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Drug gets orphan designation for MM & CLL/SLL
The European Medicines Agency (EMA) has granted orphan drug designation for selinexor (KPT-330) to treat multiple myeloma (MM) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), including Richter’s transformation.
Selinexor previously received orphan designation from both the EMA and the US Food and Drug Administration to treat patients with acute myeloid leukemia and those with diffuse large B-cell lymphoma.
Orphan designation is granted to promote the development of drugs that target rare, life-threatening or debilitating conditions and are expected to provide a significant therapeutic advantage over existing treatments.
Orphan designation qualifies a company—in this case, Karyopharm Therapeutics Inc.—for benefits that include targeted scientific advice from the EMA regarding drug development and 10 years of market exclusivity following the drug’s approval.
About selinexor
Selinexor (KPT-330) is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound. Selinexor functions by inhibiting the nuclear export protein XPO1 (also called CRM1).
This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is thought to prompt apoptosis in cancer cells while largely sparing normal cells.
Selinexor has shown promise in an ongoing phase 1 study of patients with a range of hematologic malignancies. Results of this trial were presented at the 2014 ASCO Annual Meeting.
At that point, the study included 51 patients who had received selinexor across 8 dose levels, ranging from 3 mg/m2 to 60 mg/m2.
Among the 43 patients evaluable for response, the overall response rate was 28%, and the complete response rate was 5%.
Most adverse events were gastrointestinal in nature, and most of them were grade 1 or 2. The most common adverse events were nausea, anorexia, and fatigue.
There were 3 dose-limiting toxicities, including 1 MM patient with grade 4 thrombocytopenia, 1 follicular lymphoma patient with grade 4 thrombocytopenia, and 1 CLL patient with grade 2 fatigue. 
The European Medicines Agency (EMA) has granted orphan drug designation for selinexor (KPT-330) to treat multiple myeloma (MM) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), including Richter’s transformation.
Selinexor previously received orphan designation from both the EMA and the US Food and Drug Administration to treat patients with acute myeloid leukemia and those with diffuse large B-cell lymphoma.
Orphan designation is granted to promote the development of drugs that target rare, life-threatening or debilitating conditions and are expected to provide a significant therapeutic advantage over existing treatments.
Orphan designation qualifies a company—in this case, Karyopharm Therapeutics Inc.—for benefits that include targeted scientific advice from the EMA regarding drug development and 10 years of market exclusivity following the drug’s approval.
About selinexor
Selinexor (KPT-330) is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound. Selinexor functions by inhibiting the nuclear export protein XPO1 (also called CRM1).
This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is thought to prompt apoptosis in cancer cells while largely sparing normal cells.
Selinexor has shown promise in an ongoing phase 1 study of patients with a range of hematologic malignancies. Results of this trial were presented at the 2014 ASCO Annual Meeting.
At that point, the study included 51 patients who had received selinexor across 8 dose levels, ranging from 3 mg/m2 to 60 mg/m2.
Among the 43 patients evaluable for response, the overall response rate was 28%, and the complete response rate was 5%.
Most adverse events were gastrointestinal in nature, and most of them were grade 1 or 2. The most common adverse events were nausea, anorexia, and fatigue.
There were 3 dose-limiting toxicities, including 1 MM patient with grade 4 thrombocytopenia, 1 follicular lymphoma patient with grade 4 thrombocytopenia, and 1 CLL patient with grade 2 fatigue.
The European Medicines Agency (EMA) has granted orphan drug designation for selinexor (KPT-330) to treat multiple myeloma (MM) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), including Richter’s transformation.
Selinexor previously received orphan designation from both the EMA and the US Food and Drug Administration to treat patients with acute myeloid leukemia and those with diffuse large B-cell lymphoma.
Orphan designation is granted to promote the development of drugs that target rare, life-threatening or debilitating conditions and are expected to provide a significant therapeutic advantage over existing treatments.
Orphan designation qualifies a company—in this case, Karyopharm Therapeutics Inc.—for benefits that include targeted scientific advice from the EMA regarding drug development and 10 years of market exclusivity following the drug’s approval.
About selinexor
Selinexor (KPT-330) is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound. Selinexor functions by inhibiting the nuclear export protein XPO1 (also called CRM1).
This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is thought to prompt apoptosis in cancer cells while largely sparing normal cells.
Selinexor has shown promise in an ongoing phase 1 study of patients with a range of hematologic malignancies. Results of this trial were presented at the 2014 ASCO Annual Meeting.
At that point, the study included 51 patients who had received selinexor across 8 dose levels, ranging from 3 mg/m2 to 60 mg/m2.
Among the 43 patients evaluable for response, the overall response rate was 28%, and the complete response rate was 5%.
Most adverse events were gastrointestinal in nature, and most of them were grade 1 or 2. The most common adverse events were nausea, anorexia, and fatigue.
There were 3 dose-limiting toxicities, including 1 MM patient with grade 4 thrombocytopenia, 1 follicular lymphoma patient with grade 4 thrombocytopenia, and 1 CLL patient with grade 2 fatigue.
David Henry's JCSO podcast, November 2014
Among the items featured in Dr David Henry’s monthly podcast for The Journal of Community and Supportive Oncology, are reports on congestive heart failure during induction with anthracycline-based therapy in patients with acute promyelocytic leukemia and on the impact of aprepitant on emesis control, dose intensity, and recurrence-free survival in head and neck cancer patients on cisplatin chemotherapy. Two articles focus on patient quality of life: one examines peripheral neuropathy and its impact on QoL after chemotherapy and another looks at QoL and symptoms after stereotactic body radiotherapy in early-stage lung cancer. There’s also a Case Report about a patient with superior vena cava syndrome as an initial presentation of low-grade follicular lymphoma, a feature article on choice of anesthesia during cancer surgery and patient outcomes, and a comprehensive and informative round-up of ASCO’s 2013-2014 guideline releases, updates, and endorsements.
Among the items featured in Dr David Henry’s monthly podcast for The Journal of Community and Supportive Oncology, are reports on congestive heart failure during induction with anthracycline-based therapy in patients with acute promyelocytic leukemia and on the impact of aprepitant on emesis control, dose intensity, and recurrence-free survival in head and neck cancer patients on cisplatin chemotherapy. Two articles focus on patient quality of life: one examines peripheral neuropathy and its impact on QoL after chemotherapy and another looks at QoL and symptoms after stereotactic body radiotherapy in early-stage lung cancer. There’s also a Case Report about a patient with superior vena cava syndrome as an initial presentation of low-grade follicular lymphoma, a feature article on choice of anesthesia during cancer surgery and patient outcomes, and a comprehensive and informative round-up of ASCO’s 2013-2014 guideline releases, updates, and endorsements.
Among the items featured in Dr David Henry’s monthly podcast for The Journal of Community and Supportive Oncology, are reports on congestive heart failure during induction with anthracycline-based therapy in patients with acute promyelocytic leukemia and on the impact of aprepitant on emesis control, dose intensity, and recurrence-free survival in head and neck cancer patients on cisplatin chemotherapy. Two articles focus on patient quality of life: one examines peripheral neuropathy and its impact on QoL after chemotherapy and another looks at QoL and symptoms after stereotactic body radiotherapy in early-stage lung cancer. There’s also a Case Report about a patient with superior vena cava syndrome as an initial presentation of low-grade follicular lymphoma, a feature article on choice of anesthesia during cancer surgery and patient outcomes, and a comprehensive and informative round-up of ASCO’s 2013-2014 guideline releases, updates, and endorsements.
Superior vena cava syndrome as an initial presentation of low-grade follicular lymphoma
Superior vena cava (SVC) syndrome refers to a constellation of symptoms produced by the obstruction of blood flow through the SVC, resulting in symptoms of dyspnea, facial and upper-extremity edema, cough, chest pain, and dysphagia.1 Malignancies represent 60%-85% of the etiologies of SVC syndrome. Cumulatively, lymphoma and lung cancer represent 95% of malignancy-related SVC syndrome etiologies, with non-small-cell lung cancer (NSCLC) reported in about 50% of cases, small-cell lung cancer (SCLC) in about 25%, and non-Hodgkin lymphoma (NHL) in 10 % of all cases.1,2
Click on the PDF icon at the top of this introduction to read the full article.
Superior vena cava (SVC) syndrome refers to a constellation of symptoms produced by the obstruction of blood flow through the SVC, resulting in symptoms of dyspnea, facial and upper-extremity edema, cough, chest pain, and dysphagia.1 Malignancies represent 60%-85% of the etiologies of SVC syndrome. Cumulatively, lymphoma and lung cancer represent 95% of malignancy-related SVC syndrome etiologies, with non-small-cell lung cancer (NSCLC) reported in about 50% of cases, small-cell lung cancer (SCLC) in about 25%, and non-Hodgkin lymphoma (NHL) in 10 % of all cases.1,2
Click on the PDF icon at the top of this introduction to read the full article.
Superior vena cava (SVC) syndrome refers to a constellation of symptoms produced by the obstruction of blood flow through the SVC, resulting in symptoms of dyspnea, facial and upper-extremity edema, cough, chest pain, and dysphagia.1 Malignancies represent 60%-85% of the etiologies of SVC syndrome. Cumulatively, lymphoma and lung cancer represent 95% of malignancy-related SVC syndrome etiologies, with non-small-cell lung cancer (NSCLC) reported in about 50% of cases, small-cell lung cancer (SCLC) in about 25%, and non-Hodgkin lymphoma (NHL) in 10 % of all cases.1,2
Click on the PDF icon at the top of this introduction to read the full article.
A wonderful life
Aspartame, sweetened drinks don’t increase risk of NHL
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.”
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.”
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.”
Maintenance may be unnecessary in FL
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.
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.
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.
PET-CT better predicted follicular lymphoma survival
F-18 positron emission tomography combined with low-dose computed tomography was more effective than conventional CT or the Follicular Lymphoma International Prognostic Index for predicting treatment response in patients with advanced follicular lymphoma, authors of a pooled analysis reported online in the Lancet Haemotology.
“Although these results are reassuring for patients who have a negative PET [positron emission tomography] scan, those who have a positive PET scan after first-line therapy can no longer be regarded as having an indolent disease and should be closely monitored,” wrote Dr. Judith Trotman at the University of Sydney, Australia, and her associates.
Follicular lymphoma often recurs after treatment, but predicting early relapsers has been a challenge, the investigators noted. They performed a masked review of three prospective, multicenter studies of 246 patients with follicular lymphoma, finding that patients with negative postinduction PET-CT scans (scores of less than four on the five-point Deauville scale) had median progression-free survival (PFS) of more than 6 years, compared with a median PFS of only 16.9 months for PET-positive patients (P = .0001). The markedly shorter PFS occurred even though most patients received anthracycline (CHOP/FM), the researchers said (Lancet Haematol. 2014 Sept. 18 [doi:10.1016/ S2352-3026(14)70008-0]).
Four years after induction, 63.4% of PET-negative patients were progression free, compared with only 23.2% of PET-positive patients (P less than .0001), the investigators added. And 4-year overall survival in PET-negative patients also was significantly higher than in PET-negative patients (97.1% vs. 87.2%; P less than .0001), they reported.PET status also was “much stronger” than the Follicular Lymphoma International Prognostic Index, FLIPI2, or contrast-enhanced CT for predicting outcomes in conventional responders, Dr. Trotman and her associates said. Conventional CT response only weakly predicted progression-free survival (P = .017), while a FLIPI2 score of 3-5 predicted progression-free survival (P = .011) but not overall survival. For this reason, responders historically have faced “an uncertain remission” and need close clinical follow-up, they pointed out.
The study was funded by the Lymphoma Study Association, Direction de la Recherche Clinique de l’Assistance Publique–Hôpitaux de Paris, Fondazione Italiana Linfomi, and the Italian Ministry of Health. Dr. Trotman reported uncompensated advisory relationships with Roche and Janssen, and three of 18 coauthors reported financial relationships with Merck, Celgene, Roche, Takeda, Janssen, and Spectrum. The rest reported having no conflicts of interest.
That patient outcome can be predicted with molecular imaging is good news: The question is, what should be done with this information? In clinical practice, patients with a positive scan could be followed up more closely. No data yet show that intervention with treatment after a positive PET result in patients with follicular lymphoma will improve outcome.
The results from Dr. Trotman and her colleagues might lead to several clinical research opportunities. One such possibility would be to assess if an early reaction to the PET scan result improves patient outcome. 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 (including idelalisib, ibrutinib, or ABT-199) in a novel combination.
The most crucial need is to identify biomarkers that distinguish this group of patients from those whose PET scans become negative. Once that goal is achieved, that information could be used to develop new, targeted induction regimens that improve initial treatment of the disease and, as a result, increase the number of patients with negative PET scans.
Dr. Bruce Cheson is professor of medicine and director of hematology research at Georgetown University Hospital, Washington. He reported research funding from Pharmacyclics, Gilead, Celgene, Roche-Genentech, and AbbVie, and paid consulting relationships with Pharmacyclics, Seattle Genetics, Gilead, Celgene, Roche-Genentech, Spectrum, and Mundipharma. These remarks are taken from his accompanying editorial (Lancet Haematol. 2014 Sept. 18 [doi:10.1016/S2352-3026(14)70015-8]).
That patient outcome can be predicted with molecular imaging is good news: The question is, what should be done with this information? In clinical practice, patients with a positive scan could be followed up more closely. No data yet show that intervention with treatment after a positive PET result in patients with follicular lymphoma will improve outcome.
The results from Dr. Trotman and her colleagues might lead to several clinical research opportunities. One such possibility would be to assess if an early reaction to the PET scan result improves patient outcome. 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 (including idelalisib, ibrutinib, or ABT-199) in a novel combination.
The most crucial need is to identify biomarkers that distinguish this group of patients from those whose PET scans become negative. Once that goal is achieved, that information could be used to develop new, targeted induction regimens that improve initial treatment of the disease and, as a result, increase the number of patients with negative PET scans.
Dr. Bruce Cheson is professor of medicine and director of hematology research at Georgetown University Hospital, Washington. He reported research funding from Pharmacyclics, Gilead, Celgene, Roche-Genentech, and AbbVie, and paid consulting relationships with Pharmacyclics, Seattle Genetics, Gilead, Celgene, Roche-Genentech, Spectrum, and Mundipharma. These remarks are taken from his accompanying editorial (Lancet Haematol. 2014 Sept. 18 [doi:10.1016/S2352-3026(14)70015-8]).
That patient outcome can be predicted with molecular imaging is good news: The question is, what should be done with this information? In clinical practice, patients with a positive scan could be followed up more closely. No data yet show that intervention with treatment after a positive PET result in patients with follicular lymphoma will improve outcome.
The results from Dr. Trotman and her colleagues might lead to several clinical research opportunities. One such possibility would be to assess if an early reaction to the PET scan result improves patient outcome. 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 (including idelalisib, ibrutinib, or ABT-199) in a novel combination.
The most crucial need is to identify biomarkers that distinguish this group of patients from those whose PET scans become negative. Once that goal is achieved, that information could be used to develop new, targeted induction regimens that improve initial treatment of the disease and, as a result, increase the number of patients with negative PET scans.
Dr. Bruce Cheson is professor of medicine and director of hematology research at Georgetown University Hospital, Washington. He reported research funding from Pharmacyclics, Gilead, Celgene, Roche-Genentech, and AbbVie, and paid consulting relationships with Pharmacyclics, Seattle Genetics, Gilead, Celgene, Roche-Genentech, Spectrum, and Mundipharma. These remarks are taken from his accompanying editorial (Lancet Haematol. 2014 Sept. 18 [doi:10.1016/S2352-3026(14)70015-8]).
F-18 positron emission tomography combined with low-dose computed tomography was more effective than conventional CT or the Follicular Lymphoma International Prognostic Index for predicting treatment response in patients with advanced follicular lymphoma, authors of a pooled analysis reported online in the Lancet Haemotology.
“Although these results are reassuring for patients who have a negative PET [positron emission tomography] scan, those who have a positive PET scan after first-line therapy can no longer be regarded as having an indolent disease and should be closely monitored,” wrote Dr. Judith Trotman at the University of Sydney, Australia, and her associates.
Follicular lymphoma often recurs after treatment, but predicting early relapsers has been a challenge, the investigators noted. They performed a masked review of three prospective, multicenter studies of 246 patients with follicular lymphoma, finding that patients with negative postinduction PET-CT scans (scores of less than four on the five-point Deauville scale) had median progression-free survival (PFS) of more than 6 years, compared with a median PFS of only 16.9 months for PET-positive patients (P = .0001). The markedly shorter PFS occurred even though most patients received anthracycline (CHOP/FM), the researchers said (Lancet Haematol. 2014 Sept. 18 [doi:10.1016/ S2352-3026(14)70008-0]).
Four years after induction, 63.4% of PET-negative patients were progression free, compared with only 23.2% of PET-positive patients (P less than .0001), the investigators added. And 4-year overall survival in PET-negative patients also was significantly higher than in PET-negative patients (97.1% vs. 87.2%; P less than .0001), they reported.PET status also was “much stronger” than the Follicular Lymphoma International Prognostic Index, FLIPI2, or contrast-enhanced CT for predicting outcomes in conventional responders, Dr. Trotman and her associates said. Conventional CT response only weakly predicted progression-free survival (P = .017), while a FLIPI2 score of 3-5 predicted progression-free survival (P = .011) but not overall survival. For this reason, responders historically have faced “an uncertain remission” and need close clinical follow-up, they pointed out.
The study was funded by the Lymphoma Study Association, Direction de la Recherche Clinique de l’Assistance Publique–Hôpitaux de Paris, Fondazione Italiana Linfomi, and the Italian Ministry of Health. Dr. Trotman reported uncompensated advisory relationships with Roche and Janssen, and three of 18 coauthors reported financial relationships with Merck, Celgene, Roche, Takeda, Janssen, and Spectrum. The rest reported having no conflicts of interest.
F-18 positron emission tomography combined with low-dose computed tomography was more effective than conventional CT or the Follicular Lymphoma International Prognostic Index for predicting treatment response in patients with advanced follicular lymphoma, authors of a pooled analysis reported online in the Lancet Haemotology.
“Although these results are reassuring for patients who have a negative PET [positron emission tomography] scan, those who have a positive PET scan after first-line therapy can no longer be regarded as having an indolent disease and should be closely monitored,” wrote Dr. Judith Trotman at the University of Sydney, Australia, and her associates.
Follicular lymphoma often recurs after treatment, but predicting early relapsers has been a challenge, the investigators noted. They performed a masked review of three prospective, multicenter studies of 246 patients with follicular lymphoma, finding that patients with negative postinduction PET-CT scans (scores of less than four on the five-point Deauville scale) had median progression-free survival (PFS) of more than 6 years, compared with a median PFS of only 16.9 months for PET-positive patients (P = .0001). The markedly shorter PFS occurred even though most patients received anthracycline (CHOP/FM), the researchers said (Lancet Haematol. 2014 Sept. 18 [doi:10.1016/ S2352-3026(14)70008-0]).
Four years after induction, 63.4% of PET-negative patients were progression free, compared with only 23.2% of PET-positive patients (P less than .0001), the investigators added. And 4-year overall survival in PET-negative patients also was significantly higher than in PET-negative patients (97.1% vs. 87.2%; P less than .0001), they reported.PET status also was “much stronger” than the Follicular Lymphoma International Prognostic Index, FLIPI2, or contrast-enhanced CT for predicting outcomes in conventional responders, Dr. Trotman and her associates said. Conventional CT response only weakly predicted progression-free survival (P = .017), while a FLIPI2 score of 3-5 predicted progression-free survival (P = .011) but not overall survival. For this reason, responders historically have faced “an uncertain remission” and need close clinical follow-up, they pointed out.
The study was funded by the Lymphoma Study Association, Direction de la Recherche Clinique de l’Assistance Publique–Hôpitaux de Paris, Fondazione Italiana Linfomi, and the Italian Ministry of Health. Dr. Trotman reported uncompensated advisory relationships with Roche and Janssen, and three of 18 coauthors reported financial relationships with Merck, Celgene, Roche, Takeda, Janssen, and Spectrum. The rest reported having no conflicts of interest.
Key clinical point: In patients with follicular lymphoma, PET-CT was better than conventional CT for assessing response and survival after first-line chemoimmunotherapy.
Major finding: Patients with positive postinduction PET scans were significantly less likely to be progression free at 4 years, compared with PET-negative patients (23.2% vs. 63.4%, P less than .0001), and had significantly lower 4-year overall survival (87.2% vs. 97.1%; P less than .0001).
Data source: Masked review of three multicenter prospective studies of 246 patients with follicular lymphoma who underwent postinduction PET-CT according to the five-point Deauville scale.
Disclosures: The study was funded by the Lymphoma Study Association, Direction de la Recherche Clinique de l’Assistance Publique–Hôpitaux de Paris, Fondazione Italiana Linfomi, and the Italian Ministry of Health. Dr. Trotman reported uncompensated advisory relationships with Roche and Janssen, and three of 18 coauthors reported financial relationships with Merck, Celgene, Roche, Takeda, Janssen, and Spectrum. The rest reported having no conflicts of interest.
Idelalisib approved to treat CLL, FL in EU
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.
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.
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.
Study supports new gold standard for FL
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 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 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.”
CHMP recommends ibrutinib for CLL, 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.
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.
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.