Andrew D. Bowser

Ibrutinib and checkpoint inhibitors may improve the efficacy of chimeric antigen receptor (CAR) T-cell therapies, according to investigators in two separate studies.

Meanwhile, responses to tisagenlecleucel appear to be even more durable with longer follow-up, according to preliminary results from two more CAR T-cell therapy studies slated for presentation at the annual meeting of the American Society of Hematology.

A fifth study will show that bone marrow transplant may effectively consolidate remission after CAR T-cell therapy, according to Robert A. Brodsky, MD, ASH secretary, who highlighted the studies during a media briefing.

The ibrutinib study (abstract 299) shows that administering this BTK inhibitor starting 2 weeks prior to leukapheresis and continuing until 3 months after JCAR014 could improve responses and may decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Of 16 patients in an ibrutinib cohort and 18 patients in a no-ibrutinib cohort, the proportion of responders was 88% and 56%, respectively, according to preliminary data reported in the abstract. Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients in the no-ibrutinib cohort, and 0 of 17 patients in the ibrutinib cohort.

Those findings are “early and preliminary, but very exciting” for ibrutinib in combination with this CD-19 specific CAR T-cell therapy said Dr. Brodsky, director of the division of hematology at Johns Hopkins University in Baltimore.

Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia (ALL).

In data to date, 14 patients with early CAR T-cell loss, partial response, or no response to CAR T-cell therapy received a PD-1 inhibitor.

“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said. “Sure enough, they were able to see that in roughly half of the patients. So again, very small, preliminary data, but very exciting that it is safe to give checkpoint inhibitors with CAR T-cells and it may be efficacious at getting the immune response back.”

One of the two tisagenlecleucel updates (abstract 895) showed that in the ELIANA trial, which included pediatric and young adults patients with relapsed/refractory ALL, the probability of relapse-free survival at 18 months was 66%.

“These are some very fast-growing tumors and these are refractory resistant patients, so as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.

In the other tisagenlecleucel update (abstract 1684), investigators showed sustained disease control in Juliet, the global trial including adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with 40% of patients still in remission at 18 months, according to Dr. Brodsky.

One more report Dr. Brodsky highlighted (abstract 967) will look at long-term follow-up after administration of SCRI-CAR19v1, a CD19-specific CAR T-cell product. Preliminary data suggest a survival advantage when hematopoietic stem cell transplantation is done after CAR T-cell induced remission.

“This study is very small and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.

Ibrutinib and checkpoint inhibitors may improve the efficacy of chimeric antigen receptor (CAR) T-cell therapies, according to investigators in two separate studies.

Meanwhile, responses to tisagenlecleucel appear to be even more durable with longer follow-up, according to preliminary results from two more CAR T-cell therapy studies slated for presentation at the annual meeting of the American Society of Hematology.

A fifth study will show that bone marrow transplant may effectively consolidate remission after CAR T-cell therapy, according to Robert A. Brodsky, MD, ASH secretary, who highlighted the studies during a media briefing.

The ibrutinib study (abstract 299) shows that administering this BTK inhibitor starting 2 weeks prior to leukapheresis and continuing until 3 months after JCAR014 could improve responses and may decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Of 16 patients in an ibrutinib cohort and 18 patients in a no-ibrutinib cohort, the proportion of responders was 88% and 56%, respectively, according to preliminary data reported in the abstract. Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients in the no-ibrutinib cohort, and 0 of 17 patients in the ibrutinib cohort.

Those findings are “early and preliminary, but very exciting” for ibrutinib in combination with this CD-19 specific CAR T-cell therapy said Dr. Brodsky, director of the division of hematology at Johns Hopkins University in Baltimore.

Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia (ALL).

In data to date, 14 patients with early CAR T-cell loss, partial response, or no response to CAR T-cell therapy received a PD-1 inhibitor.

“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said. “Sure enough, they were able to see that in roughly half of the patients. So again, very small, preliminary data, but very exciting that it is safe to give checkpoint inhibitors with CAR T-cells and it may be efficacious at getting the immune response back.”

One of the two tisagenlecleucel updates (abstract 895) showed that in the ELIANA trial, which included pediatric and young adults patients with relapsed/refractory ALL, the probability of relapse-free survival at 18 months was 66%.

“These are some very fast-growing tumors and these are refractory resistant patients, so as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.

In the other tisagenlecleucel update (abstract 1684), investigators showed sustained disease control in Juliet, the global trial including adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with 40% of patients still in remission at 18 months, according to Dr. Brodsky.

One more report Dr. Brodsky highlighted (abstract 967) will look at long-term follow-up after administration of SCRI-CAR19v1, a CD19-specific CAR T-cell product. Preliminary data suggest a survival advantage when hematopoietic stem cell transplantation is done after CAR T-cell induced remission.

“This study is very small and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.

Ibrutinib and checkpoint inhibitors may improve the efficacy of chimeric antigen receptor (CAR) T-cell therapies, according to investigators in two separate studies.

Meanwhile, responses to tisagenlecleucel appear to be even more durable with longer follow-up, according to preliminary results from two more CAR T-cell therapy studies slated for presentation at the annual meeting of the American Society of Hematology.

A fifth study will show that bone marrow transplant may effectively consolidate remission after CAR T-cell therapy, according to Robert A. Brodsky, MD, ASH secretary, who highlighted the studies during a media briefing.

The ibrutinib study (abstract 299) shows that administering this BTK inhibitor starting 2 weeks prior to leukapheresis and continuing until 3 months after JCAR014 could improve responses and may decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Of 16 patients in an ibrutinib cohort and 18 patients in a no-ibrutinib cohort, the proportion of responders was 88% and 56%, respectively, according to preliminary data reported in the abstract. Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients in the no-ibrutinib cohort, and 0 of 17 patients in the ibrutinib cohort.

Those findings are “early and preliminary, but very exciting” for ibrutinib in combination with this CD-19 specific CAR T-cell therapy said Dr. Brodsky, director of the division of hematology at Johns Hopkins University in Baltimore.

Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia (ALL).

In data to date, 14 patients with early CAR T-cell loss, partial response, or no response to CAR T-cell therapy received a PD-1 inhibitor.

“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said. “Sure enough, they were able to see that in roughly half of the patients. So again, very small, preliminary data, but very exciting that it is safe to give checkpoint inhibitors with CAR T-cells and it may be efficacious at getting the immune response back.”

One of the two tisagenlecleucel updates (abstract 895) showed that in the ELIANA trial, which included pediatric and young adults patients with relapsed/refractory ALL, the probability of relapse-free survival at 18 months was 66%.

“These are some very fast-growing tumors and these are refractory resistant patients, so as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.

In the other tisagenlecleucel update (abstract 1684), investigators showed sustained disease control in Juliet, the global trial including adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with 40% of patients still in remission at 18 months, according to Dr. Brodsky.

One more report Dr. Brodsky highlighted (abstract 967) will look at long-term follow-up after administration of SCRI-CAR19v1, a CD19-specific CAR T-cell product. Preliminary data suggest a survival advantage when hematopoietic stem cell transplantation is done after CAR T-cell induced remission.

“This study is very small and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.

Sickle cell disease will take center stage at the annual meeting of the American Society of Hematology.

Top studies to be featured at ASH 2018 include the first in-human presentation of a new approach to gene therapy in sickle cell disease, long-term outcomes of haploidentical transplants, mortality rates in patients prescribed opioids, and aspects of care in lower-resource countries, according to Alexis A. Thompson, MD, the current ASH president.

“These are all quite different aspects of work being done,” said Dr. Thompson, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.

In the gene therapy study (abstract 1023), investigators will report initial results of genetic targeting of the fetal-to-adult globin switch in sickle cell patients. The clinical pilot study involves autologous gene therapy utilizing microRNA-adapted shRNAs (shRNA^miR) lentiviral vector targeting BCL11A, a repressor of gamma globin expression, according to the investigators.

“We’re looking forward to seeing this initial presentation on their findings with this first administration to humans,” Dr. Thompson said in a media briefing.

In another study (abstract 162), investigators will report long-term results of familial haploidentical stem cell transplantation (HISCT) showing that high-risk sickle cell patients had significantly improved health-related quality of life in long-term follow-up.

Two years after myeloablative conditioning and familial HISCT using CD34 enrichment and mononuclear cell (CD3) addback, recipients had significant improvements in emotional and physical health-related quality of life, among other outcomes of interest, including neurocognitive outcomes.

Another study, which is interesting in the context of the national opioid epidemic, Dr. Thompson said, will show that opioid use was not associated with in-hospital mortality in patients with sickle cell disease (abstract 315).

Looking at data from the National Inpatient Sample, there was no increase in in-hospital mortality in sickle cell patients versus the general population since the onset of the epidemic, which has been documented since 2000, according to the investigators.

“It should alleviate many concerns about patients with sickle cell who, for legitimate reasons, may require high doses of opioids,” Dr. Thompson said. “While I think we’re being very mindful about opioid use in this patient population, they certainly do need these high doses, but there does not seem to be an extraordinary risk of death associated with their use.”

One final study worth watching, according to Dr. Thompson, is REACH, a prospective, multinational trial of hydroxyurea for sickle cell anemia in sub-Saharan Africa (abstract 3).

The study, which included 635 children, provides the first prospective data showing the feasibility, safety, and benefits of hydroxyurea treatment for children with sickle cell anemia in sub-Saharan Africa, according to the investigators.

The findings are “quite encouraging,” said Dr. Thompson, adding that the results looked “very similar” to the United States experience and demonstrated effective clinical trial design and execution in a lower-resource country.

Sickle cell disease will take center stage at the annual meeting of the American Society of Hematology.

Top studies to be featured at ASH 2018 include the first in-human presentation of a new approach to gene therapy in sickle cell disease, long-term outcomes of haploidentical transplants, mortality rates in patients prescribed opioids, and aspects of care in lower-resource countries, according to Alexis A. Thompson, MD, the current ASH president.

“These are all quite different aspects of work being done,” said Dr. Thompson, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.

In the gene therapy study (abstract 1023), investigators will report initial results of genetic targeting of the fetal-to-adult globin switch in sickle cell patients. The clinical pilot study involves autologous gene therapy utilizing microRNA-adapted shRNAs (shRNA^miR) lentiviral vector targeting BCL11A, a repressor of gamma globin expression, according to the investigators.

“We’re looking forward to seeing this initial presentation on their findings with this first administration to humans,” Dr. Thompson said in a media briefing.

In another study (abstract 162), investigators will report long-term results of familial haploidentical stem cell transplantation (HISCT) showing that high-risk sickle cell patients had significantly improved health-related quality of life in long-term follow-up.

Two years after myeloablative conditioning and familial HISCT using CD34 enrichment and mononuclear cell (CD3) addback, recipients had significant improvements in emotional and physical health-related quality of life, among other outcomes of interest, including neurocognitive outcomes.

Another study, which is interesting in the context of the national opioid epidemic, Dr. Thompson said, will show that opioid use was not associated with in-hospital mortality in patients with sickle cell disease (abstract 315).

Looking at data from the National Inpatient Sample, there was no increase in in-hospital mortality in sickle cell patients versus the general population since the onset of the epidemic, which has been documented since 2000, according to the investigators.

“It should alleviate many concerns about patients with sickle cell who, for legitimate reasons, may require high doses of opioids,” Dr. Thompson said. “While I think we’re being very mindful about opioid use in this patient population, they certainly do need these high doses, but there does not seem to be an extraordinary risk of death associated with their use.”

One final study worth watching, according to Dr. Thompson, is REACH, a prospective, multinational trial of hydroxyurea for sickle cell anemia in sub-Saharan Africa (abstract 3).

The study, which included 635 children, provides the first prospective data showing the feasibility, safety, and benefits of hydroxyurea treatment for children with sickle cell anemia in sub-Saharan Africa, according to the investigators.

The findings are “quite encouraging,” said Dr. Thompson, adding that the results looked “very similar” to the United States experience and demonstrated effective clinical trial design and execution in a lower-resource country.

Sickle cell disease will take center stage at the annual meeting of the American Society of Hematology.

Top studies to be featured at ASH 2018 include the first in-human presentation of a new approach to gene therapy in sickle cell disease, long-term outcomes of haploidentical transplants, mortality rates in patients prescribed opioids, and aspects of care in lower-resource countries, according to Alexis A. Thompson, MD, the current ASH president.

“These are all quite different aspects of work being done,” said Dr. Thompson, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.

In the gene therapy study (abstract 1023), investigators will report initial results of genetic targeting of the fetal-to-adult globin switch in sickle cell patients. The clinical pilot study involves autologous gene therapy utilizing microRNA-adapted shRNAs (shRNA^miR) lentiviral vector targeting BCL11A, a repressor of gamma globin expression, according to the investigators.

“We’re looking forward to seeing this initial presentation on their findings with this first administration to humans,” Dr. Thompson said in a media briefing.

In another study (abstract 162), investigators will report long-term results of familial haploidentical stem cell transplantation (HISCT) showing that high-risk sickle cell patients had significantly improved health-related quality of life in long-term follow-up.

Two years after myeloablative conditioning and familial HISCT using CD34 enrichment and mononuclear cell (CD3) addback, recipients had significant improvements in emotional and physical health-related quality of life, among other outcomes of interest, including neurocognitive outcomes.

Another study, which is interesting in the context of the national opioid epidemic, Dr. Thompson said, will show that opioid use was not associated with in-hospital mortality in patients with sickle cell disease (abstract 315).

Looking at data from the National Inpatient Sample, there was no increase in in-hospital mortality in sickle cell patients versus the general population since the onset of the epidemic, which has been documented since 2000, according to the investigators.

“It should alleviate many concerns about patients with sickle cell who, for legitimate reasons, may require high doses of opioids,” Dr. Thompson said. “While I think we’re being very mindful about opioid use in this patient population, they certainly do need these high doses, but there does not seem to be an extraordinary risk of death associated with their use.”

One final study worth watching, according to Dr. Thompson, is REACH, a prospective, multinational trial of hydroxyurea for sickle cell anemia in sub-Saharan Africa (abstract 3).

The study, which included 635 children, provides the first prospective data showing the feasibility, safety, and benefits of hydroxyurea treatment for children with sickle cell anemia in sub-Saharan Africa, according to the investigators.

The findings are “quite encouraging,” said Dr. Thompson, adding that the results looked “very similar” to the United States experience and demonstrated effective clinical trial design and execution in a lower-resource country.

follicular lymphoma

Phase 3 results suggest the biosimilar product CT-P10 is equivalent to rituximab in patients with low-tumor-burden follicular lymphoma (FL).

Overall response rates were similar—both exceeding 80%—in patients who received CT-P10 and those who received rituximab.

In addition, adverse event (AE) profiles were comparable between the treatment arms.

Larry W. Kwak, MD, PhD, of City of Hope in Duarte, California, and his colleagues reported these results in The Lancet Haematology.

CT-P10 was approved by the European Commission in 2017 and was recommended for approval by the U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee last month.

The phase 3 trial of CT-P10 included 258 patients with stage II-IV low-tumor-burden FL. They were randomized to receive CT-P10 (n=130) or rituximab (n=128).

Patients received intravenous CT-P10 or rituximab weekly for 4 weeks as induction therapy. Patients experiencing disease control went on to a maintenance phase with their assigned treatment, given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.

Efficacy

The overall response rate at 7 months was 83% in patients randomized to CT-P10 and 81% in those randomized to rituximab.

The complete response rates were 28% and 34%, respectively. The unconfirmed complete response rates were 5% and 2%, respectively. And the partial response rates were 51% and 46%, respectively.

The two treatments were deemed therapeutically equivalent, as the two-sided 90% confidence intervals for the difference in proportion of responders between CT-P10 and rituximab were within the prespecified equivalence margin of 17%.

Safety

Treatment-emergent AEs occurred in 71% of patients in the CT-P10 arm and 67% of those in the rituximab arm.

The most common treatment-emergent AEs (in the CT-P10 and rituximab arms, respectively) were:

• Infusion-related reactions (31% and 29%)
• Infections (27% and 21%)
• Worsening neutropenia (22% for both)
• Upper respiratory tract infection (12% and 11%)
• Worsening anemia (10% and 14%)
• Worsening thrombocytopenia (8% and 7%)
• Fatigue (7% and 9%)
• Diarrhea (5% for both)
• Nausea (5% for both)
• Urinary tract infection (4% and 5%)
• Headache (3% and 5%).

Serious AEs were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.

Two serious AEs—myocardial infarction and constipation—in the CT-P10 arm were considered related to treatment. None of the serious AEs in the rituximab arm were considered treatment-related.

Two patients in the CT-P10 arm discontinued treatment due to AEs—one due to myocardial infarction and one due to dermatitis. There were no AE-related discontinuations in the rituximab arm.

There were two deaths in the CT-P10 arm as of the cutoff date (January 4, 2018). One was due to myocardial infarction, and one was due to respiratory failure. The myocardial infarction was considered possibly related to treatment.

This trial was sponsored by Celltrion, the company developing CT-P10. Three study authors are employees of the company.

Dr. Kwak and several other authors not employed by Celltrion reported disclosures related to the company. Authors also reported relationships with Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.

follicular lymphoma

Phase 3 results suggest the biosimilar product CT-P10 is equivalent to rituximab in patients with low-tumor-burden follicular lymphoma (FL).

Overall response rates were similar—both exceeding 80%—in patients who received CT-P10 and those who received rituximab.

In addition, adverse event (AE) profiles were comparable between the treatment arms.

Larry W. Kwak, MD, PhD, of City of Hope in Duarte, California, and his colleagues reported these results in The Lancet Haematology.

CT-P10 was approved by the European Commission in 2017 and was recommended for approval by the U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee last month.

The phase 3 trial of CT-P10 included 258 patients with stage II-IV low-tumor-burden FL. They were randomized to receive CT-P10 (n=130) or rituximab (n=128).

Patients received intravenous CT-P10 or rituximab weekly for 4 weeks as induction therapy. Patients experiencing disease control went on to a maintenance phase with their assigned treatment, given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.

Efficacy

The overall response rate at 7 months was 83% in patients randomized to CT-P10 and 81% in those randomized to rituximab.

The complete response rates were 28% and 34%, respectively. The unconfirmed complete response rates were 5% and 2%, respectively. And the partial response rates were 51% and 46%, respectively.

The two treatments were deemed therapeutically equivalent, as the two-sided 90% confidence intervals for the difference in proportion of responders between CT-P10 and rituximab were within the prespecified equivalence margin of 17%.

Safety

Treatment-emergent AEs occurred in 71% of patients in the CT-P10 arm and 67% of those in the rituximab arm.

The most common treatment-emergent AEs (in the CT-P10 and rituximab arms, respectively) were:

• Infusion-related reactions (31% and 29%)
• Infections (27% and 21%)
• Worsening neutropenia (22% for both)
• Upper respiratory tract infection (12% and 11%)
• Worsening anemia (10% and 14%)
• Worsening thrombocytopenia (8% and 7%)
• Fatigue (7% and 9%)
• Diarrhea (5% for both)
• Nausea (5% for both)
• Urinary tract infection (4% and 5%)
• Headache (3% and 5%).

Serious AEs were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.

Two serious AEs—myocardial infarction and constipation—in the CT-P10 arm were considered related to treatment. None of the serious AEs in the rituximab arm were considered treatment-related.

Two patients in the CT-P10 arm discontinued treatment due to AEs—one due to myocardial infarction and one due to dermatitis. There were no AE-related discontinuations in the rituximab arm.

There were two deaths in the CT-P10 arm as of the cutoff date (January 4, 2018). One was due to myocardial infarction, and one was due to respiratory failure. The myocardial infarction was considered possibly related to treatment.

This trial was sponsored by Celltrion, the company developing CT-P10. Three study authors are employees of the company.

Dr. Kwak and several other authors not employed by Celltrion reported disclosures related to the company. Authors also reported relationships with Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.

follicular lymphoma

Phase 3 results suggest the biosimilar product CT-P10 is equivalent to rituximab in patients with low-tumor-burden follicular lymphoma (FL).

Overall response rates were similar—both exceeding 80%—in patients who received CT-P10 and those who received rituximab.

In addition, adverse event (AE) profiles were comparable between the treatment arms.

Larry W. Kwak, MD, PhD, of City of Hope in Duarte, California, and his colleagues reported these results in The Lancet Haematology.

CT-P10 was approved by the European Commission in 2017 and was recommended for approval by the U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee last month.

The phase 3 trial of CT-P10 included 258 patients with stage II-IV low-tumor-burden FL. They were randomized to receive CT-P10 (n=130) or rituximab (n=128).

Patients received intravenous CT-P10 or rituximab weekly for 4 weeks as induction therapy. Patients experiencing disease control went on to a maintenance phase with their assigned treatment, given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.

Efficacy

The overall response rate at 7 months was 83% in patients randomized to CT-P10 and 81% in those randomized to rituximab.

The complete response rates were 28% and 34%, respectively. The unconfirmed complete response rates were 5% and 2%, respectively. And the partial response rates were 51% and 46%, respectively.

The two treatments were deemed therapeutically equivalent, as the two-sided 90% confidence intervals for the difference in proportion of responders between CT-P10 and rituximab were within the prespecified equivalence margin of 17%.

Safety

Treatment-emergent AEs occurred in 71% of patients in the CT-P10 arm and 67% of those in the rituximab arm.

The most common treatment-emergent AEs (in the CT-P10 and rituximab arms, respectively) were:

• Infusion-related reactions (31% and 29%)
• Infections (27% and 21%)
• Worsening neutropenia (22% for both)
• Upper respiratory tract infection (12% and 11%)
• Worsening anemia (10% and 14%)
• Worsening thrombocytopenia (8% and 7%)
• Fatigue (7% and 9%)
• Diarrhea (5% for both)
• Nausea (5% for both)
• Urinary tract infection (4% and 5%)
• Headache (3% and 5%).

Serious AEs were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.

Two serious AEs—myocardial infarction and constipation—in the CT-P10 arm were considered related to treatment. None of the serious AEs in the rituximab arm were considered treatment-related.

Two patients in the CT-P10 arm discontinued treatment due to AEs—one due to myocardial infarction and one due to dermatitis. There were no AE-related discontinuations in the rituximab arm.

There were two deaths in the CT-P10 arm as of the cutoff date (January 4, 2018). One was due to myocardial infarction, and one was due to respiratory failure. The myocardial infarction was considered possibly related to treatment.

This trial was sponsored by Celltrion, the company developing CT-P10. Three study authors are employees of the company.

Dr. Kwak and several other authors not employed by Celltrion reported disclosures related to the company. Authors also reported relationships with Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.

SAN DIEGO – Oncologists spent on average 3 minutes less with minority patients than with nonminority patients at a critical transition visit to talk about a scan result related to advanced cancer, a study investigator reported.

The gap was most pronounced for visits where a negative scan result was communicated, said investigator Cardinale B. Smith, MD, PhD, director of Quality for Cancer Services, Mount Sinai Health System, New York.

Future work is needed to look at the content of these conversations to determine to what extent physician- or patient-specific factors may have contributed to this difference, according to Dr. Smith.

“This will be critically important to ensure that we provide high-quality care to our minority patients,” Dr. Smith said at the 2018 Palliative and Supportive Care in Oncology Symposium.

The study included 22 oncologists from four hospitals randomized to either a usual-care group or an intervention group that included several interventions designed to improve communication techniques related to goals-of-care conversations

Sixty-nine percent of the physicians were white, while 23% were Asian, 8% were Hispanic, and 5% were black, Dr. Smith said.

Postimaging encounters were audio recorded for 142 patients, more than half of whom were minorities; 32% were black and 26% were Hispanic, according to the investigator, while 38% were white and 4% were Asian.

Overall, time spent with minorities at the scan results visit was 11.5 minutes versus 16.5 minutes for nonminorities (P = .0007), Dr. Smith reported.

When the scan was positive, there was actually no significant difference in time spent on minority versus nonminority visits, (16 versus 18 minutes; P = .59), a finding that Dr. Smith said was “encouraging” in an interview. However, there was a marked difference in length of time spent on minority versus nonminority visits when the scans showed no progression (10 versus 15 minutes; P = .0003).

“There’s something about regular, routine visits, which are still just as important as [positive] scan visits, in which there is a difference in the time spent,” Dr. Smith said in an interview. “We’re really interested in doing a more in-depth analysis of those conversations to see what’s contributing to those differences.”

After adjusting for patient insurance, education, income progression, status, and hospital, investigators found that oncologists spent 13.5 minutes (interquartile range, 12-16) with minority patients versus 16.5 minutes (IQR, 16-19) for nonminority patients (P less than .0001).

In terms of the communications intervention, investigators found no difference in time spent with minorities versus nonminorities among the intervention or control physicians. However, the intervention was aimed at improving the rate of goals of care conversations rather than improving communication based on race or ethnicity, Dr. Smith said.

By contrast, the finding of decreased time spent in communication encounters with minority patients merits further study to see how much of the disparity is mediated by differences in patients versus oncologists, she added.

In literature on communication disparities in other care settings outside of oncology, care conversations with minorities tend to be more closed ended, as opposed to open ended – so instead of asking if a patient is doing well, a physician might start out with a declarative statement that the patient’s findings are positive, she said.

On the other hand, some literature suggests that minority patients may not question the physician as much as nonminorities, or may not spend as much time asking directed questions during the visit. “That may also contribute to decreased time spent during those encounters,” Dr. Smith added.

The research was supported by the Patient Centered Outcomes Research Institute. Dr. Smith reported honoraria and a consulting or advisory role with Teva.

SOURCE: Smith CB et al. PallOnc 2018, Abstract 19.

SAN DIEGO – Oncologists spent on average 3 minutes less with minority patients than with nonminority patients at a critical transition visit to talk about a scan result related to advanced cancer, a study investigator reported.

The gap was most pronounced for visits where a negative scan result was communicated, said investigator Cardinale B. Smith, MD, PhD, director of Quality for Cancer Services, Mount Sinai Health System, New York.

Future work is needed to look at the content of these conversations to determine to what extent physician- or patient-specific factors may have contributed to this difference, according to Dr. Smith.

“This will be critically important to ensure that we provide high-quality care to our minority patients,” Dr. Smith said at the 2018 Palliative and Supportive Care in Oncology Symposium.

The study included 22 oncologists from four hospitals randomized to either a usual-care group or an intervention group that included several interventions designed to improve communication techniques related to goals-of-care conversations

Sixty-nine percent of the physicians were white, while 23% were Asian, 8% were Hispanic, and 5% were black, Dr. Smith said.

Postimaging encounters were audio recorded for 142 patients, more than half of whom were minorities; 32% were black and 26% were Hispanic, according to the investigator, while 38% were white and 4% were Asian.

Overall, time spent with minorities at the scan results visit was 11.5 minutes versus 16.5 minutes for nonminorities (P = .0007), Dr. Smith reported.

When the scan was positive, there was actually no significant difference in time spent on minority versus nonminority visits, (16 versus 18 minutes; P = .59), a finding that Dr. Smith said was “encouraging” in an interview. However, there was a marked difference in length of time spent on minority versus nonminority visits when the scans showed no progression (10 versus 15 minutes; P = .0003).

“There’s something about regular, routine visits, which are still just as important as [positive] scan visits, in which there is a difference in the time spent,” Dr. Smith said in an interview. “We’re really interested in doing a more in-depth analysis of those conversations to see what’s contributing to those differences.”

After adjusting for patient insurance, education, income progression, status, and hospital, investigators found that oncologists spent 13.5 minutes (interquartile range, 12-16) with minority patients versus 16.5 minutes (IQR, 16-19) for nonminority patients (P less than .0001).

In terms of the communications intervention, investigators found no difference in time spent with minorities versus nonminorities among the intervention or control physicians. However, the intervention was aimed at improving the rate of goals of care conversations rather than improving communication based on race or ethnicity, Dr. Smith said.

By contrast, the finding of decreased time spent in communication encounters with minority patients merits further study to see how much of the disparity is mediated by differences in patients versus oncologists, she added.

In literature on communication disparities in other care settings outside of oncology, care conversations with minorities tend to be more closed ended, as opposed to open ended – so instead of asking if a patient is doing well, a physician might start out with a declarative statement that the patient’s findings are positive, she said.

On the other hand, some literature suggests that minority patients may not question the physician as much as nonminorities, or may not spend as much time asking directed questions during the visit. “That may also contribute to decreased time spent during those encounters,” Dr. Smith added.

The research was supported by the Patient Centered Outcomes Research Institute. Dr. Smith reported honoraria and a consulting or advisory role with Teva.

SOURCE: Smith CB et al. PallOnc 2018, Abstract 19.

SAN DIEGO – Oncologists spent on average 3 minutes less with minority patients than with nonminority patients at a critical transition visit to talk about a scan result related to advanced cancer, a study investigator reported.

The gap was most pronounced for visits where a negative scan result was communicated, said investigator Cardinale B. Smith, MD, PhD, director of Quality for Cancer Services, Mount Sinai Health System, New York.

Future work is needed to look at the content of these conversations to determine to what extent physician- or patient-specific factors may have contributed to this difference, according to Dr. Smith.

“This will be critically important to ensure that we provide high-quality care to our minority patients,” Dr. Smith said at the 2018 Palliative and Supportive Care in Oncology Symposium.

The study included 22 oncologists from four hospitals randomized to either a usual-care group or an intervention group that included several interventions designed to improve communication techniques related to goals-of-care conversations

Sixty-nine percent of the physicians were white, while 23% were Asian, 8% were Hispanic, and 5% were black, Dr. Smith said.

Postimaging encounters were audio recorded for 142 patients, more than half of whom were minorities; 32% were black and 26% were Hispanic, according to the investigator, while 38% were white and 4% were Asian.

Overall, time spent with minorities at the scan results visit was 11.5 minutes versus 16.5 minutes for nonminorities (P = .0007), Dr. Smith reported.

When the scan was positive, there was actually no significant difference in time spent on minority versus nonminority visits, (16 versus 18 minutes; P = .59), a finding that Dr. Smith said was “encouraging” in an interview. However, there was a marked difference in length of time spent on minority versus nonminority visits when the scans showed no progression (10 versus 15 minutes; P = .0003).

“There’s something about regular, routine visits, which are still just as important as [positive] scan visits, in which there is a difference in the time spent,” Dr. Smith said in an interview. “We’re really interested in doing a more in-depth analysis of those conversations to see what’s contributing to those differences.”

After adjusting for patient insurance, education, income progression, status, and hospital, investigators found that oncologists spent 13.5 minutes (interquartile range, 12-16) with minority patients versus 16.5 minutes (IQR, 16-19) for nonminority patients (P less than .0001).

In terms of the communications intervention, investigators found no difference in time spent with minorities versus nonminorities among the intervention or control physicians. However, the intervention was aimed at improving the rate of goals of care conversations rather than improving communication based on race or ethnicity, Dr. Smith said.

By contrast, the finding of decreased time spent in communication encounters with minority patients merits further study to see how much of the disparity is mediated by differences in patients versus oncologists, she added.

In literature on communication disparities in other care settings outside of oncology, care conversations with minorities tend to be more closed ended, as opposed to open ended – so instead of asking if a patient is doing well, a physician might start out with a declarative statement that the patient’s findings are positive, she said.

On the other hand, some literature suggests that minority patients may not question the physician as much as nonminorities, or may not spend as much time asking directed questions during the visit. “That may also contribute to decreased time spent during those encounters,” Dr. Smith added.

The research was supported by the Patient Centered Outcomes Research Institute. Dr. Smith reported honoraria and a consulting or advisory role with Teva.

SOURCE: Smith CB et al. PallOnc 2018, Abstract 19.

Adults with Down syndrome and dementia had a risk of death five times higher than those without dementia, according to results of a recent prospective study.

More than 70% of the individuals with Down syndrome who died over the course of follow-up had a clinical diagnosis of dementia in this longitudinal study of community dwelling participants, many of whom had factors associated with dementia such as the apolipoprotein E (APOE) genotype.

The findings of this study support an “urgent need” for clinical trials of treatment that might delay or prevent dementia in individuals with Down syndrome, said the investigators, led by Rosalyn Hithersay, MSc, of the department of forensic and neurodevelopmental sciences in the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London (United Kingdom).

“We hope that our findings can improve clinical care by identifying factors associated with increased risk for dementia and mortality risk in this population, suggesting the potentially beneficial effects of existing medication options and helping clinicians provide prognostic information for their patients,” the authors wrote in JAMA Neurology.

The risk of dementia in individuals with Down syndrome has grown to “exceptional” levels, alongside a dramatic increase in life expectancy in these patients, from just 10 years of age some 50 years ago, to nearly 64 years today, investigators said.

Although other research has confirmed that dementia is frequently recorded as a contributory factor in Down syndrome deaths in recent years, this latest study provides crude mortality rates and exploratory analyses of factors that may modify mortality and dementia risk, according to the researchers.

Their study included 211 individuals with Down syndrome who were aged at least 36 years at study entry and followed for a total of 503.92 person-years, the investigators reported.

A total of 27 individuals died during follow-up, with a median age at death of 57 years; of those individuals, 19 (70.37%) had a clinical diagnosis of dementia, according to the report.

The crude mortality rate for individuals with dementia was nearly 1,192 deaths per 10,000 person-years, compared with 232 deaths per 10,000 person-years for those with no dementia diagnosis, the investigators found.

Further analysis showed that factors independently associated with mortality in those with a dementia diagnosis included APOE genotype, dementia medication status, early-onset epilepsy, and presence of two or more comorbid conditions.

In a combined model, APOE genotype was significantly associated with mortality risk, they added.

Among the eight individuals with Down syndrome who died without a dementia diagnosis, one reportedly had early signs of cognitive decline, and two had late-onset epilepsy.

Late-onset epilepsy, identified in seven individuals (4.8%) with no dementia diagnosis in this study, was the only factor associated with mortality in individuals without dementia, conferring a 10-fold increase in risk of that outcome, according to the analysis.

“This raises the question of whether seizures can begin in the absence of other features of dementia in individuals with Down syndrome or whether these seven individuals had significant AD pathology and neurological symptoms but had yet to receive a formal dementia diagnosis,” the researchers wrote in a discussion of results.

The authors reported no conflict of interest disclosures related to the study. Their research was supported by UK National Institute for Health Research networks and participating National Health Services trusts, as well as a Wellcome Trust Strategic Award to the London Down Syndrome Consortium.

SOURCE: Hithersay R et al. JAMA Neurol. 2018 Nov 19. doi: 10.1001/jamaneurol.2018.3616

Adults with Down syndrome and dementia had a risk of death five times higher than those without dementia, according to results of a recent prospective study.

More than 70% of the individuals with Down syndrome who died over the course of follow-up had a clinical diagnosis of dementia in this longitudinal study of community dwelling participants, many of whom had factors associated with dementia such as the apolipoprotein E (APOE) genotype.

The findings of this study support an “urgent need” for clinical trials of treatment that might delay or prevent dementia in individuals with Down syndrome, said the investigators, led by Rosalyn Hithersay, MSc, of the department of forensic and neurodevelopmental sciences in the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London (United Kingdom).

“We hope that our findings can improve clinical care by identifying factors associated with increased risk for dementia and mortality risk in this population, suggesting the potentially beneficial effects of existing medication options and helping clinicians provide prognostic information for their patients,” the authors wrote in JAMA Neurology.

The risk of dementia in individuals with Down syndrome has grown to “exceptional” levels, alongside a dramatic increase in life expectancy in these patients, from just 10 years of age some 50 years ago, to nearly 64 years today, investigators said.

Although other research has confirmed that dementia is frequently recorded as a contributory factor in Down syndrome deaths in recent years, this latest study provides crude mortality rates and exploratory analyses of factors that may modify mortality and dementia risk, according to the researchers.

Their study included 211 individuals with Down syndrome who were aged at least 36 years at study entry and followed for a total of 503.92 person-years, the investigators reported.

A total of 27 individuals died during follow-up, with a median age at death of 57 years; of those individuals, 19 (70.37%) had a clinical diagnosis of dementia, according to the report.

The crude mortality rate for individuals with dementia was nearly 1,192 deaths per 10,000 person-years, compared with 232 deaths per 10,000 person-years for those with no dementia diagnosis, the investigators found.

Further analysis showed that factors independently associated with mortality in those with a dementia diagnosis included APOE genotype, dementia medication status, early-onset epilepsy, and presence of two or more comorbid conditions.

In a combined model, APOE genotype was significantly associated with mortality risk, they added.

Among the eight individuals with Down syndrome who died without a dementia diagnosis, one reportedly had early signs of cognitive decline, and two had late-onset epilepsy.

Late-onset epilepsy, identified in seven individuals (4.8%) with no dementia diagnosis in this study, was the only factor associated with mortality in individuals without dementia, conferring a 10-fold increase in risk of that outcome, according to the analysis.

“This raises the question of whether seizures can begin in the absence of other features of dementia in individuals with Down syndrome or whether these seven individuals had significant AD pathology and neurological symptoms but had yet to receive a formal dementia diagnosis,” the researchers wrote in a discussion of results.

The authors reported no conflict of interest disclosures related to the study. Their research was supported by UK National Institute for Health Research networks and participating National Health Services trusts, as well as a Wellcome Trust Strategic Award to the London Down Syndrome Consortium.

SOURCE: Hithersay R et al. JAMA Neurol. 2018 Nov 19. doi: 10.1001/jamaneurol.2018.3616

Adults with Down syndrome and dementia had a risk of death five times higher than those without dementia, according to results of a recent prospective study.

More than 70% of the individuals with Down syndrome who died over the course of follow-up had a clinical diagnosis of dementia in this longitudinal study of community dwelling participants, many of whom had factors associated with dementia such as the apolipoprotein E (APOE) genotype.

The findings of this study support an “urgent need” for clinical trials of treatment that might delay or prevent dementia in individuals with Down syndrome, said the investigators, led by Rosalyn Hithersay, MSc, of the department of forensic and neurodevelopmental sciences in the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London (United Kingdom).

“We hope that our findings can improve clinical care by identifying factors associated with increased risk for dementia and mortality risk in this population, suggesting the potentially beneficial effects of existing medication options and helping clinicians provide prognostic information for their patients,” the authors wrote in JAMA Neurology.

The risk of dementia in individuals with Down syndrome has grown to “exceptional” levels, alongside a dramatic increase in life expectancy in these patients, from just 10 years of age some 50 years ago, to nearly 64 years today, investigators said.

Although other research has confirmed that dementia is frequently recorded as a contributory factor in Down syndrome deaths in recent years, this latest study provides crude mortality rates and exploratory analyses of factors that may modify mortality and dementia risk, according to the researchers.

Their study included 211 individuals with Down syndrome who were aged at least 36 years at study entry and followed for a total of 503.92 person-years, the investigators reported.

A total of 27 individuals died during follow-up, with a median age at death of 57 years; of those individuals, 19 (70.37%) had a clinical diagnosis of dementia, according to the report.

The crude mortality rate for individuals with dementia was nearly 1,192 deaths per 10,000 person-years, compared with 232 deaths per 10,000 person-years for those with no dementia diagnosis, the investigators found.

Further analysis showed that factors independently associated with mortality in those with a dementia diagnosis included APOE genotype, dementia medication status, early-onset epilepsy, and presence of two or more comorbid conditions.

In a combined model, APOE genotype was significantly associated with mortality risk, they added.

Among the eight individuals with Down syndrome who died without a dementia diagnosis, one reportedly had early signs of cognitive decline, and two had late-onset epilepsy.

Late-onset epilepsy, identified in seven individuals (4.8%) with no dementia diagnosis in this study, was the only factor associated with mortality in individuals without dementia, conferring a 10-fold increase in risk of that outcome, according to the analysis.

“This raises the question of whether seizures can begin in the absence of other features of dementia in individuals with Down syndrome or whether these seven individuals had significant AD pathology and neurological symptoms but had yet to receive a formal dementia diagnosis,” the researchers wrote in a discussion of results.

The authors reported no conflict of interest disclosures related to the study. Their research was supported by UK National Institute for Health Research networks and participating National Health Services trusts, as well as a Wellcome Trust Strategic Award to the London Down Syndrome Consortium.

SOURCE: Hithersay R et al. JAMA Neurol. 2018 Nov 19. doi: 10.1001/jamaneurol.2018.3616

Frail older patients with acute myocardial infarction (AMI) may be at increased bleeding risk if managed with an invasive strategy, results of a large U.S. registry study suggest.

Ingram Pub.l

The increased bleeding risk was seen among frail older AMI patients who underwent cardiac catheterization, but it was not seen in those treated with more conservative medical management, according to study results.

That finding highlights the conundrum with invasive management strategies for frail patients with AMI, wrote John A. Dodson, MD, MPH, of New York University and study coinvestigators.

“Awareness of vulnerability and greater utilization of evidence-based strategies to reduce bleeding, including radial access and properly dose-adjusted anticoagulant therapies, may mitigate some bleeding events,” they wrote in JACC: Cardiovascular Interventions.

Results of this study, the first large U.S. registry analysis evaluating in-hospital bleeding risk in frail older adults with AMI, confirm findings from several previous small cohort studies linking frailty in AMI patients to in-hospital bleeding, investigators reported.

The analysis included a total of 129,330 AMI patients in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) registry who were aged at least 65 years in 2015 or 2016.

About one in six of these older patients were frail, as defined by a composite score based on impaired walking, cognition, and activities of daily living, investigators reported.

The bleeding rate was significantly higher among frail patients undergoing cardiac catheterization, at 9.4% for patients rated as having vulnerable/mild frailty and 9.9% for patients with moderate to severe frailty (P less than.001), compared with fit/well patients, whose rate was 6.5%, investigators wrote. By contrast, there was no significant difference in bleeding rates for frail versus nonfrail patients managed conservatively, they said.

After adjusting for bleeding risk factors, frailty was independently associated with increased risk of bleeding, compared with fit/well status, with odds ratios of 1.33 for vulnerable/mild frailty and 1.40 for moderate to severe frailty. Again, no association was found between frailty and bleeding risk in patients managed conservatively, according to investigators.

Frail patients in the ACTION registry were more often older and female and less likely to undergo cardiac catheterization when compared with fit or well patients, they added in the report.

Like the small cohort studies that preceded it, this large U.S. registry study shows that frailty is an “important additional risk factor” among older adults with AMI who are managed with an invasive strategy, investigators said.

“When applicable, estimation of bleeding risk in frail patients before invasive care may facilitate clinical decision making and the informed consent process,” they wrote.

The ACTION registry, an ongoing quality improvement initiative sponsored by the American College of Cardiology and the American Heart Association, started collecting frailty characteristics among hospitalized AMI patients in 2015, investigators noted.

Dr. Dodson reported support from the National Institutes of Health/National Institute on Aging and from the American Heart Association. Study coauthors provided disclosures related to Bayer, Janssen, Abbott Vascular, Jarvik Heart, LifeCuff Technologies, and Ancora Heart. JACC Cardiovasc Interv. 2018 Nov 26;11:2287-96

SOURCE: Dodson JA et al. JACC Cardiovasc Intv. 2018;11:2287-96.

Frail older patients with acute myocardial infarction (AMI) may be at increased bleeding risk if managed with an invasive strategy, results of a large U.S. registry study suggest.

Ingram Pub.l

The increased bleeding risk was seen among frail older AMI patients who underwent cardiac catheterization, but it was not seen in those treated with more conservative medical management, according to study results.

That finding highlights the conundrum with invasive management strategies for frail patients with AMI, wrote John A. Dodson, MD, MPH, of New York University and study coinvestigators.

“Awareness of vulnerability and greater utilization of evidence-based strategies to reduce bleeding, including radial access and properly dose-adjusted anticoagulant therapies, may mitigate some bleeding events,” they wrote in JACC: Cardiovascular Interventions.

Results of this study, the first large U.S. registry analysis evaluating in-hospital bleeding risk in frail older adults with AMI, confirm findings from several previous small cohort studies linking frailty in AMI patients to in-hospital bleeding, investigators reported.

The analysis included a total of 129,330 AMI patients in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) registry who were aged at least 65 years in 2015 or 2016.

About one in six of these older patients were frail, as defined by a composite score based on impaired walking, cognition, and activities of daily living, investigators reported.

The bleeding rate was significantly higher among frail patients undergoing cardiac catheterization, at 9.4% for patients rated as having vulnerable/mild frailty and 9.9% for patients with moderate to severe frailty (P less than.001), compared with fit/well patients, whose rate was 6.5%, investigators wrote. By contrast, there was no significant difference in bleeding rates for frail versus nonfrail patients managed conservatively, they said.

After adjusting for bleeding risk factors, frailty was independently associated with increased risk of bleeding, compared with fit/well status, with odds ratios of 1.33 for vulnerable/mild frailty and 1.40 for moderate to severe frailty. Again, no association was found between frailty and bleeding risk in patients managed conservatively, according to investigators.

Frail patients in the ACTION registry were more often older and female and less likely to undergo cardiac catheterization when compared with fit or well patients, they added in the report.

Like the small cohort studies that preceded it, this large U.S. registry study shows that frailty is an “important additional risk factor” among older adults with AMI who are managed with an invasive strategy, investigators said.

“When applicable, estimation of bleeding risk in frail patients before invasive care may facilitate clinical decision making and the informed consent process,” they wrote.

The ACTION registry, an ongoing quality improvement initiative sponsored by the American College of Cardiology and the American Heart Association, started collecting frailty characteristics among hospitalized AMI patients in 2015, investigators noted.

Dr. Dodson reported support from the National Institutes of Health/National Institute on Aging and from the American Heart Association. Study coauthors provided disclosures related to Bayer, Janssen, Abbott Vascular, Jarvik Heart, LifeCuff Technologies, and Ancora Heart. JACC Cardiovasc Interv. 2018 Nov 26;11:2287-96

SOURCE: Dodson JA et al. JACC Cardiovasc Intv. 2018;11:2287-96.

Frail older patients with acute myocardial infarction (AMI) may be at increased bleeding risk if managed with an invasive strategy, results of a large U.S. registry study suggest.

Ingram Pub.l

The increased bleeding risk was seen among frail older AMI patients who underwent cardiac catheterization, but it was not seen in those treated with more conservative medical management, according to study results.

That finding highlights the conundrum with invasive management strategies for frail patients with AMI, wrote John A. Dodson, MD, MPH, of New York University and study coinvestigators.

“Awareness of vulnerability and greater utilization of evidence-based strategies to reduce bleeding, including radial access and properly dose-adjusted anticoagulant therapies, may mitigate some bleeding events,” they wrote in JACC: Cardiovascular Interventions.

Results of this study, the first large U.S. registry analysis evaluating in-hospital bleeding risk in frail older adults with AMI, confirm findings from several previous small cohort studies linking frailty in AMI patients to in-hospital bleeding, investigators reported.

The analysis included a total of 129,330 AMI patients in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) registry who were aged at least 65 years in 2015 or 2016.

About one in six of these older patients were frail, as defined by a composite score based on impaired walking, cognition, and activities of daily living, investigators reported.

The bleeding rate was significantly higher among frail patients undergoing cardiac catheterization, at 9.4% for patients rated as having vulnerable/mild frailty and 9.9% for patients with moderate to severe frailty (P less than.001), compared with fit/well patients, whose rate was 6.5%, investigators wrote. By contrast, there was no significant difference in bleeding rates for frail versus nonfrail patients managed conservatively, they said.

After adjusting for bleeding risk factors, frailty was independently associated with increased risk of bleeding, compared with fit/well status, with odds ratios of 1.33 for vulnerable/mild frailty and 1.40 for moderate to severe frailty. Again, no association was found between frailty and bleeding risk in patients managed conservatively, according to investigators.

Frail patients in the ACTION registry were more often older and female and less likely to undergo cardiac catheterization when compared with fit or well patients, they added in the report.

Like the small cohort studies that preceded it, this large U.S. registry study shows that frailty is an “important additional risk factor” among older adults with AMI who are managed with an invasive strategy, investigators said.

“When applicable, estimation of bleeding risk in frail patients before invasive care may facilitate clinical decision making and the informed consent process,” they wrote.

The ACTION registry, an ongoing quality improvement initiative sponsored by the American College of Cardiology and the American Heart Association, started collecting frailty characteristics among hospitalized AMI patients in 2015, investigators noted.

Dr. Dodson reported support from the National Institutes of Health/National Institute on Aging and from the American Heart Association. Study coauthors provided disclosures related to Bayer, Janssen, Abbott Vascular, Jarvik Heart, LifeCuff Technologies, and Ancora Heart. JACC Cardiovasc Interv. 2018 Nov 26;11:2287-96

SOURCE: Dodson JA et al. JACC Cardiovasc Intv. 2018;11:2287-96.

SAN DIEGO – Certain immune-related adverse events related to PD1/PD-L1 treatment of patients with non–small cell lung cancer (NSCLC) may be more common than reported in clinical trials, a recent analysis of administrative claims data suggests.

Pneumonitis was seen in 10.9% of patients up to 60 days after the last dose of immunotherapy, according to the analysis of data from a large, U.S. commercial insurance database, presented at the Palliative and Supportive Care in Oncology Symposium.

By comparison, pneumonitis was reported in just 5.8% of NSCLC patients during treatment with the PD-1 (programmed cell death-1) inhibitor pembrolizumab in KEYNOTE-024, a pivotal randomized phase 3 clinical trial, said Elizabeth Jane Cathcart-Rake, MD, senior study author and an oncology fellow at the Mayo Clinic, Rochester, Minn.

Rates of immune-related adverse events in this study were generally higher than in clinical trials, both for common side effects and more rare conditions such as hypophysitis, according to Dr. Cathcart-Rake.

These new claims-based data might be considered complementary to clinical trial data, the researcher said.

“Together, they may give us a better sense of the broader implications of these adverse events,” she said in an interview.

Joe Rotella, MD, a board member of the American Academy for Hospice and Palliative Care Medicine, said results of this insurance database study provide a perspective on the real-world incidence of adverse events associated with immune checkpoint inhibitors.

“We’ve only been using these therapies for a few years, so this new analysis gives us more information on the prevalence of these side effects in patients as the therapies gain wider use,” Dr. Rotella said in a news release.

In the study, Dr. Cathcart-Rake and coinvestigators queried the OptumLabs Data Warehouse to identify 3,164 patients with NSCLC who received PD-1 or PD-L1 (programmed death-ligand 1) inhibitors between 2015 and 2017. They looked at incidence of adverse events both at the time of the last immunotherapy dose and at 60 days after the last dose.

The incidence of pneumonitis, just 4.9% on the last date of immunotherapy, increased to 10.9% at 60 days after the last dose, Dr. Cathcart-Rake reported.

Beyond pneumonitis, the most common immunotherapy-related toxicities at 60 days were hypothyroidism in 7.0%, arrhythmia in 6.1%, and nephritis or acute kidney injury in 5.4%, according to the investigators.

Dr. Cathcart-Rake also highlighted the incidence of some less common immunotherapy-related toxicities such as hypophysitis or hypothalamic-pituitary-adrenal axis toxicity, seen in 2.8% of patients by 60 days.

“That’s a small number, but hypophysitis can be really profound, and frequently leads to hospitalization,” she said. “I think this just gives us enough of a signal that providers really need to be on top of looking for these adverse events and to counsel patients beforehand.”

These data could also be helpful for advising hospitalists, emergency room physicians, and other providers who may not be attuned to the potential risks of cancer immunotherapy as compared with traditional cytotoxic chemotherapy, Dr. Cathcart-Rake said at the meeting cosponsored by AAHPM, ASCO, ASTRO, and MASCC.

“A patient with cancer may be on immunotherapy and their risk for infection is quite low, but they may be at a huge risk for pneumonitis, which is treated completely differently,” she said. “So I think this should just raise alarms that close clinical monitoring for these conditions is really important.”

Dr. Cathcart-Rake disclosed that her institution receives research funding from Novartis. One study coinvestigator reported consulting or advisory roles with Trovagene, Genentech, Bristol-Myers Squibb, and Abbvie.

SOURCE: Cathcart-Rake EJ et al. 2018 Palliative and Supportive Care in Oncology Symposium. Abstract 184.

SAN DIEGO – Certain immune-related adverse events related to PD1/PD-L1 treatment of patients with non–small cell lung cancer (NSCLC) may be more common than reported in clinical trials, a recent analysis of administrative claims data suggests.

Pneumonitis was seen in 10.9% of patients up to 60 days after the last dose of immunotherapy, according to the analysis of data from a large, U.S. commercial insurance database, presented at the Palliative and Supportive Care in Oncology Symposium.

By comparison, pneumonitis was reported in just 5.8% of NSCLC patients during treatment with the PD-1 (programmed cell death-1) inhibitor pembrolizumab in KEYNOTE-024, a pivotal randomized phase 3 clinical trial, said Elizabeth Jane Cathcart-Rake, MD, senior study author and an oncology fellow at the Mayo Clinic, Rochester, Minn.

Rates of immune-related adverse events in this study were generally higher than in clinical trials, both for common side effects and more rare conditions such as hypophysitis, according to Dr. Cathcart-Rake.

These new claims-based data might be considered complementary to clinical trial data, the researcher said.

“Together, they may give us a better sense of the broader implications of these adverse events,” she said in an interview.

Joe Rotella, MD, a board member of the American Academy for Hospice and Palliative Care Medicine, said results of this insurance database study provide a perspective on the real-world incidence of adverse events associated with immune checkpoint inhibitors.

“We’ve only been using these therapies for a few years, so this new analysis gives us more information on the prevalence of these side effects in patients as the therapies gain wider use,” Dr. Rotella said in a news release.

In the study, Dr. Cathcart-Rake and coinvestigators queried the OptumLabs Data Warehouse to identify 3,164 patients with NSCLC who received PD-1 or PD-L1 (programmed death-ligand 1) inhibitors between 2015 and 2017. They looked at incidence of adverse events both at the time of the last immunotherapy dose and at 60 days after the last dose.

The incidence of pneumonitis, just 4.9% on the last date of immunotherapy, increased to 10.9% at 60 days after the last dose, Dr. Cathcart-Rake reported.

Beyond pneumonitis, the most common immunotherapy-related toxicities at 60 days were hypothyroidism in 7.0%, arrhythmia in 6.1%, and nephritis or acute kidney injury in 5.4%, according to the investigators.

Dr. Cathcart-Rake also highlighted the incidence of some less common immunotherapy-related toxicities such as hypophysitis or hypothalamic-pituitary-adrenal axis toxicity, seen in 2.8% of patients by 60 days.

“That’s a small number, but hypophysitis can be really profound, and frequently leads to hospitalization,” she said. “I think this just gives us enough of a signal that providers really need to be on top of looking for these adverse events and to counsel patients beforehand.”

These data could also be helpful for advising hospitalists, emergency room physicians, and other providers who may not be attuned to the potential risks of cancer immunotherapy as compared with traditional cytotoxic chemotherapy, Dr. Cathcart-Rake said at the meeting cosponsored by AAHPM, ASCO, ASTRO, and MASCC.

“A patient with cancer may be on immunotherapy and their risk for infection is quite low, but they may be at a huge risk for pneumonitis, which is treated completely differently,” she said. “So I think this should just raise alarms that close clinical monitoring for these conditions is really important.”

Dr. Cathcart-Rake disclosed that her institution receives research funding from Novartis. One study coinvestigator reported consulting or advisory roles with Trovagene, Genentech, Bristol-Myers Squibb, and Abbvie.

SOURCE: Cathcart-Rake EJ et al. 2018 Palliative and Supportive Care in Oncology Symposium. Abstract 184.

SAN DIEGO – Certain immune-related adverse events related to PD1/PD-L1 treatment of patients with non–small cell lung cancer (NSCLC) may be more common than reported in clinical trials, a recent analysis of administrative claims data suggests.

Pneumonitis was seen in 10.9% of patients up to 60 days after the last dose of immunotherapy, according to the analysis of data from a large, U.S. commercial insurance database, presented at the Palliative and Supportive Care in Oncology Symposium.

By comparison, pneumonitis was reported in just 5.8% of NSCLC patients during treatment with the PD-1 (programmed cell death-1) inhibitor pembrolizumab in KEYNOTE-024, a pivotal randomized phase 3 clinical trial, said Elizabeth Jane Cathcart-Rake, MD, senior study author and an oncology fellow at the Mayo Clinic, Rochester, Minn.

Rates of immune-related adverse events in this study were generally higher than in clinical trials, both for common side effects and more rare conditions such as hypophysitis, according to Dr. Cathcart-Rake.

These new claims-based data might be considered complementary to clinical trial data, the researcher said.

“Together, they may give us a better sense of the broader implications of these adverse events,” she said in an interview.

Joe Rotella, MD, a board member of the American Academy for Hospice and Palliative Care Medicine, said results of this insurance database study provide a perspective on the real-world incidence of adverse events associated with immune checkpoint inhibitors.

“We’ve only been using these therapies for a few years, so this new analysis gives us more information on the prevalence of these side effects in patients as the therapies gain wider use,” Dr. Rotella said in a news release.

In the study, Dr. Cathcart-Rake and coinvestigators queried the OptumLabs Data Warehouse to identify 3,164 patients with NSCLC who received PD-1 or PD-L1 (programmed death-ligand 1) inhibitors between 2015 and 2017. They looked at incidence of adverse events both at the time of the last immunotherapy dose and at 60 days after the last dose.

The incidence of pneumonitis, just 4.9% on the last date of immunotherapy, increased to 10.9% at 60 days after the last dose, Dr. Cathcart-Rake reported.

Beyond pneumonitis, the most common immunotherapy-related toxicities at 60 days were hypothyroidism in 7.0%, arrhythmia in 6.1%, and nephritis or acute kidney injury in 5.4%, according to the investigators.

Dr. Cathcart-Rake also highlighted the incidence of some less common immunotherapy-related toxicities such as hypophysitis or hypothalamic-pituitary-adrenal axis toxicity, seen in 2.8% of patients by 60 days.

“That’s a small number, but hypophysitis can be really profound, and frequently leads to hospitalization,” she said. “I think this just gives us enough of a signal that providers really need to be on top of looking for these adverse events and to counsel patients beforehand.”

These data could also be helpful for advising hospitalists, emergency room physicians, and other providers who may not be attuned to the potential risks of cancer immunotherapy as compared with traditional cytotoxic chemotherapy, Dr. Cathcart-Rake said at the meeting cosponsored by AAHPM, ASCO, ASTRO, and MASCC.

“A patient with cancer may be on immunotherapy and their risk for infection is quite low, but they may be at a huge risk for pneumonitis, which is treated completely differently,” she said. “So I think this should just raise alarms that close clinical monitoring for these conditions is really important.”

Dr. Cathcart-Rake disclosed that her institution receives research funding from Novartis. One study coinvestigator reported consulting or advisory roles with Trovagene, Genentech, Bristol-Myers Squibb, and Abbvie.

SOURCE: Cathcart-Rake EJ et al. 2018 Palliative and Supportive Care in Oncology Symposium. Abstract 184.

The rituximab biosimilar CT-P10 has equivalent efficacy, compared with rituximab, and is well tolerated in the treatment of low–tumor-burden follicular lymphoma, according to results from a multinational, randomized, phase 3 study.

Overall response after 7 months of treatment exceeded 80% for patients assigned to CT-P10 and for those assigned to rituximab, investigators reported in the Lancet Haematology.

Adverse event profiles were comparable for rituximab and the biosimilar over that time period, while pharmacokinetics, pharmacodynamics, and immunogenicity were likewise comparable between arms, according to investigators.

“Thus, CT-P10 monotherapy is suggested as a new therapeutic option for patients with low–tumor-burden follicular lymphoma,” wrote senior author Larry W Kwak, MD, PhD, of the Comprehensive Cancer Center, City of Hope, Duarte, Calif., and his colleagues.

CT-P10, the first rituximab biosimilar to be authorized by the European Medicines Agency, has been recommended for approval in the United States by the Food and Drug Administration’s Oncologic Drugs Advisory Committee.

If approved by the FDA, CT-P10 would be the first rituximab biosimilar available in the United States, according to the company, which noted three proposed indications in non-Hodgkin lymphoma.

In the current randomized, double-blind, parallel-group, phase 3 trial, 258 patients with stage II-IV low–tumor-burden follicular lymphoma were randomly assigned to CT-P10 (130 patients) or rituximab sourced in the United States (128 patients).

Treatment consisted of an induction period of intravenous CT-P10 or rituximab weekly for 4 weeks, while patients experiencing disease control went on to a maintenance phase with their assigned treatment given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.

The primary endpoint of the study was overall response at 7 months, defined as a complete response, unconfirmed complete response, or partial response.

Overall response was seen in 83% of patients randomized to CT-P10 and 81% of patients randomized to rituximab at 7 months, Dr. Kwak and his colleagues reported.

The two treatments were deemed therapeutically equivalent, as illustrated by 90% confidence intervals within a prespecified equivalence margin of 17%, investigators said.

The most common treatment-emergent adverse events in either group were infusion-related reactions, which were of grade 1-2, except for one grade 3 reaction reported in the CT-P10 group, according to the report. Other common adverse events were upper respiratory tract infections and fatigue.

Serious adverse events were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.

The availability of a rituximab biosimilar is anticipated to reduce the cost of treatment and improve patient access, according to investigators.

Introduction of CT-P10 in the European Union was projected to save between 90 and 150 million euros over a year, enabling more than 12,500 new patients to be treated with the biosimilar, according to results of a budget impact analysis investigators cited in their report.

“Widespread adoption of a rituximab biosimilar could have a substantial effect on health care budgets and might also have effects at a societal level,” Dr. Kwak and his coauthors said in the report.

The trial was sponsored by Celltrion and three coauthors of the study were employees of the company. Dr. Kwak and several other coinvestigators not employed by Celltrion reported disclosures related to the company. Other disclosures provided related to Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.

SOURCE: Ogura M et al. Lancet Haematol. 2018 Nov;5(11):e543-53.

The rituximab biosimilar CT-P10 has equivalent efficacy, compared with rituximab, and is well tolerated in the treatment of low–tumor-burden follicular lymphoma, according to results from a multinational, randomized, phase 3 study.

Overall response after 7 months of treatment exceeded 80% for patients assigned to CT-P10 and for those assigned to rituximab, investigators reported in the Lancet Haematology.

Adverse event profiles were comparable for rituximab and the biosimilar over that time period, while pharmacokinetics, pharmacodynamics, and immunogenicity were likewise comparable between arms, according to investigators.

“Thus, CT-P10 monotherapy is suggested as a new therapeutic option for patients with low–tumor-burden follicular lymphoma,” wrote senior author Larry W Kwak, MD, PhD, of the Comprehensive Cancer Center, City of Hope, Duarte, Calif., and his colleagues.

CT-P10, the first rituximab biosimilar to be authorized by the European Medicines Agency, has been recommended for approval in the United States by the Food and Drug Administration’s Oncologic Drugs Advisory Committee.

If approved by the FDA, CT-P10 would be the first rituximab biosimilar available in the United States, according to the company, which noted three proposed indications in non-Hodgkin lymphoma.

In the current randomized, double-blind, parallel-group, phase 3 trial, 258 patients with stage II-IV low–tumor-burden follicular lymphoma were randomly assigned to CT-P10 (130 patients) or rituximab sourced in the United States (128 patients).

Treatment consisted of an induction period of intravenous CT-P10 or rituximab weekly for 4 weeks, while patients experiencing disease control went on to a maintenance phase with their assigned treatment given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.

The primary endpoint of the study was overall response at 7 months, defined as a complete response, unconfirmed complete response, or partial response.

Overall response was seen in 83% of patients randomized to CT-P10 and 81% of patients randomized to rituximab at 7 months, Dr. Kwak and his colleagues reported.

The two treatments were deemed therapeutically equivalent, as illustrated by 90% confidence intervals within a prespecified equivalence margin of 17%, investigators said.

The most common treatment-emergent adverse events in either group were infusion-related reactions, which were of grade 1-2, except for one grade 3 reaction reported in the CT-P10 group, according to the report. Other common adverse events were upper respiratory tract infections and fatigue.

Serious adverse events were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.

The availability of a rituximab biosimilar is anticipated to reduce the cost of treatment and improve patient access, according to investigators.

Introduction of CT-P10 in the European Union was projected to save between 90 and 150 million euros over a year, enabling more than 12,500 new patients to be treated with the biosimilar, according to results of a budget impact analysis investigators cited in their report.

“Widespread adoption of a rituximab biosimilar could have a substantial effect on health care budgets and might also have effects at a societal level,” Dr. Kwak and his coauthors said in the report.

The trial was sponsored by Celltrion and three coauthors of the study were employees of the company. Dr. Kwak and several other coinvestigators not employed by Celltrion reported disclosures related to the company. Other disclosures provided related to Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.

SOURCE: Ogura M et al. Lancet Haematol. 2018 Nov;5(11):e543-53.

The rituximab biosimilar CT-P10 has equivalent efficacy, compared with rituximab, and is well tolerated in the treatment of low–tumor-burden follicular lymphoma, according to results from a multinational, randomized, phase 3 study.

Overall response after 7 months of treatment exceeded 80% for patients assigned to CT-P10 and for those assigned to rituximab, investigators reported in the Lancet Haematology.

Adverse event profiles were comparable for rituximab and the biosimilar over that time period, while pharmacokinetics, pharmacodynamics, and immunogenicity were likewise comparable between arms, according to investigators.

“Thus, CT-P10 monotherapy is suggested as a new therapeutic option for patients with low–tumor-burden follicular lymphoma,” wrote senior author Larry W Kwak, MD, PhD, of the Comprehensive Cancer Center, City of Hope, Duarte, Calif., and his colleagues.

CT-P10, the first rituximab biosimilar to be authorized by the European Medicines Agency, has been recommended for approval in the United States by the Food and Drug Administration’s Oncologic Drugs Advisory Committee.

If approved by the FDA, CT-P10 would be the first rituximab biosimilar available in the United States, according to the company, which noted three proposed indications in non-Hodgkin lymphoma.

In the current randomized, double-blind, parallel-group, phase 3 trial, 258 patients with stage II-IV low–tumor-burden follicular lymphoma were randomly assigned to CT-P10 (130 patients) or rituximab sourced in the United States (128 patients).

Treatment consisted of an induction period of intravenous CT-P10 or rituximab weekly for 4 weeks, while patients experiencing disease control went on to a maintenance phase with their assigned treatment given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.

The primary endpoint of the study was overall response at 7 months, defined as a complete response, unconfirmed complete response, or partial response.

Overall response was seen in 83% of patients randomized to CT-P10 and 81% of patients randomized to rituximab at 7 months, Dr. Kwak and his colleagues reported.

The two treatments were deemed therapeutically equivalent, as illustrated by 90% confidence intervals within a prespecified equivalence margin of 17%, investigators said.

The most common treatment-emergent adverse events in either group were infusion-related reactions, which were of grade 1-2, except for one grade 3 reaction reported in the CT-P10 group, according to the report. Other common adverse events were upper respiratory tract infections and fatigue.

Serious adverse events were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.

The availability of a rituximab biosimilar is anticipated to reduce the cost of treatment and improve patient access, according to investigators.

Introduction of CT-P10 in the European Union was projected to save between 90 and 150 million euros over a year, enabling more than 12,500 new patients to be treated with the biosimilar, according to results of a budget impact analysis investigators cited in their report.

“Widespread adoption of a rituximab biosimilar could have a substantial effect on health care budgets and might also have effects at a societal level,” Dr. Kwak and his coauthors said in the report.

The trial was sponsored by Celltrion and three coauthors of the study were employees of the company. Dr. Kwak and several other coinvestigators not employed by Celltrion reported disclosures related to the company. Other disclosures provided related to Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.

SOURCE: Ogura M et al. Lancet Haematol. 2018 Nov;5(11):e543-53.

Risk stratification tools that omit lumbar puncture accurately classified most well-appearing febrile infants with invasive bacterial infections as being at low risk, results of a recent study show.

The modified Philadelphia criteria were highly sensitive for risk stratifying febrile infants, in a recent validation study based on a large, multicenter sample, investigators report. No infants with bacterial meningitis were classified as low risk using the modified criteria, which do not include routine testing of cerebrospinal fluid (CSF). Two infants with bacterial meningitis, both younger than 28 days old, were classified as low risk using the Rochester criteria, which also avoid routine lumbar puncture, investigators reported.

“Our findings support the use of the modified Philadelphia criteria without routine CSF testing for febrile infants in the second month of life,” the investigators said in their report, published in Pediatrics.

However, to confirm the safety of omitting CSF testing in low-risk febrile infants older than 28 days, a prospective study will be needed, cautioned the researchers, led by Paul L. Aronson, MD, of the department of pediatrics at Yale University in New Haven, Conn.

Nevertheless, some clinicians do not automatically perform CSF testing in infants older than 28 days because of the rarity of bacterial meningitis in that age group, they said in the report.

The study by Dr. Aronson and colleagues was based on data for infants younger than 60 days of age seen in the emergency departments of 9 hospitals between July 2011 and June 2016. The final sample included 135 infants with invasive bacterial infections, including 118 who had bacteremia without meningitis and 17 who had bacterial meningitis, along with 249 matched febrile infant controls.

A total of 25 infants with invasive bacterial infections were classified as low risk by the Rochester criteria, and 11 of those were low risk by the modified Philadelphia criteria, investigators said.

Compared with the modified Philadelphia criteria, the Rochester criteria had a lower sensitivity (81.5% vs. 91.9%; P = 0.01) and a higher specificity (59.8 vs. 34.5%; P less than 0.001).

Out of the 11 infants deemed low risk per the modified Philadelphia criteria, none were diagnosed with bacterial meningitis. By contrast, 2 of the 25 infants who were low risk per the Rochester criteria had bacterial meningitis, and both were younger than or equal to 28 days of age. “Both of these infants would have been classified as high risk per the modified Philadelphia criteria,” Dr. Aronson and his coauthors said.

Based on the findings of this study, caution should be exercised in applying low-risk criteria to infants 28 days of age or younger, according to the investigators.

“Febrile infants discharged from the emergency department without CSF testing should have close outpatient follow-up,” they wrote.

Dr. Aronson and his coauthors reported that they had no relevant disclosures. One coauthor reported serving as an expert witness in malpractice cases involving evaluation of febrile children.

SOURCE: Aronson PL et al. Pediatrics. 13 Nov 2018. doi: 10.1542/peds.2018-1879).

Risk stratification tools that omit lumbar puncture accurately classified most well-appearing febrile infants with invasive bacterial infections as being at low risk, results of a recent study show.

The modified Philadelphia criteria were highly sensitive for risk stratifying febrile infants, in a recent validation study based on a large, multicenter sample, investigators report. No infants with bacterial meningitis were classified as low risk using the modified criteria, which do not include routine testing of cerebrospinal fluid (CSF). Two infants with bacterial meningitis, both younger than 28 days old, were classified as low risk using the Rochester criteria, which also avoid routine lumbar puncture, investigators reported.

“Our findings support the use of the modified Philadelphia criteria without routine CSF testing for febrile infants in the second month of life,” the investigators said in their report, published in Pediatrics.

However, to confirm the safety of omitting CSF testing in low-risk febrile infants older than 28 days, a prospective study will be needed, cautioned the researchers, led by Paul L. Aronson, MD, of the department of pediatrics at Yale University in New Haven, Conn.

Nevertheless, some clinicians do not automatically perform CSF testing in infants older than 28 days because of the rarity of bacterial meningitis in that age group, they said in the report.

The study by Dr. Aronson and colleagues was based on data for infants younger than 60 days of age seen in the emergency departments of 9 hospitals between July 2011 and June 2016. The final sample included 135 infants with invasive bacterial infections, including 118 who had bacteremia without meningitis and 17 who had bacterial meningitis, along with 249 matched febrile infant controls.

A total of 25 infants with invasive bacterial infections were classified as low risk by the Rochester criteria, and 11 of those were low risk by the modified Philadelphia criteria, investigators said.

Compared with the modified Philadelphia criteria, the Rochester criteria had a lower sensitivity (81.5% vs. 91.9%; P = 0.01) and a higher specificity (59.8 vs. 34.5%; P less than 0.001).

Out of the 11 infants deemed low risk per the modified Philadelphia criteria, none were diagnosed with bacterial meningitis. By contrast, 2 of the 25 infants who were low risk per the Rochester criteria had bacterial meningitis, and both were younger than or equal to 28 days of age. “Both of these infants would have been classified as high risk per the modified Philadelphia criteria,” Dr. Aronson and his coauthors said.

Based on the findings of this study, caution should be exercised in applying low-risk criteria to infants 28 days of age or younger, according to the investigators.

“Febrile infants discharged from the emergency department without CSF testing should have close outpatient follow-up,” they wrote.

Dr. Aronson and his coauthors reported that they had no relevant disclosures. One coauthor reported serving as an expert witness in malpractice cases involving evaluation of febrile children.

SOURCE: Aronson PL et al. Pediatrics. 13 Nov 2018. doi: 10.1542/peds.2018-1879).

Risk stratification tools that omit lumbar puncture accurately classified most well-appearing febrile infants with invasive bacterial infections as being at low risk, results of a recent study show.

The modified Philadelphia criteria were highly sensitive for risk stratifying febrile infants, in a recent validation study based on a large, multicenter sample, investigators report. No infants with bacterial meningitis were classified as low risk using the modified criteria, which do not include routine testing of cerebrospinal fluid (CSF). Two infants with bacterial meningitis, both younger than 28 days old, were classified as low risk using the Rochester criteria, which also avoid routine lumbar puncture, investigators reported.

“Our findings support the use of the modified Philadelphia criteria without routine CSF testing for febrile infants in the second month of life,” the investigators said in their report, published in Pediatrics.

However, to confirm the safety of omitting CSF testing in low-risk febrile infants older than 28 days, a prospective study will be needed, cautioned the researchers, led by Paul L. Aronson, MD, of the department of pediatrics at Yale University in New Haven, Conn.

Nevertheless, some clinicians do not automatically perform CSF testing in infants older than 28 days because of the rarity of bacterial meningitis in that age group, they said in the report.

The study by Dr. Aronson and colleagues was based on data for infants younger than 60 days of age seen in the emergency departments of 9 hospitals between July 2011 and June 2016. The final sample included 135 infants with invasive bacterial infections, including 118 who had bacteremia without meningitis and 17 who had bacterial meningitis, along with 249 matched febrile infant controls.

A total of 25 infants with invasive bacterial infections were classified as low risk by the Rochester criteria, and 11 of those were low risk by the modified Philadelphia criteria, investigators said.

Compared with the modified Philadelphia criteria, the Rochester criteria had a lower sensitivity (81.5% vs. 91.9%; P = 0.01) and a higher specificity (59.8 vs. 34.5%; P less than 0.001).

Out of the 11 infants deemed low risk per the modified Philadelphia criteria, none were diagnosed with bacterial meningitis. By contrast, 2 of the 25 infants who were low risk per the Rochester criteria had bacterial meningitis, and both were younger than or equal to 28 days of age. “Both of these infants would have been classified as high risk per the modified Philadelphia criteria,” Dr. Aronson and his coauthors said.

Based on the findings of this study, caution should be exercised in applying low-risk criteria to infants 28 days of age or younger, according to the investigators.

“Febrile infants discharged from the emergency department without CSF testing should have close outpatient follow-up,” they wrote.

Dr. Aronson and his coauthors reported that they had no relevant disclosures. One coauthor reported serving as an expert witness in malpractice cases involving evaluation of febrile children.

SOURCE: Aronson PL et al. Pediatrics. 13 Nov 2018. doi: 10.1542/peds.2018-1879).

In patients with a new diagnosis of advanced cancer, an intervention that combined palliative care with rehabilitation helped improve quality of life, results of a randomized, single-center study suggest.

Patients had a significant improvement in their most pressing quality-of-life issues after participating in the intervention, which included individualized palliative care consultations and a patient/caregiver “school” of lectures, discussion, and physical exercise, investigators said.

These findings suggest that every patient facing an advanced cancer diagnosis should at least have an initial exploratory consultation with a specialized palliative care team, and should be offered not only the usual components of palliative care, but also cancer rehabilitation, said Lise Nottelmann, MD, of the department of oncology at Vejle Hospital in Denmark.

“We should be active as a health care system in approaching these patients and offering them this intervention, or at least a consultation exploring these aspects of quality of life,” Dr. Nottelmann said in an interview at the 2018 Palliative and Supportive Care in Oncology Symposium.

The study by Dr. Nottelmann and her colleagues, presented at the symposium, comprised 301 patients with nonresectable solid tumors, including lung, gastrointestinal, prostate, and others. Those patients were randomly allocated to the palliative rehabilitation intervention or to standard care only.

Every patient participated in two consultations with a specialized palliative care team, and then had the opportunity for individualized contact with the team in a 12-week open contact period. They were also invited to participate in the school sessions, each of which included a 20-minute lecture on topics such as physical activity and good nutrition plus a 40-minute discussion period, followed by an exercise session.

Of the patients randomized to the palliative rehabilitation intervention, 26 participated only in the initial consultations, while 59 participated in the group program, and 47 had individual consultations, Dr. Nottelmann reported.

To measure quality of life, the investigators asked patients to identify a “primary problem” that corresponded to one of 12 scales in the EORTC QLQ-C30 questionnaire related to physical and role functioning, emotional and cognitive functioning, or symptoms.

The primary endpoint of the analysis was improvement in QLQ-C30 scores at 12 weeks. The analysis was done on specific scales in the patients who identified a primary problem, combined with global QLQ-C30 scores for the remaining one-quarter of the patients who did not, Dr. Nottelmann said.

After 12 weeks, the patients in the intervention arm had a significant improvement versus the no-intervention arm as measured by a version of the EORTC QLQ-C30 questionnaire. The absolute between-group difference in scores was 3.0 (95% confidence interval, 0.0-6.0; P less than .047), according to researchers.

Starting palliative care earlier in the course of cancer, as done in this intervention, is an increasingly accepted practice, supported by large studies and recent clinical practice guidelines that recommend early integration of palliative care into the seriously ill patient’s care plan.

What was different about this intervention was the integration of rehabilitation aspects into palliative care, Dr. Nottelmann said in the interview. While not traditionally thought of as a component of palliative care, the concept of palliative rehabilitation is gaining ground, she said.

The goal of rehabilitative palliative care is to help individuals with life-limiting or terminal conditions actively self-manage their conditions so they can “live fully” and enjoy the best quality of life possible, according to Hospice UK, a national charity for hospice care in the United Kingdom.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC. Dr. Nottelmann and her colleagues reported research funding from the Danish Cancer Society. Dr. Nottelmann had no disclosures related to the presentation. One coauthor provided disclosures related to Roche, Amgen, Bayer, and Merck Sharp & Dohme.

SOURCE: Nottelmann L et al. PallOnc 2018, Abstract 75.

In patients with a new diagnosis of advanced cancer, an intervention that combined palliative care with rehabilitation helped improve quality of life, results of a randomized, single-center study suggest.

Patients had a significant improvement in their most pressing quality-of-life issues after participating in the intervention, which included individualized palliative care consultations and a patient/caregiver “school” of lectures, discussion, and physical exercise, investigators said.

These findings suggest that every patient facing an advanced cancer diagnosis should at least have an initial exploratory consultation with a specialized palliative care team, and should be offered not only the usual components of palliative care, but also cancer rehabilitation, said Lise Nottelmann, MD, of the department of oncology at Vejle Hospital in Denmark.

“We should be active as a health care system in approaching these patients and offering them this intervention, or at least a consultation exploring these aspects of quality of life,” Dr. Nottelmann said in an interview at the 2018 Palliative and Supportive Care in Oncology Symposium.

The study by Dr. Nottelmann and her colleagues, presented at the symposium, comprised 301 patients with nonresectable solid tumors, including lung, gastrointestinal, prostate, and others. Those patients were randomly allocated to the palliative rehabilitation intervention or to standard care only.

Every patient participated in two consultations with a specialized palliative care team, and then had the opportunity for individualized contact with the team in a 12-week open contact period. They were also invited to participate in the school sessions, each of which included a 20-minute lecture on topics such as physical activity and good nutrition plus a 40-minute discussion period, followed by an exercise session.

Of the patients randomized to the palliative rehabilitation intervention, 26 participated only in the initial consultations, while 59 participated in the group program, and 47 had individual consultations, Dr. Nottelmann reported.

To measure quality of life, the investigators asked patients to identify a “primary problem” that corresponded to one of 12 scales in the EORTC QLQ-C30 questionnaire related to physical and role functioning, emotional and cognitive functioning, or symptoms.

The primary endpoint of the analysis was improvement in QLQ-C30 scores at 12 weeks. The analysis was done on specific scales in the patients who identified a primary problem, combined with global QLQ-C30 scores for the remaining one-quarter of the patients who did not, Dr. Nottelmann said.

After 12 weeks, the patients in the intervention arm had a significant improvement versus the no-intervention arm as measured by a version of the EORTC QLQ-C30 questionnaire. The absolute between-group difference in scores was 3.0 (95% confidence interval, 0.0-6.0; P less than .047), according to researchers.

Starting palliative care earlier in the course of cancer, as done in this intervention, is an increasingly accepted practice, supported by large studies and recent clinical practice guidelines that recommend early integration of palliative care into the seriously ill patient’s care plan.

What was different about this intervention was the integration of rehabilitation aspects into palliative care, Dr. Nottelmann said in the interview. While not traditionally thought of as a component of palliative care, the concept of palliative rehabilitation is gaining ground, she said.

The goal of rehabilitative palliative care is to help individuals with life-limiting or terminal conditions actively self-manage their conditions so they can “live fully” and enjoy the best quality of life possible, according to Hospice UK, a national charity for hospice care in the United Kingdom.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC. Dr. Nottelmann and her colleagues reported research funding from the Danish Cancer Society. Dr. Nottelmann had no disclosures related to the presentation. One coauthor provided disclosures related to Roche, Amgen, Bayer, and Merck Sharp & Dohme.

SOURCE: Nottelmann L et al. PallOnc 2018, Abstract 75.

In patients with a new diagnosis of advanced cancer, an intervention that combined palliative care with rehabilitation helped improve quality of life, results of a randomized, single-center study suggest.

Patients had a significant improvement in their most pressing quality-of-life issues after participating in the intervention, which included individualized palliative care consultations and a patient/caregiver “school” of lectures, discussion, and physical exercise, investigators said.

These findings suggest that every patient facing an advanced cancer diagnosis should at least have an initial exploratory consultation with a specialized palliative care team, and should be offered not only the usual components of palliative care, but also cancer rehabilitation, said Lise Nottelmann, MD, of the department of oncology at Vejle Hospital in Denmark.

“We should be active as a health care system in approaching these patients and offering them this intervention, or at least a consultation exploring these aspects of quality of life,” Dr. Nottelmann said in an interview at the 2018 Palliative and Supportive Care in Oncology Symposium.

The study by Dr. Nottelmann and her colleagues, presented at the symposium, comprised 301 patients with nonresectable solid tumors, including lung, gastrointestinal, prostate, and others. Those patients were randomly allocated to the palliative rehabilitation intervention or to standard care only.

Every patient participated in two consultations with a specialized palliative care team, and then had the opportunity for individualized contact with the team in a 12-week open contact period. They were also invited to participate in the school sessions, each of which included a 20-minute lecture on topics such as physical activity and good nutrition plus a 40-minute discussion period, followed by an exercise session.

Of the patients randomized to the palliative rehabilitation intervention, 26 participated only in the initial consultations, while 59 participated in the group program, and 47 had individual consultations, Dr. Nottelmann reported.

To measure quality of life, the investigators asked patients to identify a “primary problem” that corresponded to one of 12 scales in the EORTC QLQ-C30 questionnaire related to physical and role functioning, emotional and cognitive functioning, or symptoms.

The primary endpoint of the analysis was improvement in QLQ-C30 scores at 12 weeks. The analysis was done on specific scales in the patients who identified a primary problem, combined with global QLQ-C30 scores for the remaining one-quarter of the patients who did not, Dr. Nottelmann said.

After 12 weeks, the patients in the intervention arm had a significant improvement versus the no-intervention arm as measured by a version of the EORTC QLQ-C30 questionnaire. The absolute between-group difference in scores was 3.0 (95% confidence interval, 0.0-6.0; P less than .047), according to researchers.

Starting palliative care earlier in the course of cancer, as done in this intervention, is an increasingly accepted practice, supported by large studies and recent clinical practice guidelines that recommend early integration of palliative care into the seriously ill patient’s care plan.

What was different about this intervention was the integration of rehabilitation aspects into palliative care, Dr. Nottelmann said in the interview. While not traditionally thought of as a component of palliative care, the concept of palliative rehabilitation is gaining ground, she said.

The goal of rehabilitative palliative care is to help individuals with life-limiting or terminal conditions actively self-manage their conditions so they can “live fully” and enjoy the best quality of life possible, according to Hospice UK, a national charity for hospice care in the United Kingdom.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC. Dr. Nottelmann and her colleagues reported research funding from the Danish Cancer Society. Dr. Nottelmann had no disclosures related to the presentation. One coauthor provided disclosures related to Roche, Amgen, Bayer, and Merck Sharp & Dohme.

SOURCE: Nottelmann L et al. PallOnc 2018, Abstract 75.