Aggressive Lymphomas

Micrograph showing CLL

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.

Micrograph showing CLL

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.

Micrograph showing CLL

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.

Doctor consults with cancer
patient and her father
Photo by Rhoda Baer

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.

Doctor consults with cancer
patient and her father
Photo by Rhoda Baer

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.

Doctor consults with cancer
patient and her father
Photo by Rhoda Baer

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.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

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.”

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

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.”

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

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.”

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

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.”

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

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.”

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

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.”

Drug release in a cancer cell

Image courtesy of PNAS

A diabetes medication and an antihypertensive drug may prove effective in the treatment of hematologic malignancies and other cancers, according to preclinical research published in Science Advances.

Past research has shown that metformin, a drug used to treat type 2 diabetes, has anticancer properties.

However, the usual therapeutic dose is too low to effectively fight cancer, and higher doses of metformin could be too toxic.

With the current study, researchers found that the antihypertensive drug syrosingopine enhances the anticancer efficacy of metformin without harming normal blood cells.

The team screened over a thousand drugs to find one that could boost metformin’s efficacy against cancers.

They identified syrosingopine and tested it in combination with metformin—at concentrations substantially below the drugs’ therapeutic thresholds—on a range of cancer cell lines and in mouse models of liver cancer.

Thirty-five of the 43 cell lines tested were susceptible to both syrosingopine and metformin. This included leukemia, lymphoma, and multiple myeloma cell lines.

In addition, the mice given a short course of syrosingopine and metformin experienced a reduction in the number of visible liver tumors.

The researchers also tested syrosingopine and metformin in peripheral blasts from 12 patients with acute myeloid leukemia and a patient with blast crisis chronic myeloid leukemia. All 13 samples responded to the treatment.

On the other hand, syrosingopine and metformin did not affect peripheral blood cells from healthy subjects.

“[A]lmost all tumor cells were killed by this cocktail and at doses that are actually not toxic to normal cells,” said study author Don Benjamin, of the University of Basel in Switzerland.

“And the effect was exclusively confined to cancer cells, as the blood cells from healthy donors were insensitive to the treatment.”

The researchers believe metformin functions by lowering blood glucose levels for cancer cells, starving them of essential nutrients needed for their survival. However, it is not clear how syrosingopine works in conjunction with metformin.

The team emphasized the need for more research evaluating the drugs in combination.

“We have been able to show that the 2 known drugs lead to more profound effects on cancer cell proliferation than each drug alone,” Dr Benjamin said. “The data from this study support the development of combination approaches for the treatment of cancer patients.”

Drug release in a cancer cell

Image courtesy of PNAS

A diabetes medication and an antihypertensive drug may prove effective in the treatment of hematologic malignancies and other cancers, according to preclinical research published in Science Advances.

Past research has shown that metformin, a drug used to treat type 2 diabetes, has anticancer properties.

However, the usual therapeutic dose is too low to effectively fight cancer, and higher doses of metformin could be too toxic.

With the current study, researchers found that the antihypertensive drug syrosingopine enhances the anticancer efficacy of metformin without harming normal blood cells.

The team screened over a thousand drugs to find one that could boost metformin’s efficacy against cancers.

They identified syrosingopine and tested it in combination with metformin—at concentrations substantially below the drugs’ therapeutic thresholds—on a range of cancer cell lines and in mouse models of liver cancer.

Thirty-five of the 43 cell lines tested were susceptible to both syrosingopine and metformin. This included leukemia, lymphoma, and multiple myeloma cell lines.

In addition, the mice given a short course of syrosingopine and metformin experienced a reduction in the number of visible liver tumors.

The researchers also tested syrosingopine and metformin in peripheral blasts from 12 patients with acute myeloid leukemia and a patient with blast crisis chronic myeloid leukemia. All 13 samples responded to the treatment.

On the other hand, syrosingopine and metformin did not affect peripheral blood cells from healthy subjects.

“[A]lmost all tumor cells were killed by this cocktail and at doses that are actually not toxic to normal cells,” said study author Don Benjamin, of the University of Basel in Switzerland.

“And the effect was exclusively confined to cancer cells, as the blood cells from healthy donors were insensitive to the treatment.”

The researchers believe metformin functions by lowering blood glucose levels for cancer cells, starving them of essential nutrients needed for their survival. However, it is not clear how syrosingopine works in conjunction with metformin.

The team emphasized the need for more research evaluating the drugs in combination.

“We have been able to show that the 2 known drugs lead to more profound effects on cancer cell proliferation than each drug alone,” Dr Benjamin said. “The data from this study support the development of combination approaches for the treatment of cancer patients.”

Drug release in a cancer cell

Image courtesy of PNAS

A diabetes medication and an antihypertensive drug may prove effective in the treatment of hematologic malignancies and other cancers, according to preclinical research published in Science Advances.

Past research has shown that metformin, a drug used to treat type 2 diabetes, has anticancer properties.

However, the usual therapeutic dose is too low to effectively fight cancer, and higher doses of metformin could be too toxic.

With the current study, researchers found that the antihypertensive drug syrosingopine enhances the anticancer efficacy of metformin without harming normal blood cells.

The team screened over a thousand drugs to find one that could boost metformin’s efficacy against cancers.

They identified syrosingopine and tested it in combination with metformin—at concentrations substantially below the drugs’ therapeutic thresholds—on a range of cancer cell lines and in mouse models of liver cancer.

Thirty-five of the 43 cell lines tested were susceptible to both syrosingopine and metformin. This included leukemia, lymphoma, and multiple myeloma cell lines.

In addition, the mice given a short course of syrosingopine and metformin experienced a reduction in the number of visible liver tumors.

The researchers also tested syrosingopine and metformin in peripheral blasts from 12 patients with acute myeloid leukemia and a patient with blast crisis chronic myeloid leukemia. All 13 samples responded to the treatment.

On the other hand, syrosingopine and metformin did not affect peripheral blood cells from healthy subjects.

“[A]lmost all tumor cells were killed by this cocktail and at doses that are actually not toxic to normal cells,” said study author Don Benjamin, of the University of Basel in Switzerland.

“And the effect was exclusively confined to cancer cells, as the blood cells from healthy donors were insensitive to the treatment.”

The researchers believe metformin functions by lowering blood glucose levels for cancer cells, starving them of essential nutrients needed for their survival. However, it is not clear how syrosingopine works in conjunction with metformin.

The team emphasized the need for more research evaluating the drugs in combination.

“We have been able to show that the 2 known drugs lead to more profound effects on cancer cell proliferation than each drug alone,” Dr Benjamin said. “The data from this study support the development of combination approaches for the treatment of cancer patients.”

Ofatumumab

Photo courtesy of GSK

Salvage treatment with an ofatumumab-based regimen is no better than a rituximab-based regimen for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a phase 3 study.

The study, ORCHARRD, was a comparison of ofatumumab plus cisplatin, cytarabine, and dexamethasone (O-DHAP) and rituximab plus DHAP (R-DHAP), both followed by autologous stem cell transplant (auto-SCT), in patients with relapsed/refractory DLBCL.

The data showed no significant difference between the 2 treatment arms with regard to progression-free survival (PFS), event-free survival (EFS), or overall survival (OS).

And the incidence of serious adverse events (AEs) was similar between the arms.

Gustaaf W. van Imhoff, MD, PhD, of University Medical Center Groningen in Groningen, Netherlands, and his colleagues conducted this study and reported the results in the Journal of Clinical Oncology.

The study was proposed by HOVON, sponsored by GlaxoSmithKline (GSK), and funded by GSK, Genmab A/S, and Novartis AG. Ofatumumab became an asset of Novartis AG in March 2015.

Patients and treatment

The study included 447 adults with CD20+ DLBCL who had experienced their first relapse or who were refractory to first-line treatment with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) or a similar regimen.

The patients’ median age was 57 (range, 18 to 83), 63% had stage III/IV disease, and 71% of patients either did not achieve a complete response (CR) to first-line treatment or had a CR lasting less than 1 year.

The patients were randomized to receive O-DHAP (n=222) or R-DHAP (n=225). They received ofatumumab at 1000 mg or rituximab at 375 mg/m² on days 1 and 8 of cycle 1 and day 1 of cycles 2 and 3 of DHAP (4 infusions of either drug).

The patients who had responded after 2 cycles of treatment received the third cycle, followed by high-dose therapy and auto-SCT. Failure to achieve a response after cycle 2 was included as an event.

Response and survival

The response rate was 38% with O-DHAP and 42% with R-DHAP. The CR rate was 15% and 22%, respectively.

Thirty-three percent of patients in the O-DHAP arm and 37% in the R-DHAP arm underwent auto-SCT on protocol.

At 2 years, PFS was 24% with O-DHAP and 26% with R-DHAP (hazard ratio [HR]=1.12, P=0.33).

Two-year EFS was 16% with O-DHAP and 18% with R-DHAP. (HR=1.10, P=0.35). And 2-year OS was 41% with O-DHAP and 38% with R-DHAP (HR=0.90, P=0.38).

The researchers found that having a negative PET scan after cycle 3 was associated with better PFS and OS.

Two-year PFS was 32% for patients with a positive PET scan after cycle 3 and 70% for those with a negative PET scan (P=0.001). Two-year OS was 43% for patients with positive PET scan and 78% for those with a negative PET scan (P=0.0018).

Safety

Fifty-two percent of all patients had 1 or more serious AE, and the incidence of serious AEs was similar between the treatment arms. The most common serious AEs were febrile neutropenia (13%), acute renal failure (5%), thrombocytopenia (5%), and vomiting (5%).

Fatal serious AEs occurred in 6% of patients. These were mainly related to infectious complications and occurred in a similar proportion of patients in both treatment arms.

The incidence of rash was higher in the O-DHAP arm (22% vs 9%), as was the incidence of raised serum creatinine (23% vs 16%).

Dose interruptions/delays (of either anti-CD20 therapy or chemotherapy) as a result of AEs occurred in 49% of patients in the O-DHAP arm and 30% in the R-DHAP arm.

AEs causing dose delays/interruptions included (in the O-DHAP and R-DHAP arms, respectively) neutropenia (6% and 7%), rash (9% and <1%), thrombocytopenia (5% and 4%), urticaria (6% and <1%), pyrexia (4% and 2%), febrile neutropenia (4% and 1%), hypersensitivity (4% and 1%), infusion-related reactions (5% and <1%), decrease in platelet count (2% and 3%), and pruritus (4% and 0%).

Sixteen percent of all patients had AEs that led to permanent discontinuation of study treatment. The rate of such AEs was similar between the treatment arms. The most frequent event leading to discontinuation was renal toxicity (8%).

Ofatumumab

Photo courtesy of GSK

Salvage treatment with an ofatumumab-based regimen is no better than a rituximab-based regimen for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a phase 3 study.

The study, ORCHARRD, was a comparison of ofatumumab plus cisplatin, cytarabine, and dexamethasone (O-DHAP) and rituximab plus DHAP (R-DHAP), both followed by autologous stem cell transplant (auto-SCT), in patients with relapsed/refractory DLBCL.

The data showed no significant difference between the 2 treatment arms with regard to progression-free survival (PFS), event-free survival (EFS), or overall survival (OS).

And the incidence of serious adverse events (AEs) was similar between the arms.

Gustaaf W. van Imhoff, MD, PhD, of University Medical Center Groningen in Groningen, Netherlands, and his colleagues conducted this study and reported the results in the Journal of Clinical Oncology.

The study was proposed by HOVON, sponsored by GlaxoSmithKline (GSK), and funded by GSK, Genmab A/S, and Novartis AG. Ofatumumab became an asset of Novartis AG in March 2015.

Patients and treatment

The study included 447 adults with CD20+ DLBCL who had experienced their first relapse or who were refractory to first-line treatment with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) or a similar regimen.

The patients’ median age was 57 (range, 18 to 83), 63% had stage III/IV disease, and 71% of patients either did not achieve a complete response (CR) to first-line treatment or had a CR lasting less than 1 year.

The patients were randomized to receive O-DHAP (n=222) or R-DHAP (n=225). They received ofatumumab at 1000 mg or rituximab at 375 mg/m² on days 1 and 8 of cycle 1 and day 1 of cycles 2 and 3 of DHAP (4 infusions of either drug).

The patients who had responded after 2 cycles of treatment received the third cycle, followed by high-dose therapy and auto-SCT. Failure to achieve a response after cycle 2 was included as an event.

Response and survival

The response rate was 38% with O-DHAP and 42% with R-DHAP. The CR rate was 15% and 22%, respectively.

Thirty-three percent of patients in the O-DHAP arm and 37% in the R-DHAP arm underwent auto-SCT on protocol.

At 2 years, PFS was 24% with O-DHAP and 26% with R-DHAP (hazard ratio [HR]=1.12, P=0.33).

Two-year EFS was 16% with O-DHAP and 18% with R-DHAP. (HR=1.10, P=0.35). And 2-year OS was 41% with O-DHAP and 38% with R-DHAP (HR=0.90, P=0.38).

The researchers found that having a negative PET scan after cycle 3 was associated with better PFS and OS.

Two-year PFS was 32% for patients with a positive PET scan after cycle 3 and 70% for those with a negative PET scan (P=0.001). Two-year OS was 43% for patients with positive PET scan and 78% for those with a negative PET scan (P=0.0018).

Safety

Fifty-two percent of all patients had 1 or more serious AE, and the incidence of serious AEs was similar between the treatment arms. The most common serious AEs were febrile neutropenia (13%), acute renal failure (5%), thrombocytopenia (5%), and vomiting (5%).

Fatal serious AEs occurred in 6% of patients. These were mainly related to infectious complications and occurred in a similar proportion of patients in both treatment arms.

The incidence of rash was higher in the O-DHAP arm (22% vs 9%), as was the incidence of raised serum creatinine (23% vs 16%).

Dose interruptions/delays (of either anti-CD20 therapy or chemotherapy) as a result of AEs occurred in 49% of patients in the O-DHAP arm and 30% in the R-DHAP arm.

AEs causing dose delays/interruptions included (in the O-DHAP and R-DHAP arms, respectively) neutropenia (6% and 7%), rash (9% and <1%), thrombocytopenia (5% and 4%), urticaria (6% and <1%), pyrexia (4% and 2%), febrile neutropenia (4% and 1%), hypersensitivity (4% and 1%), infusion-related reactions (5% and <1%), decrease in platelet count (2% and 3%), and pruritus (4% and 0%).

Sixteen percent of all patients had AEs that led to permanent discontinuation of study treatment. The rate of such AEs was similar between the treatment arms. The most frequent event leading to discontinuation was renal toxicity (8%).

Ofatumumab

Photo courtesy of GSK

Salvage treatment with an ofatumumab-based regimen is no better than a rituximab-based regimen for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a phase 3 study.

The study, ORCHARRD, was a comparison of ofatumumab plus cisplatin, cytarabine, and dexamethasone (O-DHAP) and rituximab plus DHAP (R-DHAP), both followed by autologous stem cell transplant (auto-SCT), in patients with relapsed/refractory DLBCL.

The data showed no significant difference between the 2 treatment arms with regard to progression-free survival (PFS), event-free survival (EFS), or overall survival (OS).

And the incidence of serious adverse events (AEs) was similar between the arms.

Gustaaf W. van Imhoff, MD, PhD, of University Medical Center Groningen in Groningen, Netherlands, and his colleagues conducted this study and reported the results in the Journal of Clinical Oncology.

The study was proposed by HOVON, sponsored by GlaxoSmithKline (GSK), and funded by GSK, Genmab A/S, and Novartis AG. Ofatumumab became an asset of Novartis AG in March 2015.

Patients and treatment

The study included 447 adults with CD20+ DLBCL who had experienced their first relapse or who were refractory to first-line treatment with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) or a similar regimen.

The patients’ median age was 57 (range, 18 to 83), 63% had stage III/IV disease, and 71% of patients either did not achieve a complete response (CR) to first-line treatment or had a CR lasting less than 1 year.

The patients were randomized to receive O-DHAP (n=222) or R-DHAP (n=225). They received ofatumumab at 1000 mg or rituximab at 375 mg/m² on days 1 and 8 of cycle 1 and day 1 of cycles 2 and 3 of DHAP (4 infusions of either drug).

The patients who had responded after 2 cycles of treatment received the third cycle, followed by high-dose therapy and auto-SCT. Failure to achieve a response after cycle 2 was included as an event.

Response and survival

The response rate was 38% with O-DHAP and 42% with R-DHAP. The CR rate was 15% and 22%, respectively.

Thirty-three percent of patients in the O-DHAP arm and 37% in the R-DHAP arm underwent auto-SCT on protocol.

At 2 years, PFS was 24% with O-DHAP and 26% with R-DHAP (hazard ratio [HR]=1.12, P=0.33).

Two-year EFS was 16% with O-DHAP and 18% with R-DHAP. (HR=1.10, P=0.35). And 2-year OS was 41% with O-DHAP and 38% with R-DHAP (HR=0.90, P=0.38).

The researchers found that having a negative PET scan after cycle 3 was associated with better PFS and OS.

Two-year PFS was 32% for patients with a positive PET scan after cycle 3 and 70% for those with a negative PET scan (P=0.001). Two-year OS was 43% for patients with positive PET scan and 78% for those with a negative PET scan (P=0.0018).

Safety

Fifty-two percent of all patients had 1 or more serious AE, and the incidence of serious AEs was similar between the treatment arms. The most common serious AEs were febrile neutropenia (13%), acute renal failure (5%), thrombocytopenia (5%), and vomiting (5%).

Fatal serious AEs occurred in 6% of patients. These were mainly related to infectious complications and occurred in a similar proportion of patients in both treatment arms.

The incidence of rash was higher in the O-DHAP arm (22% vs 9%), as was the incidence of raised serum creatinine (23% vs 16%).

Dose interruptions/delays (of either anti-CD20 therapy or chemotherapy) as a result of AEs occurred in 49% of patients in the O-DHAP arm and 30% in the R-DHAP arm.

AEs causing dose delays/interruptions included (in the O-DHAP and R-DHAP arms, respectively) neutropenia (6% and 7%), rash (9% and <1%), thrombocytopenia (5% and 4%), urticaria (6% and <1%), pyrexia (4% and 2%), febrile neutropenia (4% and 1%), hypersensitivity (4% and 1%), infusion-related reactions (5% and <1%), decrease in platelet count (2% and 3%), and pruritus (4% and 0%).

Sixteen percent of all patients had AEs that led to permanent discontinuation of study treatment. The rate of such AEs was similar between the treatment arms. The most frequent event leading to discontinuation was renal toxicity (8%).

Patients with double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) have inferior outcomes after undergoing autologous stem cell transplantation (ASCT), according to a new study published in the Journal of Clinical Oncology.

The worst outcomes were observed in patients with concurrent DELs and DHLs, and this “supports the concept that the double-hit/double-expressor biology appears to render DLBCL resistant to and less likely to be cured by chemotherapy,” write Alex Herrera, MD, an oncologist at the City of Hope, Duarte, Calif., and his colleagues.

But that said, a significant proportion of patients with relapsed/refractory DEL did experience durable remissions following ASCT, particularly those with isolated DEL without DHL.

This suggests that “the presence of DEL alone should not be considered a contraindication to ASCT,” the authors wrote (J Clin Oncol. 2016 Oct. 24. doi: 10.1200/JCO.2016.68.2740).

DHLs and DELs are subtypes of diffuse large B-cell lymphoma (DLBCL), and while they are associated with poor outcomes after standard chemoimmunotherapy, data remain limited as to outcomes of patients with relapsed or refractory disease who undergo ASCT.

The retrospective multicenter study included 117 patients with chemotherapy-sensitive relapsed/refractory DLBCL who underwent ASCT and had archival tumor material available. DEL with MYC/BCL2 coexpression was observed in 52 patients (44%) while 15 patients expressed MYC-R (13%), of whom 12 (10%) had DHL.

The median follow-up time was 45 months for survivors, and the 4-year progression-free survival (PFS) and overall survival (OS) were 54% for the entire cohort.

The 4-year PFS and OS in patients with DHL was worse as compared to those without DHL; 28% vs. 57% (P = .013), and 25% vs. 66% (P less than .001), respectively.

Those with DHL had poorer PFS (28%) and OS (25%), compared with patients with DEL but not DHL (PFS, 53% and OS, 61%) as well as patients with neither DEL nor DHL (PFS, 60% and OS, 70%; three-way P value for PFS, P = .013; OS, P = .002).

Patients with concurrent DEL and DHL had the poorest outcome, with a 4-year PFS of 0%.

After researchers adjusted for clinical characteristics, the only factors that remained significantly associated with PFS were DEL (hazard ratio, 1.8; P = .035) and DHL (HR, 2.9; P = .009). Factors that were significantly associated with OS were DHL (HR, 3.4; P = .004) and remission status at ASCT (HR for partial response, 2.4; P = .007).

Overall, patients with DHL were less likely to achieve a complete response following salvage therapy, and those with DEL and patients with DHL had a shorter time to relapse after induction therapy.

“Although some patients with relapsed/refractory DHL had long-term remission after ASCT (isolated DHL without DEL), the low survival rate in this group argues that alternative transplantation strategies, including allogeneic hematopoietic stem cell transplantation or peri-ASCT relapse prevention strategies should be studied,” they concluded.

Patients with double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) have inferior outcomes after undergoing autologous stem cell transplantation (ASCT), according to a new study published in the Journal of Clinical Oncology.

The worst outcomes were observed in patients with concurrent DELs and DHLs, and this “supports the concept that the double-hit/double-expressor biology appears to render DLBCL resistant to and less likely to be cured by chemotherapy,” write Alex Herrera, MD, an oncologist at the City of Hope, Duarte, Calif., and his colleagues.

But that said, a significant proportion of patients with relapsed/refractory DEL did experience durable remissions following ASCT, particularly those with isolated DEL without DHL.

This suggests that “the presence of DEL alone should not be considered a contraindication to ASCT,” the authors wrote (J Clin Oncol. 2016 Oct. 24. doi: 10.1200/JCO.2016.68.2740).

DHLs and DELs are subtypes of diffuse large B-cell lymphoma (DLBCL), and while they are associated with poor outcomes after standard chemoimmunotherapy, data remain limited as to outcomes of patients with relapsed or refractory disease who undergo ASCT.

The retrospective multicenter study included 117 patients with chemotherapy-sensitive relapsed/refractory DLBCL who underwent ASCT and had archival tumor material available. DEL with MYC/BCL2 coexpression was observed in 52 patients (44%) while 15 patients expressed MYC-R (13%), of whom 12 (10%) had DHL.

The median follow-up time was 45 months for survivors, and the 4-year progression-free survival (PFS) and overall survival (OS) were 54% for the entire cohort.

The 4-year PFS and OS in patients with DHL was worse as compared to those without DHL; 28% vs. 57% (P = .013), and 25% vs. 66% (P less than .001), respectively.

Those with DHL had poorer PFS (28%) and OS (25%), compared with patients with DEL but not DHL (PFS, 53% and OS, 61%) as well as patients with neither DEL nor DHL (PFS, 60% and OS, 70%; three-way P value for PFS, P = .013; OS, P = .002).

Patients with concurrent DEL and DHL had the poorest outcome, with a 4-year PFS of 0%.

After researchers adjusted for clinical characteristics, the only factors that remained significantly associated with PFS were DEL (hazard ratio, 1.8; P = .035) and DHL (HR, 2.9; P = .009). Factors that were significantly associated with OS were DHL (HR, 3.4; P = .004) and remission status at ASCT (HR for partial response, 2.4; P = .007).

Overall, patients with DHL were less likely to achieve a complete response following salvage therapy, and those with DEL and patients with DHL had a shorter time to relapse after induction therapy.

“Although some patients with relapsed/refractory DHL had long-term remission after ASCT (isolated DHL without DEL), the low survival rate in this group argues that alternative transplantation strategies, including allogeneic hematopoietic stem cell transplantation or peri-ASCT relapse prevention strategies should be studied,” they concluded.

Patients with double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) have inferior outcomes after undergoing autologous stem cell transplantation (ASCT), according to a new study published in the Journal of Clinical Oncology.

The worst outcomes were observed in patients with concurrent DELs and DHLs, and this “supports the concept that the double-hit/double-expressor biology appears to render DLBCL resistant to and less likely to be cured by chemotherapy,” write Alex Herrera, MD, an oncologist at the City of Hope, Duarte, Calif., and his colleagues.

But that said, a significant proportion of patients with relapsed/refractory DEL did experience durable remissions following ASCT, particularly those with isolated DEL without DHL.

This suggests that “the presence of DEL alone should not be considered a contraindication to ASCT,” the authors wrote (J Clin Oncol. 2016 Oct. 24. doi: 10.1200/JCO.2016.68.2740).

DHLs and DELs are subtypes of diffuse large B-cell lymphoma (DLBCL), and while they are associated with poor outcomes after standard chemoimmunotherapy, data remain limited as to outcomes of patients with relapsed or refractory disease who undergo ASCT.

The retrospective multicenter study included 117 patients with chemotherapy-sensitive relapsed/refractory DLBCL who underwent ASCT and had archival tumor material available. DEL with MYC/BCL2 coexpression was observed in 52 patients (44%) while 15 patients expressed MYC-R (13%), of whom 12 (10%) had DHL.

The median follow-up time was 45 months for survivors, and the 4-year progression-free survival (PFS) and overall survival (OS) were 54% for the entire cohort.

The 4-year PFS and OS in patients with DHL was worse as compared to those without DHL; 28% vs. 57% (P = .013), and 25% vs. 66% (P less than .001), respectively.

Those with DHL had poorer PFS (28%) and OS (25%), compared with patients with DEL but not DHL (PFS, 53% and OS, 61%) as well as patients with neither DEL nor DHL (PFS, 60% and OS, 70%; three-way P value for PFS, P = .013; OS, P = .002).

Patients with concurrent DEL and DHL had the poorest outcome, with a 4-year PFS of 0%.

After researchers adjusted for clinical characteristics, the only factors that remained significantly associated with PFS were DEL (hazard ratio, 1.8; P = .035) and DHL (HR, 2.9; P = .009). Factors that were significantly associated with OS were DHL (HR, 3.4; P = .004) and remission status at ASCT (HR for partial response, 2.4; P = .007).

Overall, patients with DHL were less likely to achieve a complete response following salvage therapy, and those with DEL and patients with DHL had a shorter time to relapse after induction therapy.

“Although some patients with relapsed/refractory DHL had long-term remission after ASCT (isolated DHL without DEL), the low survival rate in this group argues that alternative transplantation strategies, including allogeneic hematopoietic stem cell transplantation or peri-ASCT relapse prevention strategies should be studied,” they concluded.

HIV-infected individuals on antiretroviral therapy who also have chronic coinfection with hepatitis B or C virus have an increased risk of developing non-Hodgkin lymphoma, according to new research published in Annals of Internal Medicine.

Lead author Qing Wang, PhD, of the Basel Institute for Clinical Epidemiology & Biostatistics at University Hospital Basel, Switzerland, and her coauthors said there is growing evidence of an association between both chronic hepatitis B virus infection (HBV) and chronic hepatitis C virus infection (HCV), and non-Hodgkin lymphoma, with chronic immune activation and B cell proliferation suggested as potential mechanisms. However, the impact of chronic coinfection in individuals with HIV is unclear.

©vchal/Thinkstock

HIV-infected individuals on antiretroviral therapy who also have chronic coinfection with hepatitis B or C virus have an increased risk of developing non-Hodgkin lymphoma, according to new research published in Annals of Internal Medicine.

Lead author Qing Wang, PhD, of the Basel Institute for Clinical Epidemiology & Biostatistics at University Hospital Basel, Switzerland, and her coauthors said there is growing evidence of an association between both chronic hepatitis B virus infection (HBV) and chronic hepatitis C virus infection (HCV), and non-Hodgkin lymphoma, with chronic immune activation and B cell proliferation suggested as potential mechanisms. However, the impact of chronic coinfection in individuals with HIV is unclear.

©vchal/Thinkstock

HIV-infected individuals on antiretroviral therapy who also have chronic coinfection with hepatitis B or C virus have an increased risk of developing non-Hodgkin lymphoma, according to new research published in Annals of Internal Medicine.

Lead author Qing Wang, PhD, of the Basel Institute for Clinical Epidemiology & Biostatistics at University Hospital Basel, Switzerland, and her coauthors said there is growing evidence of an association between both chronic hepatitis B virus infection (HBV) and chronic hepatitis C virus infection (HCV), and non-Hodgkin lymphoma, with chronic immune activation and B cell proliferation suggested as potential mechanisms. However, the impact of chronic coinfection in individuals with HIV is unclear.

©vchal/Thinkstock

Two front-line treatment regimens for patients with high-risk diffuse large B-cell lymphomas (DLBCL) produced comparable outcomes, according to new data.

Patients who received rituximab combined with high-dose sequential chemotherapy (R-HDS) plus autologous stem-cell transplantation (ASCT) had similar results in terms of overall response rate and long-term outcomes, compared to patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

It was presumed that event-free survival would be improved with chemotherapy and ASCT, but that result was not observed at 3-year follow up, wrote Sergio Cortelazzo, MD, of Humanitas Gavazzeni, Bergamo, Italy, and coauthors.

“Our results indicate that CHOP chemotherapy, optimally supplemented by eight doses of rituximab, remains the standard of care also for this group of patients at higher risk for disease resistance or recurrence,” they wrote in a study published online ahead of print in the Journal of Clinical Oncology (J Clin Oncol. 2016 Oct 3. doi: 10.1200/JCO.2016.67.2980).

The benefit of R-HDS chemotherapy with ASCT as front-line therapy for this patient population is still a matter of debate. To address that issue, Dr. Cortelazzo and his colleagues conducted a phase III randomized trial in which 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index (IPI) score were assigned to receive either R-CHOP or R-HDS.

The primary efficacy endpoint was 3-year, event-free survival, and the results were analyzed on an intent-to-treat basis.

At a median follow-up of 5 years (range, 0.05-9.49), with an intent-to-treat analysis, the 3-year, event-free survival was 62% (95% CI, 54%-71%) for the R-CHOP arm, compared with 65% (95% CI, 56% to 74%) for those treated with R-HDS (P = .83; hazard ratio, 0.99; 95% CI, 0.66-1.48).

There was no difference in event-free survival even when analyzed within the IPI subgroups.

The 3-year progression free survival also did not significantly differ between groups; 65% in the R-CHOP arm (95% CI, 57% to 74%) versus 75% (95% CI, 67%-83%; P = .119) for the R-HDS arm in the whole population, as well as within IPI subgroups.

Of note, the 3-year disease-free survival was better in the R-HDS group (79% vs. 91%, respectively; P = .034), but this difference subsequently disappeared with longer follow-up.

Grade 3-4 hematologic toxicity was lower in the R-CHOP arm compared with the R-HDS arm, with at least one episode of neutropenia in 34% versus 84% of patients (P less than .001), anemia in 15% versus 71% of patients (P less than .001), and thrombocytopenia in 5% versus 86% (P less than .001).

The study was supported in part by the Associazione Italiana Lotta alla Leucemia sezione di Bergamo, the Associazione Italiana per la Ricerca sul Cancro, Ministero Istruzione, Universita e Ricerca and unrestricted grants from Roche SpA and Amgen, Italy. Dr Cortelazzo had no relevant disclosures. Several coauthors indicated relationships with industry.

[email protected]

Two front-line treatment regimens for patients with high-risk diffuse large B-cell lymphomas (DLBCL) produced comparable outcomes, according to new data.

Patients who received rituximab combined with high-dose sequential chemotherapy (R-HDS) plus autologous stem-cell transplantation (ASCT) had similar results in terms of overall response rate and long-term outcomes, compared to patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

It was presumed that event-free survival would be improved with chemotherapy and ASCT, but that result was not observed at 3-year follow up, wrote Sergio Cortelazzo, MD, of Humanitas Gavazzeni, Bergamo, Italy, and coauthors.

“Our results indicate that CHOP chemotherapy, optimally supplemented by eight doses of rituximab, remains the standard of care also for this group of patients at higher risk for disease resistance or recurrence,” they wrote in a study published online ahead of print in the Journal of Clinical Oncology (J Clin Oncol. 2016 Oct 3. doi: 10.1200/JCO.2016.67.2980).

The benefit of R-HDS chemotherapy with ASCT as front-line therapy for this patient population is still a matter of debate. To address that issue, Dr. Cortelazzo and his colleagues conducted a phase III randomized trial in which 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index (IPI) score were assigned to receive either R-CHOP or R-HDS.

The primary efficacy endpoint was 3-year, event-free survival, and the results were analyzed on an intent-to-treat basis.

At a median follow-up of 5 years (range, 0.05-9.49), with an intent-to-treat analysis, the 3-year, event-free survival was 62% (95% CI, 54%-71%) for the R-CHOP arm, compared with 65% (95% CI, 56% to 74%) for those treated with R-HDS (P = .83; hazard ratio, 0.99; 95% CI, 0.66-1.48).

There was no difference in event-free survival even when analyzed within the IPI subgroups.

The 3-year progression free survival also did not significantly differ between groups; 65% in the R-CHOP arm (95% CI, 57% to 74%) versus 75% (95% CI, 67%-83%; P = .119) for the R-HDS arm in the whole population, as well as within IPI subgroups.

Of note, the 3-year disease-free survival was better in the R-HDS group (79% vs. 91%, respectively; P = .034), but this difference subsequently disappeared with longer follow-up.

Grade 3-4 hematologic toxicity was lower in the R-CHOP arm compared with the R-HDS arm, with at least one episode of neutropenia in 34% versus 84% of patients (P less than .001), anemia in 15% versus 71% of patients (P less than .001), and thrombocytopenia in 5% versus 86% (P less than .001).

The study was supported in part by the Associazione Italiana Lotta alla Leucemia sezione di Bergamo, the Associazione Italiana per la Ricerca sul Cancro, Ministero Istruzione, Universita e Ricerca and unrestricted grants from Roche SpA and Amgen, Italy. Dr Cortelazzo had no relevant disclosures. Several coauthors indicated relationships with industry.

[email protected]

Two front-line treatment regimens for patients with high-risk diffuse large B-cell lymphomas (DLBCL) produced comparable outcomes, according to new data.

Patients who received rituximab combined with high-dose sequential chemotherapy (R-HDS) plus autologous stem-cell transplantation (ASCT) had similar results in terms of overall response rate and long-term outcomes, compared to patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

It was presumed that event-free survival would be improved with chemotherapy and ASCT, but that result was not observed at 3-year follow up, wrote Sergio Cortelazzo, MD, of Humanitas Gavazzeni, Bergamo, Italy, and coauthors.

“Our results indicate that CHOP chemotherapy, optimally supplemented by eight doses of rituximab, remains the standard of care also for this group of patients at higher risk for disease resistance or recurrence,” they wrote in a study published online ahead of print in the Journal of Clinical Oncology (J Clin Oncol. 2016 Oct 3. doi: 10.1200/JCO.2016.67.2980).

The benefit of R-HDS chemotherapy with ASCT as front-line therapy for this patient population is still a matter of debate. To address that issue, Dr. Cortelazzo and his colleagues conducted a phase III randomized trial in which 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index (IPI) score were assigned to receive either R-CHOP or R-HDS.

The primary efficacy endpoint was 3-year, event-free survival, and the results were analyzed on an intent-to-treat basis.

At a median follow-up of 5 years (range, 0.05-9.49), with an intent-to-treat analysis, the 3-year, event-free survival was 62% (95% CI, 54%-71%) for the R-CHOP arm, compared with 65% (95% CI, 56% to 74%) for those treated with R-HDS (P = .83; hazard ratio, 0.99; 95% CI, 0.66-1.48).

There was no difference in event-free survival even when analyzed within the IPI subgroups.

The 3-year progression free survival also did not significantly differ between groups; 65% in the R-CHOP arm (95% CI, 57% to 74%) versus 75% (95% CI, 67%-83%; P = .119) for the R-HDS arm in the whole population, as well as within IPI subgroups.

Of note, the 3-year disease-free survival was better in the R-HDS group (79% vs. 91%, respectively; P = .034), but this difference subsequently disappeared with longer follow-up.

Grade 3-4 hematologic toxicity was lower in the R-CHOP arm compared with the R-HDS arm, with at least one episode of neutropenia in 34% versus 84% of patients (P less than .001), anemia in 15% versus 71% of patients (P less than .001), and thrombocytopenia in 5% versus 86% (P less than .001).

The study was supported in part by the Associazione Italiana Lotta alla Leucemia sezione di Bergamo, the Associazione Italiana per la Ricerca sul Cancro, Ministero Istruzione, Universita e Ricerca and unrestricted grants from Roche SpA and Amgen, Italy. Dr Cortelazzo had no relevant disclosures. Several coauthors indicated relationships with industry.

[email protected]

DURBAN, SOUTH AFRICA – The 15 HIV-infected patients who have undergone allogeneic stem-cell transplant for life-threatening hematologic cancers under the auspices of the European EpiStem Consortium have uniformly demonstrated a profound and durable reduction in viral reservoir to a degree that hasn’t been approached by any other investigational cure strategy, Annemarie Wensing, MD, said at the 21st International AIDS Conference.

“We see an enormous reduction in the viral reservoir, and in two patients we cannot find any viable HIV in the blood using ultrasensitive tests. But we don’t know whether these patients are cured because they are still on antiretroviral therapy,” said Dr. Wensing of Utrecht (The Netherlands) University.

Bruce Jancin/Frontline Medical News

Non-Hodgkin’s lymphoma and Hodgkin’s lymphoma are 7-9 times more frequent in HIV-positive patients than in the general population. But allogeneic stem cell transplantation is an even higher-risk treatment in HIV-positive patients with life-threatening leukemia or lymphoma than in the HIV-negative population. Only 6 of the 15 EuroStem patients remain alive. Eight died within 4 months of the procedure and another died 2.5 years post-transplant, all from progression of their cancer or as a result of opportunistic infections arising during the immunosuppressive chemoablation that’s central to stem-cell transplantation. However, 3 of the 15 patients have survived longer than 3 years. In two of them, no HIV can be detected in blood or intestinal tissue using ultrasensitive tests, while in the third there is “only a slight trace,” according to Dr. Wensing, a clinical virologist.

EpiStem (the European Project to Guide and Investigate the Potential for HIV Cure by Stem-Cell Transplantation) is a multinational collaboration of European oncologists, infectious disease physicians, and other specialists. It was formed in response to the successful outcome of allogeneic stem cell transplantation for acute myeloid leukemia in HIV-positive Timothy Brown, more famously known as “the Berlin patient” (N Engl J Med. 2009 Feb 12;360(7):692-8). He has thus far survived 7 years off antiretroviral therapy.

Much has been made of the fact that Mr. Brown’s donor cells were homozygous for the CCR5 delta32 mutation, which confers natural resistance to HIV infection because it prevents the virus from infecting T cells. Only 1% or less of the population is homozygous for this mutation. But Dr. Wensing isn’t convinced that using donor cells with the mutation is a prerequisite for success. Indeed, while 4 of the 15 EpiStem patients received stem cells from donors homozygous for the mutation and another got donor cells heterozygous for the CCR5 delta32 mutation, the other 10 received stem cells capable of being infected by HIV – yet all 15 experienced an enormous reduction in their viral reservoir. And two of the three patients who have survived longer than 3 years got stem cells without the CCR5 delta32 mutation.

Dr. Wensing observed that a common denominator shared by Timothy Brown and the two EpiStem patients who have trace or undetectable HIV in blood or tissue samples more than 3 years post-transplant is that all three developed severe graft-versus-host disease in conjunction with their stem cell transplantation. She suspects this may have helped them to clear the infection, a hypothesis she intends to pursue further as EpiStem gathers more patients.

Eventually, if patients continue to test negative for HIV using ultrasensitive tests, it will be time to have a discussion with patients and their treating physicians as to whether they should continue on antiretroviral therapy.

“In the end it’s the patients’ decision, but they should be very well counseled because it can have medical and also psychological consequences if HIV returns,” she said.

EpiStem is funded by the American Foundation for AIDS Research Conssortium on HIV Eradication. Dr. Wensing reported having no financial conflicts regarding her presentation.

[email protected]

DURBAN, SOUTH AFRICA – The 15 HIV-infected patients who have undergone allogeneic stem-cell transplant for life-threatening hematologic cancers under the auspices of the European EpiStem Consortium have uniformly demonstrated a profound and durable reduction in viral reservoir to a degree that hasn’t been approached by any other investigational cure strategy, Annemarie Wensing, MD, said at the 21st International AIDS Conference.

“We see an enormous reduction in the viral reservoir, and in two patients we cannot find any viable HIV in the blood using ultrasensitive tests. But we don’t know whether these patients are cured because they are still on antiretroviral therapy,” said Dr. Wensing of Utrecht (The Netherlands) University.

Bruce Jancin/Frontline Medical News

Non-Hodgkin’s lymphoma and Hodgkin’s lymphoma are 7-9 times more frequent in HIV-positive patients than in the general population. But allogeneic stem cell transplantation is an even higher-risk treatment in HIV-positive patients with life-threatening leukemia or lymphoma than in the HIV-negative population. Only 6 of the 15 EuroStem patients remain alive. Eight died within 4 months of the procedure and another died 2.5 years post-transplant, all from progression of their cancer or as a result of opportunistic infections arising during the immunosuppressive chemoablation that’s central to stem-cell transplantation. However, 3 of the 15 patients have survived longer than 3 years. In two of them, no HIV can be detected in blood or intestinal tissue using ultrasensitive tests, while in the third there is “only a slight trace,” according to Dr. Wensing, a clinical virologist.

EpiStem (the European Project to Guide and Investigate the Potential for HIV Cure by Stem-Cell Transplantation) is a multinational collaboration of European oncologists, infectious disease physicians, and other specialists. It was formed in response to the successful outcome of allogeneic stem cell transplantation for acute myeloid leukemia in HIV-positive Timothy Brown, more famously known as “the Berlin patient” (N Engl J Med. 2009 Feb 12;360(7):692-8). He has thus far survived 7 years off antiretroviral therapy.

Much has been made of the fact that Mr. Brown’s donor cells were homozygous for the CCR5 delta32 mutation, which confers natural resistance to HIV infection because it prevents the virus from infecting T cells. Only 1% or less of the population is homozygous for this mutation. But Dr. Wensing isn’t convinced that using donor cells with the mutation is a prerequisite for success. Indeed, while 4 of the 15 EpiStem patients received stem cells from donors homozygous for the mutation and another got donor cells heterozygous for the CCR5 delta32 mutation, the other 10 received stem cells capable of being infected by HIV – yet all 15 experienced an enormous reduction in their viral reservoir. And two of the three patients who have survived longer than 3 years got stem cells without the CCR5 delta32 mutation.

Dr. Wensing observed that a common denominator shared by Timothy Brown and the two EpiStem patients who have trace or undetectable HIV in blood or tissue samples more than 3 years post-transplant is that all three developed severe graft-versus-host disease in conjunction with their stem cell transplantation. She suspects this may have helped them to clear the infection, a hypothesis she intends to pursue further as EpiStem gathers more patients.

Eventually, if patients continue to test negative for HIV using ultrasensitive tests, it will be time to have a discussion with patients and their treating physicians as to whether they should continue on antiretroviral therapy.

“In the end it’s the patients’ decision, but they should be very well counseled because it can have medical and also psychological consequences if HIV returns,” she said.

EpiStem is funded by the American Foundation for AIDS Research Conssortium on HIV Eradication. Dr. Wensing reported having no financial conflicts regarding her presentation.

[email protected]

DURBAN, SOUTH AFRICA – The 15 HIV-infected patients who have undergone allogeneic stem-cell transplant for life-threatening hematologic cancers under the auspices of the European EpiStem Consortium have uniformly demonstrated a profound and durable reduction in viral reservoir to a degree that hasn’t been approached by any other investigational cure strategy, Annemarie Wensing, MD, said at the 21st International AIDS Conference.

“We see an enormous reduction in the viral reservoir, and in two patients we cannot find any viable HIV in the blood using ultrasensitive tests. But we don’t know whether these patients are cured because they are still on antiretroviral therapy,” said Dr. Wensing of Utrecht (The Netherlands) University.

Bruce Jancin/Frontline Medical News

Non-Hodgkin’s lymphoma and Hodgkin’s lymphoma are 7-9 times more frequent in HIV-positive patients than in the general population. But allogeneic stem cell transplantation is an even higher-risk treatment in HIV-positive patients with life-threatening leukemia or lymphoma than in the HIV-negative population. Only 6 of the 15 EuroStem patients remain alive. Eight died within 4 months of the procedure and another died 2.5 years post-transplant, all from progression of their cancer or as a result of opportunistic infections arising during the immunosuppressive chemoablation that’s central to stem-cell transplantation. However, 3 of the 15 patients have survived longer than 3 years. In two of them, no HIV can be detected in blood or intestinal tissue using ultrasensitive tests, while in the third there is “only a slight trace,” according to Dr. Wensing, a clinical virologist.

EpiStem (the European Project to Guide and Investigate the Potential for HIV Cure by Stem-Cell Transplantation) is a multinational collaboration of European oncologists, infectious disease physicians, and other specialists. It was formed in response to the successful outcome of allogeneic stem cell transplantation for acute myeloid leukemia in HIV-positive Timothy Brown, more famously known as “the Berlin patient” (N Engl J Med. 2009 Feb 12;360(7):692-8). He has thus far survived 7 years off antiretroviral therapy.

Much has been made of the fact that Mr. Brown’s donor cells were homozygous for the CCR5 delta32 mutation, which confers natural resistance to HIV infection because it prevents the virus from infecting T cells. Only 1% or less of the population is homozygous for this mutation. But Dr. Wensing isn’t convinced that using donor cells with the mutation is a prerequisite for success. Indeed, while 4 of the 15 EpiStem patients received stem cells from donors homozygous for the mutation and another got donor cells heterozygous for the CCR5 delta32 mutation, the other 10 received stem cells capable of being infected by HIV – yet all 15 experienced an enormous reduction in their viral reservoir. And two of the three patients who have survived longer than 3 years got stem cells without the CCR5 delta32 mutation.

Dr. Wensing observed that a common denominator shared by Timothy Brown and the two EpiStem patients who have trace or undetectable HIV in blood or tissue samples more than 3 years post-transplant is that all three developed severe graft-versus-host disease in conjunction with their stem cell transplantation. She suspects this may have helped them to clear the infection, a hypothesis she intends to pursue further as EpiStem gathers more patients.

Eventually, if patients continue to test negative for HIV using ultrasensitive tests, it will be time to have a discussion with patients and their treating physicians as to whether they should continue on antiretroviral therapy.

“In the end it’s the patients’ decision, but they should be very well counseled because it can have medical and also psychological consequences if HIV returns,” she said.

EpiStem is funded by the American Foundation for AIDS Research Conssortium on HIV Eradication. Dr. Wensing reported having no financial conflicts regarding her presentation.

[email protected]