided financial support for this study. No pharmaceutical companies supported the study.

[email protected]

SOURCEs: Brown JWL et al. JAMA. 2019;321(2):175-87. doi: 10.1001/jama.2018.20588.; and Burt RK et al. JAMA. 2019;321(2):165-74. doi: 10.1001/jama.2018.18743.

LA JOLLA, CALIF. – New developments in epigenetics research were highlighted at the 11th annual T-cell Lymphoma Forum.

Vidyard Video

In a video interview, meeting cochair Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, discussed a few presentations that addressed epigenetics in T-cell lymphomas.

Stephen Baylin, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, gave the meeting’s keynote address, which focused on the idea that epigenetic therapy can enhance immune checkpoint therapy.

Susan Bates, MD, of Columbia University Medical Center, presented data that suggest romidepsin and other histone deacetylase inhibitors fight cutaneous T-cell lymphoma via epigenetic effects on gene expression, as well as DNA damage.

And Enrica Marchi, MD, PhD, of Columbia University Medical Center, discussed the use of epigenetic-based combination therapies to improve responses in T-cell lymphomas.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]

LA JOLLA, CALIF. – New developments in epigenetics research were highlighted at the 11th annual T-cell Lymphoma Forum.

Vidyard Video

In a video interview, meeting cochair Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, discussed a few presentations that addressed epigenetics in T-cell lymphomas.

Stephen Baylin, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, gave the meeting’s keynote address, which focused on the idea that epigenetic therapy can enhance immune checkpoint therapy.

Susan Bates, MD, of Columbia University Medical Center, presented data that suggest romidepsin and other histone deacetylase inhibitors fight cutaneous T-cell lymphoma via epigenetic effects on gene expression, as well as DNA damage.

And Enrica Marchi, MD, PhD, of Columbia University Medical Center, discussed the use of epigenetic-based combination therapies to improve responses in T-cell lymphomas.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]

LA JOLLA, CALIF. – New developments in epigenetics research were highlighted at the 11th annual T-cell Lymphoma Forum.

Vidyard Video

In a video interview, meeting cochair Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, discussed a few presentations that addressed epigenetics in T-cell lymphomas.

Stephen Baylin, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, gave the meeting’s keynote address, which focused on the idea that epigenetic therapy can enhance immune checkpoint therapy.

Susan Bates, MD, of Columbia University Medical Center, presented data that suggest romidepsin and other histone deacetylase inhibitors fight cutaneous T-cell lymphoma via epigenetic effects on gene expression, as well as DNA damage.

And Enrica Marchi, MD, PhD, of Columbia University Medical Center, discussed the use of epigenetic-based combination therapies to improve responses in T-cell lymphomas.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]

Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.

Jupiterimages/thinkstock

Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.

“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.

In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.

Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.

When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.

No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.

The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.

The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.

SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.

Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.

Jupiterimages/thinkstock

Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.

“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.

In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.

Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.

When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.

No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.

The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.

The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.

SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.

Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.

Jupiterimages/thinkstock

Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.

“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.

In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.

Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.

When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.

No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.

The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.

The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.

SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.

CHICAGO – Bempedoic acid, a novel oral lipid-lowering agent, reduced LDL cholesterol by 21% and high-sensitivity C-reactive protein by 24% with a side-effect profile similar to placebo in statin-intolerant hypercholesterolemic patients with or at high risk for atherosclerotic cardiovascular disease in the pivotal phase 3 CLEAR Serenity trial, Ulrich Laufs, MD, PhD, reported at the American Heart Association scientific sessions.

CLEAR Serenity is one of five pivotal phase 3 trials of bempedoic acid. The others evaluated bempedoic acid as add-on therapy to obtain additional lipid lowering in patients already on a maximum-dose statin, and in combination with ezetimibe (Zetia) as a single pill, also in patients on full-dose statin therapy. All of these trials met their efficacy and safety endpoints. The drug’s developer, Esperion Therapeutics, has announced plans to file for marketing approval of bempedoic acid and for the bempedoic acid/ezetimibe combo pill with the Food and Drug Administration and the European Medicines Agency in the first months of 2019.

CLEAR Serenity was a 24-week, double-blind, placebo-controlled trial conducted at 67 North American sites. The 345 statin-intolerant participants were randomized 2:1 to bempedoic acid at 180 mg once daily or placebo.

“I think the specific contribution of this study is, importantly, that myalgia and other muscle-related symptoms were not increased with bempedoic acid versus placebo in this population that’s statin intolerant, more than 90% of whom complained of statin-related muscle symptoms,” said Dr. Laufs, professor and chair of the department of cardiology at the University of Leipzig (Germany).

Rates of major adverse cardiovascular events were too low in this relatively short-term, modest-size trial to be informative, but the results of the previously presented CLEAR Harmony trial are reassuring in this regard, according to the cardiologist. CLEAR Harmony was a 52-week study that included 2,230 patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia whose LDL was inadequately controlled despite high-intensity statin therapy. They were randomized to add-on bempedoic acid or placebo. The adjudicated major adverse cardiovascular event rate was 4.6% in the bempedoic acid group and not significantly different at 5.7% in controls.

Definitive data on the effect of bempedoic acid on cardiovascular morbidity and mortality event rates will eventually be provided by an ongoing global randomized, double-blind, placebo-controlled trial expected to enroll more than 12,000 patients.

Rates of various types of adverse events were closely similar in the bempedoic acid and placebo groups in CLEAR Serenity, with a couple of intriguing exceptions, according to Dr. Laufs. For example, the rate of new-onset or worsening diabetes was 2.1% in the bempedoic acid group, compared with 4.5% in controls.

“This is consistent with results in the other studies in the overall bempedoic acid program. It will be something of great interest to follow up in the ongoing outcomes trial,” he said. “At this point I would feel comfortable in saying that there is no deterioration of glucose tolerance, unlike with statins. Whether there is an actual improvement or not needs to be characterized a little better.”

The other difference in the safety profile between the two study arms in CLEAR Serenity was a trend for higher uric acid levels and an increased risk of developing gout in the bempedoic acid group. Gout occurred in 1.7% of the bempedoic acid group and 0.9% of placebo-treated controls. A similar signal has been seen in the other pivotal trials, but a definitive answer as to gout risk must await the large ongoing outcomes trial, Dr. Laufs continued.

Bempedoic acid is a first-in-class oral inhibitor of ATP citrate lyase, an enzyme that is inactive in skeletal muscle – thus, the lack of myalgia complaints – and lies upstream of HMG-CoA reductase in cholesterol synthesis. When combined in a single pill with ezetimibe, which lowers LDL by stimulating the LDL receptor, the lipid-lowering impact is magnified over that of either drug alone. In the phase 3 program, the combination pill resulted in a further 35% reduction in LDL when added to a maximally tolerated statin and a 43% reduction in LDL when used as monotherapy.

Session cochair Robert H. Eckel, MD, commented that bempedoic acid appears to be poised to address a significant unmet need in preventive cardiology.

“We clearly need alternative therapies in patients with statin intolerance. We see a lot of these patients in referral centers. This drug looks safe and very effective at modifying LDL, about as much so as ezetimibe and maybe a little bit more,” said Dr. Eckel, professor of medicine and director of the lipid clinic at University of Colorado Hospital, Aurora.

Dr. Laufs reported serving as a paid consultant to Esperion Therapeutics, the study sponsor, as well as to Amgen and Sanofi.

[email protected]

CHICAGO – Bempedoic acid, a novel oral lipid-lowering agent, reduced LDL cholesterol by 21% and high-sensitivity C-reactive protein by 24% with a side-effect profile similar to placebo in statin-intolerant hypercholesterolemic patients with or at high risk for atherosclerotic cardiovascular disease in the pivotal phase 3 CLEAR Serenity trial, Ulrich Laufs, MD, PhD, reported at the American Heart Association scientific sessions.

CLEAR Serenity is one of five pivotal phase 3 trials of bempedoic acid. The others evaluated bempedoic acid as add-on therapy to obtain additional lipid lowering in patients already on a maximum-dose statin, and in combination with ezetimibe (Zetia) as a single pill, also in patients on full-dose statin therapy. All of these trials met their efficacy and safety endpoints. The drug’s developer, Esperion Therapeutics, has announced plans to file for marketing approval of bempedoic acid and for the bempedoic acid/ezetimibe combo pill with the Food and Drug Administration and the European Medicines Agency in the first months of 2019.

CLEAR Serenity was a 24-week, double-blind, placebo-controlled trial conducted at 67 North American sites. The 345 statin-intolerant participants were randomized 2:1 to bempedoic acid at 180 mg once daily or placebo.

“I think the specific contribution of this study is, importantly, that myalgia and other muscle-related symptoms were not increased with bempedoic acid versus placebo in this population that’s statin intolerant, more than 90% of whom complained of statin-related muscle symptoms,” said Dr. Laufs, professor and chair of the department of cardiology at the University of Leipzig (Germany).

Rates of major adverse cardiovascular events were too low in this relatively short-term, modest-size trial to be informative, but the results of the previously presented CLEAR Harmony trial are reassuring in this regard, according to the cardiologist. CLEAR Harmony was a 52-week study that included 2,230 patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia whose LDL was inadequately controlled despite high-intensity statin therapy. They were randomized to add-on bempedoic acid or placebo. The adjudicated major adverse cardiovascular event rate was 4.6% in the bempedoic acid group and not significantly different at 5.7% in controls.

Definitive data on the effect of bempedoic acid on cardiovascular morbidity and mortality event rates will eventually be provided by an ongoing global randomized, double-blind, placebo-controlled trial expected to enroll more than 12,000 patients.

Rates of various types of adverse events were closely similar in the bempedoic acid and placebo groups in CLEAR Serenity, with a couple of intriguing exceptions, according to Dr. Laufs. For example, the rate of new-onset or worsening diabetes was 2.1% in the bempedoic acid group, compared with 4.5% in controls.

“This is consistent with results in the other studies in the overall bempedoic acid program. It will be something of great interest to follow up in the ongoing outcomes trial,” he said. “At this point I would feel comfortable in saying that there is no deterioration of glucose tolerance, unlike with statins. Whether there is an actual improvement or not needs to be characterized a little better.”

The other difference in the safety profile between the two study arms in CLEAR Serenity was a trend for higher uric acid levels and an increased risk of developing gout in the bempedoic acid group. Gout occurred in 1.7% of the bempedoic acid group and 0.9% of placebo-treated controls. A similar signal has been seen in the other pivotal trials, but a definitive answer as to gout risk must await the large ongoing outcomes trial, Dr. Laufs continued.

Bempedoic acid is a first-in-class oral inhibitor of ATP citrate lyase, an enzyme that is inactive in skeletal muscle – thus, the lack of myalgia complaints – and lies upstream of HMG-CoA reductase in cholesterol synthesis. When combined in a single pill with ezetimibe, which lowers LDL by stimulating the LDL receptor, the lipid-lowering impact is magnified over that of either drug alone. In the phase 3 program, the combination pill resulted in a further 35% reduction in LDL when added to a maximally tolerated statin and a 43% reduction in LDL when used as monotherapy.

Session cochair Robert H. Eckel, MD, commented that bempedoic acid appears to be poised to address a significant unmet need in preventive cardiology.

“We clearly need alternative therapies in patients with statin intolerance. We see a lot of these patients in referral centers. This drug looks safe and very effective at modifying LDL, about as much so as ezetimibe and maybe a little bit more,” said Dr. Eckel, professor of medicine and director of the lipid clinic at University of Colorado Hospital, Aurora.

Dr. Laufs reported serving as a paid consultant to Esperion Therapeutics, the study sponsor, as well as to Amgen and Sanofi.

[email protected]

CHICAGO – Bempedoic acid, a novel oral lipid-lowering agent, reduced LDL cholesterol by 21% and high-sensitivity C-reactive protein by 24% with a side-effect profile similar to placebo in statin-intolerant hypercholesterolemic patients with or at high risk for atherosclerotic cardiovascular disease in the pivotal phase 3 CLEAR Serenity trial, Ulrich Laufs, MD, PhD, reported at the American Heart Association scientific sessions.

CLEAR Serenity is one of five pivotal phase 3 trials of bempedoic acid. The others evaluated bempedoic acid as add-on therapy to obtain additional lipid lowering in patients already on a maximum-dose statin, and in combination with ezetimibe (Zetia) as a single pill, also in patients on full-dose statin therapy. All of these trials met their efficacy and safety endpoints. The drug’s developer, Esperion Therapeutics, has announced plans to file for marketing approval of bempedoic acid and for the bempedoic acid/ezetimibe combo pill with the Food and Drug Administration and the European Medicines Agency in the first months of 2019.

CLEAR Serenity was a 24-week, double-blind, placebo-controlled trial conducted at 67 North American sites. The 345 statin-intolerant participants were randomized 2:1 to bempedoic acid at 180 mg once daily or placebo.

“I think the specific contribution of this study is, importantly, that myalgia and other muscle-related symptoms were not increased with bempedoic acid versus placebo in this population that’s statin intolerant, more than 90% of whom complained of statin-related muscle symptoms,” said Dr. Laufs, professor and chair of the department of cardiology at the University of Leipzig (Germany).

Rates of major adverse cardiovascular events were too low in this relatively short-term, modest-size trial to be informative, but the results of the previously presented CLEAR Harmony trial are reassuring in this regard, according to the cardiologist. CLEAR Harmony was a 52-week study that included 2,230 patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia whose LDL was inadequately controlled despite high-intensity statin therapy. They were randomized to add-on bempedoic acid or placebo. The adjudicated major adverse cardiovascular event rate was 4.6% in the bempedoic acid group and not significantly different at 5.7% in controls.

Definitive data on the effect of bempedoic acid on cardiovascular morbidity and mortality event rates will eventually be provided by an ongoing global randomized, double-blind, placebo-controlled trial expected to enroll more than 12,000 patients.

Rates of various types of adverse events were closely similar in the bempedoic acid and placebo groups in CLEAR Serenity, with a couple of intriguing exceptions, according to Dr. Laufs. For example, the rate of new-onset or worsening diabetes was 2.1% in the bempedoic acid group, compared with 4.5% in controls.

“This is consistent with results in the other studies in the overall bempedoic acid program. It will be something of great interest to follow up in the ongoing outcomes trial,” he said. “At this point I would feel comfortable in saying that there is no deterioration of glucose tolerance, unlike with statins. Whether there is an actual improvement or not needs to be characterized a little better.”

The other difference in the safety profile between the two study arms in CLEAR Serenity was a trend for higher uric acid levels and an increased risk of developing gout in the bempedoic acid group. Gout occurred in 1.7% of the bempedoic acid group and 0.9% of placebo-treated controls. A similar signal has been seen in the other pivotal trials, but a definitive answer as to gout risk must await the large ongoing outcomes trial, Dr. Laufs continued.

Bempedoic acid is a first-in-class oral inhibitor of ATP citrate lyase, an enzyme that is inactive in skeletal muscle – thus, the lack of myalgia complaints – and lies upstream of HMG-CoA reductase in cholesterol synthesis. When combined in a single pill with ezetimibe, which lowers LDL by stimulating the LDL receptor, the lipid-lowering impact is magnified over that of either drug alone. In the phase 3 program, the combination pill resulted in a further 35% reduction in LDL when added to a maximally tolerated statin and a 43% reduction in LDL when used as monotherapy.

Session cochair Robert H. Eckel, MD, commented that bempedoic acid appears to be poised to address a significant unmet need in preventive cardiology.

“We clearly need alternative therapies in patients with statin intolerance. We see a lot of these patients in referral centers. This drug looks safe and very effective at modifying LDL, about as much so as ezetimibe and maybe a little bit more,” said Dr. Eckel, professor of medicine and director of the lipid clinic at University of Colorado Hospital, Aurora.

Dr. Laufs reported serving as a paid consultant to Esperion Therapeutics, the study sponsor, as well as to Amgen and Sanofi.

[email protected]

A new smartphone app under development seeks to detect the first moments of an overdose-related respiratory crisis and summon help before it’s too late.

“We’re hoping a device that most people carry around could be transformed into technology that could save your life in an overdose,” said anesthesiologist Jacob (Jake) E. Sunshine, MD, an assistant professor with the University of Washington, Seattle, and coauthor of a study about the app’s development.

The ultimate goal is “to provide a harm reduction system that can automatically connect naloxone-equipped friends and family or emergency medical services to help prevent fatal overdose events,” Rajalakshmi Nandakumar, and her associates wrote in the study, published in Science Translational Medicine.

An estimated 70,000 people in the United States died from drug overdoses in 2017, according to a 2018 data brief from the Centers for Disease Control and Prevention. On an age-adjusted basis, the overdose death rate in 2017 was more than three times higher than in 1999.

The app, which builds on previous work aimed at detecting disordered breathing in sleep apnea, uses a “short-range active sonar system” to detect respiration in a person within the distance of about 3 feet. The approach is similar to the echolocation strategy used by a dolphin or bat, Dr. Sunshine said, and relies on sending out an audio tone that humans cannot hear.

The app’s microphone detects an “audio reflection” of the tone after it bounces off a nearby person’s body and then analyzes it to calculate the distance to the person’s chest. “We’re able to use those distances to measure when someone is taking a breath, and when they’re not taking a breath,” said Dr. Sunshine, who conceptualized the study.

If a disordered breathing pattern is detected, the app is designed to send a text message with a GPS-pinpointed location to a prespecified contact, Dr. Sunshine said. Or the app could be set to call 911.

In the study, the investigators tested the app’s algorithm at a supervised injection facility – a space designed to allow users to inject illicit drugs safely – in Vancouver. They tested the app on 94 drug users as they injected themselves; half of the users “experienced clinically important respiratory depression,” and two needed to be treated by clinic staff for overdose. Both users survived, reported Ms. Nandakumar, a PhD candidate at the University of Washington, Seattle; Shyamnath Gollakota, PhD, an associate professor at the university; and Dr. Sunshine.

The new study found that the app detected cessation of breathing for 10 seconds or longer 95.9% of the time (95% confidence interval, 86.0%-99.5%) with 97.7% specificity (95% confidence interval, 88.2%-99.9%). However, the app was less adept at identifying respiratory depression (respiratory rate equal to or less than 7 breaths per minute): The investigators reported 87.2% sensitivity (95% CI, 74.2%-95.1%) and 89.3% specificity (95% CI, 76.9%-96.4%).

Ms. Nandakumar and her associates also tested the app’s algorithm on patients undergoing anesthesia. It correctly detected disordered breathing in 19 of 20 patients.

It’s not clear how the app would work in environments full of breathing people and, potentially, breathing animals such as pets. And the app has clear limitations. Since it needs to be able to bounce audio signals off a user’s chest, it will not work if a phone is in a pocket or if a user is face down, turns around, or wanders off.

However, the app can detect sudden changes in motion, Dr. Sunshine said, and investigators are developing a way to require users to check in with the app in certain situations that might signal trouble.

“For harm reduction interventions to be efficacious, further studies with participant feedback and human factor testing are needed to ensure that the system meets the needs, values, and preferences of people who use opioids, in addition to establishing the system’s safety vis-à-vis its potential to encourage moral hazard,” the investigators wrote in the article.

The next steps are to refine the app’s user interface and figure out how to connect it to the 911 emergency-response system, Dr. Sunshine said. Meanwhile, researchers have created a company to develop the product. “We’re going to do additional development through that entity and seek [Food and Drug Administration] approval,” Dr. Sunshine said. The investigators do not plan to charge users for the product, which can be used on iPhones and Androids, he said.

The study was funded by the Foundation for Anesthesia Education and Research, the National Science Foundation, and the University of Washington’s Alcohol and Drug Abuse Institute. Dr. Sunshine, Ms. Nandakumar, and Dr. Gollakota are inventors on a provisional patient application related to the project, and all have equity stakes in a company that is developing the technology. Dr. Gollakota is a paid consultant to Jeeva Wireless and Edus Health.

SOURCE: Nandakumar R et al. Sci Transl Med. 2019 Jan 9;11(474). doi: 10.1126/scitranslmed.aau8914.

A new smartphone app under development seeks to detect the first moments of an overdose-related respiratory crisis and summon help before it’s too late.

“We’re hoping a device that most people carry around could be transformed into technology that could save your life in an overdose,” said anesthesiologist Jacob (Jake) E. Sunshine, MD, an assistant professor with the University of Washington, Seattle, and coauthor of a study about the app’s development.

The ultimate goal is “to provide a harm reduction system that can automatically connect naloxone-equipped friends and family or emergency medical services to help prevent fatal overdose events,” Rajalakshmi Nandakumar, and her associates wrote in the study, published in Science Translational Medicine.

An estimated 70,000 people in the United States died from drug overdoses in 2017, according to a 2018 data brief from the Centers for Disease Control and Prevention. On an age-adjusted basis, the overdose death rate in 2017 was more than three times higher than in 1999.

The app, which builds on previous work aimed at detecting disordered breathing in sleep apnea, uses a “short-range active sonar system” to detect respiration in a person within the distance of about 3 feet. The approach is similar to the echolocation strategy used by a dolphin or bat, Dr. Sunshine said, and relies on sending out an audio tone that humans cannot hear.

The app’s microphone detects an “audio reflection” of the tone after it bounces off a nearby person’s body and then analyzes it to calculate the distance to the person’s chest. “We’re able to use those distances to measure when someone is taking a breath, and when they’re not taking a breath,” said Dr. Sunshine, who conceptualized the study.

If a disordered breathing pattern is detected, the app is designed to send a text message with a GPS-pinpointed location to a prespecified contact, Dr. Sunshine said. Or the app could be set to call 911.

In the study, the investigators tested the app’s algorithm at a supervised injection facility – a space designed to allow users to inject illicit drugs safely – in Vancouver. They tested the app on 94 drug users as they injected themselves; half of the users “experienced clinically important respiratory depression,” and two needed to be treated by clinic staff for overdose. Both users survived, reported Ms. Nandakumar, a PhD candidate at the University of Washington, Seattle; Shyamnath Gollakota, PhD, an associate professor at the university; and Dr. Sunshine.

The new study found that the app detected cessation of breathing for 10 seconds or longer 95.9% of the time (95% confidence interval, 86.0%-99.5%) with 97.7% specificity (95% confidence interval, 88.2%-99.9%). However, the app was less adept at identifying respiratory depression (respiratory rate equal to or less than 7 breaths per minute): The investigators reported 87.2% sensitivity (95% CI, 74.2%-95.1%) and 89.3% specificity (95% CI, 76.9%-96.4%).

Ms. Nandakumar and her associates also tested the app’s algorithm on patients undergoing anesthesia. It correctly detected disordered breathing in 19 of 20 patients.

It’s not clear how the app would work in environments full of breathing people and, potentially, breathing animals such as pets. And the app has clear limitations. Since it needs to be able to bounce audio signals off a user’s chest, it will not work if a phone is in a pocket or if a user is face down, turns around, or wanders off.

However, the app can detect sudden changes in motion, Dr. Sunshine said, and investigators are developing a way to require users to check in with the app in certain situations that might signal trouble.

“For harm reduction interventions to be efficacious, further studies with participant feedback and human factor testing are needed to ensure that the system meets the needs, values, and preferences of people who use opioids, in addition to establishing the system’s safety vis-à-vis its potential to encourage moral hazard,” the investigators wrote in the article.

The next steps are to refine the app’s user interface and figure out how to connect it to the 911 emergency-response system, Dr. Sunshine said. Meanwhile, researchers have created a company to develop the product. “We’re going to do additional development through that entity and seek [Food and Drug Administration] approval,” Dr. Sunshine said. The investigators do not plan to charge users for the product, which can be used on iPhones and Androids, he said.

The study was funded by the Foundation for Anesthesia Education and Research, the National Science Foundation, and the University of Washington’s Alcohol and Drug Abuse Institute. Dr. Sunshine, Ms. Nandakumar, and Dr. Gollakota are inventors on a provisional patient application related to the project, and all have equity stakes in a company that is developing the technology. Dr. Gollakota is a paid consultant to Jeeva Wireless and Edus Health.

SOURCE: Nandakumar R et al. Sci Transl Med. 2019 Jan 9;11(474). doi: 10.1126/scitranslmed.aau8914.

A new smartphone app under development seeks to detect the first moments of an overdose-related respiratory crisis and summon help before it’s too late.

“We’re hoping a device that most people carry around could be transformed into technology that could save your life in an overdose,” said anesthesiologist Jacob (Jake) E. Sunshine, MD, an assistant professor with the University of Washington, Seattle, and coauthor of a study about the app’s development.

The ultimate goal is “to provide a harm reduction system that can automatically connect naloxone-equipped friends and family or emergency medical services to help prevent fatal overdose events,” Rajalakshmi Nandakumar, and her associates wrote in the study, published in Science Translational Medicine.

An estimated 70,000 people in the United States died from drug overdoses in 2017, according to a 2018 data brief from the Centers for Disease Control and Prevention. On an age-adjusted basis, the overdose death rate in 2017 was more than three times higher than in 1999.

The app, which builds on previous work aimed at detecting disordered breathing in sleep apnea, uses a “short-range active sonar system” to detect respiration in a person within the distance of about 3 feet. The approach is similar to the echolocation strategy used by a dolphin or bat, Dr. Sunshine said, and relies on sending out an audio tone that humans cannot hear.

The app’s microphone detects an “audio reflection” of the tone after it bounces off a nearby person’s body and then analyzes it to calculate the distance to the person’s chest. “We’re able to use those distances to measure when someone is taking a breath, and when they’re not taking a breath,” said Dr. Sunshine, who conceptualized the study.

If a disordered breathing pattern is detected, the app is designed to send a text message with a GPS-pinpointed location to a prespecified contact, Dr. Sunshine said. Or the app could be set to call 911.

In the study, the investigators tested the app’s algorithm at a supervised injection facility – a space designed to allow users to inject illicit drugs safely – in Vancouver. They tested the app on 94 drug users as they injected themselves; half of the users “experienced clinically important respiratory depression,” and two needed to be treated by clinic staff for overdose. Both users survived, reported Ms. Nandakumar, a PhD candidate at the University of Washington, Seattle; Shyamnath Gollakota, PhD, an associate professor at the university; and Dr. Sunshine.

The new study found that the app detected cessation of breathing for 10 seconds or longer 95.9% of the time (95% confidence interval, 86.0%-99.5%) with 97.7% specificity (95% confidence interval, 88.2%-99.9%). However, the app was less adept at identifying respiratory depression (respiratory rate equal to or less than 7 breaths per minute): The investigators reported 87.2% sensitivity (95% CI, 74.2%-95.1%) and 89.3% specificity (95% CI, 76.9%-96.4%).

Ms. Nandakumar and her associates also tested the app’s algorithm on patients undergoing anesthesia. It correctly detected disordered breathing in 19 of 20 patients.

It’s not clear how the app would work in environments full of breathing people and, potentially, breathing animals such as pets. And the app has clear limitations. Since it needs to be able to bounce audio signals off a user’s chest, it will not work if a phone is in a pocket or if a user is face down, turns around, or wanders off.

However, the app can detect sudden changes in motion, Dr. Sunshine said, and investigators are developing a way to require users to check in with the app in certain situations that might signal trouble.

“For harm reduction interventions to be efficacious, further studies with participant feedback and human factor testing are needed to ensure that the system meets the needs, values, and preferences of people who use opioids, in addition to establishing the system’s safety vis-à-vis its potential to encourage moral hazard,” the investigators wrote in the article.

The next steps are to refine the app’s user interface and figure out how to connect it to the 911 emergency-response system, Dr. Sunshine said. Meanwhile, researchers have created a company to develop the product. “We’re going to do additional development through that entity and seek [Food and Drug Administration] approval,” Dr. Sunshine said. The investigators do not plan to charge users for the product, which can be used on iPhones and Androids, he said.

The study was funded by the Foundation for Anesthesia Education and Research, the National Science Foundation, and the University of Washington’s Alcohol and Drug Abuse Institute. Dr. Sunshine, Ms. Nandakumar, and Dr. Gollakota are inventors on a provisional patient application related to the project, and all have equity stakes in a company that is developing the technology. Dr. Gollakota is a paid consultant to Jeeva Wireless and Edus Health.

SOURCE: Nandakumar R et al. Sci Transl Med. 2019 Jan 9;11(474). doi: 10.1126/scitranslmed.aau8914.

The patient was diagnosed with lichen spinulosus (LS) based on the physical appearance of the lesions (hyperkeratotic spiny papules forming plaques), the lack of pruritus, and negative personal history of atopic dermatitis.

Lichen spinulosus is an underreported entity, first described in 1908 by Adamson as superficial circumscribed chronic dermatitis in children and adolescents. The median age of presentation is age 16 years. There are several reports of possible associations with systemic infections such as HIV, fungi, and syphilis, as well as chronic diseases such as Crohn’s disease, Hodgkin disease, seborrhea, and secondary to certain medications such as omeprazole. There are no prior reports of infliximab being associated with LS, but it has been reported to cause other lichenoid reactions such as lichen planus and lichen planopilaris.

Clinically the lesions are characterized by asymptomatic, small (1 cm), skin color, hyperkeratotic, follicular papules that coalesce into plaques. The lesions usually occur on the extensor surfaces of the arms, neck, torso, and buttocks. Mild pruritus can occur in some patients.

The lesions in keratosis pilaris can be very similar to lichen spinulosus, but usually they don’t coalesce into plaques and are commonly present on the extensor surfaces of the arms, thighs, and cheeks. Histopathology of both conditions is very similar.

Another condition to consider includes papular eczema. The lesions in papular eczema tend to be pruritic and are not as circumscribed as LS lesions. Papular eczema responds well to the use of topical corticosteroids, while LS lesions usually do not. Lichen nitidus (LN) is characterized by monomorphic, skin color, 1-mm, flat-topped papules. Lesions tend to occur in crops rather than circumscribed papules forming plaques. LN most commonly presents on the extensor surface of the arms, trunk, dorsal hands, and genitalia. Koebner phenomenon is usually seen. Although uncommon in children, a more generalized type of follicular mucinosis can present very similar to lichen spinulosus. A recent study found LS-like lesions with associated hypopigmentation and hair loss should be suspicious for folliculotropic mycosis fungoides.

Keratolytics such as lactic acid, urea, and salicylic acid can help improve LS, although they do not cure it. Other reported treatments include the use of topical adapalene, tacalcitol cream, and tretinoin gel with hydroactive adhesive.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Email her at [email protected].

The patient was diagnosed with lichen spinulosus (LS) based on the physical appearance of the lesions (hyperkeratotic spiny papules forming plaques), the lack of pruritus, and negative personal history of atopic dermatitis.

Lichen spinulosus is an underreported entity, first described in 1908 by Adamson as superficial circumscribed chronic dermatitis in children and adolescents. The median age of presentation is age 16 years. There are several reports of possible associations with systemic infections such as HIV, fungi, and syphilis, as well as chronic diseases such as Crohn’s disease, Hodgkin disease, seborrhea, and secondary to certain medications such as omeprazole. There are no prior reports of infliximab being associated with LS, but it has been reported to cause other lichenoid reactions such as lichen planus and lichen planopilaris.

Clinically the lesions are characterized by asymptomatic, small (1 cm), skin color, hyperkeratotic, follicular papules that coalesce into plaques. The lesions usually occur on the extensor surfaces of the arms, neck, torso, and buttocks. Mild pruritus can occur in some patients.

The lesions in keratosis pilaris can be very similar to lichen spinulosus, but usually they don’t coalesce into plaques and are commonly present on the extensor surfaces of the arms, thighs, and cheeks. Histopathology of both conditions is very similar.

Another condition to consider includes papular eczema. The lesions in papular eczema tend to be pruritic and are not as circumscribed as LS lesions. Papular eczema responds well to the use of topical corticosteroids, while LS lesions usually do not. Lichen nitidus (LN) is characterized by monomorphic, skin color, 1-mm, flat-topped papules. Lesions tend to occur in crops rather than circumscribed papules forming plaques. LN most commonly presents on the extensor surface of the arms, trunk, dorsal hands, and genitalia. Koebner phenomenon is usually seen. Although uncommon in children, a more generalized type of follicular mucinosis can present very similar to lichen spinulosus. A recent study found LS-like lesions with associated hypopigmentation and hair loss should be suspicious for folliculotropic mycosis fungoides.

Keratolytics such as lactic acid, urea, and salicylic acid can help improve LS, although they do not cure it. Other reported treatments include the use of topical adapalene, tacalcitol cream, and tretinoin gel with hydroactive adhesive.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Email her at [email protected].

The patient was diagnosed with lichen spinulosus (LS) based on the physical appearance of the lesions (hyperkeratotic spiny papules forming plaques), the lack of pruritus, and negative personal history of atopic dermatitis.

Lichen spinulosus is an underreported entity, first described in 1908 by Adamson as superficial circumscribed chronic dermatitis in children and adolescents. The median age of presentation is age 16 years. There are several reports of possible associations with systemic infections such as HIV, fungi, and syphilis, as well as chronic diseases such as Crohn’s disease, Hodgkin disease, seborrhea, and secondary to certain medications such as omeprazole. There are no prior reports of infliximab being associated with LS, but it has been reported to cause other lichenoid reactions such as lichen planus and lichen planopilaris.

Clinically the lesions are characterized by asymptomatic, small (1 cm), skin color, hyperkeratotic, follicular papules that coalesce into plaques. The lesions usually occur on the extensor surfaces of the arms, neck, torso, and buttocks. Mild pruritus can occur in some patients.

The lesions in keratosis pilaris can be very similar to lichen spinulosus, but usually they don’t coalesce into plaques and are commonly present on the extensor surfaces of the arms, thighs, and cheeks. Histopathology of both conditions is very similar.

Another condition to consider includes papular eczema. The lesions in papular eczema tend to be pruritic and are not as circumscribed as LS lesions. Papular eczema responds well to the use of topical corticosteroids, while LS lesions usually do not. Lichen nitidus (LN) is characterized by monomorphic, skin color, 1-mm, flat-topped papules. Lesions tend to occur in crops rather than circumscribed papules forming plaques. LN most commonly presents on the extensor surface of the arms, trunk, dorsal hands, and genitalia. Koebner phenomenon is usually seen. Although uncommon in children, a more generalized type of follicular mucinosis can present very similar to lichen spinulosus. A recent study found LS-like lesions with associated hypopigmentation and hair loss should be suspicious for folliculotropic mycosis fungoides.

Keratolytics such as lactic acid, urea, and salicylic acid can help improve LS, although they do not cure it. Other reported treatments include the use of topical adapalene, tacalcitol cream, and tretinoin gel with hydroactive adhesive.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Email her at [email protected].

The Food and Drug Administration has approved the expanded use of Adacel (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis (Tdap) Vaccine Adsorbed) to include repeat vaccinations 8 years or more after the first vaccination in people aged 10-64 years.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The expanded indication was based on results of a randomized, controlled trial, published in the Journal of the Pediatric Infectious Diseases Society, in which more than 1,300 adults aged 18-64 years received either Adacel or a Td (tetanus-diphtheria) vaccine 8-12 years after receiving a previous dose of Adacel.

Over the course of the study, no significant difference in adverse event incidence was observed between groups. Injection-site reaction was the most common adverse event during the study, occurring in 87.7% of those who received Adacel and 88.0% of those who received the Td vaccine. Other common adverse events associated with Adacel include headache, body ache or muscle weakness, tiredness, muscle aches, and general discomfort.

“While strong vaccination programs are in place for young adolescents, a single Tdap immunization does not offer lifetime protection against pertussis due to waning immunity. The licensure of Adacel as the first Tdap vaccine in the U.S. for repeat vaccination is an important step for eligible patients and offers flexibility for health care providers to help manage their immunization schedules,” said David P. Greenberg, MD, regional medical head North America at Sanofi Pasteur, in the press release.

Find the full press release on the Sanofi website.

[email protected]

The Food and Drug Administration has approved the expanded use of Adacel (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis (Tdap) Vaccine Adsorbed) to include repeat vaccinations 8 years or more after the first vaccination in people aged 10-64 years.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The expanded indication was based on results of a randomized, controlled trial, published in the Journal of the Pediatric Infectious Diseases Society, in which more than 1,300 adults aged 18-64 years received either Adacel or a Td (tetanus-diphtheria) vaccine 8-12 years after receiving a previous dose of Adacel.

Over the course of the study, no significant difference in adverse event incidence was observed between groups. Injection-site reaction was the most common adverse event during the study, occurring in 87.7% of those who received Adacel and 88.0% of those who received the Td vaccine. Other common adverse events associated with Adacel include headache, body ache or muscle weakness, tiredness, muscle aches, and general discomfort.

“While strong vaccination programs are in place for young adolescents, a single Tdap immunization does not offer lifetime protection against pertussis due to waning immunity. The licensure of Adacel as the first Tdap vaccine in the U.S. for repeat vaccination is an important step for eligible patients and offers flexibility for health care providers to help manage their immunization schedules,” said David P. Greenberg, MD, regional medical head North America at Sanofi Pasteur, in the press release.

Find the full press release on the Sanofi website.

[email protected]

The Food and Drug Administration has approved the expanded use of Adacel (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis (Tdap) Vaccine Adsorbed) to include repeat vaccinations 8 years or more after the first vaccination in people aged 10-64 years.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The expanded indication was based on results of a randomized, controlled trial, published in the Journal of the Pediatric Infectious Diseases Society, in which more than 1,300 adults aged 18-64 years received either Adacel or a Td (tetanus-diphtheria) vaccine 8-12 years after receiving a previous dose of Adacel.

Over the course of the study, no significant difference in adverse event incidence was observed between groups. Injection-site reaction was the most common adverse event during the study, occurring in 87.7% of those who received Adacel and 88.0% of those who received the Td vaccine. Other common adverse events associated with Adacel include headache, body ache or muscle weakness, tiredness, muscle aches, and general discomfort.

“While strong vaccination programs are in place for young adolescents, a single Tdap immunization does not offer lifetime protection against pertussis due to waning immunity. The licensure of Adacel as the first Tdap vaccine in the U.S. for repeat vaccination is an important step for eligible patients and offers flexibility for health care providers to help manage their immunization schedules,” said David P. Greenberg, MD, regional medical head North America at Sanofi Pasteur, in the press release.

Find the full press release on the Sanofi website.

[email protected]

Background: Previous studies have shown that lower muscle function is associated with increased mortality; however, studies have not been able to fully examine associations with age and disease-specific mortality.

Dr. Marr is assistant professor of medicine and an academic hospitalist, University of Utah, Salt Lake City.

Background: Previous studies have shown that lower muscle function is associated with increased mortality; however, studies have not been able to fully examine associations with age and disease-specific mortality.

Dr. Marr is assistant professor of medicine and an academic hospitalist, University of Utah, Salt Lake City.

Background: Previous studies have shown that lower muscle function is associated with increased mortality; however, studies have not been able to fully examine associations with age and disease-specific mortality.

Dr. Marr is assistant professor of medicine and an academic hospitalist, University of Utah, Salt Lake City.

Checkpoint inhibitors can cause rare, but serious, hematological immune-related adverse events (hem-irAEs), which require early detection and intervention, according to a recent French study.

Immune thrombocytopenia, hemolytic anemia, and neutropenia were the most common hem-irAEs in the population, reported lead author, Nicolas Delanoy, MD, of Gustave Roussy, Université Paris-Saclay, Villejuif, France, and his colleagues.

“About 71% of patients treated have any-grade irAEs and 10% have grade 3-4 irAEs after anti-PD-1 immunotherapy,” the investigators wrote. The report is in The Lancet Haematology. “In most cases, they involve the skin, gastrointestinal tract, thyroid or endocrine glands, liver, lungs, or joints. However, all organs can potentially be affected, including the hemopoietic system.”

Despite this possibility, few reports detail the frequency or character of hematological toxicities from immunotherapy.

The present study involved 948 patients who entered into three French registries between 2014 and 2018. The first registry, consisting of 745 patients, was observed prospectively during checkpoint inhibitor therapy. The other two registries provided retrospective data on confirmed irAEs or hem-irAEs.

Among 745 patients followed during checkpoint inhibitor therapy, four developed hem-irAEs, providing an incidence rate of 0.5%. The other two databases added 31 patients with confirmed hem-irAEs, allowing for characterization of 35 total cases.

The group of 35 patients had a median age of 65 years, with more men (n = 21) than women (n = 14). Melanoma was the most common type of malignancy (43%), followed by non–small-cell lung cancer (34%), lymphoma (11%), and others. The majority of patients received nivolumab (57%), slightly fewer received pembrolizumab (40%), and a small minority received atezolizumab (3%).

Immune thrombocytopenia, hemolytic anemia, and neutropenia were the most common hem-irAEs, each occurring in nine patients (26%). Five patients (14%) had aplastic anemia or pancytopenia, two patients had bicytopenia (6%; neutropenia and anemia or thrombocytopenia and anemia), and one patient had pure red cell aplasia (3%).

Hem-irAEs resolved in 60% of patients, but two patients (6%) died due to febrile neutropenia. Overall, 71% of hem-irAEs were grade 4.

These findings suggest that hem-irAEs are rare, but they are often serious, and potentially life-threatening, the researchers noted.

In 7 of 35 patients (20%) who were rechallenged with checkpoint inhibitor therapy, 3 (43%) had recurrence of hem-irAEs. This finding should elicit caution and close monitoring if rechallenge is elected.

“This observational study encourages further, in-depth investigations of hematological immune toxicities, to search for biomarkers that can be helpful for earlier detection,” the investigators concluded.

This study was funded by Gustave Roussy and the Gustave Roussy Immunotherapy Program. Dr. Delanoy reported nonfinancial support from Sanofi and other authors reported financial relationships with pharmaceutical companies.

SOURCE: Delanoy N et al. Lancet Haematol. 2018 Dec 4. doi: 10.1016/S2352-3026(18)30175-3.

Checkpoint inhibitors can cause rare, but serious, hematological immune-related adverse events (hem-irAEs), which require early detection and intervention, according to a recent French study.

Immune thrombocytopenia, hemolytic anemia, and neutropenia were the most common hem-irAEs in the population, reported lead author, Nicolas Delanoy, MD, of Gustave Roussy, Université Paris-Saclay, Villejuif, France, and his colleagues.

“About 71% of patients treated have any-grade irAEs and 10% have grade 3-4 irAEs after anti-PD-1 immunotherapy,” the investigators wrote. The report is in The Lancet Haematology. “In most cases, they involve the skin, gastrointestinal tract, thyroid or endocrine glands, liver, lungs, or joints. However, all organs can potentially be affected, including the hemopoietic system.”

Despite this possibility, few reports detail the frequency or character of hematological toxicities from immunotherapy.

The present study involved 948 patients who entered into three French registries between 2014 and 2018. The first registry, consisting of 745 patients, was observed prospectively during checkpoint inhibitor therapy. The other two registries provided retrospective data on confirmed irAEs or hem-irAEs.

Among 745 patients followed during checkpoint inhibitor therapy, four developed hem-irAEs, providing an incidence rate of 0.5%. The other two databases added 31 patients with confirmed hem-irAEs, allowing for characterization of 35 total cases.

The group of 35 patients had a median age of 65 years, with more men (n = 21) than women (n = 14). Melanoma was the most common type of malignancy (43%), followed by non–small-cell lung cancer (34%), lymphoma (11%), and others. The majority of patients received nivolumab (57%), slightly fewer received pembrolizumab (40%), and a small minority received atezolizumab (3%).

Immune thrombocytopenia, hemolytic anemia, and neutropenia were the most common hem-irAEs, each occurring in nine patients (26%). Five patients (14%) had aplastic anemia or pancytopenia, two patients had bicytopenia (6%; neutropenia and anemia or thrombocytopenia and anemia), and one patient had pure red cell aplasia (3%).

Hem-irAEs resolved in 60% of patients, but two patients (6%) died due to febrile neutropenia. Overall, 71% of hem-irAEs were grade 4.

These findings suggest that hem-irAEs are rare, but they are often serious, and potentially life-threatening, the researchers noted.

In 7 of 35 patients (20%) who were rechallenged with checkpoint inhibitor therapy, 3 (43%) had recurrence of hem-irAEs. This finding should elicit caution and close monitoring if rechallenge is elected.

“This observational study encourages further, in-depth investigations of hematological immune toxicities, to search for biomarkers that can be helpful for earlier detection,” the investigators concluded.

This study was funded by Gustave Roussy and the Gustave Roussy Immunotherapy Program. Dr. Delanoy reported nonfinancial support from Sanofi and other authors reported financial relationships with pharmaceutical companies.

SOURCE: Delanoy N et al. Lancet Haematol. 2018 Dec 4. doi: 10.1016/S2352-3026(18)30175-3.

Checkpoint inhibitors can cause rare, but serious, hematological immune-related adverse events (hem-irAEs), which require early detection and intervention, according to a recent French study.

Immune thrombocytopenia, hemolytic anemia, and neutropenia were the most common hem-irAEs in the population, reported lead author, Nicolas Delanoy, MD, of Gustave Roussy, Université Paris-Saclay, Villejuif, France, and his colleagues.

“About 71% of patients treated have any-grade irAEs and 10% have grade 3-4 irAEs after anti-PD-1 immunotherapy,” the investigators wrote. The report is in The Lancet Haematology. “In most cases, they involve the skin, gastrointestinal tract, thyroid or endocrine glands, liver, lungs, or joints. However, all organs can potentially be affected, including the hemopoietic system.”

Despite this possibility, few reports detail the frequency or character of hematological toxicities from immunotherapy.

The present study involved 948 patients who entered into three French registries between 2014 and 2018. The first registry, consisting of 745 patients, was observed prospectively during checkpoint inhibitor therapy. The other two registries provided retrospective data on confirmed irAEs or hem-irAEs.

Among 745 patients followed during checkpoint inhibitor therapy, four developed hem-irAEs, providing an incidence rate of 0.5%. The other two databases added 31 patients with confirmed hem-irAEs, allowing for characterization of 35 total cases.

The group of 35 patients had a median age of 65 years, with more men (n = 21) than women (n = 14). Melanoma was the most common type of malignancy (43%), followed by non–small-cell lung cancer (34%), lymphoma (11%), and others. The majority of patients received nivolumab (57%), slightly fewer received pembrolizumab (40%), and a small minority received atezolizumab (3%).

Immune thrombocytopenia, hemolytic anemia, and neutropenia were the most common hem-irAEs, each occurring in nine patients (26%). Five patients (14%) had aplastic anemia or pancytopenia, two patients had bicytopenia (6%; neutropenia and anemia or thrombocytopenia and anemia), and one patient had pure red cell aplasia (3%).

Hem-irAEs resolved in 60% of patients, but two patients (6%) died due to febrile neutropenia. Overall, 71% of hem-irAEs were grade 4.

These findings suggest that hem-irAEs are rare, but they are often serious, and potentially life-threatening, the researchers noted.

In 7 of 35 patients (20%) who were rechallenged with checkpoint inhibitor therapy, 3 (43%) had recurrence of hem-irAEs. This finding should elicit caution and close monitoring if rechallenge is elected.

“This observational study encourages further, in-depth investigations of hematological immune toxicities, to search for biomarkers that can be helpful for earlier detection,” the investigators concluded.

This study was funded by Gustave Roussy and the Gustave Roussy Immunotherapy Program. Dr. Delanoy reported nonfinancial support from Sanofi and other authors reported financial relationships with pharmaceutical companies.

SOURCE: Delanoy N et al. Lancet Haematol. 2018 Dec 4. doi: 10.1016/S2352-3026(18)30175-3.