Andrew D. Bowser

Tecovirimat, an oral antiviral agent, is being advanced as a treatment for smallpox based on recently reported studies showing efficacy data in animals and safety and pharmacokinetic data in humans.

“The aggregation of the results from these multiple studies involving animals and humans supports tecovirimat as potential smallpox antiviral drug,” Douglas W. Grosenbach, PhD, of SIGA Technologies and his coauthors reported in the New England Journal of Medicine.

Tecovirimat inhibits p37, a protein that is present in all orthopoxviruses, to prevent “formation and egress of enveloped virions, which are essential for virulence,” Dr. Grosenbach and his coauthors wrote in the report.

Smallpox, caused by the variola virus, was eradicated in 1980. However, the disease remains concerning because of the potential for intentional release of variola virus in an act of bioterrorism or biowarfare, according to the authors.

“A single case of smallpox anywhere in the world would be a global health emergency,” Dr. Grosenbach and his colleagues wrote.

Available vaccines are not used because of the risk of side effects and would not be used except in the case of known or suspected variola virus exposure, they added.

Since it would be unethical to intentionally expose humans to variola virus, tecovirimat is being developed in line with the Food and Drug Administration Animal Efficacy Rule, which gives the agency the authority to approve drugs based on animal data for diseases that have a low or nonexistent rate of natural occurrence.

The first treatment developed under the Animal Efficacy Rule, was raxibacumab, a biologic approved by the FDA in December 2012 for treatment of inhalation anthrax. Subsequently, several other agents for prophylaxis or treatment of anthrax and botulism have been developed based on the rule and approved.

Tecovirimat has demonstrated protective efficacy in pilot studies conducted in rabbits infected with rabbitpox virus and nonhuman primates infected with monkeypox virus, Dr. Grosenbach and his colleagues explained in the current report.

In nonhuman primate studies, doses of 3-10 mg/kilogram provided nearly full protection from death with a survival rate of approximately 95% versus 5% for placebo, along with reduced lesion counts and viral loads, according to investigators.

In a tecovirimat clinical trial, 452 volunteers were randomized to receive the antiviral agent twice daily at 600 mg or matching placebo for 14 days. Adverse events occurred in 37.3% of tecovirimat-treated and 33.3% of placebo-treated participants, with events of grade 3 or higher occurring in 1.1% of patients in both groups.

There was one death on the tecovirimat arm, which was caused by a pulmonary embolism in a participant who had a history of recurrent deep-vein thrombosis but was not receiving anticoagulant treatment, investigators said.

Dr. Grosenbach and colleagues also presented pharmacokinetic profiles and exposures for 48 volunteers in a fed state in their report in the New England Journal of Medicine, along with pharmacokinetic data from the animal studies.

The FDA has set a target date of Aug. 8, 2018, for final action on a new drug application submitted for oral tecovirimat for treatment of smallpox, SIGA Technologies said in a May 2018 news release.

SOURCE: Grosenbach DW et al. N Engl J Med. 2018 Jul 5;379(1):44-53.

Tecovirimat, an oral antiviral agent, is being advanced as a treatment for smallpox based on recently reported studies showing efficacy data in animals and safety and pharmacokinetic data in humans.

“The aggregation of the results from these multiple studies involving animals and humans supports tecovirimat as potential smallpox antiviral drug,” Douglas W. Grosenbach, PhD, of SIGA Technologies and his coauthors reported in the New England Journal of Medicine.

Tecovirimat inhibits p37, a protein that is present in all orthopoxviruses, to prevent “formation and egress of enveloped virions, which are essential for virulence,” Dr. Grosenbach and his coauthors wrote in the report.

Smallpox, caused by the variola virus, was eradicated in 1980. However, the disease remains concerning because of the potential for intentional release of variola virus in an act of bioterrorism or biowarfare, according to the authors.

“A single case of smallpox anywhere in the world would be a global health emergency,” Dr. Grosenbach and his colleagues wrote.

Available vaccines are not used because of the risk of side effects and would not be used except in the case of known or suspected variola virus exposure, they added.

Since it would be unethical to intentionally expose humans to variola virus, tecovirimat is being developed in line with the Food and Drug Administration Animal Efficacy Rule, which gives the agency the authority to approve drugs based on animal data for diseases that have a low or nonexistent rate of natural occurrence.

The first treatment developed under the Animal Efficacy Rule, was raxibacumab, a biologic approved by the FDA in December 2012 for treatment of inhalation anthrax. Subsequently, several other agents for prophylaxis or treatment of anthrax and botulism have been developed based on the rule and approved.

Tecovirimat has demonstrated protective efficacy in pilot studies conducted in rabbits infected with rabbitpox virus and nonhuman primates infected with monkeypox virus, Dr. Grosenbach and his colleagues explained in the current report.

In nonhuman primate studies, doses of 3-10 mg/kilogram provided nearly full protection from death with a survival rate of approximately 95% versus 5% for placebo, along with reduced lesion counts and viral loads, according to investigators.

In a tecovirimat clinical trial, 452 volunteers were randomized to receive the antiviral agent twice daily at 600 mg or matching placebo for 14 days. Adverse events occurred in 37.3% of tecovirimat-treated and 33.3% of placebo-treated participants, with events of grade 3 or higher occurring in 1.1% of patients in both groups.

There was one death on the tecovirimat arm, which was caused by a pulmonary embolism in a participant who had a history of recurrent deep-vein thrombosis but was not receiving anticoagulant treatment, investigators said.

Dr. Grosenbach and colleagues also presented pharmacokinetic profiles and exposures for 48 volunteers in a fed state in their report in the New England Journal of Medicine, along with pharmacokinetic data from the animal studies.

The FDA has set a target date of Aug. 8, 2018, for final action on a new drug application submitted for oral tecovirimat for treatment of smallpox, SIGA Technologies said in a May 2018 news release.

SOURCE: Grosenbach DW et al. N Engl J Med. 2018 Jul 5;379(1):44-53.

Tecovirimat, an oral antiviral agent, is being advanced as a treatment for smallpox based on recently reported studies showing efficacy data in animals and safety and pharmacokinetic data in humans.

“The aggregation of the results from these multiple studies involving animals and humans supports tecovirimat as potential smallpox antiviral drug,” Douglas W. Grosenbach, PhD, of SIGA Technologies and his coauthors reported in the New England Journal of Medicine.

Tecovirimat inhibits p37, a protein that is present in all orthopoxviruses, to prevent “formation and egress of enveloped virions, which are essential for virulence,” Dr. Grosenbach and his coauthors wrote in the report.

Smallpox, caused by the variola virus, was eradicated in 1980. However, the disease remains concerning because of the potential for intentional release of variola virus in an act of bioterrorism or biowarfare, according to the authors.

“A single case of smallpox anywhere in the world would be a global health emergency,” Dr. Grosenbach and his colleagues wrote.

Available vaccines are not used because of the risk of side effects and would not be used except in the case of known or suspected variola virus exposure, they added.

Since it would be unethical to intentionally expose humans to variola virus, tecovirimat is being developed in line with the Food and Drug Administration Animal Efficacy Rule, which gives the agency the authority to approve drugs based on animal data for diseases that have a low or nonexistent rate of natural occurrence.

The first treatment developed under the Animal Efficacy Rule, was raxibacumab, a biologic approved by the FDA in December 2012 for treatment of inhalation anthrax. Subsequently, several other agents for prophylaxis or treatment of anthrax and botulism have been developed based on the rule and approved.

Tecovirimat has demonstrated protective efficacy in pilot studies conducted in rabbits infected with rabbitpox virus and nonhuman primates infected with monkeypox virus, Dr. Grosenbach and his colleagues explained in the current report.

In nonhuman primate studies, doses of 3-10 mg/kilogram provided nearly full protection from death with a survival rate of approximately 95% versus 5% for placebo, along with reduced lesion counts and viral loads, according to investigators.

In a tecovirimat clinical trial, 452 volunteers were randomized to receive the antiviral agent twice daily at 600 mg or matching placebo for 14 days. Adverse events occurred in 37.3% of tecovirimat-treated and 33.3% of placebo-treated participants, with events of grade 3 or higher occurring in 1.1% of patients in both groups.

There was one death on the tecovirimat arm, which was caused by a pulmonary embolism in a participant who had a history of recurrent deep-vein thrombosis but was not receiving anticoagulant treatment, investigators said.

Dr. Grosenbach and colleagues also presented pharmacokinetic profiles and exposures for 48 volunteers in a fed state in their report in the New England Journal of Medicine, along with pharmacokinetic data from the animal studies.

The FDA has set a target date of Aug. 8, 2018, for final action on a new drug application submitted for oral tecovirimat for treatment of smallpox, SIGA Technologies said in a May 2018 news release.

SOURCE: Grosenbach DW et al. N Engl J Med. 2018 Jul 5;379(1):44-53.

More than half of the patients with moderate to severe atopic dermatitis (AD) had inadequately controlled disease, which was associated with a higher patient-reported disease burden compared with those who had adequately controlled disease, in a cross-sectional study of adults with AD.

Disease control aside, patient-reported burden was generally higher in those with moderate to severe AD versus patients with mild AD, according to Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, and his coauthors.

“These results highlight the need for more effective therapies to better control AD, and support the importance of incorporating the patient perspective into assessment of AD beyond using measures of disease activity,” the researchers wrote. The study, published in JAMA Dermatology, was conducted before the introduction of dupilumab (Dupixent), the first biologic approved by the Food and Drug Administration for treatment of moderate to severe AD, the authors noted. (The study was supported by the manufacturers of dupilumab.)

The patients were in the Adults With Atopic Dermatitis Reporting on Their Experience (AD-AWARE) study, a cross-sectional analysis of burden of illness in adults with AD in clinical practices at six U.S. academic medical centers. The 1,519 patients completed a self-administered, Internet-based questionnaire during 2013-2014. Among these patients, 830 (54.6%) had moderate to severe AD.

A total of 185 patients with moderate to severe disease received systemic immunomodulators or phototherapy, and of those, more than half (103, or 55.7%) reported inadequate disease control, according to the survey results.

Regardless of disease control, the patients with moderate to severe AD had a greater burden of disease compared with patients with mild AD, according to the investigators. Those burdens included more severe pain and itching, sleep effects, anxiety and depression, and impairment of health-related quality of life, they reported.

Those with moderate to severe disease had a mean of 5.7 days per week with itchy skin, and 22.8% reported itch lasting for more than half a day, compared with a mean of 2.7 days and 2.9%, respectively, for those with mild disease, all significant differences.

Those with moderate to severe disease also reported more trouble sleeping, along with more frequent sleep disturbances, longer time transitioning into sleep, and more use of nonprescription sleep medications than those with mild disease.

Among those with moderate to severe disease, those who were inadequately controlled had a higher level of itch intensity and more frequent itching (a mean of 6.3 days per week), compared with those who were controlled (a mean of 5.7 days per week).

In a previous study looking at patient burden in a phase 2b clinical trial of dupilumab, Dr. Simpson and his coinvestigators found that adults with moderate to severe AD reported a “multidimensional burden” of disease that included disease activity, patient-reported symptoms, quality-of-life impact, and comorbidities (J Am Acad Dermatol. 2016 Mar;74[3]:491-8).

The current analysis based on the AD-AWARE study was supported by dupilumab manufacturers Regeneron Pharmaceuticals and Sanofi. Dr. Simpson reported disclosures related to Amgen, Anacor, Asubio, Celgene, Chugai, Galderma, Genentech, Medicis, Merck, and Regeneron; five of the 15 authors were employees of Sanofi or Regeneron. Other authors reported disclosures related to these and other companies.

SOURCE: Simpson EL et al. JAMA Dermatol. 2018 Jul 3. doi: 10.1001/jamadermatol.2018.1572.

More than half of the patients with moderate to severe atopic dermatitis (AD) had inadequately controlled disease, which was associated with a higher patient-reported disease burden compared with those who had adequately controlled disease, in a cross-sectional study of adults with AD.

Disease control aside, patient-reported burden was generally higher in those with moderate to severe AD versus patients with mild AD, according to Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, and his coauthors.

“These results highlight the need for more effective therapies to better control AD, and support the importance of incorporating the patient perspective into assessment of AD beyond using measures of disease activity,” the researchers wrote. The study, published in JAMA Dermatology, was conducted before the introduction of dupilumab (Dupixent), the first biologic approved by the Food and Drug Administration for treatment of moderate to severe AD, the authors noted. (The study was supported by the manufacturers of dupilumab.)

The patients were in the Adults With Atopic Dermatitis Reporting on Their Experience (AD-AWARE) study, a cross-sectional analysis of burden of illness in adults with AD in clinical practices at six U.S. academic medical centers. The 1,519 patients completed a self-administered, Internet-based questionnaire during 2013-2014. Among these patients, 830 (54.6%) had moderate to severe AD.

A total of 185 patients with moderate to severe disease received systemic immunomodulators or phototherapy, and of those, more than half (103, or 55.7%) reported inadequate disease control, according to the survey results.

Regardless of disease control, the patients with moderate to severe AD had a greater burden of disease compared with patients with mild AD, according to the investigators. Those burdens included more severe pain and itching, sleep effects, anxiety and depression, and impairment of health-related quality of life, they reported.

Those with moderate to severe disease had a mean of 5.7 days per week with itchy skin, and 22.8% reported itch lasting for more than half a day, compared with a mean of 2.7 days and 2.9%, respectively, for those with mild disease, all significant differences.

Those with moderate to severe disease also reported more trouble sleeping, along with more frequent sleep disturbances, longer time transitioning into sleep, and more use of nonprescription sleep medications than those with mild disease.

Among those with moderate to severe disease, those who were inadequately controlled had a higher level of itch intensity and more frequent itching (a mean of 6.3 days per week), compared with those who were controlled (a mean of 5.7 days per week).

In a previous study looking at patient burden in a phase 2b clinical trial of dupilumab, Dr. Simpson and his coinvestigators found that adults with moderate to severe AD reported a “multidimensional burden” of disease that included disease activity, patient-reported symptoms, quality-of-life impact, and comorbidities (J Am Acad Dermatol. 2016 Mar;74[3]:491-8).

The current analysis based on the AD-AWARE study was supported by dupilumab manufacturers Regeneron Pharmaceuticals and Sanofi. Dr. Simpson reported disclosures related to Amgen, Anacor, Asubio, Celgene, Chugai, Galderma, Genentech, Medicis, Merck, and Regeneron; five of the 15 authors were employees of Sanofi or Regeneron. Other authors reported disclosures related to these and other companies.

SOURCE: Simpson EL et al. JAMA Dermatol. 2018 Jul 3. doi: 10.1001/jamadermatol.2018.1572.

More than half of the patients with moderate to severe atopic dermatitis (AD) had inadequately controlled disease, which was associated with a higher patient-reported disease burden compared with those who had adequately controlled disease, in a cross-sectional study of adults with AD.

Disease control aside, patient-reported burden was generally higher in those with moderate to severe AD versus patients with mild AD, according to Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, and his coauthors.

“These results highlight the need for more effective therapies to better control AD, and support the importance of incorporating the patient perspective into assessment of AD beyond using measures of disease activity,” the researchers wrote. The study, published in JAMA Dermatology, was conducted before the introduction of dupilumab (Dupixent), the first biologic approved by the Food and Drug Administration for treatment of moderate to severe AD, the authors noted. (The study was supported by the manufacturers of dupilumab.)

The patients were in the Adults With Atopic Dermatitis Reporting on Their Experience (AD-AWARE) study, a cross-sectional analysis of burden of illness in adults with AD in clinical practices at six U.S. academic medical centers. The 1,519 patients completed a self-administered, Internet-based questionnaire during 2013-2014. Among these patients, 830 (54.6%) had moderate to severe AD.

A total of 185 patients with moderate to severe disease received systemic immunomodulators or phototherapy, and of those, more than half (103, or 55.7%) reported inadequate disease control, according to the survey results.

Regardless of disease control, the patients with moderate to severe AD had a greater burden of disease compared with patients with mild AD, according to the investigators. Those burdens included more severe pain and itching, sleep effects, anxiety and depression, and impairment of health-related quality of life, they reported.

Those with moderate to severe disease had a mean of 5.7 days per week with itchy skin, and 22.8% reported itch lasting for more than half a day, compared with a mean of 2.7 days and 2.9%, respectively, for those with mild disease, all significant differences.

Those with moderate to severe disease also reported more trouble sleeping, along with more frequent sleep disturbances, longer time transitioning into sleep, and more use of nonprescription sleep medications than those with mild disease.

Among those with moderate to severe disease, those who were inadequately controlled had a higher level of itch intensity and more frequent itching (a mean of 6.3 days per week), compared with those who were controlled (a mean of 5.7 days per week).

In a previous study looking at patient burden in a phase 2b clinical trial of dupilumab, Dr. Simpson and his coinvestigators found that adults with moderate to severe AD reported a “multidimensional burden” of disease that included disease activity, patient-reported symptoms, quality-of-life impact, and comorbidities (J Am Acad Dermatol. 2016 Mar;74[3]:491-8).

The current analysis based on the AD-AWARE study was supported by dupilumab manufacturers Regeneron Pharmaceuticals and Sanofi. Dr. Simpson reported disclosures related to Amgen, Anacor, Asubio, Celgene, Chugai, Galderma, Genentech, Medicis, Merck, and Regeneron; five of the 15 authors were employees of Sanofi or Regeneron. Other authors reported disclosures related to these and other companies.

SOURCE: Simpson EL et al. JAMA Dermatol. 2018 Jul 3. doi: 10.1001/jamadermatol.2018.1572.

A patient with an aggressive form of squamous cell carcinoma (SCC) experienced complete resolution of tumors following administration of human papillomavirus (HPV) vaccine, a recent case report shows.

The patient, an immunocompetent woman, aged in her 90s, with multiple inoperable cutaneous basaloid SCCs, was treated with a combination of systemic and intratumoral delivery of 9-valent HPV vaccine, authors of the case report wrote in JAMA Dermatology.

All tumors resolved within 11 months of the first intratumoral injection, according to Anna J. Nichols, MD, PhD, department of dermatology and cutaneous surgery, University of Miami, and her coauthors.

‘These findings suggest that the 9-valent HPV vaccine can provide a therapeutic option for inoperable cutaneous SCCs, in addition to its approved use to prevent anogenital HPV infection,” they wrote.

Previously, Dr. Nichols and her coinvestigators reported a reduction in SCCs and basal cell carcinoma in 2 immunocompetent patients who had received quadrivalent HPV vaccine. Those results suggested development of these keratinocyte carcinomas in immunocompetent patients may be driven in part by HPV, the investigators said at the time.

The patient in the current report was treated with 9-valent HPV vaccine in a university-based outpatient clinic between March 2016 and February 2017.

She initially received two doses of intramuscular vaccine 6 weeks apart; 3 weeks later, she received intratumoral administration of the vaccine diluted with sterile saline, followed by three additional intratumoral doses over the next 8 months.

“The marked regression of numerous SCCs after initiation of the intratumoral injections eliminated the need for additional treatment,” Dr. Nichols and her coauthors said in the report.

A reduction in tumor size and number was seen 2 weeks after the second intratumoral dose of the 9-valent HPV vaccine, and within 11 months of the first intratumoral dose, there was no clinical or histologic evidence of SCC, they said.

The patient was left with small, violet-colored scars, along with a small pink papule, histopathologic analysis of which showed mild cellular atypia of basal keratinocytes with hyperkeratosis, according to published details of the case report.

The patient experienced mild pain in some of the tumors on days of intratumoral treatment, but no other side effects were seen, according to the authors.

The patient remained tumor free at the end of follow-up in May 2018, and there was no clinical evidence of SCC recurrence at the patient’s most recent follow-up visit, 24 months after the first intratumoral HPV dose, the researchers wrote.

It’s not clear what role the systemic vaccine doses played in the therapeutic benefit the patient experienced, authors said, noting that tumors not injected directly may have regressed because of either local vaccine dispersion or systemic, immune-mediated mechanisms.

“The potent therapeutic benefit may reflect a combination of immunologic, antiviral, and antitumor effects of 9-valent HPV vaccine,” they concluded.

Dr. Nichols had no disclosures. Study coauthors Tim Ioannides, MD, and Evangelos V. Badiavas, MD, PhD, have a patent pending for the application of human papillomavirus vaccine described in the study.

SOURCE: Nichols AJ et al. JAMA Dermatol. 2018 Jul 3. doi: 10.1001/jamadermatol.2016.5703.

A patient with an aggressive form of squamous cell carcinoma (SCC) experienced complete resolution of tumors following administration of human papillomavirus (HPV) vaccine, a recent case report shows.

The patient, an immunocompetent woman, aged in her 90s, with multiple inoperable cutaneous basaloid SCCs, was treated with a combination of systemic and intratumoral delivery of 9-valent HPV vaccine, authors of the case report wrote in JAMA Dermatology.

All tumors resolved within 11 months of the first intratumoral injection, according to Anna J. Nichols, MD, PhD, department of dermatology and cutaneous surgery, University of Miami, and her coauthors.

‘These findings suggest that the 9-valent HPV vaccine can provide a therapeutic option for inoperable cutaneous SCCs, in addition to its approved use to prevent anogenital HPV infection,” they wrote.

Previously, Dr. Nichols and her coinvestigators reported a reduction in SCCs and basal cell carcinoma in 2 immunocompetent patients who had received quadrivalent HPV vaccine. Those results suggested development of these keratinocyte carcinomas in immunocompetent patients may be driven in part by HPV, the investigators said at the time.

The patient in the current report was treated with 9-valent HPV vaccine in a university-based outpatient clinic between March 2016 and February 2017.

She initially received two doses of intramuscular vaccine 6 weeks apart; 3 weeks later, she received intratumoral administration of the vaccine diluted with sterile saline, followed by three additional intratumoral doses over the next 8 months.

“The marked regression of numerous SCCs after initiation of the intratumoral injections eliminated the need for additional treatment,” Dr. Nichols and her coauthors said in the report.

A reduction in tumor size and number was seen 2 weeks after the second intratumoral dose of the 9-valent HPV vaccine, and within 11 months of the first intratumoral dose, there was no clinical or histologic evidence of SCC, they said.

The patient was left with small, violet-colored scars, along with a small pink papule, histopathologic analysis of which showed mild cellular atypia of basal keratinocytes with hyperkeratosis, according to published details of the case report.

The patient experienced mild pain in some of the tumors on days of intratumoral treatment, but no other side effects were seen, according to the authors.

The patient remained tumor free at the end of follow-up in May 2018, and there was no clinical evidence of SCC recurrence at the patient’s most recent follow-up visit, 24 months after the first intratumoral HPV dose, the researchers wrote.

It’s not clear what role the systemic vaccine doses played in the therapeutic benefit the patient experienced, authors said, noting that tumors not injected directly may have regressed because of either local vaccine dispersion or systemic, immune-mediated mechanisms.

“The potent therapeutic benefit may reflect a combination of immunologic, antiviral, and antitumor effects of 9-valent HPV vaccine,” they concluded.

Dr. Nichols had no disclosures. Study coauthors Tim Ioannides, MD, and Evangelos V. Badiavas, MD, PhD, have a patent pending for the application of human papillomavirus vaccine described in the study.

SOURCE: Nichols AJ et al. JAMA Dermatol. 2018 Jul 3. doi: 10.1001/jamadermatol.2016.5703.

A patient with an aggressive form of squamous cell carcinoma (SCC) experienced complete resolution of tumors following administration of human papillomavirus (HPV) vaccine, a recent case report shows.

The patient, an immunocompetent woman, aged in her 90s, with multiple inoperable cutaneous basaloid SCCs, was treated with a combination of systemic and intratumoral delivery of 9-valent HPV vaccine, authors of the case report wrote in JAMA Dermatology.

All tumors resolved within 11 months of the first intratumoral injection, according to Anna J. Nichols, MD, PhD, department of dermatology and cutaneous surgery, University of Miami, and her coauthors.

‘These findings suggest that the 9-valent HPV vaccine can provide a therapeutic option for inoperable cutaneous SCCs, in addition to its approved use to prevent anogenital HPV infection,” they wrote.

Previously, Dr. Nichols and her coinvestigators reported a reduction in SCCs and basal cell carcinoma in 2 immunocompetent patients who had received quadrivalent HPV vaccine. Those results suggested development of these keratinocyte carcinomas in immunocompetent patients may be driven in part by HPV, the investigators said at the time.

The patient in the current report was treated with 9-valent HPV vaccine in a university-based outpatient clinic between March 2016 and February 2017.

She initially received two doses of intramuscular vaccine 6 weeks apart; 3 weeks later, she received intratumoral administration of the vaccine diluted with sterile saline, followed by three additional intratumoral doses over the next 8 months.

“The marked regression of numerous SCCs after initiation of the intratumoral injections eliminated the need for additional treatment,” Dr. Nichols and her coauthors said in the report.

A reduction in tumor size and number was seen 2 weeks after the second intratumoral dose of the 9-valent HPV vaccine, and within 11 months of the first intratumoral dose, there was no clinical or histologic evidence of SCC, they said.

The patient was left with small, violet-colored scars, along with a small pink papule, histopathologic analysis of which showed mild cellular atypia of basal keratinocytes with hyperkeratosis, according to published details of the case report.

The patient experienced mild pain in some of the tumors on days of intratumoral treatment, but no other side effects were seen, according to the authors.

The patient remained tumor free at the end of follow-up in May 2018, and there was no clinical evidence of SCC recurrence at the patient’s most recent follow-up visit, 24 months after the first intratumoral HPV dose, the researchers wrote.

It’s not clear what role the systemic vaccine doses played in the therapeutic benefit the patient experienced, authors said, noting that tumors not injected directly may have regressed because of either local vaccine dispersion or systemic, immune-mediated mechanisms.

“The potent therapeutic benefit may reflect a combination of immunologic, antiviral, and antitumor effects of 9-valent HPV vaccine,” they concluded.

Dr. Nichols had no disclosures. Study coauthors Tim Ioannides, MD, and Evangelos V. Badiavas, MD, PhD, have a patent pending for the application of human papillomavirus vaccine described in the study.

SOURCE: Nichols AJ et al. JAMA Dermatol. 2018 Jul 3. doi: 10.1001/jamadermatol.2016.5703.

Singleton infants born to mothers who are subfertile or treated with assisted reproductive technology (ART) are at higher risk for multiple adverse health outcomes beyond prematurity, a recent retrospective study shows.

Risks of chromosomal abnormalities, infectious diseases, and cardiovascular and respiratory conditions were all increased, compared with infants born to fertile mothers, in analyses of neonatal outcomes stratified by gestational age.

This population-based study is among the first to show differences in adverse birth outcomes beyond preterm birth and, more specifically, by organ system conditions across gestational age categories, according to Sunah S. Hwang, MD, MPH, of the University of Colorado at Denver, Aurora, and her coinvestigators.

“With this approach, we offer more detailed associations between maternal fertility and the receipt of treatment along the continuum of fetal organ development and subsequent infant health conditions,” Dr. Hwang and her coauthors wrote in Pediatrics.

The study, which included singleton infants of at least 23 weeks’ gestational age born during 2004-2010, was based on data from a Massachusetts clinical ART database (MOSART) that was linked with state vital records.

Out of 350,123 infants with birth hospitalization records in the study cohort, 336,705 were born to fertile women, while 8,375 were born to women treated with ART, and 5,403 were born to subfertile women.

After adjustment for key maternal and infant characteristics, infants born to subfertile or ART-treated women were more often preterm as compared with infants to fertile mothers. Adjusted odds ratios were 1.39 (95% confidence interval, 1.26-1.54) and 1.72 (95% CI, 1.60-1.85) for infants of subfertile and ART-treated women, respectively, Dr. Hwang and her coinvestigators reported.

Infants born to subfertile or ART-treated women were also more likely to have adverse respiratory, gastrointestinal, or nutritional outcomes, with adjusted ORs ranging from 1.12 to 1.18, they added in the report.

Looking specifically at outcomes stratified by gestational age, they found an increased risk of congenital malformations, infectious diseases, and cardiovascular or respiratory outcomes, with adjusted ORs from 1.30 to 2.61, in the data published in the journal.

By contrast, there were no differences in risks of neonatal mortality, length of hospitalization, low birth weight, or neurologic and hematologic abnormalities for infants of subfertile and ART-treated women, compared with fertile women, according to Dr. Hwang and her coauthors.

These results confirm results of some previous studies that suggested a higher risk of adverse birth outcomes among infants born as singletons, according to the study authors.

“Although it is clearly accepted that multiple gestation is a significant predictor of preterm birth and low birth weight, recent studies have also revealed that, even among singleton births, mothers with infertility without ART treatment along with those who do undergo ART treatment are at higher risk for preterm delivery,” they wrote.

The study was funded by a grant from the National Institutes of Health. Authors said they had no financial relationships relevant to the study.

SOURCE: Hwang SS et al. Pediatrics. 2018 Aug;142(2):e20174069.

Singleton infants born to mothers who are subfertile or treated with assisted reproductive technology (ART) are at higher risk for multiple adverse health outcomes beyond prematurity, a recent retrospective study shows.

Risks of chromosomal abnormalities, infectious diseases, and cardiovascular and respiratory conditions were all increased, compared with infants born to fertile mothers, in analyses of neonatal outcomes stratified by gestational age.

This population-based study is among the first to show differences in adverse birth outcomes beyond preterm birth and, more specifically, by organ system conditions across gestational age categories, according to Sunah S. Hwang, MD, MPH, of the University of Colorado at Denver, Aurora, and her coinvestigators.

“With this approach, we offer more detailed associations between maternal fertility and the receipt of treatment along the continuum of fetal organ development and subsequent infant health conditions,” Dr. Hwang and her coauthors wrote in Pediatrics.

The study, which included singleton infants of at least 23 weeks’ gestational age born during 2004-2010, was based on data from a Massachusetts clinical ART database (MOSART) that was linked with state vital records.

Out of 350,123 infants with birth hospitalization records in the study cohort, 336,705 were born to fertile women, while 8,375 were born to women treated with ART, and 5,403 were born to subfertile women.

After adjustment for key maternal and infant characteristics, infants born to subfertile or ART-treated women were more often preterm as compared with infants to fertile mothers. Adjusted odds ratios were 1.39 (95% confidence interval, 1.26-1.54) and 1.72 (95% CI, 1.60-1.85) for infants of subfertile and ART-treated women, respectively, Dr. Hwang and her coinvestigators reported.

Infants born to subfertile or ART-treated women were also more likely to have adverse respiratory, gastrointestinal, or nutritional outcomes, with adjusted ORs ranging from 1.12 to 1.18, they added in the report.

Looking specifically at outcomes stratified by gestational age, they found an increased risk of congenital malformations, infectious diseases, and cardiovascular or respiratory outcomes, with adjusted ORs from 1.30 to 2.61, in the data published in the journal.

By contrast, there were no differences in risks of neonatal mortality, length of hospitalization, low birth weight, or neurologic and hematologic abnormalities for infants of subfertile and ART-treated women, compared with fertile women, according to Dr. Hwang and her coauthors.

These results confirm results of some previous studies that suggested a higher risk of adverse birth outcomes among infants born as singletons, according to the study authors.

“Although it is clearly accepted that multiple gestation is a significant predictor of preterm birth and low birth weight, recent studies have also revealed that, even among singleton births, mothers with infertility without ART treatment along with those who do undergo ART treatment are at higher risk for preterm delivery,” they wrote.

The study was funded by a grant from the National Institutes of Health. Authors said they had no financial relationships relevant to the study.

SOURCE: Hwang SS et al. Pediatrics. 2018 Aug;142(2):e20174069.

Singleton infants born to mothers who are subfertile or treated with assisted reproductive technology (ART) are at higher risk for multiple adverse health outcomes beyond prematurity, a recent retrospective study shows.

Risks of chromosomal abnormalities, infectious diseases, and cardiovascular and respiratory conditions were all increased, compared with infants born to fertile mothers, in analyses of neonatal outcomes stratified by gestational age.

This population-based study is among the first to show differences in adverse birth outcomes beyond preterm birth and, more specifically, by organ system conditions across gestational age categories, according to Sunah S. Hwang, MD, MPH, of the University of Colorado at Denver, Aurora, and her coinvestigators.

“With this approach, we offer more detailed associations between maternal fertility and the receipt of treatment along the continuum of fetal organ development and subsequent infant health conditions,” Dr. Hwang and her coauthors wrote in Pediatrics.

The study, which included singleton infants of at least 23 weeks’ gestational age born during 2004-2010, was based on data from a Massachusetts clinical ART database (MOSART) that was linked with state vital records.

Out of 350,123 infants with birth hospitalization records in the study cohort, 336,705 were born to fertile women, while 8,375 were born to women treated with ART, and 5,403 were born to subfertile women.

After adjustment for key maternal and infant characteristics, infants born to subfertile or ART-treated women were more often preterm as compared with infants to fertile mothers. Adjusted odds ratios were 1.39 (95% confidence interval, 1.26-1.54) and 1.72 (95% CI, 1.60-1.85) for infants of subfertile and ART-treated women, respectively, Dr. Hwang and her coinvestigators reported.

Infants born to subfertile or ART-treated women were also more likely to have adverse respiratory, gastrointestinal, or nutritional outcomes, with adjusted ORs ranging from 1.12 to 1.18, they added in the report.

Looking specifically at outcomes stratified by gestational age, they found an increased risk of congenital malformations, infectious diseases, and cardiovascular or respiratory outcomes, with adjusted ORs from 1.30 to 2.61, in the data published in the journal.

By contrast, there were no differences in risks of neonatal mortality, length of hospitalization, low birth weight, or neurologic and hematologic abnormalities for infants of subfertile and ART-treated women, compared with fertile women, according to Dr. Hwang and her coauthors.

These results confirm results of some previous studies that suggested a higher risk of adverse birth outcomes among infants born as singletons, according to the study authors.

“Although it is clearly accepted that multiple gestation is a significant predictor of preterm birth and low birth weight, recent studies have also revealed that, even among singleton births, mothers with infertility without ART treatment along with those who do undergo ART treatment are at higher risk for preterm delivery,” they wrote.

The study was funded by a grant from the National Institutes of Health. Authors said they had no financial relationships relevant to the study.

SOURCE: Hwang SS et al. Pediatrics. 2018 Aug;142(2):e20174069.

CHICAGO – Daratumumab in combination with carfilzomib and dexamethasone (D-Kd) was a safe and effective regimen for patients with relapsed multiple myeloma, even in those with disease refractory to lenalidomide, in an open label, phase 1b study.

The regimen was well tolerated, with low rates of neutropenia both overall and in the lenalidomide-refractory subset of patients, according to this subgroup analysis of MMY1001.

The D-Kd regimen produced deep and durable responses, with an “encouraging” median progression-free survival of approximately 14 months for lenalidomide-refractory patients, according to investigator Ajai Chari, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York.

Patients with lenalidomide-refractory multiple myeloma have often been excluded from recent phase 3 studies in the relapsed/refractory setting, Dr. Chari noted in a presentation of the data at the 2018 annual meeting of the American Society of Clinical Oncology. “With the increasing adoption of lenalidomide maintenance, based on overall survival benefit, clearly there’s a need for more data on lenalidomide-refractory, relapsed refractory myeloma.”

The analysis by Dr. Chari and his colleagues was based on 85 previously treated, carfilzomib-naive patients, of whom 51 were lenalidomide refractory, in the MMY1001 study.

Patients received carfilzomib on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg once weekly. They received daratumumab weekly for the first 2 cycles, every 2 weeks for the next 4 cycles, and every 4 weeks thereafter. Ten patients received a standard single first dose of daratumumab, while 75 received a split first dose.

Some grade 3/4 hematologic toxicities were observed, and the rate of grade 3/4 neutropenia was 21% overall. The most common nonhematologic toxicities reaching grade 3/4 included asthenia and hypertension at 12% and 14%, respectively. A similar safety profile was seen in the lenalidomide-refractory subset, according to Dr. Chari.

Grade 3 cardiac treatment-emergent adverse events were seen in seven patients, and resolved in five of them. One patient had a grade 4 event that resolved. Cardiac adverse events improved in grade upon interruption of carfilzomib, Dr. Chari said.

With a median follow-up of 12 months, the response rate was 84% overall, which was comparable to the 79% rate seen in the lenalidomide-refractory patients and 90% rate seen in the patients who were exposed to lenalidomide but not refractory, according to Dr. Chari.

Median progression-free survival had not been reached for the overall patient cohort but was 14.1 months in the lenalidomide-refractory cohort, Dr. Chari said. The 12-month rates of progression-free survival were 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.

Median overall survival was not reached overall, not reached in lenalidomide-exposed patients, and was 21.1 months in the lenalidomide-refractory group, he added.

Infusion-related reactions occurred in 5 out of 10 patients who received a standard single first infusion of daratumumab. In patients who received a split first infusion, reactions were seen in 27 (36%) on day 1 and in 3 (4%) on day 2. “Importantly, I think this study highlights the ability to do split dosing, particularly in community practices, and to improve patient convenience,” Dr. Chari said.

Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.

SOURCE: Chari A et al. ASCO 2018, Abstract 8002.

CHICAGO – Daratumumab in combination with carfilzomib and dexamethasone (D-Kd) was a safe and effective regimen for patients with relapsed multiple myeloma, even in those with disease refractory to lenalidomide, in an open label, phase 1b study.

The regimen was well tolerated, with low rates of neutropenia both overall and in the lenalidomide-refractory subset of patients, according to this subgroup analysis of MMY1001.

The D-Kd regimen produced deep and durable responses, with an “encouraging” median progression-free survival of approximately 14 months for lenalidomide-refractory patients, according to investigator Ajai Chari, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York.

Patients with lenalidomide-refractory multiple myeloma have often been excluded from recent phase 3 studies in the relapsed/refractory setting, Dr. Chari noted in a presentation of the data at the 2018 annual meeting of the American Society of Clinical Oncology. “With the increasing adoption of lenalidomide maintenance, based on overall survival benefit, clearly there’s a need for more data on lenalidomide-refractory, relapsed refractory myeloma.”

The analysis by Dr. Chari and his colleagues was based on 85 previously treated, carfilzomib-naive patients, of whom 51 were lenalidomide refractory, in the MMY1001 study.

Patients received carfilzomib on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg once weekly. They received daratumumab weekly for the first 2 cycles, every 2 weeks for the next 4 cycles, and every 4 weeks thereafter. Ten patients received a standard single first dose of daratumumab, while 75 received a split first dose.

Some grade 3/4 hematologic toxicities were observed, and the rate of grade 3/4 neutropenia was 21% overall. The most common nonhematologic toxicities reaching grade 3/4 included asthenia and hypertension at 12% and 14%, respectively. A similar safety profile was seen in the lenalidomide-refractory subset, according to Dr. Chari.

Grade 3 cardiac treatment-emergent adverse events were seen in seven patients, and resolved in five of them. One patient had a grade 4 event that resolved. Cardiac adverse events improved in grade upon interruption of carfilzomib, Dr. Chari said.

With a median follow-up of 12 months, the response rate was 84% overall, which was comparable to the 79% rate seen in the lenalidomide-refractory patients and 90% rate seen in the patients who were exposed to lenalidomide but not refractory, according to Dr. Chari.

Median progression-free survival had not been reached for the overall patient cohort but was 14.1 months in the lenalidomide-refractory cohort, Dr. Chari said. The 12-month rates of progression-free survival were 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.

Median overall survival was not reached overall, not reached in lenalidomide-exposed patients, and was 21.1 months in the lenalidomide-refractory group, he added.

Infusion-related reactions occurred in 5 out of 10 patients who received a standard single first infusion of daratumumab. In patients who received a split first infusion, reactions were seen in 27 (36%) on day 1 and in 3 (4%) on day 2. “Importantly, I think this study highlights the ability to do split dosing, particularly in community practices, and to improve patient convenience,” Dr. Chari said.

Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.

SOURCE: Chari A et al. ASCO 2018, Abstract 8002.

CHICAGO – Daratumumab in combination with carfilzomib and dexamethasone (D-Kd) was a safe and effective regimen for patients with relapsed multiple myeloma, even in those with disease refractory to lenalidomide, in an open label, phase 1b study.

The regimen was well tolerated, with low rates of neutropenia both overall and in the lenalidomide-refractory subset of patients, according to this subgroup analysis of MMY1001.

The D-Kd regimen produced deep and durable responses, with an “encouraging” median progression-free survival of approximately 14 months for lenalidomide-refractory patients, according to investigator Ajai Chari, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York.

Patients with lenalidomide-refractory multiple myeloma have often been excluded from recent phase 3 studies in the relapsed/refractory setting, Dr. Chari noted in a presentation of the data at the 2018 annual meeting of the American Society of Clinical Oncology. “With the increasing adoption of lenalidomide maintenance, based on overall survival benefit, clearly there’s a need for more data on lenalidomide-refractory, relapsed refractory myeloma.”

The analysis by Dr. Chari and his colleagues was based on 85 previously treated, carfilzomib-naive patients, of whom 51 were lenalidomide refractory, in the MMY1001 study.

Patients received carfilzomib on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg once weekly. They received daratumumab weekly for the first 2 cycles, every 2 weeks for the next 4 cycles, and every 4 weeks thereafter. Ten patients received a standard single first dose of daratumumab, while 75 received a split first dose.

Some grade 3/4 hematologic toxicities were observed, and the rate of grade 3/4 neutropenia was 21% overall. The most common nonhematologic toxicities reaching grade 3/4 included asthenia and hypertension at 12% and 14%, respectively. A similar safety profile was seen in the lenalidomide-refractory subset, according to Dr. Chari.

Grade 3 cardiac treatment-emergent adverse events were seen in seven patients, and resolved in five of them. One patient had a grade 4 event that resolved. Cardiac adverse events improved in grade upon interruption of carfilzomib, Dr. Chari said.

With a median follow-up of 12 months, the response rate was 84% overall, which was comparable to the 79% rate seen in the lenalidomide-refractory patients and 90% rate seen in the patients who were exposed to lenalidomide but not refractory, according to Dr. Chari.

Median progression-free survival had not been reached for the overall patient cohort but was 14.1 months in the lenalidomide-refractory cohort, Dr. Chari said. The 12-month rates of progression-free survival were 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.

Median overall survival was not reached overall, not reached in lenalidomide-exposed patients, and was 21.1 months in the lenalidomide-refractory group, he added.

Infusion-related reactions occurred in 5 out of 10 patients who received a standard single first infusion of daratumumab. In patients who received a split first infusion, reactions were seen in 27 (36%) on day 1 and in 3 (4%) on day 2. “Importantly, I think this study highlights the ability to do split dosing, particularly in community practices, and to improve patient convenience,” Dr. Chari said.

Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.

SOURCE: Chari A et al. ASCO 2018, Abstract 8002.

CHICAGO – For patients with relapsed/refractory multiple myeloma previously exposed to lenalidomide, the combination of pomalidomide plus bortezomib and low‐dose dexamethasone (PVd) improved response and progression-free survival, results of the phase 3 OPTIMISMM trial showed.

Risk of disease progression or death was reduced by 39%, compared with bortezomib and low-dose dexamethasone alone (Vd), among patients in the trial, of whom approximately 70% were lenalidomide refractory, reported investigator Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston.

The improvements in efficacy seen with the PVd regimen were more pronounced in patients with only one prior line of therapy, and overall, the safety profile of the triplet regimen was consistent with known toxicities of each individual agent, Dr. Richardson reported.

Together, those results “would seem to support the use of this triplet [therapy] in first relapse in patients with relapsed/refractory myeloma and prior exposure to lenalidomide,” he said at the annual meeting of the American Society of Clinical Oncology.

“This study, importantly, evaluated a clinically relevant patient population and a growing patient population who receive upfront lenalidomide and maintenance in that setting and for whom lenalidomide is no longer a viable treatment option,” Dr. Richardson added.

Lenalidomide has become a mainstay of upfront myeloma treatment, and the Food and Drug Administration recently gave approval to lenalidomide as maintenance after autologous hematopoietic stem cell transplantation. Accordingly, it’s important to understand the benefits of triplet therapies in patients progressing on lenalidomide therapy and in whom lenalidomide is no longer a treatment option, Dr. Richardson said.

Pomalidomide, a potent oral immunomodulatory agent, is already approved for relapsed/refractory myeloma after two or more previous therapies that include lenalidomide and a proteasome inhibitor in patients who progress on or within 60 days of treatment.

In the OPTIMISMM trial, 559 patients who had received prior therapy, including at least two cycles of lenalidomide, were randomized to receive either PVd or Vd until disease progression or unacceptable toxicity.

Median progression-free survival was 11.20 months for PVd versus 7.10 months for Vd (hazard ratio, 0.61; 95% confidence interval, 0.49-0.77; P less than .0001).

Progression-free survival results were “even more encouraging” in the subset of patients with only one prior line of therapy, Dr. Richardson said, reporting a median of 20.73 months for PVd versus 11.63 for Vd (HR, 0.54; 95% CI, 0.36-0.82; P = .0027).

The overall response rate was 82.2% for PVd versus 50.0% for Vd (P less than .001). In patients with only one prior line of therapy, the overall response rate was 90.1% and 54.8% for PVd and Vd, respectively (P less than .001).

The progression-free survival advantage occurred regardless of whether patients were refractory to lenalidomide, Dr. Richardson added. Median progression-free survival for PVd versus Vd was 9.53 and 5.59 months, respectively, in the lenalidomide-refractory patients (P less than .001) and 22.01 versus 11.63 months in non–lenalidomide refractory patients (P less than .001).

The side effect profile of PVd was “very much as expected,” with more neutropenia seen with the PVd than with Vd, though rates of febrile neutropenia were low, Dr. Richardson said. Likewise, the rate of infection was higher in the triplet arm, but it was generally manageable, he added.

Deep vein thrombosis and pulmonary embolism rates were low in both arms, as were the rates of secondary primary malignancies. Analysis of minimal residual disease and quality of life are ongoing.

PVd could “arguably be now an important treatment platform for future directions in combination with other strategies,” Dr. Richardson said.

The study was supported by Celgene. Dr. Richardson reported advisory board work for Celgene, Novartis, Oncopeptides, Janssen, Amgen, and Takeda, and research funding from Bristol-Myers Squibb, Celgene, and Takeda.

SOURCE: Richardson PG et al. ASCO 2018, Abstract 8001.

CHICAGO – For patients with relapsed/refractory multiple myeloma previously exposed to lenalidomide, the combination of pomalidomide plus bortezomib and low‐dose dexamethasone (PVd) improved response and progression-free survival, results of the phase 3 OPTIMISMM trial showed.

Risk of disease progression or death was reduced by 39%, compared with bortezomib and low-dose dexamethasone alone (Vd), among patients in the trial, of whom approximately 70% were lenalidomide refractory, reported investigator Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston.

The improvements in efficacy seen with the PVd regimen were more pronounced in patients with only one prior line of therapy, and overall, the safety profile of the triplet regimen was consistent with known toxicities of each individual agent, Dr. Richardson reported.

Together, those results “would seem to support the use of this triplet [therapy] in first relapse in patients with relapsed/refractory myeloma and prior exposure to lenalidomide,” he said at the annual meeting of the American Society of Clinical Oncology.

“This study, importantly, evaluated a clinically relevant patient population and a growing patient population who receive upfront lenalidomide and maintenance in that setting and for whom lenalidomide is no longer a viable treatment option,” Dr. Richardson added.

Lenalidomide has become a mainstay of upfront myeloma treatment, and the Food and Drug Administration recently gave approval to lenalidomide as maintenance after autologous hematopoietic stem cell transplantation. Accordingly, it’s important to understand the benefits of triplet therapies in patients progressing on lenalidomide therapy and in whom lenalidomide is no longer a treatment option, Dr. Richardson said.

Pomalidomide, a potent oral immunomodulatory agent, is already approved for relapsed/refractory myeloma after two or more previous therapies that include lenalidomide and a proteasome inhibitor in patients who progress on or within 60 days of treatment.

In the OPTIMISMM trial, 559 patients who had received prior therapy, including at least two cycles of lenalidomide, were randomized to receive either PVd or Vd until disease progression or unacceptable toxicity.

Median progression-free survival was 11.20 months for PVd versus 7.10 months for Vd (hazard ratio, 0.61; 95% confidence interval, 0.49-0.77; P less than .0001).

Progression-free survival results were “even more encouraging” in the subset of patients with only one prior line of therapy, Dr. Richardson said, reporting a median of 20.73 months for PVd versus 11.63 for Vd (HR, 0.54; 95% CI, 0.36-0.82; P = .0027).

The overall response rate was 82.2% for PVd versus 50.0% for Vd (P less than .001). In patients with only one prior line of therapy, the overall response rate was 90.1% and 54.8% for PVd and Vd, respectively (P less than .001).

The progression-free survival advantage occurred regardless of whether patients were refractory to lenalidomide, Dr. Richardson added. Median progression-free survival for PVd versus Vd was 9.53 and 5.59 months, respectively, in the lenalidomide-refractory patients (P less than .001) and 22.01 versus 11.63 months in non–lenalidomide refractory patients (P less than .001).

The side effect profile of PVd was “very much as expected,” with more neutropenia seen with the PVd than with Vd, though rates of febrile neutropenia were low, Dr. Richardson said. Likewise, the rate of infection was higher in the triplet arm, but it was generally manageable, he added.

Deep vein thrombosis and pulmonary embolism rates were low in both arms, as were the rates of secondary primary malignancies. Analysis of minimal residual disease and quality of life are ongoing.

PVd could “arguably be now an important treatment platform for future directions in combination with other strategies,” Dr. Richardson said.

The study was supported by Celgene. Dr. Richardson reported advisory board work for Celgene, Novartis, Oncopeptides, Janssen, Amgen, and Takeda, and research funding from Bristol-Myers Squibb, Celgene, and Takeda.

SOURCE: Richardson PG et al. ASCO 2018, Abstract 8001.

CHICAGO – For patients with relapsed/refractory multiple myeloma previously exposed to lenalidomide, the combination of pomalidomide plus bortezomib and low‐dose dexamethasone (PVd) improved response and progression-free survival, results of the phase 3 OPTIMISMM trial showed.

Risk of disease progression or death was reduced by 39%, compared with bortezomib and low-dose dexamethasone alone (Vd), among patients in the trial, of whom approximately 70% were lenalidomide refractory, reported investigator Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston.

The improvements in efficacy seen with the PVd regimen were more pronounced in patients with only one prior line of therapy, and overall, the safety profile of the triplet regimen was consistent with known toxicities of each individual agent, Dr. Richardson reported.

Together, those results “would seem to support the use of this triplet [therapy] in first relapse in patients with relapsed/refractory myeloma and prior exposure to lenalidomide,” he said at the annual meeting of the American Society of Clinical Oncology.

“This study, importantly, evaluated a clinically relevant patient population and a growing patient population who receive upfront lenalidomide and maintenance in that setting and for whom lenalidomide is no longer a viable treatment option,” Dr. Richardson added.

Lenalidomide has become a mainstay of upfront myeloma treatment, and the Food and Drug Administration recently gave approval to lenalidomide as maintenance after autologous hematopoietic stem cell transplantation. Accordingly, it’s important to understand the benefits of triplet therapies in patients progressing on lenalidomide therapy and in whom lenalidomide is no longer a treatment option, Dr. Richardson said.

Pomalidomide, a potent oral immunomodulatory agent, is already approved for relapsed/refractory myeloma after two or more previous therapies that include lenalidomide and a proteasome inhibitor in patients who progress on or within 60 days of treatment.

In the OPTIMISMM trial, 559 patients who had received prior therapy, including at least two cycles of lenalidomide, were randomized to receive either PVd or Vd until disease progression or unacceptable toxicity.

Median progression-free survival was 11.20 months for PVd versus 7.10 months for Vd (hazard ratio, 0.61; 95% confidence interval, 0.49-0.77; P less than .0001).

Progression-free survival results were “even more encouraging” in the subset of patients with only one prior line of therapy, Dr. Richardson said, reporting a median of 20.73 months for PVd versus 11.63 for Vd (HR, 0.54; 95% CI, 0.36-0.82; P = .0027).

The overall response rate was 82.2% for PVd versus 50.0% for Vd (P less than .001). In patients with only one prior line of therapy, the overall response rate was 90.1% and 54.8% for PVd and Vd, respectively (P less than .001).

The progression-free survival advantage occurred regardless of whether patients were refractory to lenalidomide, Dr. Richardson added. Median progression-free survival for PVd versus Vd was 9.53 and 5.59 months, respectively, in the lenalidomide-refractory patients (P less than .001) and 22.01 versus 11.63 months in non–lenalidomide refractory patients (P less than .001).

The side effect profile of PVd was “very much as expected,” with more neutropenia seen with the PVd than with Vd, though rates of febrile neutropenia were low, Dr. Richardson said. Likewise, the rate of infection was higher in the triplet arm, but it was generally manageable, he added.

Deep vein thrombosis and pulmonary embolism rates were low in both arms, as were the rates of secondary primary malignancies. Analysis of minimal residual disease and quality of life are ongoing.

PVd could “arguably be now an important treatment platform for future directions in combination with other strategies,” Dr. Richardson said.

The study was supported by Celgene. Dr. Richardson reported advisory board work for Celgene, Novartis, Oncopeptides, Janssen, Amgen, and Takeda, and research funding from Bristol-Myers Squibb, Celgene, and Takeda.

SOURCE: Richardson PG et al. ASCO 2018, Abstract 8001.

CHICAGO – The CD19–directed chimeric antigen receptor (CAR) T-cell product lisocabtagene maraleucel (liso-cel, JCAR017) produced durable responses in poor-prognosis patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follow-up results of a phase 1 trial show.

Nearly 90% of DLBCL patients who achieved complete response as their best response on liso-cel were alive at 1 year in the study, according to investigator Jeremy S. Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.

That result is “far superior to what we would have anticipated with conventional therapies in a largely chemorefractory DLBCL population,” Dr. Abramson said at the annual meeting of the American Society of Clinical Oncology.

The new data on liso-cel come on the heels of a second approval of a CAR T-cell therapy for DLBCL, noted Caron Jacobson, MD, of Dana-Farber Cancer Institute, Boston.

Axicabtagene ciloleucel (Yescarta) was approved in October 2017 by the U.S. Food and Drug Administration for relapsed or refractory large B-cell lymphomas, including DLBCL. In May 2018, tisagenlecleucel (Kymriah) received its second FDA approval to treat relapsed or refractory large B-cell lymphomas, including DLBCL.

CAR T-cell therapy “really has transformed outcomes for a group of patients who previously had no other standard of care and who… have a relatively short overall survival,” Dr. Jacobson said.

At the meeting, Dr. Abramson presented findings on DLBCL patients in TRANSCEND NHL 001, a phase 1, multicenter, open-label study of the CD-19 targeted CAR T-cell therapy in relapsed and refractory B-cell non-Hodgkin lymphoma.

About 90% of treated DLBCL patients had one or more poor-risk disease features, such as ECOG performance status 2 and primary refractory disease, which predict poor overall survival, according to Dr. Abramson.

Dr. Abramson’s presentation focused on 102 evaluable DLBCL patients in the dose-finding and dose-expansion cohorts of the TRANSCEND study, including a subset analysis of a core group of 73 patients who met the criteria for pivotal dose cohort of the study (1 x 10⁸ cells given as a single dose).

For the full set of 102 DLBCL patients, the best overall response rate was 75%, including a best complete remission rate of 55%, according to presented data. In the core group of 73 DLBCL patients, best overall response and complete remission rates were 80% and 59%, respectively.

Investigators saw “encouraging” durable response rates at 6 months and beyond in the core DLBCL population, according to Dr. Abramson. Of patients with a complete remission at 3 months, 88% remained in complete remission at the 6-month follow-up, and 93% of those in remission at the 6-month time point were in ongoing response at a median follow-up of 8 months.

Median overall survival had not been reached in either the full or core DLBCL cohorts with a median of 12 months follow-up, he added, noting that 90% of patients who achieved complete remission as their best response remained alive at 1 year.

In terms of adverse effects, liso-cel is showing a low and manageable toxicity profile, with very low rates of severe cytokine release syndrome (CRS) and neurotoxicity at 1% and 13%, respectively, Dr. Abramson reported.

“This anti-CD19 CAR T cell has remarkable efficacy in a group of highly refractory aggressive B-cell non-Hodgkin lymphoma patients,” said Dr. Jacobson, commenting on results of the DLBCL subset.

Based on the data presented, liso-cel is “clearly competitive” with the approved CAR T-cell therapies, though she advised caution in comparing across studies. “I don’t think that there will be a randomized study of all three agents, but I do think that we’ll start to get comparative data from single institution experiences that are using all three products,” she said.

The pivotal DLBCL cohort of TRANSCEND NHL 001 has completed accrual and results will be presented at a future meeting, Dr. Abramson said.

Dr. Abramson reported disclosures related to Celgene, Genentech/Roche, Gilead Sciences, Novartis, Seattle Genetics, and Millennium.

SOURCE: Abramson JS et al. ASCO 2018. Abstract 7505.

CHICAGO – The CD19–directed chimeric antigen receptor (CAR) T-cell product lisocabtagene maraleucel (liso-cel, JCAR017) produced durable responses in poor-prognosis patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follow-up results of a phase 1 trial show.

Nearly 90% of DLBCL patients who achieved complete response as their best response on liso-cel were alive at 1 year in the study, according to investigator Jeremy S. Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.

That result is “far superior to what we would have anticipated with conventional therapies in a largely chemorefractory DLBCL population,” Dr. Abramson said at the annual meeting of the American Society of Clinical Oncology.

The new data on liso-cel come on the heels of a second approval of a CAR T-cell therapy for DLBCL, noted Caron Jacobson, MD, of Dana-Farber Cancer Institute, Boston.

Axicabtagene ciloleucel (Yescarta) was approved in October 2017 by the U.S. Food and Drug Administration for relapsed or refractory large B-cell lymphomas, including DLBCL. In May 2018, tisagenlecleucel (Kymriah) received its second FDA approval to treat relapsed or refractory large B-cell lymphomas, including DLBCL.

CAR T-cell therapy “really has transformed outcomes for a group of patients who previously had no other standard of care and who… have a relatively short overall survival,” Dr. Jacobson said.

At the meeting, Dr. Abramson presented findings on DLBCL patients in TRANSCEND NHL 001, a phase 1, multicenter, open-label study of the CD-19 targeted CAR T-cell therapy in relapsed and refractory B-cell non-Hodgkin lymphoma.

About 90% of treated DLBCL patients had one or more poor-risk disease features, such as ECOG performance status 2 and primary refractory disease, which predict poor overall survival, according to Dr. Abramson.

Dr. Abramson’s presentation focused on 102 evaluable DLBCL patients in the dose-finding and dose-expansion cohorts of the TRANSCEND study, including a subset analysis of a core group of 73 patients who met the criteria for pivotal dose cohort of the study (1 x 10⁸ cells given as a single dose).

For the full set of 102 DLBCL patients, the best overall response rate was 75%, including a best complete remission rate of 55%, according to presented data. In the core group of 73 DLBCL patients, best overall response and complete remission rates were 80% and 59%, respectively.

Investigators saw “encouraging” durable response rates at 6 months and beyond in the core DLBCL population, according to Dr. Abramson. Of patients with a complete remission at 3 months, 88% remained in complete remission at the 6-month follow-up, and 93% of those in remission at the 6-month time point were in ongoing response at a median follow-up of 8 months.

Median overall survival had not been reached in either the full or core DLBCL cohorts with a median of 12 months follow-up, he added, noting that 90% of patients who achieved complete remission as their best response remained alive at 1 year.

In terms of adverse effects, liso-cel is showing a low and manageable toxicity profile, with very low rates of severe cytokine release syndrome (CRS) and neurotoxicity at 1% and 13%, respectively, Dr. Abramson reported.

“This anti-CD19 CAR T cell has remarkable efficacy in a group of highly refractory aggressive B-cell non-Hodgkin lymphoma patients,” said Dr. Jacobson, commenting on results of the DLBCL subset.

Based on the data presented, liso-cel is “clearly competitive” with the approved CAR T-cell therapies, though she advised caution in comparing across studies. “I don’t think that there will be a randomized study of all three agents, but I do think that we’ll start to get comparative data from single institution experiences that are using all three products,” she said.

The pivotal DLBCL cohort of TRANSCEND NHL 001 has completed accrual and results will be presented at a future meeting, Dr. Abramson said.

Dr. Abramson reported disclosures related to Celgene, Genentech/Roche, Gilead Sciences, Novartis, Seattle Genetics, and Millennium.

SOURCE: Abramson JS et al. ASCO 2018. Abstract 7505.

CHICAGO – The CD19–directed chimeric antigen receptor (CAR) T-cell product lisocabtagene maraleucel (liso-cel, JCAR017) produced durable responses in poor-prognosis patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follow-up results of a phase 1 trial show.

Nearly 90% of DLBCL patients who achieved complete response as their best response on liso-cel were alive at 1 year in the study, according to investigator Jeremy S. Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.

That result is “far superior to what we would have anticipated with conventional therapies in a largely chemorefractory DLBCL population,” Dr. Abramson said at the annual meeting of the American Society of Clinical Oncology.

The new data on liso-cel come on the heels of a second approval of a CAR T-cell therapy for DLBCL, noted Caron Jacobson, MD, of Dana-Farber Cancer Institute, Boston.

Axicabtagene ciloleucel (Yescarta) was approved in October 2017 by the U.S. Food and Drug Administration for relapsed or refractory large B-cell lymphomas, including DLBCL. In May 2018, tisagenlecleucel (Kymriah) received its second FDA approval to treat relapsed or refractory large B-cell lymphomas, including DLBCL.

CAR T-cell therapy “really has transformed outcomes for a group of patients who previously had no other standard of care and who… have a relatively short overall survival,” Dr. Jacobson said.

At the meeting, Dr. Abramson presented findings on DLBCL patients in TRANSCEND NHL 001, a phase 1, multicenter, open-label study of the CD-19 targeted CAR T-cell therapy in relapsed and refractory B-cell non-Hodgkin lymphoma.

About 90% of treated DLBCL patients had one or more poor-risk disease features, such as ECOG performance status 2 and primary refractory disease, which predict poor overall survival, according to Dr. Abramson.

Dr. Abramson’s presentation focused on 102 evaluable DLBCL patients in the dose-finding and dose-expansion cohorts of the TRANSCEND study, including a subset analysis of a core group of 73 patients who met the criteria for pivotal dose cohort of the study (1 x 10⁸ cells given as a single dose).

For the full set of 102 DLBCL patients, the best overall response rate was 75%, including a best complete remission rate of 55%, according to presented data. In the core group of 73 DLBCL patients, best overall response and complete remission rates were 80% and 59%, respectively.

Investigators saw “encouraging” durable response rates at 6 months and beyond in the core DLBCL population, according to Dr. Abramson. Of patients with a complete remission at 3 months, 88% remained in complete remission at the 6-month follow-up, and 93% of those in remission at the 6-month time point were in ongoing response at a median follow-up of 8 months.

Median overall survival had not been reached in either the full or core DLBCL cohorts with a median of 12 months follow-up, he added, noting that 90% of patients who achieved complete remission as their best response remained alive at 1 year.

In terms of adverse effects, liso-cel is showing a low and manageable toxicity profile, with very low rates of severe cytokine release syndrome (CRS) and neurotoxicity at 1% and 13%, respectively, Dr. Abramson reported.

“This anti-CD19 CAR T cell has remarkable efficacy in a group of highly refractory aggressive B-cell non-Hodgkin lymphoma patients,” said Dr. Jacobson, commenting on results of the DLBCL subset.

Based on the data presented, liso-cel is “clearly competitive” with the approved CAR T-cell therapies, though she advised caution in comparing across studies. “I don’t think that there will be a randomized study of all three agents, but I do think that we’ll start to get comparative data from single institution experiences that are using all three products,” she said.

The pivotal DLBCL cohort of TRANSCEND NHL 001 has completed accrual and results will be presented at a future meeting, Dr. Abramson said.

Dr. Abramson reported disclosures related to Celgene, Genentech/Roche, Gilead Sciences, Novartis, Seattle Genetics, and Millennium.

SOURCE: Abramson JS et al. ASCO 2018. Abstract 7505.

Ozenoxacin (Xepi cream), a potent novel topical antibacterial agent, is effective and well tolerated for treatment of impetigo in patients aged 2 months and older, according to results of a phase 3 randomized, double-blind, vehicle-controlled clinical trial.

A 1% cream formulation of ozenoxacin had a clinical and microbiologic response that was rapid and superior to placebo, investigators reported in this second phase 3 pivotal study, which demonstrated the efficacy of ozenoxacin cream in impetigo patients.

SOURCE: Rosen T et al. JAMA Dermatol. 2018 Jun 13. doi: 10.1001/jamadermatol.2018.1103.

Ozenoxacin (Xepi cream), a potent novel topical antibacterial agent, is effective and well tolerated for treatment of impetigo in patients aged 2 months and older, according to results of a phase 3 randomized, double-blind, vehicle-controlled clinical trial.

A 1% cream formulation of ozenoxacin had a clinical and microbiologic response that was rapid and superior to placebo, investigators reported in this second phase 3 pivotal study, which demonstrated the efficacy of ozenoxacin cream in impetigo patients.

SOURCE: Rosen T et al. JAMA Dermatol. 2018 Jun 13. doi: 10.1001/jamadermatol.2018.1103.

Ozenoxacin (Xepi cream), a potent novel topical antibacterial agent, is effective and well tolerated for treatment of impetigo in patients aged 2 months and older, according to results of a phase 3 randomized, double-blind, vehicle-controlled clinical trial.

A 1% cream formulation of ozenoxacin had a clinical and microbiologic response that was rapid and superior to placebo, investigators reported in this second phase 3 pivotal study, which demonstrated the efficacy of ozenoxacin cream in impetigo patients.

SOURCE: Rosen T et al. JAMA Dermatol. 2018 Jun 13. doi: 10.1001/jamadermatol.2018.1103.

Abortion performed in an ambulatory surgery center (ASC) was not associated with a significant difference in abortion-related complications, compared with procedures performed in an office-based setting, according to results of a retrospective cohort study.

Low rates of abortion-related morbidities and adverse events were observed in both ASCs and office-based settings in the study, which was based on data for 49,287 women with U.S. private health insurance who had induced abortions between 2011 and 2014.

These findings might help inform decisions about the type of facility where induced abortions are performed, according to Sarah C. M. Roberts, DrPH, of the University of California, San Francisco, and her coauthors.

The U.S. Supreme Court ruled in 2016 that a Texas law requiring abortion facilities to meet ASC standards was unconstitutional, Dr. Roberts and her coauthors wrote in JAMA.

“Despite this ruling, 13 states currently have laws that require abortions to be provided in ASCs,” the authors wrote, noting that supporters of the laws argue that these requirements make abortions safer.

The laws have requirements such as separate procedure and recovery rooms, and specified hall and door widths. “Many of these apply only at a specific gestational week or gestational duration, typically in the second trimester,” they noted, adding that over 95% of induced abortions are performed in outpatient settings such as clinics or physician offices.

Their retrospective cohort study included a total of 50,311 induced abortions, of which 89% took place in office based settings and 11% in ASCs. Nearly half (47%) were first-trimester aspiration procedures, while 27% were first-trimester medication and 26% were second trimester or later.

Abortion-related morbidity or adverse events were reported for 3.33% of procedures overall. The adjusted incidence rate was 3.25% for ASC-based procedures, and similarly, 3.33% for office-based procedures.

The overall complication rate was higher than previous estimates based on insurance claims data, they said, but the estimate of major events was similar at 0.32%, breaking down to 0.26% for ASCs and 0.33% for office-based settings. The rate of infections was 0.58% for ASCs and 0.77% for office-based settings.

This is not the first study looking at the association between abortion-related events and the procedure setting, though the literature is limited, according to Dr. Roberts and her coauthors. One previous study showed fewer abortion-related events in clinics than in hospitals, while a recent review found similar abortion-related events following first-trimester abortions in hospitals, ASCs, and office-based settings.

One limitation of the current study is that the database included only abortions that were paid for by private insurance, which represents about 15% of the nearly 1 million procedures done each year in the United States.

“Thus, findings may not be generalizable to all abortions in the United States,” Dr. Roberts and her coauthors wrote.

The study was supported by a grant from the Society of Family Planning Research Fund. Study authors reported no conflicts of interest.

SOURCE: Roberts SCM et al. JAMA. 2018 Jun 26;319(24):2497-2506.

Abortion performed in an ambulatory surgery center (ASC) was not associated with a significant difference in abortion-related complications, compared with procedures performed in an office-based setting, according to results of a retrospective cohort study.

Low rates of abortion-related morbidities and adverse events were observed in both ASCs and office-based settings in the study, which was based on data for 49,287 women with U.S. private health insurance who had induced abortions between 2011 and 2014.

These findings might help inform decisions about the type of facility where induced abortions are performed, according to Sarah C. M. Roberts, DrPH, of the University of California, San Francisco, and her coauthors.

The U.S. Supreme Court ruled in 2016 that a Texas law requiring abortion facilities to meet ASC standards was unconstitutional, Dr. Roberts and her coauthors wrote in JAMA.

“Despite this ruling, 13 states currently have laws that require abortions to be provided in ASCs,” the authors wrote, noting that supporters of the laws argue that these requirements make abortions safer.

The laws have requirements such as separate procedure and recovery rooms, and specified hall and door widths. “Many of these apply only at a specific gestational week or gestational duration, typically in the second trimester,” they noted, adding that over 95% of induced abortions are performed in outpatient settings such as clinics or physician offices.

Their retrospective cohort study included a total of 50,311 induced abortions, of which 89% took place in office based settings and 11% in ASCs. Nearly half (47%) were first-trimester aspiration procedures, while 27% were first-trimester medication and 26% were second trimester or later.

Abortion-related morbidity or adverse events were reported for 3.33% of procedures overall. The adjusted incidence rate was 3.25% for ASC-based procedures, and similarly, 3.33% for office-based procedures.

The overall complication rate was higher than previous estimates based on insurance claims data, they said, but the estimate of major events was similar at 0.32%, breaking down to 0.26% for ASCs and 0.33% for office-based settings. The rate of infections was 0.58% for ASCs and 0.77% for office-based settings.

This is not the first study looking at the association between abortion-related events and the procedure setting, though the literature is limited, according to Dr. Roberts and her coauthors. One previous study showed fewer abortion-related events in clinics than in hospitals, while a recent review found similar abortion-related events following first-trimester abortions in hospitals, ASCs, and office-based settings.

One limitation of the current study is that the database included only abortions that were paid for by private insurance, which represents about 15% of the nearly 1 million procedures done each year in the United States.

“Thus, findings may not be generalizable to all abortions in the United States,” Dr. Roberts and her coauthors wrote.

The study was supported by a grant from the Society of Family Planning Research Fund. Study authors reported no conflicts of interest.

SOURCE: Roberts SCM et al. JAMA. 2018 Jun 26;319(24):2497-2506.

Abortion performed in an ambulatory surgery center (ASC) was not associated with a significant difference in abortion-related complications, compared with procedures performed in an office-based setting, according to results of a retrospective cohort study.

Low rates of abortion-related morbidities and adverse events were observed in both ASCs and office-based settings in the study, which was based on data for 49,287 women with U.S. private health insurance who had induced abortions between 2011 and 2014.

These findings might help inform decisions about the type of facility where induced abortions are performed, according to Sarah C. M. Roberts, DrPH, of the University of California, San Francisco, and her coauthors.

The U.S. Supreme Court ruled in 2016 that a Texas law requiring abortion facilities to meet ASC standards was unconstitutional, Dr. Roberts and her coauthors wrote in JAMA.

“Despite this ruling, 13 states currently have laws that require abortions to be provided in ASCs,” the authors wrote, noting that supporters of the laws argue that these requirements make abortions safer.

The laws have requirements such as separate procedure and recovery rooms, and specified hall and door widths. “Many of these apply only at a specific gestational week or gestational duration, typically in the second trimester,” they noted, adding that over 95% of induced abortions are performed in outpatient settings such as clinics or physician offices.

Their retrospective cohort study included a total of 50,311 induced abortions, of which 89% took place in office based settings and 11% in ASCs. Nearly half (47%) were first-trimester aspiration procedures, while 27% were first-trimester medication and 26% were second trimester or later.

Abortion-related morbidity or adverse events were reported for 3.33% of procedures overall. The adjusted incidence rate was 3.25% for ASC-based procedures, and similarly, 3.33% for office-based procedures.

The overall complication rate was higher than previous estimates based on insurance claims data, they said, but the estimate of major events was similar at 0.32%, breaking down to 0.26% for ASCs and 0.33% for office-based settings. The rate of infections was 0.58% for ASCs and 0.77% for office-based settings.

This is not the first study looking at the association between abortion-related events and the procedure setting, though the literature is limited, according to Dr. Roberts and her coauthors. One previous study showed fewer abortion-related events in clinics than in hospitals, while a recent review found similar abortion-related events following first-trimester abortions in hospitals, ASCs, and office-based settings.

One limitation of the current study is that the database included only abortions that were paid for by private insurance, which represents about 15% of the nearly 1 million procedures done each year in the United States.

“Thus, findings may not be generalizable to all abortions in the United States,” Dr. Roberts and her coauthors wrote.

The study was supported by a grant from the Society of Family Planning Research Fund. Study authors reported no conflicts of interest.

SOURCE: Roberts SCM et al. JAMA. 2018 Jun 26;319(24):2497-2506.

©ASCO/Scott Morgan 2018

CHICAGO—A novel CD19-targeted T-cell therapy induced complete metabolic responses (CMRs) and no cytokine release syndrome (CRS) in patients with B-cell lymphomas in a first-in-human clinical study.

All subjects achieving CMR at the 1-month safety and efficacy assessment continued to show CMR at 3 months, investigators reported at the 2018 ASCO Annual Meeting (abstract 3049*).

The therapy is built on a novel platform, ARTEMIS, designed to match the potency of chimeric antigen receptor (CAR) T-cell therapy but trigger less cytokine release when the target is engaged, investigators explained.

That platform is “potentially a major improvement” over existing CAR-T cell therapy, said Zhi Tao Ying, MD, of Peking University Cancer Hospital & Institute in Beijing, China, and coauthors in a poster presented at ASCO.

The treatment, called ET190L1-ARTEMIS, utilizes the T-cell receptor platform and a proprietary human anti-CD19 antibody to target CD19-positive malignancies.

The investigators reported on 21 adults with CD-19 positive relapsed and refractory B-cell lymphomas who had received a median of 4 lines of previous therapy.

Patients received autologous ET190L1-ARTEMIS T cells in 1 of 3 dosing cohorts: 3 patients at 1 x 10⁶/kg, 13 at 3 x 10⁶/kg, and 5 at 6 x 10⁶/kg.

Of 17 patients completing a first-month efficacy assessment, 11 (65%) responded, including 7 CMRs and 3 partial responses. One patient had stable disease.

Seven of the 11 responders completed a third-month efficacy assessment, as of this analysis. Of 5 patients with CMR at month 1, all 5 maintained CMR at month 3. Likewise, 1 patient in partial response and 1 with stable disease at month 1 had the same response status at month 3.

There were no cases of CRS or neurotoxicity in 17 patients who completed the 1-month safety and efficacy assessment reported at ASCO. Grade 3 or greater adverse events in those subjects included lymphopenia in 17 (100%) and neutropenia in 5 (29%).

Eureka Therapeutics Inc., of Emeryville, California, is developing ET190L1-ARTEMIS. Co-investigators in this trial were from Eureka, Xi-An Jiaotong University in China, and Duke University School of Medicine in Durham, North Carolina.

A phase 1 trial of ET190L1-ARTEMIS in patients with relapsed and refractory non-Hodgkin lymphoma has been initiated at Duke University, and  investigators say another US phase 1 trial including relapsed and refractory pediatric acute lymphoblastic leukemia patients will begin later this year. 

Data in the abstract differ from that presented in the poster.

©ASCO/Scott Morgan 2018

CHICAGO—A novel CD19-targeted T-cell therapy induced complete metabolic responses (CMRs) and no cytokine release syndrome (CRS) in patients with B-cell lymphomas in a first-in-human clinical study.

All subjects achieving CMR at the 1-month safety and efficacy assessment continued to show CMR at 3 months, investigators reported at the 2018 ASCO Annual Meeting (abstract 3049*).

The therapy is built on a novel platform, ARTEMIS, designed to match the potency of chimeric antigen receptor (CAR) T-cell therapy but trigger less cytokine release when the target is engaged, investigators explained.

That platform is “potentially a major improvement” over existing CAR-T cell therapy, said Zhi Tao Ying, MD, of Peking University Cancer Hospital & Institute in Beijing, China, and coauthors in a poster presented at ASCO.

The treatment, called ET190L1-ARTEMIS, utilizes the T-cell receptor platform and a proprietary human anti-CD19 antibody to target CD19-positive malignancies.

The investigators reported on 21 adults with CD-19 positive relapsed and refractory B-cell lymphomas who had received a median of 4 lines of previous therapy.

Patients received autologous ET190L1-ARTEMIS T cells in 1 of 3 dosing cohorts: 3 patients at 1 x 10⁶/kg, 13 at 3 x 10⁶/kg, and 5 at 6 x 10⁶/kg.

Of 17 patients completing a first-month efficacy assessment, 11 (65%) responded, including 7 CMRs and 3 partial responses. One patient had stable disease.

Seven of the 11 responders completed a third-month efficacy assessment, as of this analysis. Of 5 patients with CMR at month 1, all 5 maintained CMR at month 3. Likewise, 1 patient in partial response and 1 with stable disease at month 1 had the same response status at month 3.

There were no cases of CRS or neurotoxicity in 17 patients who completed the 1-month safety and efficacy assessment reported at ASCO. Grade 3 or greater adverse events in those subjects included lymphopenia in 17 (100%) and neutropenia in 5 (29%).

Eureka Therapeutics Inc., of Emeryville, California, is developing ET190L1-ARTEMIS. Co-investigators in this trial were from Eureka, Xi-An Jiaotong University in China, and Duke University School of Medicine in Durham, North Carolina.

A phase 1 trial of ET190L1-ARTEMIS in patients with relapsed and refractory non-Hodgkin lymphoma has been initiated at Duke University, and  investigators say another US phase 1 trial including relapsed and refractory pediatric acute lymphoblastic leukemia patients will begin later this year. 

Data in the abstract differ from that presented in the poster.

©ASCO/Scott Morgan 2018

CHICAGO—A novel CD19-targeted T-cell therapy induced complete metabolic responses (CMRs) and no cytokine release syndrome (CRS) in patients with B-cell lymphomas in a first-in-human clinical study.

All subjects achieving CMR at the 1-month safety and efficacy assessment continued to show CMR at 3 months, investigators reported at the 2018 ASCO Annual Meeting (abstract 3049*).

The therapy is built on a novel platform, ARTEMIS, designed to match the potency of chimeric antigen receptor (CAR) T-cell therapy but trigger less cytokine release when the target is engaged, investigators explained.

That platform is “potentially a major improvement” over existing CAR-T cell therapy, said Zhi Tao Ying, MD, of Peking University Cancer Hospital & Institute in Beijing, China, and coauthors in a poster presented at ASCO.

The treatment, called ET190L1-ARTEMIS, utilizes the T-cell receptor platform and a proprietary human anti-CD19 antibody to target CD19-positive malignancies.

The investigators reported on 21 adults with CD-19 positive relapsed and refractory B-cell lymphomas who had received a median of 4 lines of previous therapy.

Patients received autologous ET190L1-ARTEMIS T cells in 1 of 3 dosing cohorts: 3 patients at 1 x 10⁶/kg, 13 at 3 x 10⁶/kg, and 5 at 6 x 10⁶/kg.

Of 17 patients completing a first-month efficacy assessment, 11 (65%) responded, including 7 CMRs and 3 partial responses. One patient had stable disease.

Seven of the 11 responders completed a third-month efficacy assessment, as of this analysis. Of 5 patients with CMR at month 1, all 5 maintained CMR at month 3. Likewise, 1 patient in partial response and 1 with stable disease at month 1 had the same response status at month 3.

There were no cases of CRS or neurotoxicity in 17 patients who completed the 1-month safety and efficacy assessment reported at ASCO. Grade 3 or greater adverse events in those subjects included lymphopenia in 17 (100%) and neutropenia in 5 (29%).

Eureka Therapeutics Inc., of Emeryville, California, is developing ET190L1-ARTEMIS. Co-investigators in this trial were from Eureka, Xi-An Jiaotong University in China, and Duke University School of Medicine in Durham, North Carolina.

A phase 1 trial of ET190L1-ARTEMIS in patients with relapsed and refractory non-Hodgkin lymphoma has been initiated at Duke University, and  investigators say another US phase 1 trial including relapsed and refractory pediatric acute lymphoblastic leukemia patients will begin later this year. 

Data in the abstract differ from that presented in the poster.