Leukemia, Myelodysplasia, Transplantation

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab) and TGR-1202 for the treatment of patients with chronic lymphocytic leukemia (CLL).

Ublituximab is a glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 is a next-generation PI3K delta inhibitor. Both drugs are being developed by TG Therapeutics, Inc.

Researchers have evaluated ublituximab and TGR-1202 in combination in a phase 1 trial of patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL) and non-Hodgkin lymphomas (NHLs).

Results were presented at the 2015 ASH Annual Meeting.

There was a 3+3 dose-escalation portion of the study and a dose-expansion phase. The patients received  TGR-1202 at doses ranging from 400 mg to 1200 mg and 2 different doses of ublituximab—900 mg for patients with NHL and 600 mg or 900 mg for patients with CLL/SLL.

As of ASH, there were 58 patients evaluable for efficacy and 71 evaluable for safety.

There were 10 CLL/SLL patients exposed to higher doses of TGR-1202. Among these patients, the overall response rate was 80%. Seven patients achieved a partial response, 1 achieved a complete response, and the remaining 2 patients had stable disease.

For the entire safety population, the most common adverse events were nausea (46%), diarrhea (44%), fatigue (41%), neutropenia (30%), and infusion-related reactions (25%).

Grade 3/4 adverse events included neutropenia (25%), diarrhea (3%), fatigue (3%), dyspnea (3%), pyrexia (3%), nausea (1%), infusion-related reactions (1%), sinusitis (1%), anemia (1%), hypophosphatemia (1%), and peripheral edema (1%). 

Now, the combination of ublituximab and TGR-1202 is being evaluated in the UNITY-CLL phase 3 trial for patients with previously treated or untreated CLL.

“[W]ith enrollment into our UNITY-CLL phase 3 trial currently exceeding our expectations, we expect to be able to commence a regulatory filing for the combination in 2018, and having orphan drug designation will provide certain cost-saving advantages for us during the regulatory approval process,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics. 

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab) and TGR-1202 for the treatment of patients with chronic lymphocytic leukemia (CLL).

Ublituximab is a glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 is a next-generation PI3K delta inhibitor. Both drugs are being developed by TG Therapeutics, Inc.

Researchers have evaluated ublituximab and TGR-1202 in combination in a phase 1 trial of patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL) and non-Hodgkin lymphomas (NHLs).

Results were presented at the 2015 ASH Annual Meeting.

There was a 3+3 dose-escalation portion of the study and a dose-expansion phase. The patients received  TGR-1202 at doses ranging from 400 mg to 1200 mg and 2 different doses of ublituximab—900 mg for patients with NHL and 600 mg or 900 mg for patients with CLL/SLL.

As of ASH, there were 58 patients evaluable for efficacy and 71 evaluable for safety.

There were 10 CLL/SLL patients exposed to higher doses of TGR-1202. Among these patients, the overall response rate was 80%. Seven patients achieved a partial response, 1 achieved a complete response, and the remaining 2 patients had stable disease.

For the entire safety population, the most common adverse events were nausea (46%), diarrhea (44%), fatigue (41%), neutropenia (30%), and infusion-related reactions (25%).

Grade 3/4 adverse events included neutropenia (25%), diarrhea (3%), fatigue (3%), dyspnea (3%), pyrexia (3%), nausea (1%), infusion-related reactions (1%), sinusitis (1%), anemia (1%), hypophosphatemia (1%), and peripheral edema (1%). 

Now, the combination of ublituximab and TGR-1202 is being evaluated in the UNITY-CLL phase 3 trial for patients with previously treated or untreated CLL.

“[W]ith enrollment into our UNITY-CLL phase 3 trial currently exceeding our expectations, we expect to be able to commence a regulatory filing for the combination in 2018, and having orphan drug designation will provide certain cost-saving advantages for us during the regulatory approval process,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics. 

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab) and TGR-1202 for the treatment of patients with chronic lymphocytic leukemia (CLL).

Ublituximab is a glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 is a next-generation PI3K delta inhibitor. Both drugs are being developed by TG Therapeutics, Inc.

Researchers have evaluated ublituximab and TGR-1202 in combination in a phase 1 trial of patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL) and non-Hodgkin lymphomas (NHLs).

Results were presented at the 2015 ASH Annual Meeting.

There was a 3+3 dose-escalation portion of the study and a dose-expansion phase. The patients received  TGR-1202 at doses ranging from 400 mg to 1200 mg and 2 different doses of ublituximab—900 mg for patients with NHL and 600 mg or 900 mg for patients with CLL/SLL.

As of ASH, there were 58 patients evaluable for efficacy and 71 evaluable for safety.

There were 10 CLL/SLL patients exposed to higher doses of TGR-1202. Among these patients, the overall response rate was 80%. Seven patients achieved a partial response, 1 achieved a complete response, and the remaining 2 patients had stable disease.

For the entire safety population, the most common adverse events were nausea (46%), diarrhea (44%), fatigue (41%), neutropenia (30%), and infusion-related reactions (25%).

Grade 3/4 adverse events included neutropenia (25%), diarrhea (3%), fatigue (3%), dyspnea (3%), pyrexia (3%), nausea (1%), infusion-related reactions (1%), sinusitis (1%), anemia (1%), hypophosphatemia (1%), and peripheral edema (1%). 

Now, the combination of ublituximab and TGR-1202 is being evaluated in the UNITY-CLL phase 3 trial for patients with previously treated or untreated CLL.

“[W]ith enrollment into our UNITY-CLL phase 3 trial currently exceeding our expectations, we expect to be able to commence a regulatory filing for the combination in 2018, and having orphan drug designation will provide certain cost-saving advantages for us during the regulatory approval process,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics. 

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

A yoga program for children with cancer can be carried out during cancer treatment and has quality of life (QOL) benefits for the children as well as their caregivers, according to research published in Rehabilitation Oncology.

However, the program was not feasible for all patients. More than half of those initially enrolled could not complete the study due to treatment toxicity or scheduling conflicts.

Andrea Orsey, MD, of Connecticut Children’s Medical Center in Hartford, and her colleagues conducted this research to evaluate the feasibility and effectiveness of a yoga intervention for children with cancer and their families.

The team began by conducting a survey of 20 children and adolescents with cancer and their parents/guardians.

Survey respondents expressed interest in a yoga program. But they also perceived several barriers to such a program, including concerns about side effects, pain/discomfort, and physical limitations.

With these barriers in mind, Dr Orsey and her colleagues developed a yoga intervention for pediatric cancer patients, delivered by certified yoga instructors.

The program was designed to be performed in a variety of settings and tailored to the children’s physical condition or mobility issues.

A pilot evaluation included 10 children with cancer and their caregivers. Twenty-two patient/caregiver pairs were actually enrolled, but 6 pairs withdrew because of treatment toxicity, and 6 had the study window lapse due to scheduling conflicts.

Although limited by its small size, the study suggested that yoga improved health-related QOL for both caregivers and children.

The children had significant improvements in both social and emotional QOL. They had an overall improvement in fatigue, but this was not statistically significant.

Caregivers had a significant improvement in mental health but not physical health or caregiver burden.

Both caregivers and children said they were satisfied with the yoga program and would recommend it to others.

Dr Orsey and her colleagues hope this pilot study will help guide future efforts to provide yoga to children with cancer and their families.

The researchers noted that a key issue will be coordinating yoga sessions with the medical demands of chemotherapy.

A yoga program for children with cancer can be carried out during cancer treatment and has quality of life (QOL) benefits for the children as well as their caregivers, according to research published in Rehabilitation Oncology.

However, the program was not feasible for all patients. More than half of those initially enrolled could not complete the study due to treatment toxicity or scheduling conflicts.

Andrea Orsey, MD, of Connecticut Children’s Medical Center in Hartford, and her colleagues conducted this research to evaluate the feasibility and effectiveness of a yoga intervention for children with cancer and their families.

The team began by conducting a survey of 20 children and adolescents with cancer and their parents/guardians.

Survey respondents expressed interest in a yoga program. But they also perceived several barriers to such a program, including concerns about side effects, pain/discomfort, and physical limitations.

With these barriers in mind, Dr Orsey and her colleagues developed a yoga intervention for pediatric cancer patients, delivered by certified yoga instructors.

The program was designed to be performed in a variety of settings and tailored to the children’s physical condition or mobility issues.

A pilot evaluation included 10 children with cancer and their caregivers. Twenty-two patient/caregiver pairs were actually enrolled, but 6 pairs withdrew because of treatment toxicity, and 6 had the study window lapse due to scheduling conflicts.

Although limited by its small size, the study suggested that yoga improved health-related QOL for both caregivers and children.

The children had significant improvements in both social and emotional QOL. They had an overall improvement in fatigue, but this was not statistically significant.

Caregivers had a significant improvement in mental health but not physical health or caregiver burden.

Both caregivers and children said they were satisfied with the yoga program and would recommend it to others.

Dr Orsey and her colleagues hope this pilot study will help guide future efforts to provide yoga to children with cancer and their families.

The researchers noted that a key issue will be coordinating yoga sessions with the medical demands of chemotherapy.

A yoga program for children with cancer can be carried out during cancer treatment and has quality of life (QOL) benefits for the children as well as their caregivers, according to research published in Rehabilitation Oncology.

However, the program was not feasible for all patients. More than half of those initially enrolled could not complete the study due to treatment toxicity or scheduling conflicts.

Andrea Orsey, MD, of Connecticut Children’s Medical Center in Hartford, and her colleagues conducted this research to evaluate the feasibility and effectiveness of a yoga intervention for children with cancer and their families.

The team began by conducting a survey of 20 children and adolescents with cancer and their parents/guardians.

Survey respondents expressed interest in a yoga program. But they also perceived several barriers to such a program, including concerns about side effects, pain/discomfort, and physical limitations.

With these barriers in mind, Dr Orsey and her colleagues developed a yoga intervention for pediatric cancer patients, delivered by certified yoga instructors.

The program was designed to be performed in a variety of settings and tailored to the children’s physical condition or mobility issues.

A pilot evaluation included 10 children with cancer and their caregivers. Twenty-two patient/caregiver pairs were actually enrolled, but 6 pairs withdrew because of treatment toxicity, and 6 had the study window lapse due to scheduling conflicts.

Although limited by its small size, the study suggested that yoga improved health-related QOL for both caregivers and children.

The children had significant improvements in both social and emotional QOL. They had an overall improvement in fatigue, but this was not statistically significant.

Caregivers had a significant improvement in mental health but not physical health or caregiver burden.

Both caregivers and children said they were satisfied with the yoga program and would recommend it to others.

Dr Orsey and her colleagues hope this pilot study will help guide future efforts to provide yoga to children with cancer and their families.

The researchers noted that a key issue will be coordinating yoga sessions with the medical demands of chemotherapy.

The US may see nearly 1.7 million new cancer cases in 2017 and more than 600,000 cancer-related deaths, according to a report from the American Cancer Society (ACS).

In addition to estimates for 2017, the report, “Cancer Statistics 2017,” includes the most recent data on cancer incidence, mortality, and survival in the US.

The report was published in CA: A Cancer Journal for Clinicians.

The report projects there will be 1,688,780 new cancer cases and 600,920 cancer deaths in the US this year.

This includes:

• 80,500 new cases of lymphoma and 21,210 lymphoma deaths
• 62,130 new cases of leukemia and 24,500 leukemia deaths
• 30,280 new cases of myeloma and 12,590 myeloma deaths.

The report also shows that, from 2004 to 2013, the overall cancer incidence rate was stable in women and declined by about 2% per year in men. From 2005 to 2014, the cancer death rate declined by about 1.5% annually in both men and women.

Overall, the cancer death rate dropped 25% from its peak of 215.1 (per 100,000 population) in 1991 to 161.2 (per 100,000 population) in 2014, the latest year for which data was available. This translates to about 2,143,200 fewer cancer deaths.

“The continuing drops in the cancer death rate are a powerful sign of the potential we have to reduce cancer’s deadly toll,” said Otis W. Brawley, MD, chief medical officer of the ACS.

He said the decrease in cancer death rates is the result of steady reductions in smoking and advances in early detection and treatment. The decrease is driven by decreasing death rates for the 4 major cancer sites—lung, breast, colorectal, and prostate.

The report also shows that racial disparities in cancer death rates continue to decline. The excess risk of cancer death in black men has dropped from 47% in 1990 to 21% in 2014. The black/white disparity declined similarly in women, from a peak of 20% in 1998 to 13% in 2014.

On the other hand, significant gender disparities persist for both cancer incidence and death in the US. For all cancer sites combined, the incidence rate is 20% higher in men than in women, and the cancer death rate is 40% higher in men.

Dr Brawley said the gender gap in cancer mortality largely reflects variation in the distribution of cancers that occur in men and women, much of which is due to differences in the prevalence of cancer risk factors.

The yearly “Cancer Statistics” reports have been published by ACS researchers since 1967 to inform and guide clinicians, investigators, and others in public health in prioritizing efforts to reduce the burden of cancer.

Cancer incidence data for the current report were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics.

The US may see nearly 1.7 million new cancer cases in 2017 and more than 600,000 cancer-related deaths, according to a report from the American Cancer Society (ACS).

In addition to estimates for 2017, the report, “Cancer Statistics 2017,” includes the most recent data on cancer incidence, mortality, and survival in the US.

The report was published in CA: A Cancer Journal for Clinicians.

The report projects there will be 1,688,780 new cancer cases and 600,920 cancer deaths in the US this year.

This includes:

• 80,500 new cases of lymphoma and 21,210 lymphoma deaths
• 62,130 new cases of leukemia and 24,500 leukemia deaths
• 30,280 new cases of myeloma and 12,590 myeloma deaths.

The report also shows that, from 2004 to 2013, the overall cancer incidence rate was stable in women and declined by about 2% per year in men. From 2005 to 2014, the cancer death rate declined by about 1.5% annually in both men and women.

Overall, the cancer death rate dropped 25% from its peak of 215.1 (per 100,000 population) in 1991 to 161.2 (per 100,000 population) in 2014, the latest year for which data was available. This translates to about 2,143,200 fewer cancer deaths.

“The continuing drops in the cancer death rate are a powerful sign of the potential we have to reduce cancer’s deadly toll,” said Otis W. Brawley, MD, chief medical officer of the ACS.

He said the decrease in cancer death rates is the result of steady reductions in smoking and advances in early detection and treatment. The decrease is driven by decreasing death rates for the 4 major cancer sites—lung, breast, colorectal, and prostate.

The report also shows that racial disparities in cancer death rates continue to decline. The excess risk of cancer death in black men has dropped from 47% in 1990 to 21% in 2014. The black/white disparity declined similarly in women, from a peak of 20% in 1998 to 13% in 2014.

On the other hand, significant gender disparities persist for both cancer incidence and death in the US. For all cancer sites combined, the incidence rate is 20% higher in men than in women, and the cancer death rate is 40% higher in men.

Dr Brawley said the gender gap in cancer mortality largely reflects variation in the distribution of cancers that occur in men and women, much of which is due to differences in the prevalence of cancer risk factors.

The yearly “Cancer Statistics” reports have been published by ACS researchers since 1967 to inform and guide clinicians, investigators, and others in public health in prioritizing efforts to reduce the burden of cancer.

Cancer incidence data for the current report were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics.

The US may see nearly 1.7 million new cancer cases in 2017 and more than 600,000 cancer-related deaths, according to a report from the American Cancer Society (ACS).

In addition to estimates for 2017, the report, “Cancer Statistics 2017,” includes the most recent data on cancer incidence, mortality, and survival in the US.

The report was published in CA: A Cancer Journal for Clinicians.

The report projects there will be 1,688,780 new cancer cases and 600,920 cancer deaths in the US this year.

This includes:

• 80,500 new cases of lymphoma and 21,210 lymphoma deaths
• 62,130 new cases of leukemia and 24,500 leukemia deaths
• 30,280 new cases of myeloma and 12,590 myeloma deaths.

The report also shows that, from 2004 to 2013, the overall cancer incidence rate was stable in women and declined by about 2% per year in men. From 2005 to 2014, the cancer death rate declined by about 1.5% annually in both men and women.

Overall, the cancer death rate dropped 25% from its peak of 215.1 (per 100,000 population) in 1991 to 161.2 (per 100,000 population) in 2014, the latest year for which data was available. This translates to about 2,143,200 fewer cancer deaths.

“The continuing drops in the cancer death rate are a powerful sign of the potential we have to reduce cancer’s deadly toll,” said Otis W. Brawley, MD, chief medical officer of the ACS.

He said the decrease in cancer death rates is the result of steady reductions in smoking and advances in early detection and treatment. The decrease is driven by decreasing death rates for the 4 major cancer sites—lung, breast, colorectal, and prostate.

The report also shows that racial disparities in cancer death rates continue to decline. The excess risk of cancer death in black men has dropped from 47% in 1990 to 21% in 2014. The black/white disparity declined similarly in women, from a peak of 20% in 1998 to 13% in 2014.

On the other hand, significant gender disparities persist for both cancer incidence and death in the US. For all cancer sites combined, the incidence rate is 20% higher in men than in women, and the cancer death rate is 40% higher in men.

Dr Brawley said the gender gap in cancer mortality largely reflects variation in the distribution of cancers that occur in men and women, much of which is due to differences in the prevalence of cancer risk factors.

The yearly “Cancer Statistics” reports have been published by ACS researchers since 1967 to inform and guide clinicians, investigators, and others in public health in prioritizing efforts to reduce the burden of cancer.

Cancer incidence data for the current report were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics.

The American Association for Cancer Research (AACR) has announced the first public release of cancer genomic data aggregated through the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE).

The data set includes nearly 19,000 de-identified genomic records collected from patients who were treated at 8 international institutions, making it one of the largest public cancer genomic data sets released to date.

The release includes data for 59 major cancer types, including leukemias, lymphomas, and multiple myeloma.

The genomic data and a limited amount of linked clinical data for each patient can be accessed via the AACR Project GENIE cBioPortal or from Sage Bionetworks. (Users must create an account for either site to access the data.)

“We are excited to make publicly available this very large set of clinical-grade, next-generation sequencing data obtained during routine patient care,” said Charles L. Sawyers, MD, AACR Project GENIE Steering Committee chairperson.

“These data were generated as part of routine patient care and, without AACR Project GENIE, they would likely never have been shared with the global cancer research community.”

AACR Project GENIE is a multi-phase, international data-sharing project aimed at catalyzing precision oncology through the development of a registry that aggregates and links clinical-grade cancer genomic data with clinical outcomes from tens of thousands of cancer patients treated at multiple institutions.

The newly released data are fully de-identified in compliance with the Health Insurance Portability and Accountability Act (HIPAA).

The data are derived from patients whose tumors were genetically sequenced as part of their care at any of the 8 institutions that participated in the first phase of AACR Project GENIE.

The goal of releasing these data to the cancer research community is to aid new research that will accelerate the pace of progress against cancer.

According to AACR, the data can be used to validate gene signatures of drug response or prognosis, identify new patient populations for drugs that are currently available, and uncover new drug targets and biomarkers.

“I am extremely proud that the American Association for Cancer Research, as the coordinating center for AACR Project GENIE, is delivering on its promise to make these important data publicly available just over a year after unveiling the initiative,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

To expand the AACR Project GENIE registry, the consortium is accepting applications for new participating centers. Any nonprofit institution that meets certain criteria can submit an application to become a project participant.

For more information on AACR Project GENIE, visit the project website or send an email to info@aacrgenie.org.

The American Association for Cancer Research (AACR) has announced the first public release of cancer genomic data aggregated through the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE).

The data set includes nearly 19,000 de-identified genomic records collected from patients who were treated at 8 international institutions, making it one of the largest public cancer genomic data sets released to date.

The release includes data for 59 major cancer types, including leukemias, lymphomas, and multiple myeloma.

The genomic data and a limited amount of linked clinical data for each patient can be accessed via the AACR Project GENIE cBioPortal or from Sage Bionetworks. (Users must create an account for either site to access the data.)

“We are excited to make publicly available this very large set of clinical-grade, next-generation sequencing data obtained during routine patient care,” said Charles L. Sawyers, MD, AACR Project GENIE Steering Committee chairperson.

“These data were generated as part of routine patient care and, without AACR Project GENIE, they would likely never have been shared with the global cancer research community.”

AACR Project GENIE is a multi-phase, international data-sharing project aimed at catalyzing precision oncology through the development of a registry that aggregates and links clinical-grade cancer genomic data with clinical outcomes from tens of thousands of cancer patients treated at multiple institutions.

The newly released data are fully de-identified in compliance with the Health Insurance Portability and Accountability Act (HIPAA).

The data are derived from patients whose tumors were genetically sequenced as part of their care at any of the 8 institutions that participated in the first phase of AACR Project GENIE.

The goal of releasing these data to the cancer research community is to aid new research that will accelerate the pace of progress against cancer.

According to AACR, the data can be used to validate gene signatures of drug response or prognosis, identify new patient populations for drugs that are currently available, and uncover new drug targets and biomarkers.

“I am extremely proud that the American Association for Cancer Research, as the coordinating center for AACR Project GENIE, is delivering on its promise to make these important data publicly available just over a year after unveiling the initiative,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

To expand the AACR Project GENIE registry, the consortium is accepting applications for new participating centers. Any nonprofit institution that meets certain criteria can submit an application to become a project participant.

For more information on AACR Project GENIE, visit the project website or send an email to info@aacrgenie.org.

The American Association for Cancer Research (AACR) has announced the first public release of cancer genomic data aggregated through the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE).

The data set includes nearly 19,000 de-identified genomic records collected from patients who were treated at 8 international institutions, making it one of the largest public cancer genomic data sets released to date.

The release includes data for 59 major cancer types, including leukemias, lymphomas, and multiple myeloma.

The genomic data and a limited amount of linked clinical data for each patient can be accessed via the AACR Project GENIE cBioPortal or from Sage Bionetworks. (Users must create an account for either site to access the data.)

“We are excited to make publicly available this very large set of clinical-grade, next-generation sequencing data obtained during routine patient care,” said Charles L. Sawyers, MD, AACR Project GENIE Steering Committee chairperson.

“These data were generated as part of routine patient care and, without AACR Project GENIE, they would likely never have been shared with the global cancer research community.”

AACR Project GENIE is a multi-phase, international data-sharing project aimed at catalyzing precision oncology through the development of a registry that aggregates and links clinical-grade cancer genomic data with clinical outcomes from tens of thousands of cancer patients treated at multiple institutions.

The newly released data are fully de-identified in compliance with the Health Insurance Portability and Accountability Act (HIPAA).

The data are derived from patients whose tumors were genetically sequenced as part of their care at any of the 8 institutions that participated in the first phase of AACR Project GENIE.

The goal of releasing these data to the cancer research community is to aid new research that will accelerate the pace of progress against cancer.

According to AACR, the data can be used to validate gene signatures of drug response or prognosis, identify new patient populations for drugs that are currently available, and uncover new drug targets and biomarkers.

“I am extremely proud that the American Association for Cancer Research, as the coordinating center for AACR Project GENIE, is delivering on its promise to make these important data publicly available just over a year after unveiling the initiative,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

To expand the AACR Project GENIE registry, the consortium is accepting applications for new participating centers. Any nonprofit institution that meets certain criteria can submit an application to become a project participant.

For more information on AACR Project GENIE, visit the project website or send an email to info@aacrgenie.org.

 

SAN DIEGO – Dual therapy with lenalidomide and epoetin alfa was safe and led to freedom from transfusion significantly more often than lenalidomide alone in patients with erythropoietin-refractory, lower-risk, non-del(5q) myelodysplastic syndromes, according to a randomized phase III head-to-head trial.

After 16 weeks of treatment, 33% of patients who received both lenalidomide and epoetin alfa met International Working Group 2000 criteria for major erythroid response, compared with only 14% of patients receiving lenalidomide monotherapy (P = .03), Alan F. List, MD, reported at the annual meeting of the American Society of Hematology.

H. Lee Moffitt Cancer Center

Combination therapy also worked longer – median duration of response was 25 months, versus 13 months for lenalidomide only, said Dr. List of H. Lee Moffitt Cancer Center and Research Institute in Tampa. These results illustrate the power of lenalidomide to restore sensitivity to epoetin alfa in patients with lower-risk, non-del(5q) myelodysplastic syndrome (MDS), he emphasized.

Recombinant human erythropoietin improves anemia in some cases of MDS, but salvage options are limited. “Cytokine therapy is generally ineffective in patients with high transfusion burden or elevated serum erythropoietin level,” Dr. List said.

Lenalidomide (Revlimid) promotes the in vitro expansion of primitive erythroid precursors, and in a recent phase III, placebo-controlled trial, the immunomodulator improved erythropoiesis in about 25% of lower-risk, non-del(5q) MDS patients who were azanucleoside-naïve and transfusion-dependent, with effects lasting about 8 months. In another pilot study, adding epoetin alfa to lenalidomide induced erythroid responses in 28% of MDS patients who were not responding to lenalidomide alone. “This suggests that lenalidomide overcomes resistance and augments response to recombinant human erythropoietin,” Dr. List explained.

For their phase III trial, he and his associates randomly assigned erythropoietin-refractory, lower-risk, non-del(5q) MDS patients with hemoglobin levels under 9.5 g/dL to receive lenalidomide (10 mg per day for 21 days every 28 days) with or without epoetin alfa (weekly dose, 60,000 units subcutaneously). A total of 14% of patients had previously received azanucleoside therapy, about 92% had received erythropoietic stimulating agents, and median serum erythropoietin levels were 167 and 143 mU per mL in the monotherapy and dual therapy arms, respectively.

In accordance with International Working Group 2000 criteria, the researchers defined major erythroid response as transfusion independence for least 8 consecutive weeks, with at least a 1 g/dL increase in hemoglobin levels if patients were transfusion-dependent at baseline, and at least a 2 g/dL rise in hemoglobin if they were transfusion-independent.

In an interim analysis of 163 patients, 26% of the dual therapy group and 11% of lenalidomide-only patients met this primary endpoint (P = .02). These results met predefined criteria for stopping the study, after which 34 lenalidomide nonresponders crossed over to dual therapy. In all, 21% of these patients also had a major erythroid response, Dr. List said.

A multivariable analysis that included disease duration, International Prognostic Scoring System low versus intermediate-1 risk status, baseline erythropoietin level, and prior azanucleoside exposure showed that only dual lenalidomide–epoetin alfa therapy predicted major erythroid response. Specifically, dual therapy increased the odds of this outcome by about 63% when compared with lenalidomide monotherapy (P = .03).

Secondary analyses linked major erythroid response to having more low than high molecular weight CD45 isoform. In fact, the median ratio of high to low molecular weight CD45 was 1.5 among responders and 4.2 among nonresponders (P = .04) This finding fits the hypothesis that larger CD45 isoforms keep lenalidomide from enhancing erythropoietin receptor signaling, Dr. List said. Indeed, rates of major erythroid response to lenalidomide–epoetin alfa therapy were 73% when patients had a low isoform ratio, but were only 18% when they had a high isoform ratio (P = .03). The CD45 isoform ratio distinguished responders from nonresponders with a sensitivity and specificity of 80% and 75%, respectively, Dr. List said.

Grade 3 or higher nonhematologic events affected about a quarter of patients in each arm, and rates of individual events were similar. The most common serious adverse event was fatigue (5% of patients), followed by elevated serum creatinine (3.7%). About 10% of patients in each arm died while on study.

The National Institutes of Health supported the study. Dr. List had no relevant financial disclosures.

 

SAN DIEGO – Dual therapy with lenalidomide and epoetin alfa was safe and led to freedom from transfusion significantly more often than lenalidomide alone in patients with erythropoietin-refractory, lower-risk, non-del(5q) myelodysplastic syndromes, according to a randomized phase III head-to-head trial.

After 16 weeks of treatment, 33% of patients who received both lenalidomide and epoetin alfa met International Working Group 2000 criteria for major erythroid response, compared with only 14% of patients receiving lenalidomide monotherapy (P = .03), Alan F. List, MD, reported at the annual meeting of the American Society of Hematology.

H. Lee Moffitt Cancer Center

Combination therapy also worked longer – median duration of response was 25 months, versus 13 months for lenalidomide only, said Dr. List of H. Lee Moffitt Cancer Center and Research Institute in Tampa. These results illustrate the power of lenalidomide to restore sensitivity to epoetin alfa in patients with lower-risk, non-del(5q) myelodysplastic syndrome (MDS), he emphasized.

Recombinant human erythropoietin improves anemia in some cases of MDS, but salvage options are limited. “Cytokine therapy is generally ineffective in patients with high transfusion burden or elevated serum erythropoietin level,” Dr. List said.

Lenalidomide (Revlimid) promotes the in vitro expansion of primitive erythroid precursors, and in a recent phase III, placebo-controlled trial, the immunomodulator improved erythropoiesis in about 25% of lower-risk, non-del(5q) MDS patients who were azanucleoside-naïve and transfusion-dependent, with effects lasting about 8 months. In another pilot study, adding epoetin alfa to lenalidomide induced erythroid responses in 28% of MDS patients who were not responding to lenalidomide alone. “This suggests that lenalidomide overcomes resistance and augments response to recombinant human erythropoietin,” Dr. List explained.

For their phase III trial, he and his associates randomly assigned erythropoietin-refractory, lower-risk, non-del(5q) MDS patients with hemoglobin levels under 9.5 g/dL to receive lenalidomide (10 mg per day for 21 days every 28 days) with or without epoetin alfa (weekly dose, 60,000 units subcutaneously). A total of 14% of patients had previously received azanucleoside therapy, about 92% had received erythropoietic stimulating agents, and median serum erythropoietin levels were 167 and 143 mU per mL in the monotherapy and dual therapy arms, respectively.

In accordance with International Working Group 2000 criteria, the researchers defined major erythroid response as transfusion independence for least 8 consecutive weeks, with at least a 1 g/dL increase in hemoglobin levels if patients were transfusion-dependent at baseline, and at least a 2 g/dL rise in hemoglobin if they were transfusion-independent.

In an interim analysis of 163 patients, 26% of the dual therapy group and 11% of lenalidomide-only patients met this primary endpoint (P = .02). These results met predefined criteria for stopping the study, after which 34 lenalidomide nonresponders crossed over to dual therapy. In all, 21% of these patients also had a major erythroid response, Dr. List said.

A multivariable analysis that included disease duration, International Prognostic Scoring System low versus intermediate-1 risk status, baseline erythropoietin level, and prior azanucleoside exposure showed that only dual lenalidomide–epoetin alfa therapy predicted major erythroid response. Specifically, dual therapy increased the odds of this outcome by about 63% when compared with lenalidomide monotherapy (P = .03).

Secondary analyses linked major erythroid response to having more low than high molecular weight CD45 isoform. In fact, the median ratio of high to low molecular weight CD45 was 1.5 among responders and 4.2 among nonresponders (P = .04) This finding fits the hypothesis that larger CD45 isoforms keep lenalidomide from enhancing erythropoietin receptor signaling, Dr. List said. Indeed, rates of major erythroid response to lenalidomide–epoetin alfa therapy were 73% when patients had a low isoform ratio, but were only 18% when they had a high isoform ratio (P = .03). The CD45 isoform ratio distinguished responders from nonresponders with a sensitivity and specificity of 80% and 75%, respectively, Dr. List said.

Grade 3 or higher nonhematologic events affected about a quarter of patients in each arm, and rates of individual events were similar. The most common serious adverse event was fatigue (5% of patients), followed by elevated serum creatinine (3.7%). About 10% of patients in each arm died while on study.

The National Institutes of Health supported the study. Dr. List had no relevant financial disclosures.

 

SAN DIEGO – Dual therapy with lenalidomide and epoetin alfa was safe and led to freedom from transfusion significantly more often than lenalidomide alone in patients with erythropoietin-refractory, lower-risk, non-del(5q) myelodysplastic syndromes, according to a randomized phase III head-to-head trial.

After 16 weeks of treatment, 33% of patients who received both lenalidomide and epoetin alfa met International Working Group 2000 criteria for major erythroid response, compared with only 14% of patients receiving lenalidomide monotherapy (P = .03), Alan F. List, MD, reported at the annual meeting of the American Society of Hematology.

H. Lee Moffitt Cancer Center

Combination therapy also worked longer – median duration of response was 25 months, versus 13 months for lenalidomide only, said Dr. List of H. Lee Moffitt Cancer Center and Research Institute in Tampa. These results illustrate the power of lenalidomide to restore sensitivity to epoetin alfa in patients with lower-risk, non-del(5q) myelodysplastic syndrome (MDS), he emphasized.

Recombinant human erythropoietin improves anemia in some cases of MDS, but salvage options are limited. “Cytokine therapy is generally ineffective in patients with high transfusion burden or elevated serum erythropoietin level,” Dr. List said.

Lenalidomide (Revlimid) promotes the in vitro expansion of primitive erythroid precursors, and in a recent phase III, placebo-controlled trial, the immunomodulator improved erythropoiesis in about 25% of lower-risk, non-del(5q) MDS patients who were azanucleoside-naïve and transfusion-dependent, with effects lasting about 8 months. In another pilot study, adding epoetin alfa to lenalidomide induced erythroid responses in 28% of MDS patients who were not responding to lenalidomide alone. “This suggests that lenalidomide overcomes resistance and augments response to recombinant human erythropoietin,” Dr. List explained.

For their phase III trial, he and his associates randomly assigned erythropoietin-refractory, lower-risk, non-del(5q) MDS patients with hemoglobin levels under 9.5 g/dL to receive lenalidomide (10 mg per day for 21 days every 28 days) with or without epoetin alfa (weekly dose, 60,000 units subcutaneously). A total of 14% of patients had previously received azanucleoside therapy, about 92% had received erythropoietic stimulating agents, and median serum erythropoietin levels were 167 and 143 mU per mL in the monotherapy and dual therapy arms, respectively.

In accordance with International Working Group 2000 criteria, the researchers defined major erythroid response as transfusion independence for least 8 consecutive weeks, with at least a 1 g/dL increase in hemoglobin levels if patients were transfusion-dependent at baseline, and at least a 2 g/dL rise in hemoglobin if they were transfusion-independent.

In an interim analysis of 163 patients, 26% of the dual therapy group and 11% of lenalidomide-only patients met this primary endpoint (P = .02). These results met predefined criteria for stopping the study, after which 34 lenalidomide nonresponders crossed over to dual therapy. In all, 21% of these patients also had a major erythroid response, Dr. List said.

A multivariable analysis that included disease duration, International Prognostic Scoring System low versus intermediate-1 risk status, baseline erythropoietin level, and prior azanucleoside exposure showed that only dual lenalidomide–epoetin alfa therapy predicted major erythroid response. Specifically, dual therapy increased the odds of this outcome by about 63% when compared with lenalidomide monotherapy (P = .03).

Secondary analyses linked major erythroid response to having more low than high molecular weight CD45 isoform. In fact, the median ratio of high to low molecular weight CD45 was 1.5 among responders and 4.2 among nonresponders (P = .04) This finding fits the hypothesis that larger CD45 isoforms keep lenalidomide from enhancing erythropoietin receptor signaling, Dr. List said. Indeed, rates of major erythroid response to lenalidomide–epoetin alfa therapy were 73% when patients had a low isoform ratio, but were only 18% when they had a high isoform ratio (P = .03). The CD45 isoform ratio distinguished responders from nonresponders with a sensitivity and specificity of 80% and 75%, respectively, Dr. List said.

Grade 3 or higher nonhematologic events affected about a quarter of patients in each arm, and rates of individual events were similar. The most common serious adverse event was fatigue (5% of patients), followed by elevated serum creatinine (3.7%). About 10% of patients in each arm died while on study.

The National Institutes of Health supported the study. Dr. List had no relevant financial disclosures.

Preclinical research indicates that a protein associated with obesity is also involved in the development of acute myeloid leukemia (AML) and may affect AML patients’ response to treatment.

Researchers found evidence to suggest that the fat mass- and obesity-associated protein (FTO) regulates the expression of a set of genes through a mechanism involving RNA modification, thereby increasing the reproduction of leukemia cells and prohibiting drug response. 

Jianjun Chen, PhD, of the University of Cincinnati in Ohio, and his colleagues conducted this research and reported the findings in Cancer Cell.

The team noted that N6-methyladenosine (m6A) RNA methylation is the most prevalent internal modification in messenger RNAs (mRNAs) in genes. And they found that FTO, an m6A demethylase, plays a critical oncogenic role in AML.

The researchers made this discovery by analyzing 2 microarray datasets of samples from AML as well as samples from control subjects.

The team found that FTO was highly expressed in AMLs with t(11q23)/MLL rearrangements, t(15;17)/PML-RARA, FLT3-ITD, and/or NPM1 mutations.

The high level of FTO expression contributed to leukemia cells multiplying and surviving and also promoted the development of AML in animal models and the non-response of AML cells to therapeutic agents.

Additionally, the researchers found that genes like ASB2 and RARA, which were reported to inhibit leukemia cell growth and/or mediate the response of leukemia cells to therapeutic agents, were suppressed in the AML samples with higher FTO expression.

The suppression of these genes was attributed to FTO-controlled decreased stability of their mRNA and was connected to FTO’s m6A demethylase activity.

“Our study shows, for the first time, the functional importance of the m6A modification machinery in leukemia,” Dr Chen said. “In addition, given the functional importance of FTO in the formation of leukemia and drug response, targeting FTO signaling may present a new therapeutic strategy to treat leukemia.”

“As FTO may also play a cancer-promoting role in various types of solid tumors, besides leukemia, our discoveries may have a broad impact in cancer biology and cancer therapy. Further studies are needed to advance our understanding of the critical role of FTO in various types of cancers and to develop more effective novel therapeutic strategies based on such understanding to treat cancers.”

Preclinical research indicates that a protein associated with obesity is also involved in the development of acute myeloid leukemia (AML) and may affect AML patients’ response to treatment.

Researchers found evidence to suggest that the fat mass- and obesity-associated protein (FTO) regulates the expression of a set of genes through a mechanism involving RNA modification, thereby increasing the reproduction of leukemia cells and prohibiting drug response. 

Jianjun Chen, PhD, of the University of Cincinnati in Ohio, and his colleagues conducted this research and reported the findings in Cancer Cell.

The team noted that N6-methyladenosine (m6A) RNA methylation is the most prevalent internal modification in messenger RNAs (mRNAs) in genes. And they found that FTO, an m6A demethylase, plays a critical oncogenic role in AML.

The researchers made this discovery by analyzing 2 microarray datasets of samples from AML as well as samples from control subjects.

The team found that FTO was highly expressed in AMLs with t(11q23)/MLL rearrangements, t(15;17)/PML-RARA, FLT3-ITD, and/or NPM1 mutations.

The high level of FTO expression contributed to leukemia cells multiplying and surviving and also promoted the development of AML in animal models and the non-response of AML cells to therapeutic agents.

Additionally, the researchers found that genes like ASB2 and RARA, which were reported to inhibit leukemia cell growth and/or mediate the response of leukemia cells to therapeutic agents, were suppressed in the AML samples with higher FTO expression.

The suppression of these genes was attributed to FTO-controlled decreased stability of their mRNA and was connected to FTO’s m6A demethylase activity.

“Our study shows, for the first time, the functional importance of the m6A modification machinery in leukemia,” Dr Chen said. “In addition, given the functional importance of FTO in the formation of leukemia and drug response, targeting FTO signaling may present a new therapeutic strategy to treat leukemia.”

“As FTO may also play a cancer-promoting role in various types of solid tumors, besides leukemia, our discoveries may have a broad impact in cancer biology and cancer therapy. Further studies are needed to advance our understanding of the critical role of FTO in various types of cancers and to develop more effective novel therapeutic strategies based on such understanding to treat cancers.”

Preclinical research indicates that a protein associated with obesity is also involved in the development of acute myeloid leukemia (AML) and may affect AML patients’ response to treatment.

Researchers found evidence to suggest that the fat mass- and obesity-associated protein (FTO) regulates the expression of a set of genes through a mechanism involving RNA modification, thereby increasing the reproduction of leukemia cells and prohibiting drug response. 

Jianjun Chen, PhD, of the University of Cincinnati in Ohio, and his colleagues conducted this research and reported the findings in Cancer Cell.

The team noted that N6-methyladenosine (m6A) RNA methylation is the most prevalent internal modification in messenger RNAs (mRNAs) in genes. And they found that FTO, an m6A demethylase, plays a critical oncogenic role in AML.

The researchers made this discovery by analyzing 2 microarray datasets of samples from AML as well as samples from control subjects.

The team found that FTO was highly expressed in AMLs with t(11q23)/MLL rearrangements, t(15;17)/PML-RARA, FLT3-ITD, and/or NPM1 mutations.

The high level of FTO expression contributed to leukemia cells multiplying and surviving and also promoted the development of AML in animal models and the non-response of AML cells to therapeutic agents.

Additionally, the researchers found that genes like ASB2 and RARA, which were reported to inhibit leukemia cell growth and/or mediate the response of leukemia cells to therapeutic agents, were suppressed in the AML samples with higher FTO expression.

The suppression of these genes was attributed to FTO-controlled decreased stability of their mRNA and was connected to FTO’s m6A demethylase activity.

“Our study shows, for the first time, the functional importance of the m6A modification machinery in leukemia,” Dr Chen said. “In addition, given the functional importance of FTO in the formation of leukemia and drug response, targeting FTO signaling may present a new therapeutic strategy to treat leukemia.”

“As FTO may also play a cancer-promoting role in various types of solid tumors, besides leukemia, our discoveries may have a broad impact in cancer biology and cancer therapy. Further studies are needed to advance our understanding of the critical role of FTO in various types of cancers and to develop more effective novel therapeutic strategies based on such understanding to treat cancers.”

Results of a small study suggest a single dose of the hallucinogenic drug psilocybin, when combined with counseling, can significantly lessen psychological distress in cancer patients for months at a time.

The study showed that psychological counseling and a single dose of psilocybin brought relief from distress that lasted for more than 6 months in a majority of the subjects monitored.

This was based on clinical evaluation scores for anxiety and depression.

“Our results represent the strongest evidence to date of a clinical benefit from psilocybin therapy, with the potential to transform care for patients with cancer-related psychological distress,” said study author Stephen Ross, MD, of New York University School of Medicine in New York, New York.

“If larger clinical trials prove successful, then we could ultimately have available a safe, effective, and inexpensive medication—dispensed under strict control—to alleviate the distress that increases suicide rates among cancer patients.”

Dr Ross and his colleagues reported the results of their study in the Journal of Psychopharmacology alongside a related study and 11 accompanying editorials.

Dr Ross’s study included 29 patients with cancer-related anxiety and depression. Their mean age was 56, and 62% were female. Ninety percent were Caucasian, and 10% were classified as “other” race.

Patients had breast cancer (31%), reproductive cancers (28%), digestive cancers (17%), leukemia/lymphoma (14%), and other cancers (10%).

All patients had been diagnosed as suffering from serious psychological distress related to their disease.

Treatment

Half of the patients were randomly assigned to receive a 0.3 mg/kg dose of psilocybin, and half received a vitamin placebo (250 mg of niacin) known to produce a “rush” that mimics a hallucinogenic drug experience.

Approximately half way through the study’s monitoring period (after 7 weeks), all patients switched treatments. Those who initially received psilocybin took a single dose of niacin, and vice-versa. Neither patients nor researchers knew who had first received psilocybin or placebo.

All patients were provided with tailored counseling from a psychiatrist, psychologist, nurse, or social worker. And the patients were monitored for side effects and improvements in their mental state.

Safety

The researchers said there were no serious adverse events (AEs), either medical or psychiatric, that were attributed to psilocybin.

The most common medical AEs that were attributable to psilocybin were non-clinically significant elevations in blood pressure and heart rate (76%), headaches/migraines (28%), and nausea (14%).

The most common psychiatric AEs attributable to psilocybin were transient anxiety (17%) and transient psychotic-like symptoms (7%; 1 case of transient paranoid ideation and 1 case of transient thought disorder).
 
Efficacy

The researchers said that, prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression.

Specifically, patients who received psilocybin first had significant improvements in responses on the Hospital Anxiety and Depression Scale and the Beck Depression Inventory, when compared to patients who received niacin first.

The differences were significant 1 day after the patients’ first session and 7 weeks after the first session (P≤0.01 for all).

At the 6.5-month follow-up, 60% to 80% of participants continued with clinically significant reductions in depression or anxiety.

The researchers said a key finding of this study was that improvements in clinical evaluation scores for anxiety and depression lasted for the study’s extended monitoring period, which was 8 months for those who took psilocybin first.

Patients also reported post-psilocybin improvements in their quality of life, such as going out more, greater energy, getting along better with family members, and doing well at work. Some reported variations of spirituality, unusual peacefulness, and increased feelings of altruism.

“Our study showed that psilocybin facilitated experiences that drove reductions in psychological distress,” said study author Anthony Bossis, PhD, of New York University School of Medicine. “And if it’s true for cancer care, then it could apply to other stressful medical conditions.”

He cautioned that patients should not consume psilocybin on their own or without supervision from a physician and a trained counselor.

“Psilocybin therapy may not work for everyone,” he noted. “And some groups, such as people with schizophrenia, as well as adolescents, should not be treated with it.”

Results of a small study suggest a single dose of the hallucinogenic drug psilocybin, when combined with counseling, can significantly lessen psychological distress in cancer patients for months at a time.

The study showed that psychological counseling and a single dose of psilocybin brought relief from distress that lasted for more than 6 months in a majority of the subjects monitored.

This was based on clinical evaluation scores for anxiety and depression.

“Our results represent the strongest evidence to date of a clinical benefit from psilocybin therapy, with the potential to transform care for patients with cancer-related psychological distress,” said study author Stephen Ross, MD, of New York University School of Medicine in New York, New York.

“If larger clinical trials prove successful, then we could ultimately have available a safe, effective, and inexpensive medication—dispensed under strict control—to alleviate the distress that increases suicide rates among cancer patients.”

Dr Ross and his colleagues reported the results of their study in the Journal of Psychopharmacology alongside a related study and 11 accompanying editorials.

Dr Ross’s study included 29 patients with cancer-related anxiety and depression. Their mean age was 56, and 62% were female. Ninety percent were Caucasian, and 10% were classified as “other” race.

Patients had breast cancer (31%), reproductive cancers (28%), digestive cancers (17%), leukemia/lymphoma (14%), and other cancers (10%).

All patients had been diagnosed as suffering from serious psychological distress related to their disease.

Treatment

Half of the patients were randomly assigned to receive a 0.3 mg/kg dose of psilocybin, and half received a vitamin placebo (250 mg of niacin) known to produce a “rush” that mimics a hallucinogenic drug experience.

Approximately half way through the study’s monitoring period (after 7 weeks), all patients switched treatments. Those who initially received psilocybin took a single dose of niacin, and vice-versa. Neither patients nor researchers knew who had first received psilocybin or placebo.

All patients were provided with tailored counseling from a psychiatrist, psychologist, nurse, or social worker. And the patients were monitored for side effects and improvements in their mental state.

Safety

The researchers said there were no serious adverse events (AEs), either medical or psychiatric, that were attributed to psilocybin.

The most common medical AEs that were attributable to psilocybin were non-clinically significant elevations in blood pressure and heart rate (76%), headaches/migraines (28%), and nausea (14%).

The most common psychiatric AEs attributable to psilocybin were transient anxiety (17%) and transient psychotic-like symptoms (7%; 1 case of transient paranoid ideation and 1 case of transient thought disorder).
 
Efficacy

The researchers said that, prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression.

Specifically, patients who received psilocybin first had significant improvements in responses on the Hospital Anxiety and Depression Scale and the Beck Depression Inventory, when compared to patients who received niacin first.

The differences were significant 1 day after the patients’ first session and 7 weeks after the first session (P≤0.01 for all).

At the 6.5-month follow-up, 60% to 80% of participants continued with clinically significant reductions in depression or anxiety.

The researchers said a key finding of this study was that improvements in clinical evaluation scores for anxiety and depression lasted for the study’s extended monitoring period, which was 8 months for those who took psilocybin first.

Patients also reported post-psilocybin improvements in their quality of life, such as going out more, greater energy, getting along better with family members, and doing well at work. Some reported variations of spirituality, unusual peacefulness, and increased feelings of altruism.

“Our study showed that psilocybin facilitated experiences that drove reductions in psychological distress,” said study author Anthony Bossis, PhD, of New York University School of Medicine. “And if it’s true for cancer care, then it could apply to other stressful medical conditions.”

He cautioned that patients should not consume psilocybin on their own or without supervision from a physician and a trained counselor.

“Psilocybin therapy may not work for everyone,” he noted. “And some groups, such as people with schizophrenia, as well as adolescents, should not be treated with it.”

Results of a small study suggest a single dose of the hallucinogenic drug psilocybin, when combined with counseling, can significantly lessen psychological distress in cancer patients for months at a time.

The study showed that psychological counseling and a single dose of psilocybin brought relief from distress that lasted for more than 6 months in a majority of the subjects monitored.

This was based on clinical evaluation scores for anxiety and depression.

“Our results represent the strongest evidence to date of a clinical benefit from psilocybin therapy, with the potential to transform care for patients with cancer-related psychological distress,” said study author Stephen Ross, MD, of New York University School of Medicine in New York, New York.

“If larger clinical trials prove successful, then we could ultimately have available a safe, effective, and inexpensive medication—dispensed under strict control—to alleviate the distress that increases suicide rates among cancer patients.”

Dr Ross and his colleagues reported the results of their study in the Journal of Psychopharmacology alongside a related study and 11 accompanying editorials.

Dr Ross’s study included 29 patients with cancer-related anxiety and depression. Their mean age was 56, and 62% were female. Ninety percent were Caucasian, and 10% were classified as “other” race.

Patients had breast cancer (31%), reproductive cancers (28%), digestive cancers (17%), leukemia/lymphoma (14%), and other cancers (10%).

All patients had been diagnosed as suffering from serious psychological distress related to their disease.

Treatment

Half of the patients were randomly assigned to receive a 0.3 mg/kg dose of psilocybin, and half received a vitamin placebo (250 mg of niacin) known to produce a “rush” that mimics a hallucinogenic drug experience.

Approximately half way through the study’s monitoring period (after 7 weeks), all patients switched treatments. Those who initially received psilocybin took a single dose of niacin, and vice-versa. Neither patients nor researchers knew who had first received psilocybin or placebo.

All patients were provided with tailored counseling from a psychiatrist, psychologist, nurse, or social worker. And the patients were monitored for side effects and improvements in their mental state.

Safety

The researchers said there were no serious adverse events (AEs), either medical or psychiatric, that were attributed to psilocybin.

The most common medical AEs that were attributable to psilocybin were non-clinically significant elevations in blood pressure and heart rate (76%), headaches/migraines (28%), and nausea (14%).

The most common psychiatric AEs attributable to psilocybin were transient anxiety (17%) and transient psychotic-like symptoms (7%; 1 case of transient paranoid ideation and 1 case of transient thought disorder).
 
Efficacy

The researchers said that, prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression.

Specifically, patients who received psilocybin first had significant improvements in responses on the Hospital Anxiety and Depression Scale and the Beck Depression Inventory, when compared to patients who received niacin first.

The differences were significant 1 day after the patients’ first session and 7 weeks after the first session (P≤0.01 for all).

At the 6.5-month follow-up, 60% to 80% of participants continued with clinically significant reductions in depression or anxiety.

The researchers said a key finding of this study was that improvements in clinical evaluation scores for anxiety and depression lasted for the study’s extended monitoring period, which was 8 months for those who took psilocybin first.

Patients also reported post-psilocybin improvements in their quality of life, such as going out more, greater energy, getting along better with family members, and doing well at work. Some reported variations of spirituality, unusual peacefulness, and increased feelings of altruism.

“Our study showed that psilocybin facilitated experiences that drove reductions in psychological distress,” said study author Anthony Bossis, PhD, of New York University School of Medicine. “And if it’s true for cancer care, then it could apply to other stressful medical conditions.”

He cautioned that patients should not consume psilocybin on their own or without supervision from a physician and a trained counselor.

“Psilocybin therapy may not work for everyone,” he noted. “And some groups, such as people with schizophrenia, as well as adolescents, should not be treated with it.”

The quest to understand a prolonged infection in an infant with acute myeloid leukemia (AML) has led to the discovery of a mutation that allows bacteria to tolerate antibiotic therapy.

Researchers described this discovery in the journal mBio.

“These findings detail a ‘perfect storm’ for development of antibiotic tolerance by bacteria that already pose a clinical challenge,” said study author Jason Rosch, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“The same conditions may be present in other patients with immune systems that have been compromised by chemotherapy or disease,” added co-author Joshua Wolf, MBBS, also of St. Jude.

The “perfect storm” involved a patient who was 6 weeks old when she was diagnosed with AML. The treatment wiped out her white blood cells, and, despite infection-control measures, she developed a bloodstream infection with vancomycin-resistant Enterococcus faecium (VRE).

The infection persisted for 26 days and only resolved after her immune system recovered. She then successfully completed AML treatment.

In-depth DNA sequencing of 22 VRE samples collected during the patient’s infection helped researchers link the prolonged infection to a point mutation in the relA gene of VRE.

The mutation inappropriately activated the stringent response pathway, which bacteria use to survive under stress and to tolerate antibiotics.

The mutation resulted in elevated levels of the signaling molecule alarmone, and this likely primed the bacteria to survive exposure to multiple antibiotics, the researchers said.

The team also noted that relA-mutant VRE was susceptible to the antibiotics linezolid and daptomycin in minimum inhibitory concentration testing and during planktonic growth.

However, when growing in biofilm, relA-mutant VRE could tolerate high doses of both antibiotics.

“This mutation has particular clinical significance because the antibiotics involved, linezolid and daptomycin, are the last line of defense against VRE infection,” Dr Wolf said.

Among the compounds in development for the treatment of bacterial biofilms is the experimental antibiotic ADEP-4. In this study, ADEP-4 killed relA-mutant and non-mutant VRE growing in biofilm in the lab.

“In the future, compounds like ADEP-4 may provide a new approach to resolving persistent infections,” Dr Wolf said.

Dr Rosch noted that evidence gleaned from tracking the evolution of VRE throughout the infection suggested the patient’s immune-compromised state was essential to survival of the mutant VRE.

Gene transcription was altered significantly in relA-mutant VRE and produced biofilms that were less robust and possibly unlikely to otherwise survive.

“The case expands our understanding of the role of the stringent response in susceptibility and tolerance to a wide range of antibiotics, especially in biofilms,” Dr Rosch said. “It also demonstrates that these mutations can develop and gain a foothold during a human infection.”

The quest to understand a prolonged infection in an infant with acute myeloid leukemia (AML) has led to the discovery of a mutation that allows bacteria to tolerate antibiotic therapy.

Researchers described this discovery in the journal mBio.

“These findings detail a ‘perfect storm’ for development of antibiotic tolerance by bacteria that already pose a clinical challenge,” said study author Jason Rosch, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“The same conditions may be present in other patients with immune systems that have been compromised by chemotherapy or disease,” added co-author Joshua Wolf, MBBS, also of St. Jude.

The “perfect storm” involved a patient who was 6 weeks old when she was diagnosed with AML. The treatment wiped out her white blood cells, and, despite infection-control measures, she developed a bloodstream infection with vancomycin-resistant Enterococcus faecium (VRE).

The infection persisted for 26 days and only resolved after her immune system recovered. She then successfully completed AML treatment.

In-depth DNA sequencing of 22 VRE samples collected during the patient’s infection helped researchers link the prolonged infection to a point mutation in the relA gene of VRE.

The mutation inappropriately activated the stringent response pathway, which bacteria use to survive under stress and to tolerate antibiotics.

The mutation resulted in elevated levels of the signaling molecule alarmone, and this likely primed the bacteria to survive exposure to multiple antibiotics, the researchers said.

The team also noted that relA-mutant VRE was susceptible to the antibiotics linezolid and daptomycin in minimum inhibitory concentration testing and during planktonic growth.

However, when growing in biofilm, relA-mutant VRE could tolerate high doses of both antibiotics.

“This mutation has particular clinical significance because the antibiotics involved, linezolid and daptomycin, are the last line of defense against VRE infection,” Dr Wolf said.

Among the compounds in development for the treatment of bacterial biofilms is the experimental antibiotic ADEP-4. In this study, ADEP-4 killed relA-mutant and non-mutant VRE growing in biofilm in the lab.

“In the future, compounds like ADEP-4 may provide a new approach to resolving persistent infections,” Dr Wolf said.

Dr Rosch noted that evidence gleaned from tracking the evolution of VRE throughout the infection suggested the patient’s immune-compromised state was essential to survival of the mutant VRE.

Gene transcription was altered significantly in relA-mutant VRE and produced biofilms that were less robust and possibly unlikely to otherwise survive.

“The case expands our understanding of the role of the stringent response in susceptibility and tolerance to a wide range of antibiotics, especially in biofilms,” Dr Rosch said. “It also demonstrates that these mutations can develop and gain a foothold during a human infection.”

The quest to understand a prolonged infection in an infant with acute myeloid leukemia (AML) has led to the discovery of a mutation that allows bacteria to tolerate antibiotic therapy.

Researchers described this discovery in the journal mBio.

“These findings detail a ‘perfect storm’ for development of antibiotic tolerance by bacteria that already pose a clinical challenge,” said study author Jason Rosch, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“The same conditions may be present in other patients with immune systems that have been compromised by chemotherapy or disease,” added co-author Joshua Wolf, MBBS, also of St. Jude.

The “perfect storm” involved a patient who was 6 weeks old when she was diagnosed with AML. The treatment wiped out her white blood cells, and, despite infection-control measures, she developed a bloodstream infection with vancomycin-resistant Enterococcus faecium (VRE).

The infection persisted for 26 days and only resolved after her immune system recovered. She then successfully completed AML treatment.

In-depth DNA sequencing of 22 VRE samples collected during the patient’s infection helped researchers link the prolonged infection to a point mutation in the relA gene of VRE.

The mutation inappropriately activated the stringent response pathway, which bacteria use to survive under stress and to tolerate antibiotics.

The mutation resulted in elevated levels of the signaling molecule alarmone, and this likely primed the bacteria to survive exposure to multiple antibiotics, the researchers said.

The team also noted that relA-mutant VRE was susceptible to the antibiotics linezolid and daptomycin in minimum inhibitory concentration testing and during planktonic growth.

However, when growing in biofilm, relA-mutant VRE could tolerate high doses of both antibiotics.

“This mutation has particular clinical significance because the antibiotics involved, linezolid and daptomycin, are the last line of defense against VRE infection,” Dr Wolf said.

Among the compounds in development for the treatment of bacterial biofilms is the experimental antibiotic ADEP-4. In this study, ADEP-4 killed relA-mutant and non-mutant VRE growing in biofilm in the lab.

“In the future, compounds like ADEP-4 may provide a new approach to resolving persistent infections,” Dr Wolf said.

Dr Rosch noted that evidence gleaned from tracking the evolution of VRE throughout the infection suggested the patient’s immune-compromised state was essential to survival of the mutant VRE.

Gene transcription was altered significantly in relA-mutant VRE and produced biofilms that were less robust and possibly unlikely to otherwise survive.

“The case expands our understanding of the role of the stringent response in susceptibility and tolerance to a wide range of antibiotics, especially in biofilms,” Dr Rosch said. “It also demonstrates that these mutations can develop and gain a foothold during a human infection.”

One-time treatment with the hallucinogenic drug psilocybin may provide long-term relief of existential anxiety in patients with life-threatening cancers, according to a small study.

After receiving a single high dose of the drug, most of the patients studied reported decreases in depression and anxiety as well as increases in quality of life and optimism.

These improvements were sustained at 6 months of follow-up.

“The most interesting and remarkable finding is that a single dose of psilocybin, which lasts 4 to 6 hours, produced enduring decreases in depression and anxiety symptoms, and this may represent a fascinating new model for treating some psychiatric conditions,” said study author Roland Griffiths, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr Griffiths said this study grew out of a decade of research at Johns Hopkins on the effects of psilocybin in healthy volunteers, which showed that psilocybin can consistently produce positive changes in mood, behavior, and spirituality when administered to carefully screened and prepared participants.

The current study was designed to see if psilocybin could produce similar results in psychologically distressed cancer patients.

The results were published in the Journal of Psychopharmacology alongside a similar study and 11 accompanying editorials.

For their study, Dr Griffiths and his colleagues recruited 51 participants diagnosed with life-threatening cancers, most of which were recurrent or metastatic.

Types of cancer included breast (n=13), upper aerodigestive (n=7), gastrointestinal (n=4), genitourinary (n=18), and “other” cancers (n=1), as well as hematologic malignancies (n=8).

All participants had been given a formal psychiatric diagnosis, including an anxiety or depressive disorder.

Half of the participants were female, and they had an average age of 56. Ninety-two percent were white, 4% were black, and 2% were Asian.

Treatment

Each participant had 2 treatment sessions scheduled 5 weeks apart. In 1 session, they received a capsule containing a very low dose (1 or 3 mg per 70 kg) of psilocybin that was meant to act as a “control” because the dose was too low to produce effects.

In the other session, participants received a capsule with what is considered a moderate or high dose (22 or 30 mg per 70 kg).

To minimize expectancy effects, the participants and the staff members supervising the sessions were told that participants would receive psilocybin on both sessions, but they did not know that all participants would receive a high dose and a low dose.

Blood pressure and mood were monitored throughout the sessions.

Two monitors aided participants during each session, encouraging them to lie down, wear an eye mask, listen to music through headphones, and direct their attention on their inner experience. If anxiety or confusion arose, the monitors provided reassurance to the participants.

Participants, staff, and community observers rated participants’ moods, attitudes, and behaviors throughout the study.

The researchers assessed each participant via questionnaires and structured interviews before the first session, 7 hours after taking the psilocybin, 5 weeks after each session, and 6 months after the second session.

Adverse events

Thirty-four percent of participants had an episode of elevated systolic blood pressure (>160 mm Hg at 1 or more time-point) in the high-dose psilocybin session, and 17% of participants had such an episode in the low-dose session.

Thirteen percent and 2%, respectively, had an episode of elevated diastolic blood pressure (>100 mm Hg at 1 or more time-point). None of these episodes met criteria for medical intervention.

During the high-dose psilocybin session, 15% of patients experienced nausea or vomiting. There were no such events during the low-dose session.

Three participants reported mild to moderate headaches after the high-dose session.

Twenty-one percent of patients reported physical discomfort during the high-dose session, as did 8% of patients during the low-dose session.

Psychological discomfort occurred in 32% and 12% of participants, respectively. The researchers said there were no cases of hallucinogen persisting perception disorder or prolonged psychosis.

Efficacy outcomes

Most participants reported experiencing changes in visual perception, emotions, and thinking after taking high-dose psilocybin. They also reported experiences of psychological insight and profound, deeply meaningful experiences.

Six months after the final session of treatment, about 80% of participants continued to show clinically significant decreases in depressed mood and anxiety, according to clinician assessment.

According to the participants themselves, 83% had increases in well-being or life satisfaction at 6 months after treatment.

Sixty-seven percent of participants rated the experience as one of the top 5 meaningful experiences in their lives, and 70% rated the experience as one of their top 5 spiritually significant lifetime events.

“Before beginning the study, it wasn’t clear to me that this treatment would be helpful, since cancer patients may experience profound hopelessness in response to their diagnosis, which is often followed by multiple surgeries and prolonged chemotherapy,” Dr Griffiths said.

“I could imagine that cancer patients would receive psilocybin, look into the existential void, and come out even more fearful. However, the positive changes in attitudes, moods, and behavior that we documented in healthy volunteers were replicated in cancer patients.”

One-time treatment with the hallucinogenic drug psilocybin may provide long-term relief of existential anxiety in patients with life-threatening cancers, according to a small study.

After receiving a single high dose of the drug, most of the patients studied reported decreases in depression and anxiety as well as increases in quality of life and optimism.

These improvements were sustained at 6 months of follow-up.

“The most interesting and remarkable finding is that a single dose of psilocybin, which lasts 4 to 6 hours, produced enduring decreases in depression and anxiety symptoms, and this may represent a fascinating new model for treating some psychiatric conditions,” said study author Roland Griffiths, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr Griffiths said this study grew out of a decade of research at Johns Hopkins on the effects of psilocybin in healthy volunteers, which showed that psilocybin can consistently produce positive changes in mood, behavior, and spirituality when administered to carefully screened and prepared participants.

The current study was designed to see if psilocybin could produce similar results in psychologically distressed cancer patients.

The results were published in the Journal of Psychopharmacology alongside a similar study and 11 accompanying editorials.

For their study, Dr Griffiths and his colleagues recruited 51 participants diagnosed with life-threatening cancers, most of which were recurrent or metastatic.

Types of cancer included breast (n=13), upper aerodigestive (n=7), gastrointestinal (n=4), genitourinary (n=18), and “other” cancers (n=1), as well as hematologic malignancies (n=8).

All participants had been given a formal psychiatric diagnosis, including an anxiety or depressive disorder.

Half of the participants were female, and they had an average age of 56. Ninety-two percent were white, 4% were black, and 2% were Asian.

Treatment

Each participant had 2 treatment sessions scheduled 5 weeks apart. In 1 session, they received a capsule containing a very low dose (1 or 3 mg per 70 kg) of psilocybin that was meant to act as a “control” because the dose was too low to produce effects.

In the other session, participants received a capsule with what is considered a moderate or high dose (22 or 30 mg per 70 kg).

To minimize expectancy effects, the participants and the staff members supervising the sessions were told that participants would receive psilocybin on both sessions, but they did not know that all participants would receive a high dose and a low dose.

Blood pressure and mood were monitored throughout the sessions.

Two monitors aided participants during each session, encouraging them to lie down, wear an eye mask, listen to music through headphones, and direct their attention on their inner experience. If anxiety or confusion arose, the monitors provided reassurance to the participants.

Participants, staff, and community observers rated participants’ moods, attitudes, and behaviors throughout the study.

The researchers assessed each participant via questionnaires and structured interviews before the first session, 7 hours after taking the psilocybin, 5 weeks after each session, and 6 months after the second session.

Adverse events

Thirty-four percent of participants had an episode of elevated systolic blood pressure (>160 mm Hg at 1 or more time-point) in the high-dose psilocybin session, and 17% of participants had such an episode in the low-dose session.

Thirteen percent and 2%, respectively, had an episode of elevated diastolic blood pressure (>100 mm Hg at 1 or more time-point). None of these episodes met criteria for medical intervention.

During the high-dose psilocybin session, 15% of patients experienced nausea or vomiting. There were no such events during the low-dose session.

Three participants reported mild to moderate headaches after the high-dose session.

Twenty-one percent of patients reported physical discomfort during the high-dose session, as did 8% of patients during the low-dose session.

Psychological discomfort occurred in 32% and 12% of participants, respectively. The researchers said there were no cases of hallucinogen persisting perception disorder or prolonged psychosis.

Efficacy outcomes

Most participants reported experiencing changes in visual perception, emotions, and thinking after taking high-dose psilocybin. They also reported experiences of psychological insight and profound, deeply meaningful experiences.

Six months after the final session of treatment, about 80% of participants continued to show clinically significant decreases in depressed mood and anxiety, according to clinician assessment.

According to the participants themselves, 83% had increases in well-being or life satisfaction at 6 months after treatment.

Sixty-seven percent of participants rated the experience as one of the top 5 meaningful experiences in their lives, and 70% rated the experience as one of their top 5 spiritually significant lifetime events.

“Before beginning the study, it wasn’t clear to me that this treatment would be helpful, since cancer patients may experience profound hopelessness in response to their diagnosis, which is often followed by multiple surgeries and prolonged chemotherapy,” Dr Griffiths said.

“I could imagine that cancer patients would receive psilocybin, look into the existential void, and come out even more fearful. However, the positive changes in attitudes, moods, and behavior that we documented in healthy volunteers were replicated in cancer patients.”

One-time treatment with the hallucinogenic drug psilocybin may provide long-term relief of existential anxiety in patients with life-threatening cancers, according to a small study.

After receiving a single high dose of the drug, most of the patients studied reported decreases in depression and anxiety as well as increases in quality of life and optimism.

These improvements were sustained at 6 months of follow-up.

“The most interesting and remarkable finding is that a single dose of psilocybin, which lasts 4 to 6 hours, produced enduring decreases in depression and anxiety symptoms, and this may represent a fascinating new model for treating some psychiatric conditions,” said study author Roland Griffiths, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr Griffiths said this study grew out of a decade of research at Johns Hopkins on the effects of psilocybin in healthy volunteers, which showed that psilocybin can consistently produce positive changes in mood, behavior, and spirituality when administered to carefully screened and prepared participants.

The current study was designed to see if psilocybin could produce similar results in psychologically distressed cancer patients.

The results were published in the Journal of Psychopharmacology alongside a similar study and 11 accompanying editorials.

For their study, Dr Griffiths and his colleagues recruited 51 participants diagnosed with life-threatening cancers, most of which were recurrent or metastatic.

Types of cancer included breast (n=13), upper aerodigestive (n=7), gastrointestinal (n=4), genitourinary (n=18), and “other” cancers (n=1), as well as hematologic malignancies (n=8).

All participants had been given a formal psychiatric diagnosis, including an anxiety or depressive disorder.

Half of the participants were female, and they had an average age of 56. Ninety-two percent were white, 4% were black, and 2% were Asian.

Treatment

Each participant had 2 treatment sessions scheduled 5 weeks apart. In 1 session, they received a capsule containing a very low dose (1 or 3 mg per 70 kg) of psilocybin that was meant to act as a “control” because the dose was too low to produce effects.

In the other session, participants received a capsule with what is considered a moderate or high dose (22 or 30 mg per 70 kg).

To minimize expectancy effects, the participants and the staff members supervising the sessions were told that participants would receive psilocybin on both sessions, but they did not know that all participants would receive a high dose and a low dose.

Blood pressure and mood were monitored throughout the sessions.

Two monitors aided participants during each session, encouraging them to lie down, wear an eye mask, listen to music through headphones, and direct their attention on their inner experience. If anxiety or confusion arose, the monitors provided reassurance to the participants.

Participants, staff, and community observers rated participants’ moods, attitudes, and behaviors throughout the study.

The researchers assessed each participant via questionnaires and structured interviews before the first session, 7 hours after taking the psilocybin, 5 weeks after each session, and 6 months after the second session.

Adverse events

Thirty-four percent of participants had an episode of elevated systolic blood pressure (>160 mm Hg at 1 or more time-point) in the high-dose psilocybin session, and 17% of participants had such an episode in the low-dose session.

Thirteen percent and 2%, respectively, had an episode of elevated diastolic blood pressure (>100 mm Hg at 1 or more time-point). None of these episodes met criteria for medical intervention.

During the high-dose psilocybin session, 15% of patients experienced nausea or vomiting. There were no such events during the low-dose session.

Three participants reported mild to moderate headaches after the high-dose session.

Twenty-one percent of patients reported physical discomfort during the high-dose session, as did 8% of patients during the low-dose session.

Psychological discomfort occurred in 32% and 12% of participants, respectively. The researchers said there were no cases of hallucinogen persisting perception disorder or prolonged psychosis.

Efficacy outcomes

Most participants reported experiencing changes in visual perception, emotions, and thinking after taking high-dose psilocybin. They also reported experiences of psychological insight and profound, deeply meaningful experiences.

Six months after the final session of treatment, about 80% of participants continued to show clinically significant decreases in depressed mood and anxiety, according to clinician assessment.

According to the participants themselves, 83% had increases in well-being or life satisfaction at 6 months after treatment.

Sixty-seven percent of participants rated the experience as one of the top 5 meaningful experiences in their lives, and 70% rated the experience as one of their top 5 spiritually significant lifetime events.

“Before beginning the study, it wasn’t clear to me that this treatment would be helpful, since cancer patients may experience profound hopelessness in response to their diagnosis, which is often followed by multiple surgeries and prolonged chemotherapy,” Dr Griffiths said.

“I could imagine that cancer patients would receive psilocybin, look into the existential void, and come out even more fearful. However, the positive changes in attitudes, moods, and behavior that we documented in healthy volunteers were replicated in cancer patients.”

Preclinical research has revealed potential therapeutic targets for

myelodysplastic syndromes (MDS).

Investigators

found evidence to suggest that TRAF6, a toll-like receptor effector

with ubiquitin ligase activity, plays a key role in MDS.

So TRAF6 and

proteins regulated by TRAF6 may be therapeutic targets for MDS.

Daniel Starczynowski, PhD, of Cincinnati Children’s Hospital Medical Center in Ohio, and his colleagues reported these findings in Nature Immunology.

The investigators first found that TRAF6 is overexpressed in hematopoietic stem/progenitor cells from MDS patients.

To more closely examine the role of TRAF6 in MDS, the team created mouse models in which the protein was overexpressed.

“We found that TRAF6 overexpression in mouse hematopoietic stem cells results in impaired blood cell formation and bone marrow failure,” Dr Starczynowski said.

Further investigation revealed that hnRNPA1, an RNA-binding protein and auxiliary splicing factor, is a substrate of TRAF6. And TRAF6 ubiquitination of hnRNPA1 regulates alternative splicing of Arhgap1.

This activates the GTP-binding Rho family protein Cdc42 and accounts for the defects observed in hematopoietic stem/progenitor cells that express TRAF6.

All of these proteins could be potential treatment targets for cases of MDS triggered by overexpression of TRAF6, according to Dr Starczynowski, who said future studies will test their therapeutic potential in mouse models of MDS.

“Based on our paper, a number of therapeutic approaches can be tested and directed against TRAF6 and other related proteins responsible for MDS,” he said.

Beyond the potential for new therapeutic approaches in MDS, this research revealed a new and critical immune-related function for TRAF6, according to the investigators.

TRAF6 regulates RNA isoform expression in response to various pathogens. In the context of the current study, TRAF6’s regulation of RNA isoform expression is important to the function of hematopoietic cells and reveals another dimension to how cells respond to infection, Dr Starczynowski said.

Preclinical research has revealed potential therapeutic targets for

myelodysplastic syndromes (MDS).

Investigators

found evidence to suggest that TRAF6, a toll-like receptor effector

with ubiquitin ligase activity, plays a key role in MDS.

So TRAF6 and

proteins regulated by TRAF6 may be therapeutic targets for MDS.

Daniel Starczynowski, PhD, of Cincinnati Children’s Hospital Medical Center in Ohio, and his colleagues reported these findings in Nature Immunology.

The investigators first found that TRAF6 is overexpressed in hematopoietic stem/progenitor cells from MDS patients.

To more closely examine the role of TRAF6 in MDS, the team created mouse models in which the protein was overexpressed.

“We found that TRAF6 overexpression in mouse hematopoietic stem cells results in impaired blood cell formation and bone marrow failure,” Dr Starczynowski said.

Further investigation revealed that hnRNPA1, an RNA-binding protein and auxiliary splicing factor, is a substrate of TRAF6. And TRAF6 ubiquitination of hnRNPA1 regulates alternative splicing of Arhgap1.

This activates the GTP-binding Rho family protein Cdc42 and accounts for the defects observed in hematopoietic stem/progenitor cells that express TRAF6.

All of these proteins could be potential treatment targets for cases of MDS triggered by overexpression of TRAF6, according to Dr Starczynowski, who said future studies will test their therapeutic potential in mouse models of MDS.

“Based on our paper, a number of therapeutic approaches can be tested and directed against TRAF6 and other related proteins responsible for MDS,” he said.

Beyond the potential for new therapeutic approaches in MDS, this research revealed a new and critical immune-related function for TRAF6, according to the investigators.

TRAF6 regulates RNA isoform expression in response to various pathogens. In the context of the current study, TRAF6’s regulation of RNA isoform expression is important to the function of hematopoietic cells and reveals another dimension to how cells respond to infection, Dr Starczynowski said.

Preclinical research has revealed potential therapeutic targets for

myelodysplastic syndromes (MDS).

Investigators

found evidence to suggest that TRAF6, a toll-like receptor effector

with ubiquitin ligase activity, plays a key role in MDS.

So TRAF6 and

proteins regulated by TRAF6 may be therapeutic targets for MDS.

Daniel Starczynowski, PhD, of Cincinnati Children’s Hospital Medical Center in Ohio, and his colleagues reported these findings in Nature Immunology.

The investigators first found that TRAF6 is overexpressed in hematopoietic stem/progenitor cells from MDS patients.

To more closely examine the role of TRAF6 in MDS, the team created mouse models in which the protein was overexpressed.

“We found that TRAF6 overexpression in mouse hematopoietic stem cells results in impaired blood cell formation and bone marrow failure,” Dr Starczynowski said.

Further investigation revealed that hnRNPA1, an RNA-binding protein and auxiliary splicing factor, is a substrate of TRAF6. And TRAF6 ubiquitination of hnRNPA1 regulates alternative splicing of Arhgap1.

This activates the GTP-binding Rho family protein Cdc42 and accounts for the defects observed in hematopoietic stem/progenitor cells that express TRAF6.

All of these proteins could be potential treatment targets for cases of MDS triggered by overexpression of TRAF6, according to Dr Starczynowski, who said future studies will test their therapeutic potential in mouse models of MDS.

“Based on our paper, a number of therapeutic approaches can be tested and directed against TRAF6 and other related proteins responsible for MDS,” he said.

Beyond the potential for new therapeutic approaches in MDS, this research revealed a new and critical immune-related function for TRAF6, according to the investigators.

TRAF6 regulates RNA isoform expression in response to various pathogens. In the context of the current study, TRAF6’s regulation of RNA isoform expression is important to the function of hematopoietic cells and reveals another dimension to how cells respond to infection, Dr Starczynowski said.