Aggressive Lymphomas

Micrograph showing DLBCL

Researchers have reported the first known case of central nervous system (CNS) lymphoma responding to chimeric antigen receptor (CAR) T-cell therapy.

The investigational CAR T-cell therapy JCAR017 induced complete remission of brain metastasis in a patient with refractory diffuse large B-cell lymphoma (DLBCL).

When a subcutaneous tumor began to recur 2 months after the patient received JCAR017 and a surgical biopsy was performed, the CAR T cells spontaneously re-expanded and the tumor again went into remission.

While the patient eventually relapsed and died more than a year after receiving JCAR017, the brain tumor never recurred.

“Brain involvement in DLBCL carries a grave prognosis, and the ability to induce a complete and durable response with conventional therapies is rare,” said Jeremy Abramson, MD, of Massachusetts General Hospital in Boston.

“In addition, all available CAR T-cell trials have excluded patients with central nervous system involvement. This result has implications not only for secondary DLBCL like this case but also for primary central nervous system lymphoma, for which treatment options are similarly limited after relapse and few patents are cured.”

Dr Abramson and his colleagues described this case in a letter to NEJM. The patient was involved in a trial of JCAR017, which was sponsored by Juno Therapeutics.

The patient was a 68-year-old woman with germinal center B-cell-like DLBCL with a BCL2 rearrangement and multiple copies of MYC and BCL6.

The patients’ disease was refractory to conventional chemotherapy and an 8/8 HLA-matched stem cell transplant. After she enrolled in a phase 1 trial of JCAR017, the patient was found to have a new lesion in the right temporal lobe of her brain.

One month after the patient received JCAR017—given after lymphodepletion with fludarabine and cyclophosphamide—imaging showed complete remission of the brain lesion.

The subcutaneous lesion that recurred 2 months later disappeared after the biopsy with no further treatment. Blood testing showed an expansion of CAR T cells that coincided with the tumor’s regression.

While re-expansion of CAR T cells has been reported in response to other immunotherapy drugs, this is the first report of such a response to a biopsy.

“Typically, the drugs we use to fight cancer and other diseases wear off over time,” Dr Abramson said. “This spontaneous re-expansion after biopsy highlights this therapy as something entirely different, a ‘living drug’ that can re-expand and proliferate in response to biologic stimuli.”

Micrograph showing DLBCL

Researchers have reported the first known case of central nervous system (CNS) lymphoma responding to chimeric antigen receptor (CAR) T-cell therapy.

The investigational CAR T-cell therapy JCAR017 induced complete remission of brain metastasis in a patient with refractory diffuse large B-cell lymphoma (DLBCL).

When a subcutaneous tumor began to recur 2 months after the patient received JCAR017 and a surgical biopsy was performed, the CAR T cells spontaneously re-expanded and the tumor again went into remission.

While the patient eventually relapsed and died more than a year after receiving JCAR017, the brain tumor never recurred.

“Brain involvement in DLBCL carries a grave prognosis, and the ability to induce a complete and durable response with conventional therapies is rare,” said Jeremy Abramson, MD, of Massachusetts General Hospital in Boston.

“In addition, all available CAR T-cell trials have excluded patients with central nervous system involvement. This result has implications not only for secondary DLBCL like this case but also for primary central nervous system lymphoma, for which treatment options are similarly limited after relapse and few patents are cured.”

Dr Abramson and his colleagues described this case in a letter to NEJM. The patient was involved in a trial of JCAR017, which was sponsored by Juno Therapeutics.

The patient was a 68-year-old woman with germinal center B-cell-like DLBCL with a BCL2 rearrangement and multiple copies of MYC and BCL6.

The patients’ disease was refractory to conventional chemotherapy and an 8/8 HLA-matched stem cell transplant. After she enrolled in a phase 1 trial of JCAR017, the patient was found to have a new lesion in the right temporal lobe of her brain.

One month after the patient received JCAR017—given after lymphodepletion with fludarabine and cyclophosphamide—imaging showed complete remission of the brain lesion.

The subcutaneous lesion that recurred 2 months later disappeared after the biopsy with no further treatment. Blood testing showed an expansion of CAR T cells that coincided with the tumor’s regression.

While re-expansion of CAR T cells has been reported in response to other immunotherapy drugs, this is the first report of such a response to a biopsy.

“Typically, the drugs we use to fight cancer and other diseases wear off over time,” Dr Abramson said. “This spontaneous re-expansion after biopsy highlights this therapy as something entirely different, a ‘living drug’ that can re-expand and proliferate in response to biologic stimuli.”

Micrograph showing DLBCL

Researchers have reported the first known case of central nervous system (CNS) lymphoma responding to chimeric antigen receptor (CAR) T-cell therapy.

The investigational CAR T-cell therapy JCAR017 induced complete remission of brain metastasis in a patient with refractory diffuse large B-cell lymphoma (DLBCL).

When a subcutaneous tumor began to recur 2 months after the patient received JCAR017 and a surgical biopsy was performed, the CAR T cells spontaneously re-expanded and the tumor again went into remission.

While the patient eventually relapsed and died more than a year after receiving JCAR017, the brain tumor never recurred.

“Brain involvement in DLBCL carries a grave prognosis, and the ability to induce a complete and durable response with conventional therapies is rare,” said Jeremy Abramson, MD, of Massachusetts General Hospital in Boston.

“In addition, all available CAR T-cell trials have excluded patients with central nervous system involvement. This result has implications not only for secondary DLBCL like this case but also for primary central nervous system lymphoma, for which treatment options are similarly limited after relapse and few patents are cured.”

Dr Abramson and his colleagues described this case in a letter to NEJM. The patient was involved in a trial of JCAR017, which was sponsored by Juno Therapeutics.

The patient was a 68-year-old woman with germinal center B-cell-like DLBCL with a BCL2 rearrangement and multiple copies of MYC and BCL6.

The patients’ disease was refractory to conventional chemotherapy and an 8/8 HLA-matched stem cell transplant. After she enrolled in a phase 1 trial of JCAR017, the patient was found to have a new lesion in the right temporal lobe of her brain.

One month after the patient received JCAR017—given after lymphodepletion with fludarabine and cyclophosphamide—imaging showed complete remission of the brain lesion.

The subcutaneous lesion that recurred 2 months later disappeared after the biopsy with no further treatment. Blood testing showed an expansion of CAR T cells that coincided with the tumor’s regression.

While re-expansion of CAR T cells has been reported in response to other immunotherapy drugs, this is the first report of such a response to a biopsy.

“Typically, the drugs we use to fight cancer and other diseases wear off over time,” Dr Abramson said. “This spontaneous re-expansion after biopsy highlights this therapy as something entirely different, a ‘living drug’ that can re-expand and proliferate in response to biologic stimuli.”

Follicular lymphoma

The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for obinutuzumab (Gazyva®).

With this sBLA, Genentech is seeking approval for obinutuzumab to be used, first in combination with chemotherapy and then alone as maintenance, in patients with previously untreated follicular lymphoma (FL).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the sBLA for obinutuzumab by December 23, 2017.

The sBLA is supported by results of the GALLIUM study, which were presented at the 2016 ASH Annual Meeting.

About obinutuzumab

Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.

The drug is FDA-approved for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.

Obinutuzumab is also approved to treat FL patients who relapse after, or are refractory to, a rituximab-containing regimen. In these patients, obinutuzumab is given first in combination with bendamustine and then alone as maintenance.

The full prescribing information for obinutuzumab is available at http://www.Gazyva.com.

About the GALLIUM study

GALLIUM enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.

Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).

The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.

Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).

There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).

The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.

The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.

Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).

Follicular lymphoma

The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for obinutuzumab (Gazyva®).

With this sBLA, Genentech is seeking approval for obinutuzumab to be used, first in combination with chemotherapy and then alone as maintenance, in patients with previously untreated follicular lymphoma (FL).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the sBLA for obinutuzumab by December 23, 2017.

The sBLA is supported by results of the GALLIUM study, which were presented at the 2016 ASH Annual Meeting.

About obinutuzumab

Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.

The drug is FDA-approved for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.

Obinutuzumab is also approved to treat FL patients who relapse after, or are refractory to, a rituximab-containing regimen. In these patients, obinutuzumab is given first in combination with bendamustine and then alone as maintenance.

The full prescribing information for obinutuzumab is available at http://www.Gazyva.com.

About the GALLIUM study

GALLIUM enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.

Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).

The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.

Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).

There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).

The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.

The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.

Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).

Follicular lymphoma

The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for obinutuzumab (Gazyva®).

With this sBLA, Genentech is seeking approval for obinutuzumab to be used, first in combination with chemotherapy and then alone as maintenance, in patients with previously untreated follicular lymphoma (FL).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the sBLA for obinutuzumab by December 23, 2017.

The sBLA is supported by results of the GALLIUM study, which were presented at the 2016 ASH Annual Meeting.

About obinutuzumab

Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.

The drug is FDA-approved for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.

Obinutuzumab is also approved to treat FL patients who relapse after, or are refractory to, a rituximab-containing regimen. In these patients, obinutuzumab is given first in combination with bendamustine and then alone as maintenance.

The full prescribing information for obinutuzumab is available at http://www.Gazyva.com.

About the GALLIUM study

GALLIUM enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.

Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).

The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.

Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).

There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).

The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.

The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.

Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).

Photo by Bill Branson

New research suggests survivors of childhood cancer can incur high out-of-pocket medical costs into adulthood and may forgo healthcare to lessen this financial burden.

The study showed that childhood cancer survivors (CCSs) were more likely than non-CCSs to have out-of-pocket medical costs that were at least 10% of their annual income.

And these high costs were associated with delaying care or skipping it altogether.

These findings were published in the Journal of Clinical Oncology.

“Survivors who reported spending a higher percentage of their income on out-of-pocket medical costs were not only more likely to report financial burden, they also were at risk for undertaking behaviors potentially detrimental to their health in order to save money,” said study author Ryan Nipp, MD, of Massachusetts General Hospital Cancer Center in Boston.

“While studies have identified associations between financial burden and patients’ treatment outcomes, quality of life, and even survival among adults with cancer, as far as we know, this is the first to report these associations in survivors of childhood cancer.”

For this research, Dr Nipp and his colleagues surveyed participants in the Childhood Cancer Survivor Study. This included adults who had been treated for childhood cancers between 1970 and 1986 along with a control group of siblings not affected by cancer.

In 2011 and 2012, participants were asked to provide information about their health insurance, the out-of-pocket healthcare costs they paid during the previous year, and sociodemographic information such as annual income and employment status.

The researchers also asked participants whether medical costs posed a financial burden and, if so, what measures they had taken to deal with that burden.

Study population

The researchers received complete responses from 580 CCSs and 173 of their siblings without a history of cancer. The most common cancer diagnosis was leukemia (33%), followed by Hodgkin lymphoma (14%), while non-Hodgkin lymphoma was less common (7%).

CCSs were a mean of 30.2 years from diagnosis. Use of chemotherapy (77%), radiation (66%), and surgery (81%) were common. Few patients had cancer recurrence (13%) or second cancers (5%).

There was no significant difference between CCSs and their siblings with regard to age at the time of the survey (P=0.071), household income (P=0.053), education (P=0.345), health insurance status (P=0.317), or having at least 1 hospitalization in the past year (P=0.270).

However, CCSs were significantly more likely than siblings to have chronic health conditions (P<0.001). Forty percent of CCSs had severe or life-threatening chronic conditions, compared to 17% of siblings.

Seventy-six percent of CCSs and 80% of siblings were employed. Twenty-nine percent of CCSs and 39% of siblings had household incomes exceeding $100,000. Twelve percent of CCSs and 5% of siblings had household incomes below $20,000.

Ninety-one percent of CCSs and 93% of siblings were insured. Most subjects in both groups (81% and 87%, respectively) had employer-sponsored insurance.

Results

CCSs were significantly more likely than their siblings to have out-of-pocket medical costs that were at least 10% of their annual income—10% and 3%, respectively (P<0.001).

Among CCSs, those with higher out-of-pocket costs (≥10% vs <10% of income) were more likely to have household incomes below $50,000 (odds ratio [OR]=5.5) and to report being hospitalized in the past year (OR=2.3).

CCSs with a higher percentage of their income spent on out-of-pocket costs were also more likely to:

• Have problems paying their medical bills (OR=8.8)
• Report inability to pay for basic costs of living such as food, heat, or rent (OR=6.1)
• Defer healthcare for a medical problem (OR=3.1)
• Skip a test, treatment, or follow-up (OR=2.1)
• Consider filing for bankruptcy (OR=6.4).

“A more comprehensive understanding of the relationship between high out-of-pocket medical costs and the adverse effects of increased financial burden on cancer survivors could be instrumental in helping us identify those at risk for higher costs to help us address their financial challenges and improve health outcomes,” Dr Nipp said.

“It could also help inform policy changes to help meet the unique needs of cancer survivors and improve our understanding of how both higher costs and resulting financial burden influence patients’ approach to their medical care and decision-making.”

Photo by Bill Branson

New research suggests survivors of childhood cancer can incur high out-of-pocket medical costs into adulthood and may forgo healthcare to lessen this financial burden.

The study showed that childhood cancer survivors (CCSs) were more likely than non-CCSs to have out-of-pocket medical costs that were at least 10% of their annual income.

And these high costs were associated with delaying care or skipping it altogether.

These findings were published in the Journal of Clinical Oncology.

“Survivors who reported spending a higher percentage of their income on out-of-pocket medical costs were not only more likely to report financial burden, they also were at risk for undertaking behaviors potentially detrimental to their health in order to save money,” said study author Ryan Nipp, MD, of Massachusetts General Hospital Cancer Center in Boston.

“While studies have identified associations between financial burden and patients’ treatment outcomes, quality of life, and even survival among adults with cancer, as far as we know, this is the first to report these associations in survivors of childhood cancer.”

For this research, Dr Nipp and his colleagues surveyed participants in the Childhood Cancer Survivor Study. This included adults who had been treated for childhood cancers between 1970 and 1986 along with a control group of siblings not affected by cancer.

In 2011 and 2012, participants were asked to provide information about their health insurance, the out-of-pocket healthcare costs they paid during the previous year, and sociodemographic information such as annual income and employment status.

The researchers also asked participants whether medical costs posed a financial burden and, if so, what measures they had taken to deal with that burden.

Study population

The researchers received complete responses from 580 CCSs and 173 of their siblings without a history of cancer. The most common cancer diagnosis was leukemia (33%), followed by Hodgkin lymphoma (14%), while non-Hodgkin lymphoma was less common (7%).

CCSs were a mean of 30.2 years from diagnosis. Use of chemotherapy (77%), radiation (66%), and surgery (81%) were common. Few patients had cancer recurrence (13%) or second cancers (5%).

There was no significant difference between CCSs and their siblings with regard to age at the time of the survey (P=0.071), household income (P=0.053), education (P=0.345), health insurance status (P=0.317), or having at least 1 hospitalization in the past year (P=0.270).

However, CCSs were significantly more likely than siblings to have chronic health conditions (P<0.001). Forty percent of CCSs had severe or life-threatening chronic conditions, compared to 17% of siblings.

Seventy-six percent of CCSs and 80% of siblings were employed. Twenty-nine percent of CCSs and 39% of siblings had household incomes exceeding $100,000. Twelve percent of CCSs and 5% of siblings had household incomes below $20,000.

Ninety-one percent of CCSs and 93% of siblings were insured. Most subjects in both groups (81% and 87%, respectively) had employer-sponsored insurance.

Results

CCSs were significantly more likely than their siblings to have out-of-pocket medical costs that were at least 10% of their annual income—10% and 3%, respectively (P<0.001).

Among CCSs, those with higher out-of-pocket costs (≥10% vs <10% of income) were more likely to have household incomes below $50,000 (odds ratio [OR]=5.5) and to report being hospitalized in the past year (OR=2.3).

CCSs with a higher percentage of their income spent on out-of-pocket costs were also more likely to:

• Have problems paying their medical bills (OR=8.8)
• Report inability to pay for basic costs of living such as food, heat, or rent (OR=6.1)
• Defer healthcare for a medical problem (OR=3.1)
• Skip a test, treatment, or follow-up (OR=2.1)
• Consider filing for bankruptcy (OR=6.4).

“A more comprehensive understanding of the relationship between high out-of-pocket medical costs and the adverse effects of increased financial burden on cancer survivors could be instrumental in helping us identify those at risk for higher costs to help us address their financial challenges and improve health outcomes,” Dr Nipp said.

“It could also help inform policy changes to help meet the unique needs of cancer survivors and improve our understanding of how both higher costs and resulting financial burden influence patients’ approach to their medical care and decision-making.”

Photo by Bill Branson

New research suggests survivors of childhood cancer can incur high out-of-pocket medical costs into adulthood and may forgo healthcare to lessen this financial burden.

The study showed that childhood cancer survivors (CCSs) were more likely than non-CCSs to have out-of-pocket medical costs that were at least 10% of their annual income.

And these high costs were associated with delaying care or skipping it altogether.

These findings were published in the Journal of Clinical Oncology.

“Survivors who reported spending a higher percentage of their income on out-of-pocket medical costs were not only more likely to report financial burden, they also were at risk for undertaking behaviors potentially detrimental to their health in order to save money,” said study author Ryan Nipp, MD, of Massachusetts General Hospital Cancer Center in Boston.

“While studies have identified associations between financial burden and patients’ treatment outcomes, quality of life, and even survival among adults with cancer, as far as we know, this is the first to report these associations in survivors of childhood cancer.”

For this research, Dr Nipp and his colleagues surveyed participants in the Childhood Cancer Survivor Study. This included adults who had been treated for childhood cancers between 1970 and 1986 along with a control group of siblings not affected by cancer.

In 2011 and 2012, participants were asked to provide information about their health insurance, the out-of-pocket healthcare costs they paid during the previous year, and sociodemographic information such as annual income and employment status.

The researchers also asked participants whether medical costs posed a financial burden and, if so, what measures they had taken to deal with that burden.

Study population

The researchers received complete responses from 580 CCSs and 173 of their siblings without a history of cancer. The most common cancer diagnosis was leukemia (33%), followed by Hodgkin lymphoma (14%), while non-Hodgkin lymphoma was less common (7%).

CCSs were a mean of 30.2 years from diagnosis. Use of chemotherapy (77%), radiation (66%), and surgery (81%) were common. Few patients had cancer recurrence (13%) or second cancers (5%).

There was no significant difference between CCSs and their siblings with regard to age at the time of the survey (P=0.071), household income (P=0.053), education (P=0.345), health insurance status (P=0.317), or having at least 1 hospitalization in the past year (P=0.270).

However, CCSs were significantly more likely than siblings to have chronic health conditions (P<0.001). Forty percent of CCSs had severe or life-threatening chronic conditions, compared to 17% of siblings.

Seventy-six percent of CCSs and 80% of siblings were employed. Twenty-nine percent of CCSs and 39% of siblings had household incomes exceeding $100,000. Twelve percent of CCSs and 5% of siblings had household incomes below $20,000.

Ninety-one percent of CCSs and 93% of siblings were insured. Most subjects in both groups (81% and 87%, respectively) had employer-sponsored insurance.

Results

CCSs were significantly more likely than their siblings to have out-of-pocket medical costs that were at least 10% of their annual income—10% and 3%, respectively (P<0.001).

Among CCSs, those with higher out-of-pocket costs (≥10% vs <10% of income) were more likely to have household incomes below $50,000 (odds ratio [OR]=5.5) and to report being hospitalized in the past year (OR=2.3).

CCSs with a higher percentage of their income spent on out-of-pocket costs were also more likely to:

• Have problems paying their medical bills (OR=8.8)
• Report inability to pay for basic costs of living such as food, heat, or rent (OR=6.1)
• Defer healthcare for a medical problem (OR=3.1)
• Skip a test, treatment, or follow-up (OR=2.1)
• Consider filing for bankruptcy (OR=6.4).

“A more comprehensive understanding of the relationship between high out-of-pocket medical costs and the adverse effects of increased financial burden on cancer survivors could be instrumental in helping us identify those at risk for higher costs to help us address their financial challenges and improve health outcomes,” Dr Nipp said.

“It could also help inform policy changes to help meet the unique needs of cancer survivors and improve our understanding of how both higher costs and resulting financial burden influence patients’ approach to their medical care and decision-making.”

Photo by Bill Branson

The US Food and Drug Administration (FDA) has granted orphan drug designation to SENS-401 to be used for the prevention of platinum-induced ototoxicity in pediatric patients.

Platinum-based chemotherapies, particularly cisplatin, can induce severe hearing loss in cancer patients, but there is no pharmaceutical agent approved to treat this side effect.

“Hearing loss in pediatric oncology patients is one of the most frequent side effects of cisplatin treatment and may disable them for the rest of their lives,” said Nawal Ouzren, CEO of Sensorion, the company developing SENS-401.

“Based on its unique profile and the data generated to date, we believe SENS-401 has the potential to be a safe and effective treatment for this serious medical condition where a significant unmet need exists. As such, we look forward to working with the FDA and EMA [European Medicines Agency] to set up an IND [investigational new drug application] and design a phase 2 clinical trial in order to evaluate SENS-401 in this indication.”

About SENS-401

SENS-401 (R-azasetron besylate) is a small molecule intended to protect and preserve inner ear tissue when lesions cause progressive or sequelar hearing impairments. The drug can be taken orally or via an injection.

SENS-401 is one of the two enantiomer forms of SENS-218 (azasetron), a racemic molecule belonging to the family of setrons marketed in Asia under the name Serotone. Pharmacological and pharmacokinetic tests have shown a superior profile for SENS-401 compared with the other enantiomer or the racemic form.

Healthy subjects demonstrated a “very good clinical tolerance” to SENS-401 in a phase 1 study, according to Sensorion. The company is planning to launch a phase 2 trial of the drug for platinum-induced ototoxicity in 2018.

About orphan designation

The FDA grants orphan designation to products 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.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has granted orphan drug designation to SENS-401 to be used for the prevention of platinum-induced ototoxicity in pediatric patients.

Platinum-based chemotherapies, particularly cisplatin, can induce severe hearing loss in cancer patients, but there is no pharmaceutical agent approved to treat this side effect.

“Hearing loss in pediatric oncology patients is one of the most frequent side effects of cisplatin treatment and may disable them for the rest of their lives,” said Nawal Ouzren, CEO of Sensorion, the company developing SENS-401.

“Based on its unique profile and the data generated to date, we believe SENS-401 has the potential to be a safe and effective treatment for this serious medical condition where a significant unmet need exists. As such, we look forward to working with the FDA and EMA [European Medicines Agency] to set up an IND [investigational new drug application] and design a phase 2 clinical trial in order to evaluate SENS-401 in this indication.”

About SENS-401

SENS-401 (R-azasetron besylate) is a small molecule intended to protect and preserve inner ear tissue when lesions cause progressive or sequelar hearing impairments. The drug can be taken orally or via an injection.

SENS-401 is one of the two enantiomer forms of SENS-218 (azasetron), a racemic molecule belonging to the family of setrons marketed in Asia under the name Serotone. Pharmacological and pharmacokinetic tests have shown a superior profile for SENS-401 compared with the other enantiomer or the racemic form.

Healthy subjects demonstrated a “very good clinical tolerance” to SENS-401 in a phase 1 study, according to Sensorion. The company is planning to launch a phase 2 trial of the drug for platinum-induced ototoxicity in 2018.

About orphan designation

The FDA grants orphan designation to products 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.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has granted orphan drug designation to SENS-401 to be used for the prevention of platinum-induced ototoxicity in pediatric patients.

Platinum-based chemotherapies, particularly cisplatin, can induce severe hearing loss in cancer patients, but there is no pharmaceutical agent approved to treat this side effect.

“Hearing loss in pediatric oncology patients is one of the most frequent side effects of cisplatin treatment and may disable them for the rest of their lives,” said Nawal Ouzren, CEO of Sensorion, the company developing SENS-401.

“Based on its unique profile and the data generated to date, we believe SENS-401 has the potential to be a safe and effective treatment for this serious medical condition where a significant unmet need exists. As such, we look forward to working with the FDA and EMA [European Medicines Agency] to set up an IND [investigational new drug application] and design a phase 2 clinical trial in order to evaluate SENS-401 in this indication.”

About SENS-401

SENS-401 (R-azasetron besylate) is a small molecule intended to protect and preserve inner ear tissue when lesions cause progressive or sequelar hearing impairments. The drug can be taken orally or via an injection.

SENS-401 is one of the two enantiomer forms of SENS-218 (azasetron), a racemic molecule belonging to the family of setrons marketed in Asia under the name Serotone. Pharmacological and pharmacokinetic tests have shown a superior profile for SENS-401 compared with the other enantiomer or the racemic form.

Healthy subjects demonstrated a “very good clinical tolerance” to SENS-401 in a phase 1 study, according to Sensorion. The company is planning to launch a phase 2 trial of the drug for platinum-induced ototoxicity in 2018.

About orphan designation

The FDA grants orphan designation to products 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.

Image by Ed Uthman

An investigational antibody has demonstrated activity against acute myeloid leukemia (AML), multiple myeloma (MM), and non-Hodgkin lymphoma (NHL), according to researchers.

PF-06747143 is a humanized CXCR4 immunoglobulin G1 (IgG1) antibody that binds to CXCR4 and inhibits both CXCL12-mediated signaling pathways and cell migration.

Whether given alone or in combination with chemotherapy, PF-06747143 demonstrated efficacy in mouse models of NHL, MM, and AML.

Treatment involving PF-06747143—alone or in combination—eradicated more cancer cells than did standard treatment options.

These results were published in Blood Advances. The research was sponsored by Pfizer, Inc., the company developing PF-06747143.

“One of the major limitations we see in treating blood cancers is the failure to clear cancer cells from the bone marrow,” said study author Flavia Pernasetti, PhD, of Pfizer Oncology Research and Development.

“Because the bone marrow allows the cancer cells to flourish, removing these cells is an essential step in treating these malignancies effectively.”

With this goal in mind, Dr Pernasetti and her colleagues looked to the mechanisms that control the movement of cells into the bone marrow (BM) in the first place—the chemokine receptor CXCR4 and its ligand CXCL12.

The researchers created PF-06747143, which attacks and kills cancer cells directly but also removes cancer cells from the BM so they can be killed by other treatments.

Results in NHL

The researchers first tested PF-06747143 in an NHL Ramos xenograft model. Mice received PF-06747143 or a control IgG1 antibody at 10 mg/kg on days 1 and 8.

PF-06747143 significantly inhibited tumor growth compared to the control antibody (P<0.0001). Seventy percent of PF-06747143-treated mice had tumor volumes below their initial size at the end of the study.

PF-06747143 produced a dose-dependent response that was sustained until the end of the study, even after treatment was stopped.

Results in MM

The researchers tested PF-06747143 in a disseminated MM model, in which the OPM2-Luc tumor cells were implanted intravenously and migrated spontaneously to the BM.

Mice received PF-06747143 or IgG1 control at 10 mg/kg weekly for 5 doses. Other mice received melphalan at 1 mg/kg twice a week for a total of 4 cycles.

On day 30, PF-06747143 had significantly inhibited BM tumor growth compared to the control antibody or melphalan (P<0.0001).

PF-06747143-treated mice also had a significant survival benefit. The median survival was 33.5 days for mice that received the control antibody and 36 days for mice treated with melphalan. However, there were no deaths in the PF-06747143-treated mice by day 50, which marked the end of the study (P<0.0001).

The researchers also tested PF-06747143 at a lower dose (1 mg/kg weekly for a total of 7 doses), both alone and in combination with bortezomib (0.5 mg/kg twice a week for a total of 4 cycles).

The median survival was 34 days in the control mice, 44 days in mice that received bortezomib alone, and 47 days in mice that received PF-06747143 alone. However, there were no deaths in the combination arm at day 51, which was the end of the study (P<0.0003).

Results in AML

The researchers tested PF-06747143 in an AML disseminated tumor model using MV4-11 cells.

They compared PF-06747143 (given at 0.1, 1, or 10 mg/kg weekly for 4 doses) to the chemotherapeutic agent daunorubicin (2 mg/kg on days 1, 3, and 5), the FLT3 inhibitor crenolanib (7.5 mg/kg twice a day, on days 11-15 and 25-29), and a control IgG1 antibody (10 mg/kg weekly for 4 doses).

PF-06747143 (at 10 mg/kg), daunorubicin, and crenolanib all significantly reduced the number of tumor cells in the peripheral blood and BM when compared with the control antibody (P<0.05).

PF-06746143 treatment (at 10 mg/kg) reduced the number of AML cells in the BM by 95.9%, while daunorubicin reduced them by 84.5% and crenolanib by 80.5%.

The median survival was 36 days for mice that received PF-06747143 at 0.1 mg/kg, 41 days for mice that received the control antibody, 47 days for mice that received PF-06747143 at 1 mg/kg, and 63 days for mice that received PF-06747143 at 10 mg/kg.

The researchers also found that PF-06747143 had a “strong combinatorial effect” with daunorubicin and cytarabine in a chemotherapy-resistant model of AML. The team noted that only 36% of BM cells are positive for CXCR4 in this model.

Treatment with PF-06747143 alone reduced the percentage of AML cells in the BM to 80%, combination daunorubicin and cytarabine reduced it to 27%, and combination PF-06747143, daunorubicin, and cytarabine reduced the percentage of AML cells in the BM to 0.3%.

“Our preliminary preclinical results are encouraging,” Dr Pernasetti said, “and we are very excited to see how our antibody fares in clinical testing.”

PF-06747143 is currently being evaluated in a phase 1 trial of AML patients.

Image by Ed Uthman

An investigational antibody has demonstrated activity against acute myeloid leukemia (AML), multiple myeloma (MM), and non-Hodgkin lymphoma (NHL), according to researchers.

PF-06747143 is a humanized CXCR4 immunoglobulin G1 (IgG1) antibody that binds to CXCR4 and inhibits both CXCL12-mediated signaling pathways and cell migration.

Whether given alone or in combination with chemotherapy, PF-06747143 demonstrated efficacy in mouse models of NHL, MM, and AML.

Treatment involving PF-06747143—alone or in combination—eradicated more cancer cells than did standard treatment options.

These results were published in Blood Advances. The research was sponsored by Pfizer, Inc., the company developing PF-06747143.

“One of the major limitations we see in treating blood cancers is the failure to clear cancer cells from the bone marrow,” said study author Flavia Pernasetti, PhD, of Pfizer Oncology Research and Development.

“Because the bone marrow allows the cancer cells to flourish, removing these cells is an essential step in treating these malignancies effectively.”

With this goal in mind, Dr Pernasetti and her colleagues looked to the mechanisms that control the movement of cells into the bone marrow (BM) in the first place—the chemokine receptor CXCR4 and its ligand CXCL12.

The researchers created PF-06747143, which attacks and kills cancer cells directly but also removes cancer cells from the BM so they can be killed by other treatments.

Results in NHL

The researchers first tested PF-06747143 in an NHL Ramos xenograft model. Mice received PF-06747143 or a control IgG1 antibody at 10 mg/kg on days 1 and 8.

PF-06747143 significantly inhibited tumor growth compared to the control antibody (P<0.0001). Seventy percent of PF-06747143-treated mice had tumor volumes below their initial size at the end of the study.

PF-06747143 produced a dose-dependent response that was sustained until the end of the study, even after treatment was stopped.

Results in MM

The researchers tested PF-06747143 in a disseminated MM model, in which the OPM2-Luc tumor cells were implanted intravenously and migrated spontaneously to the BM.

Mice received PF-06747143 or IgG1 control at 10 mg/kg weekly for 5 doses. Other mice received melphalan at 1 mg/kg twice a week for a total of 4 cycles.

On day 30, PF-06747143 had significantly inhibited BM tumor growth compared to the control antibody or melphalan (P<0.0001).

PF-06747143-treated mice also had a significant survival benefit. The median survival was 33.5 days for mice that received the control antibody and 36 days for mice treated with melphalan. However, there were no deaths in the PF-06747143-treated mice by day 50, which marked the end of the study (P<0.0001).

The researchers also tested PF-06747143 at a lower dose (1 mg/kg weekly for a total of 7 doses), both alone and in combination with bortezomib (0.5 mg/kg twice a week for a total of 4 cycles).

The median survival was 34 days in the control mice, 44 days in mice that received bortezomib alone, and 47 days in mice that received PF-06747143 alone. However, there were no deaths in the combination arm at day 51, which was the end of the study (P<0.0003).

Results in AML

The researchers tested PF-06747143 in an AML disseminated tumor model using MV4-11 cells.

They compared PF-06747143 (given at 0.1, 1, or 10 mg/kg weekly for 4 doses) to the chemotherapeutic agent daunorubicin (2 mg/kg on days 1, 3, and 5), the FLT3 inhibitor crenolanib (7.5 mg/kg twice a day, on days 11-15 and 25-29), and a control IgG1 antibody (10 mg/kg weekly for 4 doses).

PF-06747143 (at 10 mg/kg), daunorubicin, and crenolanib all significantly reduced the number of tumor cells in the peripheral blood and BM when compared with the control antibody (P<0.05).

PF-06746143 treatment (at 10 mg/kg) reduced the number of AML cells in the BM by 95.9%, while daunorubicin reduced them by 84.5% and crenolanib by 80.5%.

The median survival was 36 days for mice that received PF-06747143 at 0.1 mg/kg, 41 days for mice that received the control antibody, 47 days for mice that received PF-06747143 at 1 mg/kg, and 63 days for mice that received PF-06747143 at 10 mg/kg.

The researchers also found that PF-06747143 had a “strong combinatorial effect” with daunorubicin and cytarabine in a chemotherapy-resistant model of AML. The team noted that only 36% of BM cells are positive for CXCR4 in this model.

Treatment with PF-06747143 alone reduced the percentage of AML cells in the BM to 80%, combination daunorubicin and cytarabine reduced it to 27%, and combination PF-06747143, daunorubicin, and cytarabine reduced the percentage of AML cells in the BM to 0.3%.

“Our preliminary preclinical results are encouraging,” Dr Pernasetti said, “and we are very excited to see how our antibody fares in clinical testing.”

PF-06747143 is currently being evaluated in a phase 1 trial of AML patients.

Image by Ed Uthman

An investigational antibody has demonstrated activity against acute myeloid leukemia (AML), multiple myeloma (MM), and non-Hodgkin lymphoma (NHL), according to researchers.

PF-06747143 is a humanized CXCR4 immunoglobulin G1 (IgG1) antibody that binds to CXCR4 and inhibits both CXCL12-mediated signaling pathways and cell migration.

Whether given alone or in combination with chemotherapy, PF-06747143 demonstrated efficacy in mouse models of NHL, MM, and AML.

Treatment involving PF-06747143—alone or in combination—eradicated more cancer cells than did standard treatment options.

These results were published in Blood Advances. The research was sponsored by Pfizer, Inc., the company developing PF-06747143.

“One of the major limitations we see in treating blood cancers is the failure to clear cancer cells from the bone marrow,” said study author Flavia Pernasetti, PhD, of Pfizer Oncology Research and Development.

“Because the bone marrow allows the cancer cells to flourish, removing these cells is an essential step in treating these malignancies effectively.”

With this goal in mind, Dr Pernasetti and her colleagues looked to the mechanisms that control the movement of cells into the bone marrow (BM) in the first place—the chemokine receptor CXCR4 and its ligand CXCL12.

The researchers created PF-06747143, which attacks and kills cancer cells directly but also removes cancer cells from the BM so they can be killed by other treatments.

Results in NHL

The researchers first tested PF-06747143 in an NHL Ramos xenograft model. Mice received PF-06747143 or a control IgG1 antibody at 10 mg/kg on days 1 and 8.

PF-06747143 significantly inhibited tumor growth compared to the control antibody (P<0.0001). Seventy percent of PF-06747143-treated mice had tumor volumes below their initial size at the end of the study.

PF-06747143 produced a dose-dependent response that was sustained until the end of the study, even after treatment was stopped.

Results in MM

The researchers tested PF-06747143 in a disseminated MM model, in which the OPM2-Luc tumor cells were implanted intravenously and migrated spontaneously to the BM.

Mice received PF-06747143 or IgG1 control at 10 mg/kg weekly for 5 doses. Other mice received melphalan at 1 mg/kg twice a week for a total of 4 cycles.

On day 30, PF-06747143 had significantly inhibited BM tumor growth compared to the control antibody or melphalan (P<0.0001).

PF-06747143-treated mice also had a significant survival benefit. The median survival was 33.5 days for mice that received the control antibody and 36 days for mice treated with melphalan. However, there were no deaths in the PF-06747143-treated mice by day 50, which marked the end of the study (P<0.0001).

The researchers also tested PF-06747143 at a lower dose (1 mg/kg weekly for a total of 7 doses), both alone and in combination with bortezomib (0.5 mg/kg twice a week for a total of 4 cycles).

The median survival was 34 days in the control mice, 44 days in mice that received bortezomib alone, and 47 days in mice that received PF-06747143 alone. However, there were no deaths in the combination arm at day 51, which was the end of the study (P<0.0003).

Results in AML

The researchers tested PF-06747143 in an AML disseminated tumor model using MV4-11 cells.

They compared PF-06747143 (given at 0.1, 1, or 10 mg/kg weekly for 4 doses) to the chemotherapeutic agent daunorubicin (2 mg/kg on days 1, 3, and 5), the FLT3 inhibitor crenolanib (7.5 mg/kg twice a day, on days 11-15 and 25-29), and a control IgG1 antibody (10 mg/kg weekly for 4 doses).

PF-06747143 (at 10 mg/kg), daunorubicin, and crenolanib all significantly reduced the number of tumor cells in the peripheral blood and BM when compared with the control antibody (P<0.05).

PF-06746143 treatment (at 10 mg/kg) reduced the number of AML cells in the BM by 95.9%, while daunorubicin reduced them by 84.5% and crenolanib by 80.5%.

The median survival was 36 days for mice that received PF-06747143 at 0.1 mg/kg, 41 days for mice that received the control antibody, 47 days for mice that received PF-06747143 at 1 mg/kg, and 63 days for mice that received PF-06747143 at 10 mg/kg.

The researchers also found that PF-06747143 had a “strong combinatorial effect” with daunorubicin and cytarabine in a chemotherapy-resistant model of AML. The team noted that only 36% of BM cells are positive for CXCR4 in this model.

Treatment with PF-06747143 alone reduced the percentage of AML cells in the BM to 80%, combination daunorubicin and cytarabine reduced it to 27%, and combination PF-06747143, daunorubicin, and cytarabine reduced the percentage of AML cells in the BM to 0.3%.

“Our preliminary preclinical results are encouraging,” Dr Pernasetti said, “and we are very excited to see how our antibody fares in clinical testing.”

PF-06747143 is currently being evaluated in a phase 1 trial of AML patients.

Obinutuzumab with CHOP therapy did not improve progression-free survival, compared with rituximab plus CHOP, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to results from a phase 3 trial published in the Journal of Clinical Oncology. (2017 Aug 10. doi: 10.1200/JCO.2017.73.3402)

The findings suggest that obinutuzumab, a glycoengineered, type II, anti-CD20 monoclonal antibody, might not offer a benefit over standard treatment with rituximab, an anti-CD20 monoclonal antibody, when used with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).

A total of 1,418 patients were enrolled at 207 centers in 29 countries in the GOYA trial and were randomly assigned to one regimen or the other. The mean duration of exposure to the drugs was 25 weeks for both. The progression-free survival was 69.6% for obinutuzumab-CHOP – also known as G-CHOP – and 66.9% for rituximab-CHOP, not a statistically significant difference, wrote Umberto Vitolo, MD, of University-Hospital Città della Salute e della Scienza, Torino, Italy, and his fellow investigators.

The rate of adverse events was similar between the two groups. The lack of superiority of obinutuzumab comes after findings of its superiority in untreated follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). The investigators suggested that this may be a sign that obinutuzumab’s efficacy is best seen in less aggressive disease types.

“Given the advantages of G-based therapy in patients with FL and CLL, the lack of benefit of G-CHOP in patients with DLBCL in the GOYA study was unexpected, and the reasons for it are unclear,” they wrote. “This lack of benefit might simply have resulted from the differences in biologic and clinical profiles between indolent lymphoproliferative diseases, such as FL and CLL, and aggressive ones, such as DLBCL.”

The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi.

Obinutuzumab with CHOP therapy did not improve progression-free survival, compared with rituximab plus CHOP, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to results from a phase 3 trial published in the Journal of Clinical Oncology. (2017 Aug 10. doi: 10.1200/JCO.2017.73.3402)

The findings suggest that obinutuzumab, a glycoengineered, type II, anti-CD20 monoclonal antibody, might not offer a benefit over standard treatment with rituximab, an anti-CD20 monoclonal antibody, when used with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).

A total of 1,418 patients were enrolled at 207 centers in 29 countries in the GOYA trial and were randomly assigned to one regimen or the other. The mean duration of exposure to the drugs was 25 weeks for both. The progression-free survival was 69.6% for obinutuzumab-CHOP – also known as G-CHOP – and 66.9% for rituximab-CHOP, not a statistically significant difference, wrote Umberto Vitolo, MD, of University-Hospital Città della Salute e della Scienza, Torino, Italy, and his fellow investigators.

The rate of adverse events was similar between the two groups. The lack of superiority of obinutuzumab comes after findings of its superiority in untreated follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). The investigators suggested that this may be a sign that obinutuzumab’s efficacy is best seen in less aggressive disease types.

“Given the advantages of G-based therapy in patients with FL and CLL, the lack of benefit of G-CHOP in patients with DLBCL in the GOYA study was unexpected, and the reasons for it are unclear,” they wrote. “This lack of benefit might simply have resulted from the differences in biologic and clinical profiles between indolent lymphoproliferative diseases, such as FL and CLL, and aggressive ones, such as DLBCL.”

The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi.

Obinutuzumab with CHOP therapy did not improve progression-free survival, compared with rituximab plus CHOP, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to results from a phase 3 trial published in the Journal of Clinical Oncology. (2017 Aug 10. doi: 10.1200/JCO.2017.73.3402)

The findings suggest that obinutuzumab, a glycoengineered, type II, anti-CD20 monoclonal antibody, might not offer a benefit over standard treatment with rituximab, an anti-CD20 monoclonal antibody, when used with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).

A total of 1,418 patients were enrolled at 207 centers in 29 countries in the GOYA trial and were randomly assigned to one regimen or the other. The mean duration of exposure to the drugs was 25 weeks for both. The progression-free survival was 69.6% for obinutuzumab-CHOP – also known as G-CHOP – and 66.9% for rituximab-CHOP, not a statistically significant difference, wrote Umberto Vitolo, MD, of University-Hospital Città della Salute e della Scienza, Torino, Italy, and his fellow investigators.

The rate of adverse events was similar between the two groups. The lack of superiority of obinutuzumab comes after findings of its superiority in untreated follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). The investigators suggested that this may be a sign that obinutuzumab’s efficacy is best seen in less aggressive disease types.

“Given the advantages of G-based therapy in patients with FL and CLL, the lack of benefit of G-CHOP in patients with DLBCL in the GOYA study was unexpected, and the reasons for it are unclear,” they wrote. “This lack of benefit might simply have resulted from the differences in biologic and clinical profiles between indolent lymphoproliferative diseases, such as FL and CLL, and aggressive ones, such as DLBCL.”

The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi.

Treatment with the ALK-inhibitor crizotinib produced high response rates in pediatric patients with ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMTs), according to phase 2 trial results.

“The robust and sustained clinical responses to crizotinib in patients with relapsed or refractory ALK-driven ALCL and IMT highlight the importance of this oncogene and the sensitivity to ALK inhibition in these diseases,” said Yaël P. Mossé, MD, of Children’s Hospital of Philadelphia, and her associates.

Twenty-six patients with recurrent ALCL and 14 with unresectable IMTs – not older than 22 years – were enrolled. Six of the ALCL patients were treated at 165 mg/m² (ALCL165) and 20 at 280 mg/m² (ALCL280), which was found to be the recommended phase 2 dose. Ten of the ALCL280 patients had been treated at an equivalent to this dose in phase 1 and they were included in the phase 2 analysis. Those in the ALCL280 group tended to be older, at a median age of 12.2 years, than the other patients in the study, the investigators reported (J Clin Oncol. 2017 Aug 8 doi: 10.1200/JCO.2017.73.4830).

Eight of the IMT patients were enrolled in a dose-escalation portion of the study, with one receiving a 100 mg/m² dose, one receiving 165 mg/m², and the other six receiving 280 mg/m². The other six were treated at 280 mg/m². All of the IMT patient results are presented as one pool because those at the lower doses had toxicity and responses similar to those in patients given the higher dose.

Sixteen of 20 patients in the ALCL280 group – 80% – had a complete response, two had a partial response, and two were found to have stable disease. The median duration of treatment in this group was 0.4 years, and the median time to the first partial or complete response was 27 days. In the ALCL165 group, five of six, or 83%, had a complete response, along with one found to have stable disease. This group had a median treatment duration of 2.79 years, and the median time to the first partial or complete response was 26.5 days.

In the IMT group, 5 of 14, or 36%, had a complete response; 7, or 50%, had a partial response, and 2 had stable disease. They received treatment for a median of 1.63 years, and the median time to the first partial or complete response was 28.5 days.

Investigators reported that at least one grade 3 or 4 adverse event occurred in 83% of patients in the ALCL165 group, in all of the patients in the ALCL280 group, and in 71% in the IMT group. Adverse events considered possibly, probably, or definitely related to the study treatment occurred in 33% of the ALCL165 group, in 85% of the ALCL280 group, and in 57% of the IMT group. The most common adverse event was a decreased neutrophil count.

“Notable objective and sustained responses were observed in patients with ALK fusion-positive ALCL and IMT,” the investigators wrote, “establishing a precedent in pediatric oncology for studying the early-phase activity of a targeted agent in a biomarker-selected and histology-independent cohort of patients.

“In the cohort of patients with ALK-positive unresectable IMTs,” they continued, “ALK inhibition was a highly effective therapy and supports consideration of frontline therapy with crizotinib, a strategy that could also be relevant to adults with this rare disease.”

[email protected]

Treatment with the ALK-inhibitor crizotinib produced high response rates in pediatric patients with ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMTs), according to phase 2 trial results.

“The robust and sustained clinical responses to crizotinib in patients with relapsed or refractory ALK-driven ALCL and IMT highlight the importance of this oncogene and the sensitivity to ALK inhibition in these diseases,” said Yaël P. Mossé, MD, of Children’s Hospital of Philadelphia, and her associates.

Twenty-six patients with recurrent ALCL and 14 with unresectable IMTs – not older than 22 years – were enrolled. Six of the ALCL patients were treated at 165 mg/m² (ALCL165) and 20 at 280 mg/m² (ALCL280), which was found to be the recommended phase 2 dose. Ten of the ALCL280 patients had been treated at an equivalent to this dose in phase 1 and they were included in the phase 2 analysis. Those in the ALCL280 group tended to be older, at a median age of 12.2 years, than the other patients in the study, the investigators reported (J Clin Oncol. 2017 Aug 8 doi: 10.1200/JCO.2017.73.4830).

Eight of the IMT patients were enrolled in a dose-escalation portion of the study, with one receiving a 100 mg/m² dose, one receiving 165 mg/m², and the other six receiving 280 mg/m². The other six were treated at 280 mg/m². All of the IMT patient results are presented as one pool because those at the lower doses had toxicity and responses similar to those in patients given the higher dose.

Sixteen of 20 patients in the ALCL280 group – 80% – had a complete response, two had a partial response, and two were found to have stable disease. The median duration of treatment in this group was 0.4 years, and the median time to the first partial or complete response was 27 days. In the ALCL165 group, five of six, or 83%, had a complete response, along with one found to have stable disease. This group had a median treatment duration of 2.79 years, and the median time to the first partial or complete response was 26.5 days.

In the IMT group, 5 of 14, or 36%, had a complete response; 7, or 50%, had a partial response, and 2 had stable disease. They received treatment for a median of 1.63 years, and the median time to the first partial or complete response was 28.5 days.

Investigators reported that at least one grade 3 or 4 adverse event occurred in 83% of patients in the ALCL165 group, in all of the patients in the ALCL280 group, and in 71% in the IMT group. Adverse events considered possibly, probably, or definitely related to the study treatment occurred in 33% of the ALCL165 group, in 85% of the ALCL280 group, and in 57% of the IMT group. The most common adverse event was a decreased neutrophil count.

“Notable objective and sustained responses were observed in patients with ALK fusion-positive ALCL and IMT,” the investigators wrote, “establishing a precedent in pediatric oncology for studying the early-phase activity of a targeted agent in a biomarker-selected and histology-independent cohort of patients.

“In the cohort of patients with ALK-positive unresectable IMTs,” they continued, “ALK inhibition was a highly effective therapy and supports consideration of frontline therapy with crizotinib, a strategy that could also be relevant to adults with this rare disease.”

[email protected]

Treatment with the ALK-inhibitor crizotinib produced high response rates in pediatric patients with ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMTs), according to phase 2 trial results.

“The robust and sustained clinical responses to crizotinib in patients with relapsed or refractory ALK-driven ALCL and IMT highlight the importance of this oncogene and the sensitivity to ALK inhibition in these diseases,” said Yaël P. Mossé, MD, of Children’s Hospital of Philadelphia, and her associates.

Twenty-six patients with recurrent ALCL and 14 with unresectable IMTs – not older than 22 years – were enrolled. Six of the ALCL patients were treated at 165 mg/m² (ALCL165) and 20 at 280 mg/m² (ALCL280), which was found to be the recommended phase 2 dose. Ten of the ALCL280 patients had been treated at an equivalent to this dose in phase 1 and they were included in the phase 2 analysis. Those in the ALCL280 group tended to be older, at a median age of 12.2 years, than the other patients in the study, the investigators reported (J Clin Oncol. 2017 Aug 8 doi: 10.1200/JCO.2017.73.4830).

Eight of the IMT patients were enrolled in a dose-escalation portion of the study, with one receiving a 100 mg/m² dose, one receiving 165 mg/m², and the other six receiving 280 mg/m². The other six were treated at 280 mg/m². All of the IMT patient results are presented as one pool because those at the lower doses had toxicity and responses similar to those in patients given the higher dose.

Sixteen of 20 patients in the ALCL280 group – 80% – had a complete response, two had a partial response, and two were found to have stable disease. The median duration of treatment in this group was 0.4 years, and the median time to the first partial or complete response was 27 days. In the ALCL165 group, five of six, or 83%, had a complete response, along with one found to have stable disease. This group had a median treatment duration of 2.79 years, and the median time to the first partial or complete response was 26.5 days.

In the IMT group, 5 of 14, or 36%, had a complete response; 7, or 50%, had a partial response, and 2 had stable disease. They received treatment for a median of 1.63 years, and the median time to the first partial or complete response was 28.5 days.

Investigators reported that at least one grade 3 or 4 adverse event occurred in 83% of patients in the ALCL165 group, in all of the patients in the ALCL280 group, and in 71% in the IMT group. Adverse events considered possibly, probably, or definitely related to the study treatment occurred in 33% of the ALCL165 group, in 85% of the ALCL280 group, and in 57% of the IMT group. The most common adverse event was a decreased neutrophil count.

“Notable objective and sustained responses were observed in patients with ALK fusion-positive ALCL and IMT,” the investigators wrote, “establishing a precedent in pediatric oncology for studying the early-phase activity of a targeted agent in a biomarker-selected and histology-independent cohort of patients.

“In the cohort of patients with ALK-positive unresectable IMTs,” they continued, “ALK inhibition was a highly effective therapy and supports consideration of frontline therapy with crizotinib, a strategy that could also be relevant to adults with this rare disease.”

[email protected]

Image by Andre E.X. Brown

Patients newly diagnosed with cancer may have a short-term increased risk of arterial thromboembolism, according to a new study.

The research showed that, within 6 months of their diagnosis, cancer patients had a rate of arterial thromboembolism that was more than double the rate in matched control patients without cancer.

However, the risk of arterial thromboembolism varied by cancer type.

Babak B. Navi, MD, of Weill Cornell Medicine in New York, New York, and his colleagues reported these findings in the Journal of the American College of Cardiology.

The researchers used the Surveillance Epidemiology and End Results–Medicare linked database to identify patients with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, pancreatic, or gastric cancer or non-Hodgkin lymphoma from 2002 to 2011.

The team matched these patients (by demographics and comorbidities) to Medicare enrollees without cancer, collecting data on 279,719 pairs of subjects. The subjects were followed through 2012.

Arterial thromboembolism

The study’s primary outcome was the cumulative incidence of arterial thromboembolism, defined as any inpatient or outpatient diagnosis of myocardial infarction or ischemic stroke.

The incidence of arterial thromboembolism at 3 months was 3.4% in cancer patients and 1.1% in controls. At 6 months, it was 4.7% and 2.2%, respectively. At 1 year, it was 6.5% and 4.2%, respectively. And at 2 years, it was 9.1% and 8.1%, respectively.

The hazard ratios (HRs) for arterial thromboembolism among cancer patients were 5.2 at 0 to 1 month, 2.1 at 1 to 3 months, 1.4 at 3 to 6 months, 1.1 at 6 to 9 months, and 1.1 at 9 to 12 months.

The risk of arterial thromboembolism varied by cancer type, with the greatest excess risk observed in lung cancer. The 6-month cumulative incidence was 8.3% in lung cancer patients and 2.4% in matched controls (P<0.001).

In patients with non-Hodgkin lymphoma, the 6-month cumulative incidence of arterial thromboembolism was 5.4%, compared to 2.2% in matched controls (P<0.001).

Myocardial infarction

The cumulative incidence of myocardial infarction at 3 months was 1.4% in cancer patients and 0.3% in controls.

At 6 months, it was 2.0% and 0.7%, respectively. At 1 year, it was 2.6% and 1.4%, respectively. And at 2 years, it was 3.7% and 2.8%, respectively.

The HRs for myocardial infarction among cancer patients were 7.3 at 0 to 1 month, 3.0 at 1 to 3 months, 1.8 at 3 to 6 months, 1.3 at 6 to 9 months, and 1.0 at 9 to 12 months.

Ischemic stroke

The cumulative incidence of ischemic stroke at 3 months was 2.1% in cancer patients and 0.8% in controls.

At 6 months, it was 3.0% and 1.6%, respectively. At 1 year, it was 4.3% and 3.1%, respectively. And at 2 years, it was 6.1% and 5.8%, respectively.

The HRs for ischemic stroke among cancer patients were 4.5 at 0 to 1 month, 1.7 at 1 to 3 months, 1.3 at 3 to 6 months, 1.0 at 6 to 9 months, and 1.1 at 9 to 12 months.

The researchers said these findings raise the question of whether patients with newly diagnosed cancer should be considered for antithrombotic and statin medicines for primary prevention of cardiovascular disease.

The team stressed that because patients with cancer are also prone to bleeding due to frequent coagulopathy and invasive procedures, carefully designed clinical trials are needed to answer these questions.

Image by Andre E.X. Brown

Patients newly diagnosed with cancer may have a short-term increased risk of arterial thromboembolism, according to a new study.

The research showed that, within 6 months of their diagnosis, cancer patients had a rate of arterial thromboembolism that was more than double the rate in matched control patients without cancer.

However, the risk of arterial thromboembolism varied by cancer type.

Babak B. Navi, MD, of Weill Cornell Medicine in New York, New York, and his colleagues reported these findings in the Journal of the American College of Cardiology.

The researchers used the Surveillance Epidemiology and End Results–Medicare linked database to identify patients with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, pancreatic, or gastric cancer or non-Hodgkin lymphoma from 2002 to 2011.

The team matched these patients (by demographics and comorbidities) to Medicare enrollees without cancer, collecting data on 279,719 pairs of subjects. The subjects were followed through 2012.

Arterial thromboembolism

The study’s primary outcome was the cumulative incidence of arterial thromboembolism, defined as any inpatient or outpatient diagnosis of myocardial infarction or ischemic stroke.

The incidence of arterial thromboembolism at 3 months was 3.4% in cancer patients and 1.1% in controls. At 6 months, it was 4.7% and 2.2%, respectively. At 1 year, it was 6.5% and 4.2%, respectively. And at 2 years, it was 9.1% and 8.1%, respectively.

The hazard ratios (HRs) for arterial thromboembolism among cancer patients were 5.2 at 0 to 1 month, 2.1 at 1 to 3 months, 1.4 at 3 to 6 months, 1.1 at 6 to 9 months, and 1.1 at 9 to 12 months.

The risk of arterial thromboembolism varied by cancer type, with the greatest excess risk observed in lung cancer. The 6-month cumulative incidence was 8.3% in lung cancer patients and 2.4% in matched controls (P<0.001).

In patients with non-Hodgkin lymphoma, the 6-month cumulative incidence of arterial thromboembolism was 5.4%, compared to 2.2% in matched controls (P<0.001).

Myocardial infarction

The cumulative incidence of myocardial infarction at 3 months was 1.4% in cancer patients and 0.3% in controls.

At 6 months, it was 2.0% and 0.7%, respectively. At 1 year, it was 2.6% and 1.4%, respectively. And at 2 years, it was 3.7% and 2.8%, respectively.

The HRs for myocardial infarction among cancer patients were 7.3 at 0 to 1 month, 3.0 at 1 to 3 months, 1.8 at 3 to 6 months, 1.3 at 6 to 9 months, and 1.0 at 9 to 12 months.

Ischemic stroke

The cumulative incidence of ischemic stroke at 3 months was 2.1% in cancer patients and 0.8% in controls.

At 6 months, it was 3.0% and 1.6%, respectively. At 1 year, it was 4.3% and 3.1%, respectively. And at 2 years, it was 6.1% and 5.8%, respectively.

The HRs for ischemic stroke among cancer patients were 4.5 at 0 to 1 month, 1.7 at 1 to 3 months, 1.3 at 3 to 6 months, 1.0 at 6 to 9 months, and 1.1 at 9 to 12 months.

The researchers said these findings raise the question of whether patients with newly diagnosed cancer should be considered for antithrombotic and statin medicines for primary prevention of cardiovascular disease.

The team stressed that because patients with cancer are also prone to bleeding due to frequent coagulopathy and invasive procedures, carefully designed clinical trials are needed to answer these questions.

Image by Andre E.X. Brown

Patients newly diagnosed with cancer may have a short-term increased risk of arterial thromboembolism, according to a new study.

The research showed that, within 6 months of their diagnosis, cancer patients had a rate of arterial thromboembolism that was more than double the rate in matched control patients without cancer.

However, the risk of arterial thromboembolism varied by cancer type.

Babak B. Navi, MD, of Weill Cornell Medicine in New York, New York, and his colleagues reported these findings in the Journal of the American College of Cardiology.

The researchers used the Surveillance Epidemiology and End Results–Medicare linked database to identify patients with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, pancreatic, or gastric cancer or non-Hodgkin lymphoma from 2002 to 2011.

The team matched these patients (by demographics and comorbidities) to Medicare enrollees without cancer, collecting data on 279,719 pairs of subjects. The subjects were followed through 2012.

Arterial thromboembolism

The study’s primary outcome was the cumulative incidence of arterial thromboembolism, defined as any inpatient or outpatient diagnosis of myocardial infarction or ischemic stroke.

The incidence of arterial thromboembolism at 3 months was 3.4% in cancer patients and 1.1% in controls. At 6 months, it was 4.7% and 2.2%, respectively. At 1 year, it was 6.5% and 4.2%, respectively. And at 2 years, it was 9.1% and 8.1%, respectively.

The hazard ratios (HRs) for arterial thromboembolism among cancer patients were 5.2 at 0 to 1 month, 2.1 at 1 to 3 months, 1.4 at 3 to 6 months, 1.1 at 6 to 9 months, and 1.1 at 9 to 12 months.

The risk of arterial thromboembolism varied by cancer type, with the greatest excess risk observed in lung cancer. The 6-month cumulative incidence was 8.3% in lung cancer patients and 2.4% in matched controls (P<0.001).

In patients with non-Hodgkin lymphoma, the 6-month cumulative incidence of arterial thromboembolism was 5.4%, compared to 2.2% in matched controls (P<0.001).

Myocardial infarction

The cumulative incidence of myocardial infarction at 3 months was 1.4% in cancer patients and 0.3% in controls.

At 6 months, it was 2.0% and 0.7%, respectively. At 1 year, it was 2.6% and 1.4%, respectively. And at 2 years, it was 3.7% and 2.8%, respectively.

The HRs for myocardial infarction among cancer patients were 7.3 at 0 to 1 month, 3.0 at 1 to 3 months, 1.8 at 3 to 6 months, 1.3 at 6 to 9 months, and 1.0 at 9 to 12 months.

Ischemic stroke

The cumulative incidence of ischemic stroke at 3 months was 2.1% in cancer patients and 0.8% in controls.

At 6 months, it was 3.0% and 1.6%, respectively. At 1 year, it was 4.3% and 3.1%, respectively. And at 2 years, it was 6.1% and 5.8%, respectively.

The HRs for ischemic stroke among cancer patients were 4.5 at 0 to 1 month, 1.7 at 1 to 3 months, 1.3 at 3 to 6 months, 1.0 at 6 to 9 months, and 1.1 at 9 to 12 months.

The researchers said these findings raise the question of whether patients with newly diagnosed cancer should be considered for antithrombotic and statin medicines for primary prevention of cardiovascular disease.

The team stressed that because patients with cancer are also prone to bleeding due to frequent coagulopathy and invasive procedures, carefully designed clinical trials are needed to answer these questions.

Micrograph showing DLBCL

Results from the SCHOLAR-1 study revealed poor outcomes of salvage therapy in patients with refractory diffuse large B-cell lymphoma (DLBCL).

This retrospective study included data on patients enrolled in 2 randomized trials and 2 academic databases.

The patients had primary refractory disease, were refractory to second-line or later therapy, or had relapsed within 12 months of autologous stem cell transplant (ASCT).

Twenty-six percent of patients responded to salvage therapy, with 7% achieving a complete response (CR).

The median overall survival (OS) was 6.3 months, and 20% of patients were still alive at 2 years’ follow-up.

Christian Gisselbrecht, MD, of Saint Louis Hospital in Paris, France, and his colleagues reported these findings in Blood. SCHOLAR-1 was funded through an unrestricted grant from Kite Pharma.

“SCHOLAR-1 demonstrates the uniformly poor treatment outcomes for patients with aggressive non-Hodgkin lymphoma and emphasizes the need for breakthrough therapies for these refractory patients,” Dr Gisselbrecht said.

Patient characteristics

The study included pooled, patient-level data from 2 phase 3 trials and 2 databases:

• The Canadian Cancer Trials Group study LY.12 (n=219)
• The Lymphoma Academic Research Organization’s CORAL study  (n=170)
• A cohort from MD Anderson Cancer Center (n=165)
• A cohort from the Molecular Epidemiology Resource of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (n=82).

There were a total of 636 patients who met criteria for refractory DLBCL, which included primary mediastinal B-cell lymphoma and transformed follicular lymphoma.

Twenty-eight percent of patients were primary refractory, 50% were refractory to second-line or later therapy, and 22% had relapsed within 12 months of transplant.

The patients’ median age was 55 (range, 19-81), and 64% were male. Seventy-three percent had an ECOG performance status of 0-1, 14% had a status of 2-4, and 13% were missing this data. Seventy-two percent of patients had stage III-IV disease, 27% had stage I-II disease, and less than 1% were missing this data.

Treatments

The MD Anderson cohort included patients who were relapsed/refractory to initial rituximab-containing chemotherapy, had failed salvage platinum-containing chemotherapy, and received a second salvage therapy at MD Anderson.

The University of Iowa/Mayo Clinic cohort included unselected, newly diagnosed patients with lymphoma who entered prospective documentation of primary and subsequent treatments and outcomes.

In the LY.12 study, patients were enrolled upon relapse after anthracycline-containing therapy and randomized to 1 of 2 salvage regimens, with a goal of consolidative ASCT.

The CORAL study enrolled patients in their first relapse or whose lymphoma was refractory to first-line therapy. They were randomized to 1 of 2 salvage regimens, with a goal of consolidative ASCT.

In the LY.12 and CORAL studies, eligible patients with CD20+ lymphoma were randomized to rituximab maintenance or observation post-ASCT.

Response

In all, 523 patients were evaluated for response. The overall response rate (ORR) was 26%, with a 7% CR rate and an 18% partial response rate.

Among patients with primary refractory disease, the ORR was 20%, and the CR rate was 3%.

Among patients who were refractory to second-line or later therapy, the ORR was 26%, and the CR rate was 10%.

Among patients who relapsed after transplant, the ORR was 34%, and the CR rate was 15%.

Survival

A total of 603 patients were evaluated for survival.

The median OS from the start of salvage therapy was 6.3 months (range, 5.9-7.0). The 1-year OS rate was 28%, and the 2-year OS was 20%.

Among primary refractory patients, the median OS was 7.1 months (range, 6.0-8.1), 1-year OS was 29%, and 2-year OS was 24%.

Among patient who were refractory to second-line or later therapy, the median OS was 6.1 months (range, 5.2-7.0), 1-year OS was 26%, and 2-year OS was 17%.

Among patients who relapsed after transplant, the median OS was 6.2 months (range, 5.2-7.6), 1-year OS was 32%, and 2-year OS was 19%.

“Although 60% to 70% of non-Hodgkin lymphoma patients survive 5 years after rituximab-based chemotherapy and autologous stem cell transplant, nearly half of them either do not respond or relapse shortly after transplant,” Dr Gisselbrecht noted.

“SCHOLAR-1 provides a rigorous measure of outcomes for these patients who do not benefit from currently available therapies, and this landmark study will serve as an important historical control for evaluating new therapeutic candidates in the field of non-Hodgkin lymphoma.”

Micrograph showing DLBCL

Results from the SCHOLAR-1 study revealed poor outcomes of salvage therapy in patients with refractory diffuse large B-cell lymphoma (DLBCL).

This retrospective study included data on patients enrolled in 2 randomized trials and 2 academic databases.

The patients had primary refractory disease, were refractory to second-line or later therapy, or had relapsed within 12 months of autologous stem cell transplant (ASCT).

Twenty-six percent of patients responded to salvage therapy, with 7% achieving a complete response (CR).

The median overall survival (OS) was 6.3 months, and 20% of patients were still alive at 2 years’ follow-up.

Christian Gisselbrecht, MD, of Saint Louis Hospital in Paris, France, and his colleagues reported these findings in Blood. SCHOLAR-1 was funded through an unrestricted grant from Kite Pharma.

“SCHOLAR-1 demonstrates the uniformly poor treatment outcomes for patients with aggressive non-Hodgkin lymphoma and emphasizes the need for breakthrough therapies for these refractory patients,” Dr Gisselbrecht said.

Patient characteristics

The study included pooled, patient-level data from 2 phase 3 trials and 2 databases:

• The Canadian Cancer Trials Group study LY.12 (n=219)
• The Lymphoma Academic Research Organization’s CORAL study  (n=170)
• A cohort from MD Anderson Cancer Center (n=165)
• A cohort from the Molecular Epidemiology Resource of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (n=82).

There were a total of 636 patients who met criteria for refractory DLBCL, which included primary mediastinal B-cell lymphoma and transformed follicular lymphoma.

Twenty-eight percent of patients were primary refractory, 50% were refractory to second-line or later therapy, and 22% had relapsed within 12 months of transplant.

The patients’ median age was 55 (range, 19-81), and 64% were male. Seventy-three percent had an ECOG performance status of 0-1, 14% had a status of 2-4, and 13% were missing this data. Seventy-two percent of patients had stage III-IV disease, 27% had stage I-II disease, and less than 1% were missing this data.

Treatments

The MD Anderson cohort included patients who were relapsed/refractory to initial rituximab-containing chemotherapy, had failed salvage platinum-containing chemotherapy, and received a second salvage therapy at MD Anderson.

The University of Iowa/Mayo Clinic cohort included unselected, newly diagnosed patients with lymphoma who entered prospective documentation of primary and subsequent treatments and outcomes.

In the LY.12 study, patients were enrolled upon relapse after anthracycline-containing therapy and randomized to 1 of 2 salvage regimens, with a goal of consolidative ASCT.

The CORAL study enrolled patients in their first relapse or whose lymphoma was refractory to first-line therapy. They were randomized to 1 of 2 salvage regimens, with a goal of consolidative ASCT.

In the LY.12 and CORAL studies, eligible patients with CD20+ lymphoma were randomized to rituximab maintenance or observation post-ASCT.

Response

In all, 523 patients were evaluated for response. The overall response rate (ORR) was 26%, with a 7% CR rate and an 18% partial response rate.

Among patients with primary refractory disease, the ORR was 20%, and the CR rate was 3%.

Among patients who were refractory to second-line or later therapy, the ORR was 26%, and the CR rate was 10%.

Among patients who relapsed after transplant, the ORR was 34%, and the CR rate was 15%.

Survival

A total of 603 patients were evaluated for survival.

The median OS from the start of salvage therapy was 6.3 months (range, 5.9-7.0). The 1-year OS rate was 28%, and the 2-year OS was 20%.

Among primary refractory patients, the median OS was 7.1 months (range, 6.0-8.1), 1-year OS was 29%, and 2-year OS was 24%.

Among patient who were refractory to second-line or later therapy, the median OS was 6.1 months (range, 5.2-7.0), 1-year OS was 26%, and 2-year OS was 17%.

Among patients who relapsed after transplant, the median OS was 6.2 months (range, 5.2-7.6), 1-year OS was 32%, and 2-year OS was 19%.

“Although 60% to 70% of non-Hodgkin lymphoma patients survive 5 years after rituximab-based chemotherapy and autologous stem cell transplant, nearly half of them either do not respond or relapse shortly after transplant,” Dr Gisselbrecht noted.

“SCHOLAR-1 provides a rigorous measure of outcomes for these patients who do not benefit from currently available therapies, and this landmark study will serve as an important historical control for evaluating new therapeutic candidates in the field of non-Hodgkin lymphoma.”

Micrograph showing DLBCL

Results from the SCHOLAR-1 study revealed poor outcomes of salvage therapy in patients with refractory diffuse large B-cell lymphoma (DLBCL).

This retrospective study included data on patients enrolled in 2 randomized trials and 2 academic databases.

The patients had primary refractory disease, were refractory to second-line or later therapy, or had relapsed within 12 months of autologous stem cell transplant (ASCT).

Twenty-six percent of patients responded to salvage therapy, with 7% achieving a complete response (CR).

The median overall survival (OS) was 6.3 months, and 20% of patients were still alive at 2 years’ follow-up.

Christian Gisselbrecht, MD, of Saint Louis Hospital in Paris, France, and his colleagues reported these findings in Blood. SCHOLAR-1 was funded through an unrestricted grant from Kite Pharma.

“SCHOLAR-1 demonstrates the uniformly poor treatment outcomes for patients with aggressive non-Hodgkin lymphoma and emphasizes the need for breakthrough therapies for these refractory patients,” Dr Gisselbrecht said.

Patient characteristics

The study included pooled, patient-level data from 2 phase 3 trials and 2 databases:

• The Canadian Cancer Trials Group study LY.12 (n=219)
• The Lymphoma Academic Research Organization’s CORAL study  (n=170)
• A cohort from MD Anderson Cancer Center (n=165)
• A cohort from the Molecular Epidemiology Resource of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (n=82).

There were a total of 636 patients who met criteria for refractory DLBCL, which included primary mediastinal B-cell lymphoma and transformed follicular lymphoma.

Twenty-eight percent of patients were primary refractory, 50% were refractory to second-line or later therapy, and 22% had relapsed within 12 months of transplant.

The patients’ median age was 55 (range, 19-81), and 64% were male. Seventy-three percent had an ECOG performance status of 0-1, 14% had a status of 2-4, and 13% were missing this data. Seventy-two percent of patients had stage III-IV disease, 27% had stage I-II disease, and less than 1% were missing this data.

Treatments

The MD Anderson cohort included patients who were relapsed/refractory to initial rituximab-containing chemotherapy, had failed salvage platinum-containing chemotherapy, and received a second salvage therapy at MD Anderson.

The University of Iowa/Mayo Clinic cohort included unselected, newly diagnosed patients with lymphoma who entered prospective documentation of primary and subsequent treatments and outcomes.

In the LY.12 study, patients were enrolled upon relapse after anthracycline-containing therapy and randomized to 1 of 2 salvage regimens, with a goal of consolidative ASCT.

The CORAL study enrolled patients in their first relapse or whose lymphoma was refractory to first-line therapy. They were randomized to 1 of 2 salvage regimens, with a goal of consolidative ASCT.

In the LY.12 and CORAL studies, eligible patients with CD20+ lymphoma were randomized to rituximab maintenance or observation post-ASCT.

Response

In all, 523 patients were evaluated for response. The overall response rate (ORR) was 26%, with a 7% CR rate and an 18% partial response rate.

Among patients with primary refractory disease, the ORR was 20%, and the CR rate was 3%.

Among patients who were refractory to second-line or later therapy, the ORR was 26%, and the CR rate was 10%.

Among patients who relapsed after transplant, the ORR was 34%, and the CR rate was 15%.

Survival

A total of 603 patients were evaluated for survival.

The median OS from the start of salvage therapy was 6.3 months (range, 5.9-7.0). The 1-year OS rate was 28%, and the 2-year OS was 20%.

Among primary refractory patients, the median OS was 7.1 months (range, 6.0-8.1), 1-year OS was 29%, and 2-year OS was 24%.

Among patient who were refractory to second-line or later therapy, the median OS was 6.1 months (range, 5.2-7.0), 1-year OS was 26%, and 2-year OS was 17%.

Among patients who relapsed after transplant, the median OS was 6.2 months (range, 5.2-7.6), 1-year OS was 32%, and 2-year OS was 19%.

“Although 60% to 70% of non-Hodgkin lymphoma patients survive 5 years after rituximab-based chemotherapy and autologous stem cell transplant, nearly half of them either do not respond or relapse shortly after transplant,” Dr Gisselbrecht noted.

“SCHOLAR-1 provides a rigorous measure of outcomes for these patients who do not benefit from currently available therapies, and this landmark study will serve as an important historical control for evaluating new therapeutic candidates in the field of non-Hodgkin lymphoma.”

Solid organ transplant recipients contribute a disproportionate fraction of pediatric non-Hodgkin lymphoma (NHL) cases, especially diffuse large B-cell lymphoma cases (DLBCL), according to an analysis of data drawn from transplant and cancer registries.

Investigators calculated that the incidence of NHL for the pediatric transplant population was 257 times higher than the general population, after analysis from the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012. The incidence of NHL for the pediatric transplant population was 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general population. Furthermore, transplant recipients made up a much larger proportion of general population DLBCL cases (7.62%; 95% CI, 6.35%-8.88%).

In the general population, the most common subtypes were DLBCL (25% of cases), Burkitt lymphoma (24%), and precursor cell lymphoblastic lymphoma (20%). Among NHLs diagnosed in transplant recipients, 65% were DLBCL, and 9% were Burkitt lymphoma, whereas there were no cases of precursor cell lymphoblastic lymphoma, reported Elizabeth L. Yanik, PhD, of Washington University, St. Louis, and her associates (Cancer. 2017 Jul 31. doi: 10.1002/cncr.30923).

The increased risk of NHL and other cancers for organ transplant recipients is primarily the result of the immunosuppressant medications administered after transplantation, leading to an increased risk of infection-related cancers, the authors said.

“NHL cases are largely attributable to EBV [Epstein-Barr virus] infections that occur while recipients are immunosuppressed, as evidenced by the high prevalence of EBV detectable in NHL tumors and particularly in cases diagnosed during the heavily immunosuppressed period early after transplantation,” wrote Dr. Yanik and her colleagues. “Patients who experience a primary EBV infection after transplantation are particularly susceptible because transplant recipients have a higher NHL risk if they are seronegative for EBV before transplantation.”

Among those at risk, Dr. Yanik and fellow investigators found transplant patients younger than 5 years were the most susceptible to NHL, making up 19.79% of those diagnosed with DLBCL.

The proportion of NHL in solid organ transplant recipients within the entire pediatric NHL population has risen over time, from 1.66% of the NHL population during 1990-1994 to 3.73% during 2010-2012.

“This trend is driven by the rising prevalence of transplant recipients in the general population and not by increases in NHL risk among transplant recipients,” noted Dr. Yanik and her coauthors. “The proportion of NHL diagnoses attributable to transplant recipients has grown over time, and it is likely that this population will be an important source of pediatric NHL cases in the future.”

This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.

[email protected]

On Twitter @eaztweets

Solid organ transplant recipients contribute a disproportionate fraction of pediatric non-Hodgkin lymphoma (NHL) cases, especially diffuse large B-cell lymphoma cases (DLBCL), according to an analysis of data drawn from transplant and cancer registries.

Investigators calculated that the incidence of NHL for the pediatric transplant population was 257 times higher than the general population, after analysis from the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012. The incidence of NHL for the pediatric transplant population was 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general population. Furthermore, transplant recipients made up a much larger proportion of general population DLBCL cases (7.62%; 95% CI, 6.35%-8.88%).

In the general population, the most common subtypes were DLBCL (25% of cases), Burkitt lymphoma (24%), and precursor cell lymphoblastic lymphoma (20%). Among NHLs diagnosed in transplant recipients, 65% were DLBCL, and 9% were Burkitt lymphoma, whereas there were no cases of precursor cell lymphoblastic lymphoma, reported Elizabeth L. Yanik, PhD, of Washington University, St. Louis, and her associates (Cancer. 2017 Jul 31. doi: 10.1002/cncr.30923).

The increased risk of NHL and other cancers for organ transplant recipients is primarily the result of the immunosuppressant medications administered after transplantation, leading to an increased risk of infection-related cancers, the authors said.

“NHL cases are largely attributable to EBV [Epstein-Barr virus] infections that occur while recipients are immunosuppressed, as evidenced by the high prevalence of EBV detectable in NHL tumors and particularly in cases diagnosed during the heavily immunosuppressed period early after transplantation,” wrote Dr. Yanik and her colleagues. “Patients who experience a primary EBV infection after transplantation are particularly susceptible because transplant recipients have a higher NHL risk if they are seronegative for EBV before transplantation.”

Among those at risk, Dr. Yanik and fellow investigators found transplant patients younger than 5 years were the most susceptible to NHL, making up 19.79% of those diagnosed with DLBCL.

The proportion of NHL in solid organ transplant recipients within the entire pediatric NHL population has risen over time, from 1.66% of the NHL population during 1990-1994 to 3.73% during 2010-2012.

“This trend is driven by the rising prevalence of transplant recipients in the general population and not by increases in NHL risk among transplant recipients,” noted Dr. Yanik and her coauthors. “The proportion of NHL diagnoses attributable to transplant recipients has grown over time, and it is likely that this population will be an important source of pediatric NHL cases in the future.”

This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.

[email protected]

On Twitter @eaztweets

Solid organ transplant recipients contribute a disproportionate fraction of pediatric non-Hodgkin lymphoma (NHL) cases, especially diffuse large B-cell lymphoma cases (DLBCL), according to an analysis of data drawn from transplant and cancer registries.

Investigators calculated that the incidence of NHL for the pediatric transplant population was 257 times higher than the general population, after analysis from the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012. The incidence of NHL for the pediatric transplant population was 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general population. Furthermore, transplant recipients made up a much larger proportion of general population DLBCL cases (7.62%; 95% CI, 6.35%-8.88%).

In the general population, the most common subtypes were DLBCL (25% of cases), Burkitt lymphoma (24%), and precursor cell lymphoblastic lymphoma (20%). Among NHLs diagnosed in transplant recipients, 65% were DLBCL, and 9% were Burkitt lymphoma, whereas there were no cases of precursor cell lymphoblastic lymphoma, reported Elizabeth L. Yanik, PhD, of Washington University, St. Louis, and her associates (Cancer. 2017 Jul 31. doi: 10.1002/cncr.30923).

The increased risk of NHL and other cancers for organ transplant recipients is primarily the result of the immunosuppressant medications administered after transplantation, leading to an increased risk of infection-related cancers, the authors said.

“NHL cases are largely attributable to EBV [Epstein-Barr virus] infections that occur while recipients are immunosuppressed, as evidenced by the high prevalence of EBV detectable in NHL tumors and particularly in cases diagnosed during the heavily immunosuppressed period early after transplantation,” wrote Dr. Yanik and her colleagues. “Patients who experience a primary EBV infection after transplantation are particularly susceptible because transplant recipients have a higher NHL risk if they are seronegative for EBV before transplantation.”

Among those at risk, Dr. Yanik and fellow investigators found transplant patients younger than 5 years were the most susceptible to NHL, making up 19.79% of those diagnosed with DLBCL.

The proportion of NHL in solid organ transplant recipients within the entire pediatric NHL population has risen over time, from 1.66% of the NHL population during 1990-1994 to 3.73% during 2010-2012.

“This trend is driven by the rising prevalence of transplant recipients in the general population and not by increases in NHL risk among transplant recipients,” noted Dr. Yanik and her coauthors. “The proportion of NHL diagnoses attributable to transplant recipients has grown over time, and it is likely that this population will be an important source of pediatric NHL cases in the future.”

This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.

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