Follicular Lymphoma

 

 

Sodas and other sweetened

beverages at the supermarket

 

Consuming aspartame and drinking sweetened beverages do not increase a person’s risk of developing non-Hodgkin lymphoma (NHL), according to research published in the Journal of Nutrition.

Investigators analyzed information from more than 100,000 men and women in the US.

The results suggested that neither aspartame intake nor the consumption of sugar-sweetened or artificially sweetened beverages were associated with an increased risk of NHL.

Marjorie L. McCullough, SCD, RD, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this research, analyzing data from the nutrition cohort of the Cancer Prevention Study II, an assessment of cancer incidence

and mortality in the US.

Study subjects first completed a questionnaire in 1992, noting information related to diet and other lifestyle factors. They completed follow-up questionnaires in 1999 and 2003, which included questions related to the consumption of sugar-sweetened and artificially sweetened beverages, as well as tabletop sweeteners containing aspartame.

Among the 100,442 adult men and women who provided information on diet and lifestyle factors in 1999, there were 1196 NHL cases verified during a 10-year follow-up period.

The investigators assessed the risk of NHL associated with sweetened beverage and aspartame consumption, adjusted for the subjects’ smoking status, body mass index, and history of diabetes.

The analysis revealed that, in women and men combined, there was no association between NHL risk and the consumption of 1 or more servings (355 mL) of artificially sweetened beverages. Compared to nondrinkers, subjects who drank artificially sweetened beverages had a risk ratio (RR) of 0.92 (P=0.14).

Similarly, there was no association between NHL risk and sugar-sweetened beverages. Compared to nondrinkers, the RR for sugar-sweetened beverage drinkers was 1.10 (P=0.62).

Furthermore, subjects’ overall aspartame intake, which was estimated from artificially sweetened carbonated beverage consumption and the use of aspartame packets, was not associated with NHL risk.

The RR was 1.02 (P=0.69) for the top quintile (which had a median aspartame intake of 145 mg per day) vs the bottom quintile (which had a median aspartame intake of 0 mg per day).

The investigators also found that associations between disease and sweetened beverage consumption or aspartame intake were generally null for specific NHL subtypes, including multiple myeloma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, and other B-cell lymphomas.

“The study supports the decades of research that have continued to find that aspartame is safe for use in foods and beverages,” said Haley Stevens, PhD, President of the Calorie Control Council. “It also supports the conclusions of the National Cancer Institute, who have determined that aspartame does not increase a person’s risk of developing cancer.”

 

 

Sodas and other sweetened

beverages at the supermarket

 

Consuming aspartame and drinking sweetened beverages do not increase a person’s risk of developing non-Hodgkin lymphoma (NHL), according to research published in the Journal of Nutrition.

Investigators analyzed information from more than 100,000 men and women in the US.

The results suggested that neither aspartame intake nor the consumption of sugar-sweetened or artificially sweetened beverages were associated with an increased risk of NHL.

Marjorie L. McCullough, SCD, RD, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this research, analyzing data from the nutrition cohort of the Cancer Prevention Study II, an assessment of cancer incidence

and mortality in the US.

Study subjects first completed a questionnaire in 1992, noting information related to diet and other lifestyle factors. They completed follow-up questionnaires in 1999 and 2003, which included questions related to the consumption of sugar-sweetened and artificially sweetened beverages, as well as tabletop sweeteners containing aspartame.

Among the 100,442 adult men and women who provided information on diet and lifestyle factors in 1999, there were 1196 NHL cases verified during a 10-year follow-up period.

The investigators assessed the risk of NHL associated with sweetened beverage and aspartame consumption, adjusted for the subjects’ smoking status, body mass index, and history of diabetes.

The analysis revealed that, in women and men combined, there was no association between NHL risk and the consumption of 1 or more servings (355 mL) of artificially sweetened beverages. Compared to nondrinkers, subjects who drank artificially sweetened beverages had a risk ratio (RR) of 0.92 (P=0.14).

Similarly, there was no association between NHL risk and sugar-sweetened beverages. Compared to nondrinkers, the RR for sugar-sweetened beverage drinkers was 1.10 (P=0.62).

Furthermore, subjects’ overall aspartame intake, which was estimated from artificially sweetened carbonated beverage consumption and the use of aspartame packets, was not associated with NHL risk.

The RR was 1.02 (P=0.69) for the top quintile (which had a median aspartame intake of 145 mg per day) vs the bottom quintile (which had a median aspartame intake of 0 mg per day).

The investigators also found that associations between disease and sweetened beverage consumption or aspartame intake were generally null for specific NHL subtypes, including multiple myeloma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, and other B-cell lymphomas.

“The study supports the decades of research that have continued to find that aspartame is safe for use in foods and beverages,” said Haley Stevens, PhD, President of the Calorie Control Council. “It also supports the conclusions of the National Cancer Institute, who have determined that aspartame does not increase a person’s risk of developing cancer.”

 

 

Sodas and other sweetened

beverages at the supermarket

 

Consuming aspartame and drinking sweetened beverages do not increase a person’s risk of developing non-Hodgkin lymphoma (NHL), according to research published in the Journal of Nutrition.

Investigators analyzed information from more than 100,000 men and women in the US.

The results suggested that neither aspartame intake nor the consumption of sugar-sweetened or artificially sweetened beverages were associated with an increased risk of NHL.

Marjorie L. McCullough, SCD, RD, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this research, analyzing data from the nutrition cohort of the Cancer Prevention Study II, an assessment of cancer incidence

and mortality in the US.

Study subjects first completed a questionnaire in 1992, noting information related to diet and other lifestyle factors. They completed follow-up questionnaires in 1999 and 2003, which included questions related to the consumption of sugar-sweetened and artificially sweetened beverages, as well as tabletop sweeteners containing aspartame.

Among the 100,442 adult men and women who provided information on diet and lifestyle factors in 1999, there were 1196 NHL cases verified during a 10-year follow-up period.

The investigators assessed the risk of NHL associated with sweetened beverage and aspartame consumption, adjusted for the subjects’ smoking status, body mass index, and history of diabetes.

The analysis revealed that, in women and men combined, there was no association between NHL risk and the consumption of 1 or more servings (355 mL) of artificially sweetened beverages. Compared to nondrinkers, subjects who drank artificially sweetened beverages had a risk ratio (RR) of 0.92 (P=0.14).

Similarly, there was no association between NHL risk and sugar-sweetened beverages. Compared to nondrinkers, the RR for sugar-sweetened beverage drinkers was 1.10 (P=0.62).

Furthermore, subjects’ overall aspartame intake, which was estimated from artificially sweetened carbonated beverage consumption and the use of aspartame packets, was not associated with NHL risk.

The RR was 1.02 (P=0.69) for the top quintile (which had a median aspartame intake of 145 mg per day) vs the bottom quintile (which had a median aspartame intake of 0 mg per day).

The investigators also found that associations between disease and sweetened beverage consumption or aspartame intake were generally null for specific NHL subtypes, including multiple myeloma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, and other B-cell lymphomas.

“The study supports the decades of research that have continued to find that aspartame is safe for use in foods and beverages,” said Haley Stevens, PhD, President of the Calorie Control Council. “It also supports the conclusions of the National Cancer Institute, who have determined that aspartame does not increase a person’s risk of developing cancer.”

 

 

Drugs in vials

Credit: Bill Branson

 

New research suggests maintenance therapy may not be necessary for patients with follicular lymphoma (FL) who have a low tumor burden.

Investigators compared rituximab re-treatment with rituximab maintenance in nearly 300 FL patients, and results showed no significant difference between the treatment groups in the time to disease recurrence.

The researchers also noted that the re-treatment strategy was more cost-effective.

“For those 2 reasons, we recommend a retreatment strategy over a maintenance strategy in this patient population,” said Brad S. Kahl, MD, of the University of Wisconsin in Madison.

Dr Kahl and his colleagues described this research—the RESORT trial—in the Journal of Clinical Oncology. Early results from this trial were previously presented at the 2011 ASH Annual Meeting.

The team evaluated 289 patients with previously untreated, low-tumor-burden FL. All patients responded to initial treatment with rituximab (4 doses).

Patients were then randomized to receive maintenance therapy—a single dose of rituximab every 3 months until treatment failure—or rituximab re-treatment upon disease recurrence. Patients receiving re-treatment could receive rituximab every time they experienced progression, until treatment failure.

The median number of rituximab doses was 4 in the re-treatment arm and 18 in the maintenance arm. Three-year freedom from cytotoxic therapy was 84% in the re-treatment arm and 95% in the maintenance arm (P=0.03).

There was no significant difference between the arms in the time to disease recurrence. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years in the re-treatment arm and 4.3 years in the maintenance arm (P=0.54).

The researchers found no difference in health-related quality of life or anxiety between the treatment arms.

They also said grade 3 to 5 adverse events were infrequent in both arms. One patient developed progressive multifocal leukoencephalopathy after the 15th maintenance dose of rituximab and died.

Second malignancies were reported in 16 patients receiving re-treatment and 14 patients on maintenance therapy, but there were no obvious trends toward specific cancers.

“The study shows that a rituximab re-treatment strategy provides comparable disease control to a maintenance strategy in low-tumor-burden follicular lymphoma,” Dr Kahl said. “In addition, a re-treatment strategy is more cost-effective, as it requires about a quarter as much drug utilization.”

The study was accompanied by an editorial saying these results should change clinical practice.

 

 

Drugs in vials

Credit: Bill Branson

 

New research suggests maintenance therapy may not be necessary for patients with follicular lymphoma (FL) who have a low tumor burden.

Investigators compared rituximab re-treatment with rituximab maintenance in nearly 300 FL patients, and results showed no significant difference between the treatment groups in the time to disease recurrence.

The researchers also noted that the re-treatment strategy was more cost-effective.

“For those 2 reasons, we recommend a retreatment strategy over a maintenance strategy in this patient population,” said Brad S. Kahl, MD, of the University of Wisconsin in Madison.

Dr Kahl and his colleagues described this research—the RESORT trial—in the Journal of Clinical Oncology. Early results from this trial were previously presented at the 2011 ASH Annual Meeting.

The team evaluated 289 patients with previously untreated, low-tumor-burden FL. All patients responded to initial treatment with rituximab (4 doses).

Patients were then randomized to receive maintenance therapy—a single dose of rituximab every 3 months until treatment failure—or rituximab re-treatment upon disease recurrence. Patients receiving re-treatment could receive rituximab every time they experienced progression, until treatment failure.

The median number of rituximab doses was 4 in the re-treatment arm and 18 in the maintenance arm. Three-year freedom from cytotoxic therapy was 84% in the re-treatment arm and 95% in the maintenance arm (P=0.03).

There was no significant difference between the arms in the time to disease recurrence. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years in the re-treatment arm and 4.3 years in the maintenance arm (P=0.54).

The researchers found no difference in health-related quality of life or anxiety between the treatment arms.

They also said grade 3 to 5 adverse events were infrequent in both arms. One patient developed progressive multifocal leukoencephalopathy after the 15th maintenance dose of rituximab and died.

Second malignancies were reported in 16 patients receiving re-treatment and 14 patients on maintenance therapy, but there were no obvious trends toward specific cancers.

“The study shows that a rituximab re-treatment strategy provides comparable disease control to a maintenance strategy in low-tumor-burden follicular lymphoma,” Dr Kahl said. “In addition, a re-treatment strategy is more cost-effective, as it requires about a quarter as much drug utilization.”

The study was accompanied by an editorial saying these results should change clinical practice.

 

 

Drugs in vials

Credit: Bill Branson

 

New research suggests maintenance therapy may not be necessary for patients with follicular lymphoma (FL) who have a low tumor burden.

Investigators compared rituximab re-treatment with rituximab maintenance in nearly 300 FL patients, and results showed no significant difference between the treatment groups in the time to disease recurrence.

The researchers also noted that the re-treatment strategy was more cost-effective.

“For those 2 reasons, we recommend a retreatment strategy over a maintenance strategy in this patient population,” said Brad S. Kahl, MD, of the University of Wisconsin in Madison.

Dr Kahl and his colleagues described this research—the RESORT trial—in the Journal of Clinical Oncology. Early results from this trial were previously presented at the 2011 ASH Annual Meeting.

The team evaluated 289 patients with previously untreated, low-tumor-burden FL. All patients responded to initial treatment with rituximab (4 doses).

Patients were then randomized to receive maintenance therapy—a single dose of rituximab every 3 months until treatment failure—or rituximab re-treatment upon disease recurrence. Patients receiving re-treatment could receive rituximab every time they experienced progression, until treatment failure.

The median number of rituximab doses was 4 in the re-treatment arm and 18 in the maintenance arm. Three-year freedom from cytotoxic therapy was 84% in the re-treatment arm and 95% in the maintenance arm (P=0.03).

There was no significant difference between the arms in the time to disease recurrence. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years in the re-treatment arm and 4.3 years in the maintenance arm (P=0.54).

The researchers found no difference in health-related quality of life or anxiety between the treatment arms.

They also said grade 3 to 5 adverse events were infrequent in both arms. One patient developed progressive multifocal leukoencephalopathy after the 15th maintenance dose of rituximab and died.

Second malignancies were reported in 16 patients receiving re-treatment and 14 patients on maintenance therapy, but there were no obvious trends toward specific cancers.

“The study shows that a rituximab re-treatment strategy provides comparable disease control to a maintenance strategy in low-tumor-burden follicular lymphoma,” Dr Kahl said. “In addition, a re-treatment strategy is more cost-effective, as it requires about a quarter as much drug utilization.”

The study was accompanied by an editorial saying these results should change clinical practice.

 

 

Micrograph showing FL

 

The European Commission has granted marketing authorization for the PI3K delta inhibitor idelalisib (Zydelig) to treat chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL) in the European Union.

The drug is now approved for use in combination with rituximab for CLL patients who have received at least 1 prior therapy or as first-line treatment in CLL patients who have 17p deletion or TP53 mutation and are not eligible for chemo-immunotherapy.

Idelalisib is also approved as monotherapy for FL patients who were refractory to 2 prior lines of treatment.

These approvals are based on data from 2 clinical trials—Study 116 and Study 101-09.

Study 116: Idelalisib in CLL

This phase 3 trial was stopped early because idelalisib had a significant impact on progression-free survival.

The study included 220 CLL patients who could not receive chemotherapy. Half were randomized to receive idelalisib plus rituximab, and the other half were randomized to rituximab plus placebo.

Patients in the rituximab-idelalisib arm had a much higher overall response rate than patients in the rituximab-placebo arm—81% and 13%, respectively (P<0.001). There were no complete responses.

At 24 weeks, the rate of progression-free survival was 93% in the rituximab-idelalisib arm and 46% in the rituximab-placebo arm (P<0.001). The median progression-free survival was 5.5 months in the rituximab-placebo arm and not reached in the rituximab-idelalisib arm (P<0.001).

At 12 months, the overall survival rate was 92% in the rituximab-idelalisib arm and 80% in the rituximab-placebo arm (P=0.02).

Most adverse events, in either treatment arm, were grade 2 or lower. The most common events in the rituximab-idelalisib arm were pyrexia, fatigue, nausea, chills, and diarrhea. In the rituximab-placebo arm, the most common events were infusion-related reactions, fatigue, cough, nausea, and dyspnea.

There were more serious adverse events in the rituximab-idelalisib arm than in the rituximab-placebo arm—40% and 35%, respectively. The most frequent serious events were pneumonia, pyrexia, and febrile neutropenia (in both treatment arms).

Study 101-09: Idelalisib in FL

This phase 2 trial enrolled 125 patients with indolent non-Hodgkin lymphoma who were refractory to rituximab and chemotherapy containing an alkylating agent. Patients received idelalisib monotherapy.

Of the 72 subjects with FL, 54% achieved a response, and 8% had a complete response. The median duration of response was not reached (range, 0-14.8 months).

Improvements in survival or disease-related symptoms have not been established.

In all patients, the most common grade 3 or higher adverse events were neutropenia (27%), elevations in aminotransferase levels (13%), diarrhea (13%), and pneumonia (7%).

Idelalisib is under development by Gilead Sciences. The drug is already approved in the US for the aforementioned indications, as well as to treat small lymphocytic lymphoma.

 

 

Micrograph showing FL

 

The European Commission has granted marketing authorization for the PI3K delta inhibitor idelalisib (Zydelig) to treat chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL) in the European Union.

The drug is now approved for use in combination with rituximab for CLL patients who have received at least 1 prior therapy or as first-line treatment in CLL patients who have 17p deletion or TP53 mutation and are not eligible for chemo-immunotherapy.

Idelalisib is also approved as monotherapy for FL patients who were refractory to 2 prior lines of treatment.

These approvals are based on data from 2 clinical trials—Study 116 and Study 101-09.

Study 116: Idelalisib in CLL

This phase 3 trial was stopped early because idelalisib had a significant impact on progression-free survival.

The study included 220 CLL patients who could not receive chemotherapy. Half were randomized to receive idelalisib plus rituximab, and the other half were randomized to rituximab plus placebo.

Patients in the rituximab-idelalisib arm had a much higher overall response rate than patients in the rituximab-placebo arm—81% and 13%, respectively (P<0.001). There were no complete responses.

At 24 weeks, the rate of progression-free survival was 93% in the rituximab-idelalisib arm and 46% in the rituximab-placebo arm (P<0.001). The median progression-free survival was 5.5 months in the rituximab-placebo arm and not reached in the rituximab-idelalisib arm (P<0.001).

At 12 months, the overall survival rate was 92% in the rituximab-idelalisib arm and 80% in the rituximab-placebo arm (P=0.02).

Most adverse events, in either treatment arm, were grade 2 or lower. The most common events in the rituximab-idelalisib arm were pyrexia, fatigue, nausea, chills, and diarrhea. In the rituximab-placebo arm, the most common events were infusion-related reactions, fatigue, cough, nausea, and dyspnea.

There were more serious adverse events in the rituximab-idelalisib arm than in the rituximab-placebo arm—40% and 35%, respectively. The most frequent serious events were pneumonia, pyrexia, and febrile neutropenia (in both treatment arms).

Study 101-09: Idelalisib in FL

This phase 2 trial enrolled 125 patients with indolent non-Hodgkin lymphoma who were refractory to rituximab and chemotherapy containing an alkylating agent. Patients received idelalisib monotherapy.

Of the 72 subjects with FL, 54% achieved a response, and 8% had a complete response. The median duration of response was not reached (range, 0-14.8 months).

Improvements in survival or disease-related symptoms have not been established.

In all patients, the most common grade 3 or higher adverse events were neutropenia (27%), elevations in aminotransferase levels (13%), diarrhea (13%), and pneumonia (7%).

Idelalisib is under development by Gilead Sciences. The drug is already approved in the US for the aforementioned indications, as well as to treat small lymphocytic lymphoma.

 

 

Micrograph showing FL

 

The European Commission has granted marketing authorization for the PI3K delta inhibitor idelalisib (Zydelig) to treat chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL) in the European Union.

The drug is now approved for use in combination with rituximab for CLL patients who have received at least 1 prior therapy or as first-line treatment in CLL patients who have 17p deletion or TP53 mutation and are not eligible for chemo-immunotherapy.

Idelalisib is also approved as monotherapy for FL patients who were refractory to 2 prior lines of treatment.

These approvals are based on data from 2 clinical trials—Study 116 and Study 101-09.

Study 116: Idelalisib in CLL

This phase 3 trial was stopped early because idelalisib had a significant impact on progression-free survival.

The study included 220 CLL patients who could not receive chemotherapy. Half were randomized to receive idelalisib plus rituximab, and the other half were randomized to rituximab plus placebo.

Patients in the rituximab-idelalisib arm had a much higher overall response rate than patients in the rituximab-placebo arm—81% and 13%, respectively (P<0.001). There were no complete responses.

At 24 weeks, the rate of progression-free survival was 93% in the rituximab-idelalisib arm and 46% in the rituximab-placebo arm (P<0.001). The median progression-free survival was 5.5 months in the rituximab-placebo arm and not reached in the rituximab-idelalisib arm (P<0.001).

At 12 months, the overall survival rate was 92% in the rituximab-idelalisib arm and 80% in the rituximab-placebo arm (P=0.02).

Most adverse events, in either treatment arm, were grade 2 or lower. The most common events in the rituximab-idelalisib arm were pyrexia, fatigue, nausea, chills, and diarrhea. In the rituximab-placebo arm, the most common events were infusion-related reactions, fatigue, cough, nausea, and dyspnea.

There were more serious adverse events in the rituximab-idelalisib arm than in the rituximab-placebo arm—40% and 35%, respectively. The most frequent serious events were pneumonia, pyrexia, and febrile neutropenia (in both treatment arms).

Study 101-09: Idelalisib in FL

This phase 2 trial enrolled 125 patients with indolent non-Hodgkin lymphoma who were refractory to rituximab and chemotherapy containing an alkylating agent. Patients received idelalisib monotherapy.

Of the 72 subjects with FL, 54% achieved a response, and 8% had a complete response. The median duration of response was not reached (range, 0-14.8 months).

Improvements in survival or disease-related symptoms have not been established.

In all patients, the most common grade 3 or higher adverse events were neutropenia (27%), elevations in aminotransferase levels (13%), diarrhea (13%), and pneumonia (7%).

Idelalisib is under development by Gilead Sciences. The drug is already approved in the US for the aforementioned indications, as well as to treat small lymphocytic lymphoma.

 

 

PET-CT scanner

 

PET-CT should be the new standard for response assessment in patients with follicular lymphoma (FL), according to researchers.

The group found evidence suggesting that PET-CT is more accurate than conventional CT in measuring treatment response and predicting survival in patients with FL.

“Our findings have important implications for patients with follicular lymphoma,” said study author Judith Trotman, MBChB, of the University of Sydney in Australia.

“Compared to conventional CT scanning, PET-CT is more accurate in mapping out the lymphoma and better identifies the majority of patients who have a prolonged remission after treatment.”

Dr Trotman and her colleagues reported these findings in The Lancet Haematology. The results will also be discussed at the International Workshop on PET in Lymphoma in Menton, France, which is taking place September 19-20.

By assessing imaging performed in 3 clinical trials, the researchers examined the link between PET-CT status and survival following first-line immunochemotherapy for advanced FL.

Independent, masked reviewers evaluated scans of 246 patients who underwent both PET-CT and traditional CT imaging within 3 months of their last dose of therapy. Patients were followed for a median of 54.8 months.

Seventeen percent of patients had a positive post-induction PET scan, according to a cutoff of 4 or higher on the 5PS.

When the researchers compared patients with a positive PET scan to those with a negative scan, the hazard ratio (HR) for progression-free survival (PFS) was 3.9 (P<0.0001). For overall survival, the HR was 6.7 (P=0.0002).

The 4-year PFS was 23.2% in patients with a positive PET scan and 63.4% in those who had a negative PET scan (P<0.0001). The 4-year overall survival was 87.2% and 97.1%, respectively (P<0.0001).

The researchers also discovered that conventional CT-based response—complete response or unconfirmed complete response compared to partial response—was weakly predictive of PFS. The HR was 1.7 (P=0.017).

“Our study shows that PET-CT is much better in evaluating treatment response and is an early predictor of survival,” Dr Trotman said. “This greater accuracy will assist physicians to more effectively monitor their patients.”

“We expect this research will result in PET-CT imaging replacing CT, becoming the new gold standard to evaluate patients with follicular lymphoma after treatment. Importantly, it will be a platform for future studies of response-adapted therapies aimed to improve the poor outcomes for those patients who remain PET-positive.”

This study may also pave the way for several new research opportunities, according to Bruce Cheson, MD, of Georgetown University in Washington DC, who wrote a comment article related to this study.

“One such possibility would be to assess if an early reaction to the PET scan result improves patient outcome,” he wrote. “Thus, patients with a positive PET scan after induction therapy could be randomly assigned to either deferred treatment until disease progression or immediate intervention.”

“A preferable alternative would be to introduce a unique agent at that time, such as the newly developed small molecules (eg, idelalisib, ibrutinib, or ABT-199) in a novel combination.”

 

 

PET-CT scanner

 

PET-CT should be the new standard for response assessment in patients with follicular lymphoma (FL), according to researchers.

The group found evidence suggesting that PET-CT is more accurate than conventional CT in measuring treatment response and predicting survival in patients with FL.

“Our findings have important implications for patients with follicular lymphoma,” said study author Judith Trotman, MBChB, of the University of Sydney in Australia.

“Compared to conventional CT scanning, PET-CT is more accurate in mapping out the lymphoma and better identifies the majority of patients who have a prolonged remission after treatment.”

Dr Trotman and her colleagues reported these findings in The Lancet Haematology. The results will also be discussed at the International Workshop on PET in Lymphoma in Menton, France, which is taking place September 19-20.

By assessing imaging performed in 3 clinical trials, the researchers examined the link between PET-CT status and survival following first-line immunochemotherapy for advanced FL.

Independent, masked reviewers evaluated scans of 246 patients who underwent both PET-CT and traditional CT imaging within 3 months of their last dose of therapy. Patients were followed for a median of 54.8 months.

Seventeen percent of patients had a positive post-induction PET scan, according to a cutoff of 4 or higher on the 5PS.

When the researchers compared patients with a positive PET scan to those with a negative scan, the hazard ratio (HR) for progression-free survival (PFS) was 3.9 (P<0.0001). For overall survival, the HR was 6.7 (P=0.0002).

The 4-year PFS was 23.2% in patients with a positive PET scan and 63.4% in those who had a negative PET scan (P<0.0001). The 4-year overall survival was 87.2% and 97.1%, respectively (P<0.0001).

The researchers also discovered that conventional CT-based response—complete response or unconfirmed complete response compared to partial response—was weakly predictive of PFS. The HR was 1.7 (P=0.017).

“Our study shows that PET-CT is much better in evaluating treatment response and is an early predictor of survival,” Dr Trotman said. “This greater accuracy will assist physicians to more effectively monitor their patients.”

“We expect this research will result in PET-CT imaging replacing CT, becoming the new gold standard to evaluate patients with follicular lymphoma after treatment. Importantly, it will be a platform for future studies of response-adapted therapies aimed to improve the poor outcomes for those patients who remain PET-positive.”

This study may also pave the way for several new research opportunities, according to Bruce Cheson, MD, of Georgetown University in Washington DC, who wrote a comment article related to this study.

“One such possibility would be to assess if an early reaction to the PET scan result improves patient outcome,” he wrote. “Thus, patients with a positive PET scan after induction therapy could be randomly assigned to either deferred treatment until disease progression or immediate intervention.”

“A preferable alternative would be to introduce a unique agent at that time, such as the newly developed small molecules (eg, idelalisib, ibrutinib, or ABT-199) in a novel combination.”

 

 

PET-CT scanner

 

PET-CT should be the new standard for response assessment in patients with follicular lymphoma (FL), according to researchers.

The group found evidence suggesting that PET-CT is more accurate than conventional CT in measuring treatment response and predicting survival in patients with FL.

“Our findings have important implications for patients with follicular lymphoma,” said study author Judith Trotman, MBChB, of the University of Sydney in Australia.

“Compared to conventional CT scanning, PET-CT is more accurate in mapping out the lymphoma and better identifies the majority of patients who have a prolonged remission after treatment.”

Dr Trotman and her colleagues reported these findings in The Lancet Haematology. The results will also be discussed at the International Workshop on PET in Lymphoma in Menton, France, which is taking place September 19-20.

By assessing imaging performed in 3 clinical trials, the researchers examined the link between PET-CT status and survival following first-line immunochemotherapy for advanced FL.

Independent, masked reviewers evaluated scans of 246 patients who underwent both PET-CT and traditional CT imaging within 3 months of their last dose of therapy. Patients were followed for a median of 54.8 months.

Seventeen percent of patients had a positive post-induction PET scan, according to a cutoff of 4 or higher on the 5PS.

When the researchers compared patients with a positive PET scan to those with a negative scan, the hazard ratio (HR) for progression-free survival (PFS) was 3.9 (P<0.0001). For overall survival, the HR was 6.7 (P=0.0002).

The 4-year PFS was 23.2% in patients with a positive PET scan and 63.4% in those who had a negative PET scan (P<0.0001). The 4-year overall survival was 87.2% and 97.1%, respectively (P<0.0001).

The researchers also discovered that conventional CT-based response—complete response or unconfirmed complete response compared to partial response—was weakly predictive of PFS. The HR was 1.7 (P=0.017).

“Our study shows that PET-CT is much better in evaluating treatment response and is an early predictor of survival,” Dr Trotman said. “This greater accuracy will assist physicians to more effectively monitor their patients.”

“We expect this research will result in PET-CT imaging replacing CT, becoming the new gold standard to evaluate patients with follicular lymphoma after treatment. Importantly, it will be a platform for future studies of response-adapted therapies aimed to improve the poor outcomes for those patients who remain PET-positive.”

This study may also pave the way for several new research opportunities, according to Bruce Cheson, MD, of Georgetown University in Washington DC, who wrote a comment article related to this study.

“One such possibility would be to assess if an early reaction to the PET scan result improves patient outcome,” he wrote. “Thus, patients with a positive PET scan after induction therapy could be randomly assigned to either deferred treatment until disease progression or immediate intervention.”

“A preferable alternative would be to introduce a unique agent at that time, such as the newly developed small molecules (eg, idelalisib, ibrutinib, or ABT-199) in a novel combination.”

 

 

Micrograph showing MCL

 

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending marketing authorization for ibrutinib (Imbruvica).

The committee is endorsing the Bruton’s tyrosine kinase (BTK) inhibitor for use in adults with relapsed or refractory mantle cell lymphoma (MCL) and certain adults with chronic lymphocytic leukemia (CLL).

This includes untreated CLL patients with 17p deletion or TP53 mutation who cannot receive chemo-immunotherapy and patients who have received at least 1 prior therapy.

The European Commission will take the CHMP’s opinion into account when deciding whether to authorize the commercialization of ibrutinib in the European Union.

The CHMP based its recommendations on data from 2 CLL studies—the phase 3 RESONATE trial (PCYC-1112) and a phase 1b/2 trial (PCYC-1102)—as well as a phase 2 trial (PCYC-1104) in MCL.

RESONATE trial

Results of RESONATE were recently presented at the 2014 EHA Congress. The trial included 391 patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL).

Patients were randomized to receive ibrutinib (n=195) or ofatumumab (n=196). Patients in the ofatumumab arm were allowed to cross over to ibrutinib if they progressed (n=57). The median time on study was 9.4 months.

The best overall response rate was higher in the ibrutinib arm than the ofatumumab arm, at 78% and 11%, respectively. And ibrutinib significantly prolonged progression-free survival. The median was 8.1 months in the ofatumumab arm and was not reached in the ibrutinib arm (P<0.0001).

Ibrutinib significantly prolonged overall survival as well. The median overall survival was not reached in either arm, but the hazard ratio was 0.434 (P=0.0049).

Adverse events occurred in 99% of patients in the ibrutinib arm and 98% of those in the ofatumumab arm. Grade 3/4 events occurred in 51% and 39%, respectively.

Atrial fibrillation, bleeding-related events, diarrhea, and arthralgia were more common in the ibrutinib arm. Infusion-related reactions, peripheral sensory neuropathy, urticaria, night sweats, and pruritus were more common in the ofatumumab arm.

PCYC-1102: Ibrutinib in CLL/SLL

Results of this phase 1b/2 trial were published in The Lancet Oncology in January. The trial enrolled 29 patients with previously untreated CLL and 2 with SLL.

They received 28-day cycles of once-daily ibrutinib at 420 mg or 840 mg. The 840 mg dose was discontinued after enrollment had begun because the doses showed comparable activity.

After a median follow-up of 22.1 months, 71% of patients achieved an objective response. Four patients (13%) had a complete response. The median time to response was 1.9 months.

Study investigators did not establish whether ibrutinib confers improvements in survival or disease-related symptoms.

Common adverse events included diarrhea (68%), nausea (48%), fatigue (32%), peripheral edema (29%), hypertension (29%), dizziness (26%), dyspepsia (26%), upper respiratory tract infection (26%), arthralgia (23%), constipation (23%), urinary tract infection (23%), and vomiting (23%).

Grade 3 adverse events included diarrhea (13%), fatigue (3%), hypertension (6%), dizziness (3%), urinary tract infection (3%), headache (3%), back pain (3%), and neutropenia (3%). One patient (3%) had grade 4 thrombocytopenia.

PCYC-1104 trial: Ibrutinib in MCL

Results of this trial were presented at ASH 2012 and published in NEJM in 2013. The NEJM data included 111 patients who received ibrutinib at 560 mg daily in continuous, 28-day cycles until disease progression.

The overall response rate was 68%, with a complete response rate of 21% and a partial response rate of 47%. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months.

The estimated progression-free survival was 13.9 months, and the overall survival was not reached. The estimated rate of overall survival was 58% at 18 months.

Common nonhematologic adverse events included diarrhea (50%), fatigue (41%), nausea (31%), peripheral edema (28%), dyspnea (27%), constipation (25%), upper respiratory tract infection (23%), vomiting (23%), and decreased appetite (21%). The most common grade 3, 4, or 5 infection was pneumonia (6%).

Grade 3 and 4 hematologic adverse events included neutropenia (16%), thrombocytopenia (11%), and anemia (10%). Grade 3 bleeding events occurred in 5 patients.

About ibrutinib

Ibrutinib works by inhibiting BTK, a protein involved in mediating the cellular signaling pathways that control B-cell maturation and survival. In malignant B cells, there is excessive signaling through the B-cell receptor signaling pathway, which includes BTK.

Ibrutinib forms a strong covalent bond with BTK, which inhibits the excessive transmission of cell survival signals within the malignant B cells and stops their excessive build-up in protected environmental areas such as the lymph nodes.

Ibrutinib is being studied alone and in combination with other treatments in several hematologic malignancies, including CLL, MCL, Waldenstrom’s macroglobulinemia, diffuse large B-cell lymphoma, follicular lymphoma, and multiple myeloma.

Ibrutinib received accelerated approval from the US Food and Drug Administration in November 2013 to treat MCL. The drug received accelerated approval in February 2014 to treat CLL patients who have received at least 1 prior therapy.

Ibrutinib is also approved in Israel for the treatment of adults with MCL who have received at least 1 prior therapy.

Ibrutinib is under development by Janssen and Pharmacyclics. The companies co-market ibrutinib in the US, but, pending the drug’s approval, Janssen will market ibrutinib in the rest of the world.

 

 

Micrograph showing MCL

 

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending marketing authorization for ibrutinib (Imbruvica).

The committee is endorsing the Bruton’s tyrosine kinase (BTK) inhibitor for use in adults with relapsed or refractory mantle cell lymphoma (MCL) and certain adults with chronic lymphocytic leukemia (CLL).

This includes untreated CLL patients with 17p deletion or TP53 mutation who cannot receive chemo-immunotherapy and patients who have received at least 1 prior therapy.

The European Commission will take the CHMP’s opinion into account when deciding whether to authorize the commercialization of ibrutinib in the European Union.

The CHMP based its recommendations on data from 2 CLL studies—the phase 3 RESONATE trial (PCYC-1112) and a phase 1b/2 trial (PCYC-1102)—as well as a phase 2 trial (PCYC-1104) in MCL.

RESONATE trial

Results of RESONATE were recently presented at the 2014 EHA Congress. The trial included 391 patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL).

Patients were randomized to receive ibrutinib (n=195) or ofatumumab (n=196). Patients in the ofatumumab arm were allowed to cross over to ibrutinib if they progressed (n=57). The median time on study was 9.4 months.

The best overall response rate was higher in the ibrutinib arm than the ofatumumab arm, at 78% and 11%, respectively. And ibrutinib significantly prolonged progression-free survival. The median was 8.1 months in the ofatumumab arm and was not reached in the ibrutinib arm (P<0.0001).

Ibrutinib significantly prolonged overall survival as well. The median overall survival was not reached in either arm, but the hazard ratio was 0.434 (P=0.0049).

Adverse events occurred in 99% of patients in the ibrutinib arm and 98% of those in the ofatumumab arm. Grade 3/4 events occurred in 51% and 39%, respectively.

Atrial fibrillation, bleeding-related events, diarrhea, and arthralgia were more common in the ibrutinib arm. Infusion-related reactions, peripheral sensory neuropathy, urticaria, night sweats, and pruritus were more common in the ofatumumab arm.

PCYC-1102: Ibrutinib in CLL/SLL

Results of this phase 1b/2 trial were published in The Lancet Oncology in January. The trial enrolled 29 patients with previously untreated CLL and 2 with SLL.

They received 28-day cycles of once-daily ibrutinib at 420 mg or 840 mg. The 840 mg dose was discontinued after enrollment had begun because the doses showed comparable activity.

After a median follow-up of 22.1 months, 71% of patients achieved an objective response. Four patients (13%) had a complete response. The median time to response was 1.9 months.

Study investigators did not establish whether ibrutinib confers improvements in survival or disease-related symptoms.

Common adverse events included diarrhea (68%), nausea (48%), fatigue (32%), peripheral edema (29%), hypertension (29%), dizziness (26%), dyspepsia (26%), upper respiratory tract infection (26%), arthralgia (23%), constipation (23%), urinary tract infection (23%), and vomiting (23%).

Grade 3 adverse events included diarrhea (13%), fatigue (3%), hypertension (6%), dizziness (3%), urinary tract infection (3%), headache (3%), back pain (3%), and neutropenia (3%). One patient (3%) had grade 4 thrombocytopenia.

PCYC-1104 trial: Ibrutinib in MCL

Results of this trial were presented at ASH 2012 and published in NEJM in 2013. The NEJM data included 111 patients who received ibrutinib at 560 mg daily in continuous, 28-day cycles until disease progression.

The overall response rate was 68%, with a complete response rate of 21% and a partial response rate of 47%. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months.

The estimated progression-free survival was 13.9 months, and the overall survival was not reached. The estimated rate of overall survival was 58% at 18 months.

Common nonhematologic adverse events included diarrhea (50%), fatigue (41%), nausea (31%), peripheral edema (28%), dyspnea (27%), constipation (25%), upper respiratory tract infection (23%), vomiting (23%), and decreased appetite (21%). The most common grade 3, 4, or 5 infection was pneumonia (6%).

Grade 3 and 4 hematologic adverse events included neutropenia (16%), thrombocytopenia (11%), and anemia (10%). Grade 3 bleeding events occurred in 5 patients.

About ibrutinib

Ibrutinib works by inhibiting BTK, a protein involved in mediating the cellular signaling pathways that control B-cell maturation and survival. In malignant B cells, there is excessive signaling through the B-cell receptor signaling pathway, which includes BTK.

Ibrutinib forms a strong covalent bond with BTK, which inhibits the excessive transmission of cell survival signals within the malignant B cells and stops their excessive build-up in protected environmental areas such as the lymph nodes.

Ibrutinib is being studied alone and in combination with other treatments in several hematologic malignancies, including CLL, MCL, Waldenstrom’s macroglobulinemia, diffuse large B-cell lymphoma, follicular lymphoma, and multiple myeloma.

Ibrutinib received accelerated approval from the US Food and Drug Administration in November 2013 to treat MCL. The drug received accelerated approval in February 2014 to treat CLL patients who have received at least 1 prior therapy.

Ibrutinib is also approved in Israel for the treatment of adults with MCL who have received at least 1 prior therapy.

Ibrutinib is under development by Janssen and Pharmacyclics. The companies co-market ibrutinib in the US, but, pending the drug’s approval, Janssen will market ibrutinib in the rest of the world.

 

 

Micrograph showing MCL

 

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending marketing authorization for ibrutinib (Imbruvica).

The committee is endorsing the Bruton’s tyrosine kinase (BTK) inhibitor for use in adults with relapsed or refractory mantle cell lymphoma (MCL) and certain adults with chronic lymphocytic leukemia (CLL).

This includes untreated CLL patients with 17p deletion or TP53 mutation who cannot receive chemo-immunotherapy and patients who have received at least 1 prior therapy.

The European Commission will take the CHMP’s opinion into account when deciding whether to authorize the commercialization of ibrutinib in the European Union.

The CHMP based its recommendations on data from 2 CLL studies—the phase 3 RESONATE trial (PCYC-1112) and a phase 1b/2 trial (PCYC-1102)—as well as a phase 2 trial (PCYC-1104) in MCL.

RESONATE trial

Results of RESONATE were recently presented at the 2014 EHA Congress. The trial included 391 patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL).

Patients were randomized to receive ibrutinib (n=195) or ofatumumab (n=196). Patients in the ofatumumab arm were allowed to cross over to ibrutinib if they progressed (n=57). The median time on study was 9.4 months.

The best overall response rate was higher in the ibrutinib arm than the ofatumumab arm, at 78% and 11%, respectively. And ibrutinib significantly prolonged progression-free survival. The median was 8.1 months in the ofatumumab arm and was not reached in the ibrutinib arm (P<0.0001).

Ibrutinib significantly prolonged overall survival as well. The median overall survival was not reached in either arm, but the hazard ratio was 0.434 (P=0.0049).

Adverse events occurred in 99% of patients in the ibrutinib arm and 98% of those in the ofatumumab arm. Grade 3/4 events occurred in 51% and 39%, respectively.

Atrial fibrillation, bleeding-related events, diarrhea, and arthralgia were more common in the ibrutinib arm. Infusion-related reactions, peripheral sensory neuropathy, urticaria, night sweats, and pruritus were more common in the ofatumumab arm.

PCYC-1102: Ibrutinib in CLL/SLL

Results of this phase 1b/2 trial were published in The Lancet Oncology in January. The trial enrolled 29 patients with previously untreated CLL and 2 with SLL.

They received 28-day cycles of once-daily ibrutinib at 420 mg or 840 mg. The 840 mg dose was discontinued after enrollment had begun because the doses showed comparable activity.

After a median follow-up of 22.1 months, 71% of patients achieved an objective response. Four patients (13%) had a complete response. The median time to response was 1.9 months.

Study investigators did not establish whether ibrutinib confers improvements in survival or disease-related symptoms.

Common adverse events included diarrhea (68%), nausea (48%), fatigue (32%), peripheral edema (29%), hypertension (29%), dizziness (26%), dyspepsia (26%), upper respiratory tract infection (26%), arthralgia (23%), constipation (23%), urinary tract infection (23%), and vomiting (23%).

Grade 3 adverse events included diarrhea (13%), fatigue (3%), hypertension (6%), dizziness (3%), urinary tract infection (3%), headache (3%), back pain (3%), and neutropenia (3%). One patient (3%) had grade 4 thrombocytopenia.

PCYC-1104 trial: Ibrutinib in MCL

Results of this trial were presented at ASH 2012 and published in NEJM in 2013. The NEJM data included 111 patients who received ibrutinib at 560 mg daily in continuous, 28-day cycles until disease progression.

The overall response rate was 68%, with a complete response rate of 21% and a partial response rate of 47%. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months.

The estimated progression-free survival was 13.9 months, and the overall survival was not reached. The estimated rate of overall survival was 58% at 18 months.

Common nonhematologic adverse events included diarrhea (50%), fatigue (41%), nausea (31%), peripheral edema (28%), dyspnea (27%), constipation (25%), upper respiratory tract infection (23%), vomiting (23%), and decreased appetite (21%). The most common grade 3, 4, or 5 infection was pneumonia (6%).

Grade 3 and 4 hematologic adverse events included neutropenia (16%), thrombocytopenia (11%), and anemia (10%). Grade 3 bleeding events occurred in 5 patients.

About ibrutinib

Ibrutinib works by inhibiting BTK, a protein involved in mediating the cellular signaling pathways that control B-cell maturation and survival. In malignant B cells, there is excessive signaling through the B-cell receptor signaling pathway, which includes BTK.

Ibrutinib forms a strong covalent bond with BTK, which inhibits the excessive transmission of cell survival signals within the malignant B cells and stops their excessive build-up in protected environmental areas such as the lymph nodes.

Ibrutinib is being studied alone and in combination with other treatments in several hematologic malignancies, including CLL, MCL, Waldenstrom’s macroglobulinemia, diffuse large B-cell lymphoma, follicular lymphoma, and multiple myeloma.

Ibrutinib received accelerated approval from the US Food and Drug Administration in November 2013 to treat MCL. The drug received accelerated approval in February 2014 to treat CLL patients who have received at least 1 prior therapy.

Ibrutinib is also approved in Israel for the treatment of adults with MCL who have received at least 1 prior therapy.

Ibrutinib is under development by Janssen and Pharmacyclics. The companies co-market ibrutinib in the US, but, pending the drug’s approval, Janssen will market ibrutinib in the rest of the world.

 

 

Micrograph showing FL

 

Days after gaining approval for 3 indications in the US, idelalisib (Zydelig) has earned a positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP).

The CHMP is recommending the PI3K delta inhibitor for the treatment of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).

If approved, the drug would be used as monotherapy for adults with FL that is refractory to 2 prior lines of treatment.

Idelalisib would also be used in combination with rituximab for adults with CLL who have received at least 1 prior therapy or as first-line treatment in CLL patients who have 17p deletion or TP53 mutation and cannot receive chemo-immunotherapy.

The CHMP’s recommendation for idelalisib (150 mg film-coated tablets) will be reviewed by the European Commission, which has the authority to approve medicines for use in the 28 countries of the European Union.

The CHMP’s positive opinion of idelalisib is based on data from 2 clinical trials—Study 116 and Study 101-09.

Study 116: Idelalisib in CLL

This phase 3 trial was stopped early because idelalisib had a significant impact on progression-free survival.

The study included 220 CLL patients who could not receive chemotherapy. Half were randomized to receive idelalisib plus rituximab, and the other half were randomized to rituximab plus placebo.

Patients in the idelalisib arm had a much higher overall response rate than patients in the placebo arm—81% and 13%, respectively (P<0.001). But all responses were partial.

At 24 weeks, the rate of progression-free survival was 93% in the idelalisib arm and 46% in the placebo arm (P<0.001). The median progression-free survival was 5.5 months in the placebo arm and not reached in the idelalisib arm (P<0.001).

At 12 months, the overall survival rate was 92% in the idelalisib arm and 80% in the placebo arm (P=0.02).

Most adverse events, in either treatment arm, were grade 2 or lower. The most common events in the idelalisib arm were pyrexia, fatigue, nausea, chills, and diarrhea. In the placebo arm, the most common events were infusion-related reactions, fatigue, cough, nausea, and dyspnea.

There were more serious adverse events in the idelalisib arm than in the placebo arm—40% and 35%, respectively. The most frequent serious events were pneumonia, pyrexia, and febrile neutropenia (in both treatment arms).

Study 101-09: Idelalisib in FL

In this phase 2 trial, idelalisib was given as a single agent to patients with indolent non-Hodgkin lymphoma who were refractory to rituximab and chemotherapy containing an alkylating agent.

In the 72 patients with FL, the overall response rate was 54%, and the complete response rate was 8%. The median duration of response was not reached (range, 0-14.8 months).

Improvements in patient survival or disease-related symptoms have not been established.

The most common grade 3 or higher adverse events were neutropenia (27%), elevations in aminotransferase levels (13%), diarrhea (13%), and pneumonia (7%).

About idelalisib 

Idelalisib is an oral inhibitor of PI3K delta, a protein that plays a role in the activation, proliferation, and viability of B cells. PI3K delta signaling is active in many B-cell leukemias and lymphomas, and, by inhibiting the protein, idelalisib blocks several cellular signaling pathways that drive B-cell viability.

Idelalisib is being developed by Gilead Sciences. On July 23, the drug received US Food and Drug Administration approval for use in combination with rituximab to treat patients with relapsed CLL who cannot receive rituximab alone. The agency also granted idelalisib accelerated approval to treat patients with relapsed FL or small lymphocytic lymphoma who have received at least 2 prior systemic therapies.

 

 

Micrograph showing FL

 

Days after gaining approval for 3 indications in the US, idelalisib (Zydelig) has earned a positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP).

The CHMP is recommending the PI3K delta inhibitor for the treatment of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).

If approved, the drug would be used as monotherapy for adults with FL that is refractory to 2 prior lines of treatment.

Idelalisib would also be used in combination with rituximab for adults with CLL who have received at least 1 prior therapy or as first-line treatment in CLL patients who have 17p deletion or TP53 mutation and cannot receive chemo-immunotherapy.

The CHMP’s recommendation for idelalisib (150 mg film-coated tablets) will be reviewed by the European Commission, which has the authority to approve medicines for use in the 28 countries of the European Union.

The CHMP’s positive opinion of idelalisib is based on data from 2 clinical trials—Study 116 and Study 101-09.

Study 116: Idelalisib in CLL

This phase 3 trial was stopped early because idelalisib had a significant impact on progression-free survival.

The study included 220 CLL patients who could not receive chemotherapy. Half were randomized to receive idelalisib plus rituximab, and the other half were randomized to rituximab plus placebo.

Patients in the idelalisib arm had a much higher overall response rate than patients in the placebo arm—81% and 13%, respectively (P<0.001). But all responses were partial.

At 24 weeks, the rate of progression-free survival was 93% in the idelalisib arm and 46% in the placebo arm (P<0.001). The median progression-free survival was 5.5 months in the placebo arm and not reached in the idelalisib arm (P<0.001).

At 12 months, the overall survival rate was 92% in the idelalisib arm and 80% in the placebo arm (P=0.02).

Most adverse events, in either treatment arm, were grade 2 or lower. The most common events in the idelalisib arm were pyrexia, fatigue, nausea, chills, and diarrhea. In the placebo arm, the most common events were infusion-related reactions, fatigue, cough, nausea, and dyspnea.

There were more serious adverse events in the idelalisib arm than in the placebo arm—40% and 35%, respectively. The most frequent serious events were pneumonia, pyrexia, and febrile neutropenia (in both treatment arms).

Study 101-09: Idelalisib in FL

In this phase 2 trial, idelalisib was given as a single agent to patients with indolent non-Hodgkin lymphoma who were refractory to rituximab and chemotherapy containing an alkylating agent.

In the 72 patients with FL, the overall response rate was 54%, and the complete response rate was 8%. The median duration of response was not reached (range, 0-14.8 months).

Improvements in patient survival or disease-related symptoms have not been established.

The most common grade 3 or higher adverse events were neutropenia (27%), elevations in aminotransferase levels (13%), diarrhea (13%), and pneumonia (7%).

About idelalisib 

Idelalisib is an oral inhibitor of PI3K delta, a protein that plays a role in the activation, proliferation, and viability of B cells. PI3K delta signaling is active in many B-cell leukemias and lymphomas, and, by inhibiting the protein, idelalisib blocks several cellular signaling pathways that drive B-cell viability.

Idelalisib is being developed by Gilead Sciences. On July 23, the drug received US Food and Drug Administration approval for use in combination with rituximab to treat patients with relapsed CLL who cannot receive rituximab alone. The agency also granted idelalisib accelerated approval to treat patients with relapsed FL or small lymphocytic lymphoma who have received at least 2 prior systemic therapies.

 

 

Micrograph showing FL

 

Days after gaining approval for 3 indications in the US, idelalisib (Zydelig) has earned a positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP).

The CHMP is recommending the PI3K delta inhibitor for the treatment of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).

If approved, the drug would be used as monotherapy for adults with FL that is refractory to 2 prior lines of treatment.

Idelalisib would also be used in combination with rituximab for adults with CLL who have received at least 1 prior therapy or as first-line treatment in CLL patients who have 17p deletion or TP53 mutation and cannot receive chemo-immunotherapy.

The CHMP’s recommendation for idelalisib (150 mg film-coated tablets) will be reviewed by the European Commission, which has the authority to approve medicines for use in the 28 countries of the European Union.

The CHMP’s positive opinion of idelalisib is based on data from 2 clinical trials—Study 116 and Study 101-09.

Study 116: Idelalisib in CLL

This phase 3 trial was stopped early because idelalisib had a significant impact on progression-free survival.

The study included 220 CLL patients who could not receive chemotherapy. Half were randomized to receive idelalisib plus rituximab, and the other half were randomized to rituximab plus placebo.

Patients in the idelalisib arm had a much higher overall response rate than patients in the placebo arm—81% and 13%, respectively (P<0.001). But all responses were partial.

At 24 weeks, the rate of progression-free survival was 93% in the idelalisib arm and 46% in the placebo arm (P<0.001). The median progression-free survival was 5.5 months in the placebo arm and not reached in the idelalisib arm (P<0.001).

At 12 months, the overall survival rate was 92% in the idelalisib arm and 80% in the placebo arm (P=0.02).

Most adverse events, in either treatment arm, were grade 2 or lower. The most common events in the idelalisib arm were pyrexia, fatigue, nausea, chills, and diarrhea. In the placebo arm, the most common events were infusion-related reactions, fatigue, cough, nausea, and dyspnea.

There were more serious adverse events in the idelalisib arm than in the placebo arm—40% and 35%, respectively. The most frequent serious events were pneumonia, pyrexia, and febrile neutropenia (in both treatment arms).

Study 101-09: Idelalisib in FL

In this phase 2 trial, idelalisib was given as a single agent to patients with indolent non-Hodgkin lymphoma who were refractory to rituximab and chemotherapy containing an alkylating agent.

In the 72 patients with FL, the overall response rate was 54%, and the complete response rate was 8%. The median duration of response was not reached (range, 0-14.8 months).

Improvements in patient survival or disease-related symptoms have not been established.

The most common grade 3 or higher adverse events were neutropenia (27%), elevations in aminotransferase levels (13%), diarrhea (13%), and pneumonia (7%).

About idelalisib 

Idelalisib is an oral inhibitor of PI3K delta, a protein that plays a role in the activation, proliferation, and viability of B cells. PI3K delta signaling is active in many B-cell leukemias and lymphomas, and, by inhibiting the protein, idelalisib blocks several cellular signaling pathways that drive B-cell viability.

Idelalisib is being developed by Gilead Sciences. On July 23, the drug received US Food and Drug Administration approval for use in combination with rituximab to treat patients with relapsed CLL who cannot receive rituximab alone. The agency also granted idelalisib accelerated approval to treat patients with relapsed FL or small lymphocytic lymphoma who have received at least 2 prior systemic therapies.

The US Food and Drug Administration (FDA) has approved the PI3K delta inhibitor idelalisib (Zydelig) for the treatment of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma (FL).

The drug was granted traditional approval for use in combination with rituximab to treat patients with relapsed CLL who cannot receive rituximab alone.

Idelalisib has also received accelerated approval to treat patients with relapsed FL or SLL who have received at least 2 prior systemic therapies.

The FDA’s accelerated approval program allows for approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.

This program provides earlier patient access to a drug while the developer—in this case, Gilead Sciences—conducts trials confirming the drug’s benefit.

Idelalisib in CLL: Results of a phase 3 study

The approval of idelalisib in CLL is based on results of a phase 3 trial (Study 116), which was stopped early because idelalisib had a significant impact on progression-free survival.

The study included 220 CLL patients who could not receive chemotherapy. Half were randomized to receive idelalisib plus rituximab, and the other half were randomized to rituximab plus placebo.

Patients in the idelalisib arm had a much higher overall response rate than patients in the placebo arm—81% and 13%, respectively (P<0.001). But all responses were partial responses.

At 24 weeks, the rate of progression-free survival was 93% in the idelalisib arm and 46% in the placebo arm (P<0.001). The median progression-free survival was 5.5 months in the placebo arm and not reached in the idelalisib arm (P<0.001).

At 12 months, the overall survival rate was 92% in the idelalisib arm and 80% in the placebo arm (P=0.02).

Most adverse events, in either treatment group, were grade 2 or lower. The most common events in the idelalisib arm were pyrexia, fatigue, nausea, chills, and diarrhea. In the placebo arm, the most common events were infusion-related reactions, fatigue, cough, nausea, and dyspnea.

There were more serious adverse events in the idelalisib arm than in the placebo arm—40% and 35%, respectively. The most frequent serious events were pneumonia, pyrexia, and febrile neutropenia (in both treatment arms).

Idelalisib in FL and SLL: Results of a phase 2 study

Idelalisib’s accelerated approval in FL and SLL is supported by data from a single-arm, phase 2 trial (Study 101-09).

The drug was given as a single agent to patients who were refractory to rituximab and alkylating-agent-containing chemotherapy. Seventy-two patients had FL, and 26 had SLL.

The overall response rate was 54% in FL and 58% in SLL. Eight percent of FL responses were complete, and all responses in SLL patients were partial.

The median duration of response was 11.9 months in SLL patients (range, 0-14.7 months) but was not reached in FL patients (range, 0-14.8 months).

Improvements in patient survival or disease-related symptoms have not been established.

In all patients, the most common grade 3 or higher adverse events were neutropenia (27%), elevations in aminotransferase levels (13%), diarrhea (13%), and pneumonia (7%).

About idelalisib: Dosing, boxed warning and REMS

Idelalisib is an oral inhibitor of PI3K delta, a protein that plays a role in the activation, proliferation, and viability of B cells. PI3K delta signaling is active in many B-cell leukemias and lymphomas, and, by inhibiting the protein, idelalisib blocks several cellular signaling pathways that drive B-cell viability.

The drug is available as 150 mg and 100 mg tablets, administered orally twice-daily, but 150 mg is the recommended starting dose.

Idelalisib has a boxed warning on its label communicating the risks of fatal and serious toxicities, which include hepatic toxicity, severe diarrhea, colitis, pneumonitis, and intestinal perforation.

The drug is being approved with a risk evaluation and mitigation strategy (REMS) comprised of a communication plan to ensure healthcare providers are fully informed about these risks. For more information on this program, visit www.ZydeligREMS.com.

The US Food and Drug Administration (FDA) has approved the PI3K delta inhibitor idelalisib (Zydelig) for the treatment of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma (FL).

The drug was granted traditional approval for use in combination with rituximab to treat patients with relapsed CLL who cannot receive rituximab alone.

Idelalisib has also received accelerated approval to treat patients with relapsed FL or SLL who have received at least 2 prior systemic therapies.

The FDA’s accelerated approval program allows for approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.

This program provides earlier patient access to a drug while the developer—in this case, Gilead Sciences—conducts trials confirming the drug’s benefit.

Idelalisib in CLL: Results of a phase 3 study

The approval of idelalisib in CLL is based on results of a phase 3 trial (Study 116), which was stopped early because idelalisib had a significant impact on progression-free survival.

The study included 220 CLL patients who could not receive chemotherapy. Half were randomized to receive idelalisib plus rituximab, and the other half were randomized to rituximab plus placebo.

Patients in the idelalisib arm had a much higher overall response rate than patients in the placebo arm—81% and 13%, respectively (P<0.001). But all responses were partial responses.

At 24 weeks, the rate of progression-free survival was 93% in the idelalisib arm and 46% in the placebo arm (P<0.001). The median progression-free survival was 5.5 months in the placebo arm and not reached in the idelalisib arm (P<0.001).

At 12 months, the overall survival rate was 92% in the idelalisib arm and 80% in the placebo arm (P=0.02).

Most adverse events, in either treatment group, were grade 2 or lower. The most common events in the idelalisib arm were pyrexia, fatigue, nausea, chills, and diarrhea. In the placebo arm, the most common events were infusion-related reactions, fatigue, cough, nausea, and dyspnea.

There were more serious adverse events in the idelalisib arm than in the placebo arm—40% and 35%, respectively. The most frequent serious events were pneumonia, pyrexia, and febrile neutropenia (in both treatment arms).

Idelalisib in FL and SLL: Results of a phase 2 study

Idelalisib’s accelerated approval in FL and SLL is supported by data from a single-arm, phase 2 trial (Study 101-09).

The drug was given as a single agent to patients who were refractory to rituximab and alkylating-agent-containing chemotherapy. Seventy-two patients had FL, and 26 had SLL.

The overall response rate was 54% in FL and 58% in SLL. Eight percent of FL responses were complete, and all responses in SLL patients were partial.

The median duration of response was 11.9 months in SLL patients (range, 0-14.7 months) but was not reached in FL patients (range, 0-14.8 months).

Improvements in patient survival or disease-related symptoms have not been established.

In all patients, the most common grade 3 or higher adverse events were neutropenia (27%), elevations in aminotransferase levels (13%), diarrhea (13%), and pneumonia (7%).

About idelalisib: Dosing, boxed warning and REMS

Idelalisib is an oral inhibitor of PI3K delta, a protein that plays a role in the activation, proliferation, and viability of B cells. PI3K delta signaling is active in many B-cell leukemias and lymphomas, and, by inhibiting the protein, idelalisib blocks several cellular signaling pathways that drive B-cell viability.

The drug is available as 150 mg and 100 mg tablets, administered orally twice-daily, but 150 mg is the recommended starting dose.

Idelalisib has a boxed warning on its label communicating the risks of fatal and serious toxicities, which include hepatic toxicity, severe diarrhea, colitis, pneumonitis, and intestinal perforation.

The drug is being approved with a risk evaluation and mitigation strategy (REMS) comprised of a communication plan to ensure healthcare providers are fully informed about these risks. For more information on this program, visit www.ZydeligREMS.com.

The US Food and Drug Administration (FDA) has approved the PI3K delta inhibitor idelalisib (Zydelig) for the treatment of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma (FL).

The drug was granted traditional approval for use in combination with rituximab to treat patients with relapsed CLL who cannot receive rituximab alone.

Idelalisib has also received accelerated approval to treat patients with relapsed FL or SLL who have received at least 2 prior systemic therapies.

The FDA’s accelerated approval program allows for approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.

This program provides earlier patient access to a drug while the developer—in this case, Gilead Sciences—conducts trials confirming the drug’s benefit.

Idelalisib in CLL: Results of a phase 3 study

The approval of idelalisib in CLL is based on results of a phase 3 trial (Study 116), which was stopped early because idelalisib had a significant impact on progression-free survival.

The study included 220 CLL patients who could not receive chemotherapy. Half were randomized to receive idelalisib plus rituximab, and the other half were randomized to rituximab plus placebo.

Patients in the idelalisib arm had a much higher overall response rate than patients in the placebo arm—81% and 13%, respectively (P<0.001). But all responses were partial responses.

At 24 weeks, the rate of progression-free survival was 93% in the idelalisib arm and 46% in the placebo arm (P<0.001). The median progression-free survival was 5.5 months in the placebo arm and not reached in the idelalisib arm (P<0.001).

At 12 months, the overall survival rate was 92% in the idelalisib arm and 80% in the placebo arm (P=0.02).

Most adverse events, in either treatment group, were grade 2 or lower. The most common events in the idelalisib arm were pyrexia, fatigue, nausea, chills, and diarrhea. In the placebo arm, the most common events were infusion-related reactions, fatigue, cough, nausea, and dyspnea.

There were more serious adverse events in the idelalisib arm than in the placebo arm—40% and 35%, respectively. The most frequent serious events were pneumonia, pyrexia, and febrile neutropenia (in both treatment arms).

Idelalisib in FL and SLL: Results of a phase 2 study

Idelalisib’s accelerated approval in FL and SLL is supported by data from a single-arm, phase 2 trial (Study 101-09).

The drug was given as a single agent to patients who were refractory to rituximab and alkylating-agent-containing chemotherapy. Seventy-two patients had FL, and 26 had SLL.

The overall response rate was 54% in FL and 58% in SLL. Eight percent of FL responses were complete, and all responses in SLL patients were partial.

The median duration of response was 11.9 months in SLL patients (range, 0-14.7 months) but was not reached in FL patients (range, 0-14.8 months).

Improvements in patient survival or disease-related symptoms have not been established.

In all patients, the most common grade 3 or higher adverse events were neutropenia (27%), elevations in aminotransferase levels (13%), diarrhea (13%), and pneumonia (7%).

About idelalisib: Dosing, boxed warning and REMS

Idelalisib is an oral inhibitor of PI3K delta, a protein that plays a role in the activation, proliferation, and viability of B cells. PI3K delta signaling is active in many B-cell leukemias and lymphomas, and, by inhibiting the protein, idelalisib blocks several cellular signaling pathways that drive B-cell viability.

The drug is available as 150 mg and 100 mg tablets, administered orally twice-daily, but 150 mg is the recommended starting dose.

Idelalisib has a boxed warning on its label communicating the risks of fatal and serious toxicities, which include hepatic toxicity, severe diarrhea, colitis, pneumonitis, and intestinal perforation.

The drug is being approved with a risk evaluation and mitigation strategy (REMS) comprised of a communication plan to ensure healthcare providers are fully informed about these risks. For more information on this program, visit www.ZydeligREMS.com.