Follicular Lymphoma

 

 

Woman sunbathing

 

Vitamin D deficiency may negatively impact outcomes in patients with follicular lymphoma (FL), according to research published in the Journal of Clinical Oncology.

The study showed that FL patients with vitamin D deficiency had inferior progression-free survival (PFS) and overall survival (OS) compared to patients with higher vitamin D levels.

According to researchers, this suggests serum vitamin D might be the first potentially modifiable factor to be associated with survival in FL.

However, additional research is needed to determine the effects of vitamin D supplementation in these patients.

Jonathan W. Friedberg, MD, of the Wilmot Cancer Institute at the University of Rochester in New York, and his colleagues conducted this research, analyzing data from 2 cohorts of FL patients.

One cohort consisted of patients derived from 3 SWOG trials (S9800, S9911, and S0016), and the other consisted of patients from a Lymphoma Study Association (LYSA) trial known as PRIMA.

SWOG patients had received CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab), and LYSA patients had received rituximab plus chemotherapy (and were randomized to rituximab maintenance or observation).

SWOG cohort

After a median follow-up of 5.4 years, patients with vitamin D deficiency (defined as <20 ng/mL) had significantly inferior PFS (hazard ratio [HR]=2.00; P=0.011) and OS (HR=3.57; P=0.003) compared to patients with higher vitamin D levels.

Results were similar when the researchers adjusted for other variables, such as prognostic index (IPI), body mass index, and latitude (≥ vs <35°N). For PFS, the adjusted HR was 1.97 (P=0.023). And for OS, the adjusted HR was 4.16 (P=0.002).

Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but neither result was significant.

LYSA cohort

After a median follow-up of 6.6 years, patients with vitamin D deficiency (defined as <10 ng/mL) had significantly inferior PFS (HR=1.66; P=0.013) but not OS (HR=1.84; P=0.14) compared to patients with higher vitamin D levels.

Results were similar when the researchers adjusted for other variables, such as prognostic index (FLIPI), body mass index, latitude (Europe vs Australia), and hemoglobin. For PFS, the adjusted HR was 1.50 (P=0.095). For OS, the adjusted HR was 1.92 (P=0.192).

Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but only the association with OS reached statistical significance (HR=5.32; P=0.037).

Dr Friedberg said that, taken together, these results suggest vitamin D levels may be a modifiable factor associated with prognosis in patients with FL.

“Our data, replicated internationally, supports other published observations linking vitamin D deficiency with inferior cancer outcomes,” he said. “However, the mechanisms of this link are likely complex and require further study.”

 

 

Woman sunbathing

 

Vitamin D deficiency may negatively impact outcomes in patients with follicular lymphoma (FL), according to research published in the Journal of Clinical Oncology.

The study showed that FL patients with vitamin D deficiency had inferior progression-free survival (PFS) and overall survival (OS) compared to patients with higher vitamin D levels.

According to researchers, this suggests serum vitamin D might be the first potentially modifiable factor to be associated with survival in FL.

However, additional research is needed to determine the effects of vitamin D supplementation in these patients.

Jonathan W. Friedberg, MD, of the Wilmot Cancer Institute at the University of Rochester in New York, and his colleagues conducted this research, analyzing data from 2 cohorts of FL patients.

One cohort consisted of patients derived from 3 SWOG trials (S9800, S9911, and S0016), and the other consisted of patients from a Lymphoma Study Association (LYSA) trial known as PRIMA.

SWOG patients had received CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab), and LYSA patients had received rituximab plus chemotherapy (and were randomized to rituximab maintenance or observation).

SWOG cohort

After a median follow-up of 5.4 years, patients with vitamin D deficiency (defined as <20 ng/mL) had significantly inferior PFS (hazard ratio [HR]=2.00; P=0.011) and OS (HR=3.57; P=0.003) compared to patients with higher vitamin D levels.

Results were similar when the researchers adjusted for other variables, such as prognostic index (IPI), body mass index, and latitude (≥ vs <35°N). For PFS, the adjusted HR was 1.97 (P=0.023). And for OS, the adjusted HR was 4.16 (P=0.002).

Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but neither result was significant.

LYSA cohort

After a median follow-up of 6.6 years, patients with vitamin D deficiency (defined as <10 ng/mL) had significantly inferior PFS (HR=1.66; P=0.013) but not OS (HR=1.84; P=0.14) compared to patients with higher vitamin D levels.

Results were similar when the researchers adjusted for other variables, such as prognostic index (FLIPI), body mass index, latitude (Europe vs Australia), and hemoglobin. For PFS, the adjusted HR was 1.50 (P=0.095). For OS, the adjusted HR was 1.92 (P=0.192).

Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but only the association with OS reached statistical significance (HR=5.32; P=0.037).

Dr Friedberg said that, taken together, these results suggest vitamin D levels may be a modifiable factor associated with prognosis in patients with FL.

“Our data, replicated internationally, supports other published observations linking vitamin D deficiency with inferior cancer outcomes,” he said. “However, the mechanisms of this link are likely complex and require further study.”

 

 

Woman sunbathing

 

Vitamin D deficiency may negatively impact outcomes in patients with follicular lymphoma (FL), according to research published in the Journal of Clinical Oncology.

The study showed that FL patients with vitamin D deficiency had inferior progression-free survival (PFS) and overall survival (OS) compared to patients with higher vitamin D levels.

According to researchers, this suggests serum vitamin D might be the first potentially modifiable factor to be associated with survival in FL.

However, additional research is needed to determine the effects of vitamin D supplementation in these patients.

Jonathan W. Friedberg, MD, of the Wilmot Cancer Institute at the University of Rochester in New York, and his colleagues conducted this research, analyzing data from 2 cohorts of FL patients.

One cohort consisted of patients derived from 3 SWOG trials (S9800, S9911, and S0016), and the other consisted of patients from a Lymphoma Study Association (LYSA) trial known as PRIMA.

SWOG patients had received CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab), and LYSA patients had received rituximab plus chemotherapy (and were randomized to rituximab maintenance or observation).

SWOG cohort

After a median follow-up of 5.4 years, patients with vitamin D deficiency (defined as <20 ng/mL) had significantly inferior PFS (hazard ratio [HR]=2.00; P=0.011) and OS (HR=3.57; P=0.003) compared to patients with higher vitamin D levels.

Results were similar when the researchers adjusted for other variables, such as prognostic index (IPI), body mass index, and latitude (≥ vs <35°N). For PFS, the adjusted HR was 1.97 (P=0.023). And for OS, the adjusted HR was 4.16 (P=0.002).

Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but neither result was significant.

LYSA cohort

After a median follow-up of 6.6 years, patients with vitamin D deficiency (defined as <10 ng/mL) had significantly inferior PFS (HR=1.66; P=0.013) but not OS (HR=1.84; P=0.14) compared to patients with higher vitamin D levels.

Results were similar when the researchers adjusted for other variables, such as prognostic index (FLIPI), body mass index, latitude (Europe vs Australia), and hemoglobin. For PFS, the adjusted HR was 1.50 (P=0.095). For OS, the adjusted HR was 1.92 (P=0.192).

Multivariable analysis of vitamin D by tertile confirmed that the lowest tertile of vitamin D was associated with a greater increase in the risk of either progression or death, but only the association with OS reached statistical significance (HR=5.32; P=0.037).

Dr Friedberg said that, taken together, these results suggest vitamin D levels may be a modifiable factor associated with prognosis in patients with FL.

“Our data, replicated internationally, supports other published observations linking vitamin D deficiency with inferior cancer outcomes,” he said. “However, the mechanisms of this link are likely complex and require further study.”

 

 

Farmer spraying pesticide

Photo by John Messina

 

The International Agency for Research on Cancer (IARC), the specialized cancer agency of the World Health Organization, has found evidence suggesting that 5 organophosphate pesticides may be carcinogenic.

The IARC classified the herbicide glyphosate and the insecticides malathion and diazinon as “probably carcinogenic” to humans and the insecticides tetrachlorvinphos and parathion as “possibly carcinogenic” to humans.

A summary of these findings has been published in The Lancet Oncology.

Glyphosate

For the herbicide glyphosate, the IARC found limited evidence of carcinogenicity in humans. Case-control studies of occupational exposure to glyphosate in the US, Canada, and Sweden showed increased risks for non-Hodgkin lymphoma (NHL).

However, the Agricultural Health Study (AHS) showed no significantly increased risk of NHL in subjects exposed to glyphosate.

A study of community residents showed increases in blood markers of chromosomal damage after glyphosate formulations were sprayed nearby. And glyphosate was shown to cause DNA and chromosomal damage in human cells, although bacterial mutagenesis tests were negative.

In studies of male mice, glyphosate increased the incidence of renal tubule carcinoma and hemangiosarcoma. Glyphosate also increased the incidence of pancreatic islet-cell adenoma in male rats, and a glyphosate formulation promoted skin tumors in mice.

The IARC said glyphosate has the highest global production volume of all herbicides. It is used in agriculture, forestry, urban, and home applications.

Glyphosate has been detected in the air during spraying, in water, and in food. The general population is exposed to the chemical primarily by living near sprayed areas, home use, and diet. But the IARC said the level of exposure observed is generally low.

Malathion

The IARC classified malathion as “probably carcinogenic” for humans based on limited evidence linking the insecticide to NHL and prostate cancer. Occupational use of malathion was associated with an increased risk of prostate cancer in a Canadian case-control study and in the AHS.

Studies of occupational exposures in the US, Canada, and Sweden revealed positive associations between malathion and NHL. However, results of the AHS did not show an association between the insecticide and NHL.

Studies showed that malathion induced DNA and chromosomal damage in humans and animals, although bacterial mutagenesis tests were negative. Results also suggested malathion disrupts hormone pathways.

Experiments in mice showed malathion increased the incidence of hepatocellular adenoma or carcinoma (combined). In rats, the insecticide increased the incidence of thyroid carcinoma in males, hepatocellular adenoma or carcinoma (combined) in females, and mammary gland adenocarcinoma after subcutaneous injection in females.

The IARC said malathion is used in “substantial volumes throughout the world” to control insects in agricultural and residential areas.

Workers may be exposed to malathion during the use and production of the product. The general population may be exposed if they live near sprayed areas, use the product at home, or consume food exposed to the chemical.

Diazinon

The IARC classified diazinon as “probably carcinogenic” for humans based on limited evidence linking the insecticide to NHL, leukemia, and lung cancer.

Two multicenter, case-control studies of agricultural exposures suggested a positive association between diazinon and NHL. The AHS showed positive associations with specific subtypes of NHL but no overall increased risk of NHL. The AHS also suggested an increased risk of leukemia and lung cancer in subjects exposed to diazinon.

Evidence suggested that diazinon induced DNA or chromosomal damage in human and mammalian cells in vitro. In vivo, diazinon increased the incidence of hepatocellular carcinoma in mice and leukemia or lymphoma (combined) in rats, but only in males receiving the low dose in each study.

Diazinon has been used to control insects in agricultural and residential areas. The IARC said production volumes have been relatively low and decreased further after 2006 due to restrictions in the US and the European Union (EU). There was limited information on the use of this pesticide in other countries.

Tetrachlorvinphos

The insecticide tetrachlorvinphos was classified as “possibly carcinogenic” to humans based on convincing evidence that the agent causes cancer in lab animals. The IARC said the evidence in humans was inadequate.

However, tetrachlorvinphos was shown to induce hepatocellular tumors (benign or malignant) in mice, renal tubule tumors (benign or malignant) in male mice, and spleen hemangioma in male rats.

Tetrachlorvinphos is banned in the EU. In the US, the insecticide is still used on livestock and pets (in flea collars). The IARC said there was no information available on tetrachlorvinphos use in other countries.

Parathion

The insecticide parathion was classified as “possibly carcinogenic” to humans based on convincing evidence that the agent causes cancer in lab animals.

Researchers have observed associations between the insecticide and cancers in several tissues in occupational studies. But the IARC said the evidence that parathion is carcinogenic in humans remains sparse.

Experiments in mice showed that parathion increased the incidence of bronchioloalveolar adenoma and/or carcinoma in males and lymphoma in females. In rats, parathion induced adrenal cortical adenoma or carcinoma (combined), malignant pancreatic tumors, and thyroid follicular cell adenoma in males, and mammary gland adenocarcinoma (after subcutaneous injection in females).

Parathion use has been severely restricted since the 1980s, and all authorized uses of this chemical were cancelled in the EU and the US by 2003.

 

 

Farmer spraying pesticide

Photo by John Messina

 

The International Agency for Research on Cancer (IARC), the specialized cancer agency of the World Health Organization, has found evidence suggesting that 5 organophosphate pesticides may be carcinogenic.

The IARC classified the herbicide glyphosate and the insecticides malathion and diazinon as “probably carcinogenic” to humans and the insecticides tetrachlorvinphos and parathion as “possibly carcinogenic” to humans.

A summary of these findings has been published in The Lancet Oncology.

Glyphosate

For the herbicide glyphosate, the IARC found limited evidence of carcinogenicity in humans. Case-control studies of occupational exposure to glyphosate in the US, Canada, and Sweden showed increased risks for non-Hodgkin lymphoma (NHL).

However, the Agricultural Health Study (AHS) showed no significantly increased risk of NHL in subjects exposed to glyphosate.

A study of community residents showed increases in blood markers of chromosomal damage after glyphosate formulations were sprayed nearby. And glyphosate was shown to cause DNA and chromosomal damage in human cells, although bacterial mutagenesis tests were negative.

In studies of male mice, glyphosate increased the incidence of renal tubule carcinoma and hemangiosarcoma. Glyphosate also increased the incidence of pancreatic islet-cell adenoma in male rats, and a glyphosate formulation promoted skin tumors in mice.

The IARC said glyphosate has the highest global production volume of all herbicides. It is used in agriculture, forestry, urban, and home applications.

Glyphosate has been detected in the air during spraying, in water, and in food. The general population is exposed to the chemical primarily by living near sprayed areas, home use, and diet. But the IARC said the level of exposure observed is generally low.

Malathion

The IARC classified malathion as “probably carcinogenic” for humans based on limited evidence linking the insecticide to NHL and prostate cancer. Occupational use of malathion was associated with an increased risk of prostate cancer in a Canadian case-control study and in the AHS.

Studies of occupational exposures in the US, Canada, and Sweden revealed positive associations between malathion and NHL. However, results of the AHS did not show an association between the insecticide and NHL.

Studies showed that malathion induced DNA and chromosomal damage in humans and animals, although bacterial mutagenesis tests were negative. Results also suggested malathion disrupts hormone pathways.

Experiments in mice showed malathion increased the incidence of hepatocellular adenoma or carcinoma (combined). In rats, the insecticide increased the incidence of thyroid carcinoma in males, hepatocellular adenoma or carcinoma (combined) in females, and mammary gland adenocarcinoma after subcutaneous injection in females.

The IARC said malathion is used in “substantial volumes throughout the world” to control insects in agricultural and residential areas.

Workers may be exposed to malathion during the use and production of the product. The general population may be exposed if they live near sprayed areas, use the product at home, or consume food exposed to the chemical.

Diazinon

The IARC classified diazinon as “probably carcinogenic” for humans based on limited evidence linking the insecticide to NHL, leukemia, and lung cancer.

Two multicenter, case-control studies of agricultural exposures suggested a positive association between diazinon and NHL. The AHS showed positive associations with specific subtypes of NHL but no overall increased risk of NHL. The AHS also suggested an increased risk of leukemia and lung cancer in subjects exposed to diazinon.

Evidence suggested that diazinon induced DNA or chromosomal damage in human and mammalian cells in vitro. In vivo, diazinon increased the incidence of hepatocellular carcinoma in mice and leukemia or lymphoma (combined) in rats, but only in males receiving the low dose in each study.

Diazinon has been used to control insects in agricultural and residential areas. The IARC said production volumes have been relatively low and decreased further after 2006 due to restrictions in the US and the European Union (EU). There was limited information on the use of this pesticide in other countries.

Tetrachlorvinphos

The insecticide tetrachlorvinphos was classified as “possibly carcinogenic” to humans based on convincing evidence that the agent causes cancer in lab animals. The IARC said the evidence in humans was inadequate.

However, tetrachlorvinphos was shown to induce hepatocellular tumors (benign or malignant) in mice, renal tubule tumors (benign or malignant) in male mice, and spleen hemangioma in male rats.

Tetrachlorvinphos is banned in the EU. In the US, the insecticide is still used on livestock and pets (in flea collars). The IARC said there was no information available on tetrachlorvinphos use in other countries.

Parathion

The insecticide parathion was classified as “possibly carcinogenic” to humans based on convincing evidence that the agent causes cancer in lab animals.

Researchers have observed associations between the insecticide and cancers in several tissues in occupational studies. But the IARC said the evidence that parathion is carcinogenic in humans remains sparse.

Experiments in mice showed that parathion increased the incidence of bronchioloalveolar adenoma and/or carcinoma in males and lymphoma in females. In rats, parathion induced adrenal cortical adenoma or carcinoma (combined), malignant pancreatic tumors, and thyroid follicular cell adenoma in males, and mammary gland adenocarcinoma (after subcutaneous injection in females).

Parathion use has been severely restricted since the 1980s, and all authorized uses of this chemical were cancelled in the EU and the US by 2003.

 

 

Farmer spraying pesticide

Photo by John Messina

 

The International Agency for Research on Cancer (IARC), the specialized cancer agency of the World Health Organization, has found evidence suggesting that 5 organophosphate pesticides may be carcinogenic.

The IARC classified the herbicide glyphosate and the insecticides malathion and diazinon as “probably carcinogenic” to humans and the insecticides tetrachlorvinphos and parathion as “possibly carcinogenic” to humans.

A summary of these findings has been published in The Lancet Oncology.

Glyphosate

For the herbicide glyphosate, the IARC found limited evidence of carcinogenicity in humans. Case-control studies of occupational exposure to glyphosate in the US, Canada, and Sweden showed increased risks for non-Hodgkin lymphoma (NHL).

However, the Agricultural Health Study (AHS) showed no significantly increased risk of NHL in subjects exposed to glyphosate.

A study of community residents showed increases in blood markers of chromosomal damage after glyphosate formulations were sprayed nearby. And glyphosate was shown to cause DNA and chromosomal damage in human cells, although bacterial mutagenesis tests were negative.

In studies of male mice, glyphosate increased the incidence of renal tubule carcinoma and hemangiosarcoma. Glyphosate also increased the incidence of pancreatic islet-cell adenoma in male rats, and a glyphosate formulation promoted skin tumors in mice.

The IARC said glyphosate has the highest global production volume of all herbicides. It is used in agriculture, forestry, urban, and home applications.

Glyphosate has been detected in the air during spraying, in water, and in food. The general population is exposed to the chemical primarily by living near sprayed areas, home use, and diet. But the IARC said the level of exposure observed is generally low.

Malathion

The IARC classified malathion as “probably carcinogenic” for humans based on limited evidence linking the insecticide to NHL and prostate cancer. Occupational use of malathion was associated with an increased risk of prostate cancer in a Canadian case-control study and in the AHS.

Studies of occupational exposures in the US, Canada, and Sweden revealed positive associations between malathion and NHL. However, results of the AHS did not show an association between the insecticide and NHL.

Studies showed that malathion induced DNA and chromosomal damage in humans and animals, although bacterial mutagenesis tests were negative. Results also suggested malathion disrupts hormone pathways.

Experiments in mice showed malathion increased the incidence of hepatocellular adenoma or carcinoma (combined). In rats, the insecticide increased the incidence of thyroid carcinoma in males, hepatocellular adenoma or carcinoma (combined) in females, and mammary gland adenocarcinoma after subcutaneous injection in females.

The IARC said malathion is used in “substantial volumes throughout the world” to control insects in agricultural and residential areas.

Workers may be exposed to malathion during the use and production of the product. The general population may be exposed if they live near sprayed areas, use the product at home, or consume food exposed to the chemical.

Diazinon

The IARC classified diazinon as “probably carcinogenic” for humans based on limited evidence linking the insecticide to NHL, leukemia, and lung cancer.

Two multicenter, case-control studies of agricultural exposures suggested a positive association between diazinon and NHL. The AHS showed positive associations with specific subtypes of NHL but no overall increased risk of NHL. The AHS also suggested an increased risk of leukemia and lung cancer in subjects exposed to diazinon.

Evidence suggested that diazinon induced DNA or chromosomal damage in human and mammalian cells in vitro. In vivo, diazinon increased the incidence of hepatocellular carcinoma in mice and leukemia or lymphoma (combined) in rats, but only in males receiving the low dose in each study.

Diazinon has been used to control insects in agricultural and residential areas. The IARC said production volumes have been relatively low and decreased further after 2006 due to restrictions in the US and the European Union (EU). There was limited information on the use of this pesticide in other countries.

Tetrachlorvinphos

The insecticide tetrachlorvinphos was classified as “possibly carcinogenic” to humans based on convincing evidence that the agent causes cancer in lab animals. The IARC said the evidence in humans was inadequate.

However, tetrachlorvinphos was shown to induce hepatocellular tumors (benign or malignant) in mice, renal tubule tumors (benign or malignant) in male mice, and spleen hemangioma in male rats.

Tetrachlorvinphos is banned in the EU. In the US, the insecticide is still used on livestock and pets (in flea collars). The IARC said there was no information available on tetrachlorvinphos use in other countries.

Parathion

The insecticide parathion was classified as “possibly carcinogenic” to humans based on convincing evidence that the agent causes cancer in lab animals.

Researchers have observed associations between the insecticide and cancers in several tissues in occupational studies. But the IARC said the evidence that parathion is carcinogenic in humans remains sparse.

Experiments in mice showed that parathion increased the incidence of bronchioloalveolar adenoma and/or carcinoma in males and lymphoma in females. In rats, parathion induced adrenal cortical adenoma or carcinoma (combined), malignant pancreatic tumors, and thyroid follicular cell adenoma in males, and mammary gland adenocarcinoma (after subcutaneous injection in females).

Parathion use has been severely restricted since the 1980s, and all authorized uses of this chemical were cancelled in the EU and the US by 2003.

 

 

Monoclonal antibodies

Credit: Linda Bartlett

 

SAN FRANCISCO—Maintenance therapy with the anti-CD20 monoclonal antibody ofatumumab improves progression-free survival (PFS), but not overall survival (OS), in patients with relapsed chronic lymphocytic leukemia (CLL), according to an interim analysis of the PROLONG study.

The median PFS was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive maintenance (P<0.0001).

But there was no significant difference in the median OS, which was not reached in either treatment arm.

Marinus H.J. van Oers, MD, PhD, of the Academisch Medisch Centrum and HOVON in Amsterdam, The Netherlands, reported these results at the 2014 ASH Annual Meeting (abstract 21*). The study was sponsored by GlaxoSmithKline, makers of ofatumumab.

“[A]s of 2014, still we cannot say that we are able to cure CLL,” Dr van Oers noted. “And CLL is characterized by decreasing response duration with subsequent lines of treatment. In this respect, but also a number of other respects, there are similarities in biological behavior between CLL and follicular lymphoma.”

“There is definitely a role—although it’s somewhat debated—for maintenance treatment in follicular lymphoma. Therefore, it is rational to explore safe and effective maintenance treatment in CLL as well.”

To that end, Dr van Oers and his colleagues compared ofatumumab maintenance to observation in patients who were in remission after induction treatment for relapsed CLL. The team enrolled 474 patients who were in complete or partial remission after their 2nd- or 3rd-line treatment for CLL.

Patients were randomized to observation (n=236) or to receive ofatumumab (n=238) at 300 mg, followed 1 week later by 1000 mg every 8 weeks for up to 2 years. Patients on ofatumumab also received premedication with acetaminophen, antihistamine, and glucocorticoid.

The patients were stratified by the number and type of prior therapy, as well as remission status after induction treatment, and baseline characteristics were similar between the two treatment arms.

“The median age was about 65, and about 30% of patients were older than 70 years,” Dr van Oers noted. “[There was] a male preponderance, as you would expect, and the time since diagnosis was somewhere between 5 and 6 years.”

“Most patients were in [partial response], actually 80%, and most patients had received 2 prior regimens, about 70%. As for prior treatments, 80% of patients had received effective immuno-chemotherapy.”

“In both arms, there were only a few patients with unfavorable cytogenetics—11q and 17p deletion. [As for] β2 microglobulin, two-thirds [of patients in both arms] had low levels. And, in both arms, there were almost twice as many IGVH-mutated as unmutated patients.”

Patient outcomes

The median follow-up was 19.1 months. The study’s primary endpoint was PFS, which was defined as the time from randomization to the date of disease progression or death from any cause.

The median PFS was significantly longer in the ofatumumab arm than in the observation arm, at 29.4 months and 15.2 months, respectively (hazard ratio [HR]=0.50; P<0.0001).

Similarly, the time to the start of patients’ next therapy was significantly longer in the ofatumumab arm than in the in observation arm—a median of 38 months and 31.1 months, respectively (HR=0.66, P=0.108).

However, there was no significant difference in OS, which was not reached in either arm (HR=0.85, P=0.4877).

Adverse events (AEs) occurred in 86% of patients in the ofatumumab arm and 72% of patients in the observation arm (P<0.001). Sixty percent of AEs were considered related to ofatumumab. None of the AEs led to study withdrawal.

Grade 3 or higher AEs occurred in 46% of patients in the ofatumumab arm and 28% in the observation arm. They included neutropenia (24% and 10%, respectively; P<0.001), infections (13% and 8%, respectively), thrombocytopenia (2% and 3%, respectively), and infusion-related reactions (1% and 0%, respectively).

There were 5 deaths in the observation arm—1 due to progression and 4 due to causes other than progression, infection, or secondary malignancy. There were 2 deaths in the ofatumumab arm—1 due to infection/sepsis and 1 due to an “other” cause.

“So based on this planned interim analysis, we can conclude that ofatumumab maintenance in relapsed CLL results in a highly significant and clinically meaningful improvement of progression-free survival,” Dr van Oers said in closing.

“It significantly prolongs time to next treatment, it’s well-tolerated, and it’s associated with an adverse event profile which is quite characteristic of anti-CD20 monoclonal antibodies.”

*Information in the abstract differs from that presented at the meeting.

 

 

Monoclonal antibodies

Credit: Linda Bartlett

 

SAN FRANCISCO—Maintenance therapy with the anti-CD20 monoclonal antibody ofatumumab improves progression-free survival (PFS), but not overall survival (OS), in patients with relapsed chronic lymphocytic leukemia (CLL), according to an interim analysis of the PROLONG study.

The median PFS was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive maintenance (P<0.0001).

But there was no significant difference in the median OS, which was not reached in either treatment arm.

Marinus H.J. van Oers, MD, PhD, of the Academisch Medisch Centrum and HOVON in Amsterdam, The Netherlands, reported these results at the 2014 ASH Annual Meeting (abstract 21*). The study was sponsored by GlaxoSmithKline, makers of ofatumumab.

“[A]s of 2014, still we cannot say that we are able to cure CLL,” Dr van Oers noted. “And CLL is characterized by decreasing response duration with subsequent lines of treatment. In this respect, but also a number of other respects, there are similarities in biological behavior between CLL and follicular lymphoma.”

“There is definitely a role—although it’s somewhat debated—for maintenance treatment in follicular lymphoma. Therefore, it is rational to explore safe and effective maintenance treatment in CLL as well.”

To that end, Dr van Oers and his colleagues compared ofatumumab maintenance to observation in patients who were in remission after induction treatment for relapsed CLL. The team enrolled 474 patients who were in complete or partial remission after their 2nd- or 3rd-line treatment for CLL.

Patients were randomized to observation (n=236) or to receive ofatumumab (n=238) at 300 mg, followed 1 week later by 1000 mg every 8 weeks for up to 2 years. Patients on ofatumumab also received premedication with acetaminophen, antihistamine, and glucocorticoid.

The patients were stratified by the number and type of prior therapy, as well as remission status after induction treatment, and baseline characteristics were similar between the two treatment arms.

“The median age was about 65, and about 30% of patients were older than 70 years,” Dr van Oers noted. “[There was] a male preponderance, as you would expect, and the time since diagnosis was somewhere between 5 and 6 years.”

“Most patients were in [partial response], actually 80%, and most patients had received 2 prior regimens, about 70%. As for prior treatments, 80% of patients had received effective immuno-chemotherapy.”

“In both arms, there were only a few patients with unfavorable cytogenetics—11q and 17p deletion. [As for] β2 microglobulin, two-thirds [of patients in both arms] had low levels. And, in both arms, there were almost twice as many IGVH-mutated as unmutated patients.”

Patient outcomes

The median follow-up was 19.1 months. The study’s primary endpoint was PFS, which was defined as the time from randomization to the date of disease progression or death from any cause.

The median PFS was significantly longer in the ofatumumab arm than in the observation arm, at 29.4 months and 15.2 months, respectively (hazard ratio [HR]=0.50; P<0.0001).

Similarly, the time to the start of patients’ next therapy was significantly longer in the ofatumumab arm than in the in observation arm—a median of 38 months and 31.1 months, respectively (HR=0.66, P=0.108).

However, there was no significant difference in OS, which was not reached in either arm (HR=0.85, P=0.4877).

Adverse events (AEs) occurred in 86% of patients in the ofatumumab arm and 72% of patients in the observation arm (P<0.001). Sixty percent of AEs were considered related to ofatumumab. None of the AEs led to study withdrawal.

Grade 3 or higher AEs occurred in 46% of patients in the ofatumumab arm and 28% in the observation arm. They included neutropenia (24% and 10%, respectively; P<0.001), infections (13% and 8%, respectively), thrombocytopenia (2% and 3%, respectively), and infusion-related reactions (1% and 0%, respectively).

There were 5 deaths in the observation arm—1 due to progression and 4 due to causes other than progression, infection, or secondary malignancy. There were 2 deaths in the ofatumumab arm—1 due to infection/sepsis and 1 due to an “other” cause.

“So based on this planned interim analysis, we can conclude that ofatumumab maintenance in relapsed CLL results in a highly significant and clinically meaningful improvement of progression-free survival,” Dr van Oers said in closing.

“It significantly prolongs time to next treatment, it’s well-tolerated, and it’s associated with an adverse event profile which is quite characteristic of anti-CD20 monoclonal antibodies.”

*Information in the abstract differs from that presented at the meeting.

 

 

Monoclonal antibodies

Credit: Linda Bartlett

 

SAN FRANCISCO—Maintenance therapy with the anti-CD20 monoclonal antibody ofatumumab improves progression-free survival (PFS), but not overall survival (OS), in patients with relapsed chronic lymphocytic leukemia (CLL), according to an interim analysis of the PROLONG study.

The median PFS was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive maintenance (P<0.0001).

But there was no significant difference in the median OS, which was not reached in either treatment arm.

Marinus H.J. van Oers, MD, PhD, of the Academisch Medisch Centrum and HOVON in Amsterdam, The Netherlands, reported these results at the 2014 ASH Annual Meeting (abstract 21*). The study was sponsored by GlaxoSmithKline, makers of ofatumumab.

“[A]s of 2014, still we cannot say that we are able to cure CLL,” Dr van Oers noted. “And CLL is characterized by decreasing response duration with subsequent lines of treatment. In this respect, but also a number of other respects, there are similarities in biological behavior between CLL and follicular lymphoma.”

“There is definitely a role—although it’s somewhat debated—for maintenance treatment in follicular lymphoma. Therefore, it is rational to explore safe and effective maintenance treatment in CLL as well.”

To that end, Dr van Oers and his colleagues compared ofatumumab maintenance to observation in patients who were in remission after induction treatment for relapsed CLL. The team enrolled 474 patients who were in complete or partial remission after their 2nd- or 3rd-line treatment for CLL.

Patients were randomized to observation (n=236) or to receive ofatumumab (n=238) at 300 mg, followed 1 week later by 1000 mg every 8 weeks for up to 2 years. Patients on ofatumumab also received premedication with acetaminophen, antihistamine, and glucocorticoid.

The patients were stratified by the number and type of prior therapy, as well as remission status after induction treatment, and baseline characteristics were similar between the two treatment arms.

“The median age was about 65, and about 30% of patients were older than 70 years,” Dr van Oers noted. “[There was] a male preponderance, as you would expect, and the time since diagnosis was somewhere between 5 and 6 years.”

“Most patients were in [partial response], actually 80%, and most patients had received 2 prior regimens, about 70%. As for prior treatments, 80% of patients had received effective immuno-chemotherapy.”

“In both arms, there were only a few patients with unfavorable cytogenetics—11q and 17p deletion. [As for] β2 microglobulin, two-thirds [of patients in both arms] had low levels. And, in both arms, there were almost twice as many IGVH-mutated as unmutated patients.”

Patient outcomes

The median follow-up was 19.1 months. The study’s primary endpoint was PFS, which was defined as the time from randomization to the date of disease progression or death from any cause.

The median PFS was significantly longer in the ofatumumab arm than in the observation arm, at 29.4 months and 15.2 months, respectively (hazard ratio [HR]=0.50; P<0.0001).

Similarly, the time to the start of patients’ next therapy was significantly longer in the ofatumumab arm than in the in observation arm—a median of 38 months and 31.1 months, respectively (HR=0.66, P=0.108).

However, there was no significant difference in OS, which was not reached in either arm (HR=0.85, P=0.4877).

Adverse events (AEs) occurred in 86% of patients in the ofatumumab arm and 72% of patients in the observation arm (P<0.001). Sixty percent of AEs were considered related to ofatumumab. None of the AEs led to study withdrawal.

Grade 3 or higher AEs occurred in 46% of patients in the ofatumumab arm and 28% in the observation arm. They included neutropenia (24% and 10%, respectively; P<0.001), infections (13% and 8%, respectively), thrombocytopenia (2% and 3%, respectively), and infusion-related reactions (1% and 0%, respectively).

There were 5 deaths in the observation arm—1 due to progression and 4 due to causes other than progression, infection, or secondary malignancy. There were 2 deaths in the ofatumumab arm—1 due to infection/sepsis and 1 due to an “other” cause.

“So based on this planned interim analysis, we can conclude that ofatumumab maintenance in relapsed CLL results in a highly significant and clinically meaningful improvement of progression-free survival,” Dr van Oers said in closing.

“It significantly prolongs time to next treatment, it’s well-tolerated, and it’s associated with an adverse event profile which is quite characteristic of anti-CD20 monoclonal antibodies.”

*Information in the abstract differs from that presented at the meeting.

SAN FRANCISCO—Follicular lymphoma (FL) patients who receive high-dose therapy with autologous stem cell transplant (HDT/ASCT) after they’ve responded to chemotherapy can achieve long-term cancer-free survival, new research suggests.

The study showed that many patients transplanted in complete remission (CR) did not relapse and could be considered cured.

Patients transplanted in their first CR fared the best, as median progression-free survival (PFS) and overall survival (OS) times were not reached.

But even patients transplanted in their second/third CR or in their first partial remission (PR) survived a median of 15 years or more, although their PFS times were shorter, at about 14 years and 3 years, respectively.

Carlos Grande García, MD, of Hospital Universitario 12 de Octubre in Madrid, Spain, presented these results at the 2014 ASH Annual Meeting (abstract 675.)*

“In follicular lymphoma patients, intensification with high-dose therapy and autologous stem cell support offers an advantage in terms of progression-free survival in comparison with conventional chemo,” he said. “But, so far, no randomized studies have yet shown any overall survival advantage.”

“Follicular lymphoma has a long natural course, and most patients have received different salvage therapies. Probably, this is why the available phase 3 studies have had insufficient time to confirm the impact on OS.”

To investigate the impact of HDT/ASCT on OS, Dr Grande García and his colleagues conducted a retrospective study of 655 FL patients who received HDT/ASCT from 1989 to 2007. Patients with histological transformation, those undergoing a second transplant, and those with a follow-up of less than 7 years were excluded.

Patient characteristics

The median follow-up was 12 years from HDT/ASCT and 14.4 years from diagnosis. At diagnosis, the median patient age was 47, 49.6% of patients were male, and 90% had stage III/IV disease.

According to FLIPI, 33% of patients were good risk, 36% were intermediate risk, and 31% were poor risk. According to FLIPI-2, the percentages were 22%, 38%, and 40%, respectively. Thirty percent of patients had received rituximab prior to HDT/ASCT.

Thirty-one percent of patients (n=203) were in their first CR at the time of transplant, 43% of whom required more than one line of therapy to reach first CR.

Thirty-one percent of patients (n=202) were in second or third CR, 21.5% (n=149) were in first PR, 12.5% (n=81) were in sensitive relapse (defined as a response other than CR or first PR), and 5% (n=29) had overt disease (which included untreated relapsed disease, first refractory disease, and second refractory disease).

Patients received a variety of conditioning regimens, including total-body irradiation plus cyclophosphamide, BEAM (carmustine, etoposide, cytarabine, and melphalan), BEAC (carmustine, etoposide, cytarabine, and cyclophosphamide), and other regimens. They received stem cells from peripheral blood (81%), bone marrow (14%), or both sources (5%).

There were 4 graft failures and 17 early toxic deaths. Thirty-one percent of patients experienced grade 3/4 hematologic toxicities.

PFS and OS

In all patients, the median PFS was 9.25 years, and the median OS was 19.5 years.

When the researchers looked at outcomes according to patients’ status at transplant, they found the median OS and PFS were not reached among patients in first CR. At a median follow-up of 12.75 years, the OS rate was 72%, and the PFS rate was 68%.

“Beginning at 10 years from transplantation, only 6 patients have died,” Dr Grande García noted, “one from disease progression, 3 from second malignancy, [and] 2 from unrelated causes.”

For patients in second or third CR, the median OS was not reached, and the median PFS was 13.9 years. For those in first PR, the median OS was 15 years, and the median PFS was 2.6 years.

For patients with sensitive disease, the median OS was 5.1 years, and the median PFS was 2 years. For those with overt disease, the median OS was 4.4 years, and the median PFS was 0.5 years.

In multivariate analysis, the following characteristics were significant predictors of OS: being older than 47 years of age (hazard ratio [HR]=1.74, P=0.0001), female sex (HR=0.58, P=0.00004), status at HDT/ASCT (HR=2.06, P<10^-5), and receipt of rituximab prior to HDT/ASCT (HR=0.61, P=0.004).

Significant predictors of PFS included age (HR=1.34, P=0.01), sex (HR=0.64, P<10^-5), status at HDT/ASCT (HR=2.15, P<10^-5), and rituximab use (HR=0.67, P=0.003).

For patients transplanted in first CR, only sex was a significant predictor of PFS (HR=0.48, P=0.008) and OS (HR=0.43, P=0.007).

Secondary malignancies

Overall, 13% of patients developed secondary malignancies, of which 46% were solid neoplasias, 44% were myelodysplastic syndromes/acute myeloid leukemias, and 10% were other malignancies.

The incidence of secondary malignancies at 10 years was 3.5%, and the median time from HDT/ASCT to diagnosis was 16 years. There were no significant differences in the rate of secondary malignancy according to a patient’s status at HDT/ASCT or according to the use of rituximab.

“The incidence of second malignancies is not higher than that reported in other series without transplantation,” Dr Grande García noted.

“[HDT/ASCT] is highly effective, even for patients with poor initial features. A significant number of patients transplanted in CR never relapse and may be considered cured.”

*Information in the abstract differs from that presented at the meeting.

SAN FRANCISCO—Follicular lymphoma (FL) patients who receive high-dose therapy with autologous stem cell transplant (HDT/ASCT) after they’ve responded to chemotherapy can achieve long-term cancer-free survival, new research suggests.

The study showed that many patients transplanted in complete remission (CR) did not relapse and could be considered cured.

Patients transplanted in their first CR fared the best, as median progression-free survival (PFS) and overall survival (OS) times were not reached.

But even patients transplanted in their second/third CR or in their first partial remission (PR) survived a median of 15 years or more, although their PFS times were shorter, at about 14 years and 3 years, respectively.

Carlos Grande García, MD, of Hospital Universitario 12 de Octubre in Madrid, Spain, presented these results at the 2014 ASH Annual Meeting (abstract 675.)*

“In follicular lymphoma patients, intensification with high-dose therapy and autologous stem cell support offers an advantage in terms of progression-free survival in comparison with conventional chemo,” he said. “But, so far, no randomized studies have yet shown any overall survival advantage.”

“Follicular lymphoma has a long natural course, and most patients have received different salvage therapies. Probably, this is why the available phase 3 studies have had insufficient time to confirm the impact on OS.”

To investigate the impact of HDT/ASCT on OS, Dr Grande García and his colleagues conducted a retrospective study of 655 FL patients who received HDT/ASCT from 1989 to 2007. Patients with histological transformation, those undergoing a second transplant, and those with a follow-up of less than 7 years were excluded.

Patient characteristics

The median follow-up was 12 years from HDT/ASCT and 14.4 years from diagnosis. At diagnosis, the median patient age was 47, 49.6% of patients were male, and 90% had stage III/IV disease.

According to FLIPI, 33% of patients were good risk, 36% were intermediate risk, and 31% were poor risk. According to FLIPI-2, the percentages were 22%, 38%, and 40%, respectively. Thirty percent of patients had received rituximab prior to HDT/ASCT.

Thirty-one percent of patients (n=203) were in their first CR at the time of transplant, 43% of whom required more than one line of therapy to reach first CR.

Thirty-one percent of patients (n=202) were in second or third CR, 21.5% (n=149) were in first PR, 12.5% (n=81) were in sensitive relapse (defined as a response other than CR or first PR), and 5% (n=29) had overt disease (which included untreated relapsed disease, first refractory disease, and second refractory disease).

Patients received a variety of conditioning regimens, including total-body irradiation plus cyclophosphamide, BEAM (carmustine, etoposide, cytarabine, and melphalan), BEAC (carmustine, etoposide, cytarabine, and cyclophosphamide), and other regimens. They received stem cells from peripheral blood (81%), bone marrow (14%), or both sources (5%).

There were 4 graft failures and 17 early toxic deaths. Thirty-one percent of patients experienced grade 3/4 hematologic toxicities.

PFS and OS

In all patients, the median PFS was 9.25 years, and the median OS was 19.5 years.

When the researchers looked at outcomes according to patients’ status at transplant, they found the median OS and PFS were not reached among patients in first CR. At a median follow-up of 12.75 years, the OS rate was 72%, and the PFS rate was 68%.

“Beginning at 10 years from transplantation, only 6 patients have died,” Dr Grande García noted, “one from disease progression, 3 from second malignancy, [and] 2 from unrelated causes.”

For patients in second or third CR, the median OS was not reached, and the median PFS was 13.9 years. For those in first PR, the median OS was 15 years, and the median PFS was 2.6 years.

For patients with sensitive disease, the median OS was 5.1 years, and the median PFS was 2 years. For those with overt disease, the median OS was 4.4 years, and the median PFS was 0.5 years.

In multivariate analysis, the following characteristics were significant predictors of OS: being older than 47 years of age (hazard ratio [HR]=1.74, P=0.0001), female sex (HR=0.58, P=0.00004), status at HDT/ASCT (HR=2.06, P<10^-5), and receipt of rituximab prior to HDT/ASCT (HR=0.61, P=0.004).

Significant predictors of PFS included age (HR=1.34, P=0.01), sex (HR=0.64, P<10^-5), status at HDT/ASCT (HR=2.15, P<10^-5), and rituximab use (HR=0.67, P=0.003).

For patients transplanted in first CR, only sex was a significant predictor of PFS (HR=0.48, P=0.008) and OS (HR=0.43, P=0.007).

Secondary malignancies

Overall, 13% of patients developed secondary malignancies, of which 46% were solid neoplasias, 44% were myelodysplastic syndromes/acute myeloid leukemias, and 10% were other malignancies.

The incidence of secondary malignancies at 10 years was 3.5%, and the median time from HDT/ASCT to diagnosis was 16 years. There were no significant differences in the rate of secondary malignancy according to a patient’s status at HDT/ASCT or according to the use of rituximab.

“The incidence of second malignancies is not higher than that reported in other series without transplantation,” Dr Grande García noted.

“[HDT/ASCT] is highly effective, even for patients with poor initial features. A significant number of patients transplanted in CR never relapse and may be considered cured.”

*Information in the abstract differs from that presented at the meeting.

SAN FRANCISCO—Follicular lymphoma (FL) patients who receive high-dose therapy with autologous stem cell transplant (HDT/ASCT) after they’ve responded to chemotherapy can achieve long-term cancer-free survival, new research suggests.

The study showed that many patients transplanted in complete remission (CR) did not relapse and could be considered cured.

Patients transplanted in their first CR fared the best, as median progression-free survival (PFS) and overall survival (OS) times were not reached.

But even patients transplanted in their second/third CR or in their first partial remission (PR) survived a median of 15 years or more, although their PFS times were shorter, at about 14 years and 3 years, respectively.

Carlos Grande García, MD, of Hospital Universitario 12 de Octubre in Madrid, Spain, presented these results at the 2014 ASH Annual Meeting (abstract 675.)*

“In follicular lymphoma patients, intensification with high-dose therapy and autologous stem cell support offers an advantage in terms of progression-free survival in comparison with conventional chemo,” he said. “But, so far, no randomized studies have yet shown any overall survival advantage.”

“Follicular lymphoma has a long natural course, and most patients have received different salvage therapies. Probably, this is why the available phase 3 studies have had insufficient time to confirm the impact on OS.”

To investigate the impact of HDT/ASCT on OS, Dr Grande García and his colleagues conducted a retrospective study of 655 FL patients who received HDT/ASCT from 1989 to 2007. Patients with histological transformation, those undergoing a second transplant, and those with a follow-up of less than 7 years were excluded.

Patient characteristics

The median follow-up was 12 years from HDT/ASCT and 14.4 years from diagnosis. At diagnosis, the median patient age was 47, 49.6% of patients were male, and 90% had stage III/IV disease.

According to FLIPI, 33% of patients were good risk, 36% were intermediate risk, and 31% were poor risk. According to FLIPI-2, the percentages were 22%, 38%, and 40%, respectively. Thirty percent of patients had received rituximab prior to HDT/ASCT.

Thirty-one percent of patients (n=203) were in their first CR at the time of transplant, 43% of whom required more than one line of therapy to reach first CR.

Thirty-one percent of patients (n=202) were in second or third CR, 21.5% (n=149) were in first PR, 12.5% (n=81) were in sensitive relapse (defined as a response other than CR or first PR), and 5% (n=29) had overt disease (which included untreated relapsed disease, first refractory disease, and second refractory disease).

Patients received a variety of conditioning regimens, including total-body irradiation plus cyclophosphamide, BEAM (carmustine, etoposide, cytarabine, and melphalan), BEAC (carmustine, etoposide, cytarabine, and cyclophosphamide), and other regimens. They received stem cells from peripheral blood (81%), bone marrow (14%), or both sources (5%).

There were 4 graft failures and 17 early toxic deaths. Thirty-one percent of patients experienced grade 3/4 hematologic toxicities.

PFS and OS

In all patients, the median PFS was 9.25 years, and the median OS was 19.5 years.

When the researchers looked at outcomes according to patients’ status at transplant, they found the median OS and PFS were not reached among patients in first CR. At a median follow-up of 12.75 years, the OS rate was 72%, and the PFS rate was 68%.

“Beginning at 10 years from transplantation, only 6 patients have died,” Dr Grande García noted, “one from disease progression, 3 from second malignancy, [and] 2 from unrelated causes.”

For patients in second or third CR, the median OS was not reached, and the median PFS was 13.9 years. For those in first PR, the median OS was 15 years, and the median PFS was 2.6 years.

For patients with sensitive disease, the median OS was 5.1 years, and the median PFS was 2 years. For those with overt disease, the median OS was 4.4 years, and the median PFS was 0.5 years.

In multivariate analysis, the following characteristics were significant predictors of OS: being older than 47 years of age (hazard ratio [HR]=1.74, P=0.0001), female sex (HR=0.58, P=0.00004), status at HDT/ASCT (HR=2.06, P<10^-5), and receipt of rituximab prior to HDT/ASCT (HR=0.61, P=0.004).

Significant predictors of PFS included age (HR=1.34, P=0.01), sex (HR=0.64, P<10^-5), status at HDT/ASCT (HR=2.15, P<10^-5), and rituximab use (HR=0.67, P=0.003).

For patients transplanted in first CR, only sex was a significant predictor of PFS (HR=0.48, P=0.008) and OS (HR=0.43, P=0.007).

Secondary malignancies

Overall, 13% of patients developed secondary malignancies, of which 46% were solid neoplasias, 44% were myelodysplastic syndromes/acute myeloid leukemias, and 10% were other malignancies.

The incidence of secondary malignancies at 10 years was 3.5%, and the median time from HDT/ASCT to diagnosis was 16 years. There were no significant differences in the rate of secondary malignancy according to a patient’s status at HDT/ASCT or according to the use of rituximab.

“The incidence of second malignancies is not higher than that reported in other series without transplantation,” Dr Grande García noted.

“[HDT/ASCT] is highly effective, even for patients with poor initial features. A significant number of patients transplanted in CR never relapse and may be considered cured.”

*Information in the abstract differs from that presented at the meeting.

Autologous stem-cell transplantation can be highly effective in securing better long-term results for patients undergoing rituximab-based chemotherapy for transformed indolent lymphoma with high-grade histologies, according to a retrospective study published online in Annals of Oncology.

ASCT improved outcomes in patients with sequential TIL (S-TIL), but not in those with composite/discordant TIL (CD-TIL). The benefits of ASCT were greater in patients who were rituximab-naive at transformation, wrote Dr. Carsten Madsen of Denmark’s Aarhus University Hospital, and his coauthors (Ann. Oncol. 2014 Nov. 18 [doi: 10.1093/annonc/mdu537]).

Patients with “CD-TIL had a better outcome than [did those with] S-TIL regardless of treatment strategy at transformation. With regard to ASCT in particular, we found that it had a beneficial influence on outcome limited to S-TIL,” the investigators concluded.

In a multicenter cohort study, Dr. Madsen and his associates used the National Danish Pathology Registry to identify patients aged 18-68 years with histologically verified TIL diagnosed between 1999 and 2012 at the Aarhus, Odense, and Aalborg university hospitals in Denmark. Researchers looked for TIL, defined as “a biopsy proven IL in addition to a DLBCL [diffuse large B-cell lymphoma] lesion that was either coexisting at primary diagnosis or histologically ascertained over time through a subsequent biopsy.” In total, 85 patients were selected for the study – 72 subjects with follicular lymphoma at histological grades between 1 and 3A, and 13 subjects with otherwise unspecified forms of indolent lymphoma (IL).

Data for all patients were used to calculate 5-year overall survival (OS) and progression-free survival (PFS) rates. Calculations were done in three cohorts: an “all TIL” whole cohort, a CD-TIL cohort of subjects with “coexisting evidence of both indolent and aggressive histology at diagnosis,” and an S-TIL cohort of subjects who transformed after having indolent lymphoma for a prolonged period of time.

Of the 85 subjects, 54 (64%) received ASCT consolidation and 31 (36%) did not.

In the “all TIL” cohort, the OS and PFS rates were higher in subjects who received rituximab-containing regimens and ASCT compared with those who received only the chemotherapy. The OS rates were 67% vs. 48% (P = .11); the PFS rates were 60% versus 30% (P = .02).

There was no evidence of an advantage in the CD-TIL cohort, the OS rates were 76% for the combined therapy versus 67% for those given rituximab-based chemo only (P = .66), and the PFS rates were 71% versus 36% (P = .54).

The sequential TIL cohort, however, saw improvements in both OS and PFS – 62% versus 36% (P = .07) and 53% versus 6% (P = .002), respectively – regardless of whether or not patients had previously received rituximab-based chemo.

Prospective clinical trials, specifically designed for TIL patients, should be encouraged to investigate the optimal treatment strategy for this still largely unmet clinical need, the researchers concluded.

The authors disclosed no conflicts of interest.

[email protected]

Autologous stem-cell transplantation can be highly effective in securing better long-term results for patients undergoing rituximab-based chemotherapy for transformed indolent lymphoma with high-grade histologies, according to a retrospective study published online in Annals of Oncology.

ASCT improved outcomes in patients with sequential TIL (S-TIL), but not in those with composite/discordant TIL (CD-TIL). The benefits of ASCT were greater in patients who were rituximab-naive at transformation, wrote Dr. Carsten Madsen of Denmark’s Aarhus University Hospital, and his coauthors (Ann. Oncol. 2014 Nov. 18 [doi: 10.1093/annonc/mdu537]).

Patients with “CD-TIL had a better outcome than [did those with] S-TIL regardless of treatment strategy at transformation. With regard to ASCT in particular, we found that it had a beneficial influence on outcome limited to S-TIL,” the investigators concluded.

In a multicenter cohort study, Dr. Madsen and his associates used the National Danish Pathology Registry to identify patients aged 18-68 years with histologically verified TIL diagnosed between 1999 and 2012 at the Aarhus, Odense, and Aalborg university hospitals in Denmark. Researchers looked for TIL, defined as “a biopsy proven IL in addition to a DLBCL [diffuse large B-cell lymphoma] lesion that was either coexisting at primary diagnosis or histologically ascertained over time through a subsequent biopsy.” In total, 85 patients were selected for the study – 72 subjects with follicular lymphoma at histological grades between 1 and 3A, and 13 subjects with otherwise unspecified forms of indolent lymphoma (IL).

Data for all patients were used to calculate 5-year overall survival (OS) and progression-free survival (PFS) rates. Calculations were done in three cohorts: an “all TIL” whole cohort, a CD-TIL cohort of subjects with “coexisting evidence of both indolent and aggressive histology at diagnosis,” and an S-TIL cohort of subjects who transformed after having indolent lymphoma for a prolonged period of time.

Of the 85 subjects, 54 (64%) received ASCT consolidation and 31 (36%) did not.

In the “all TIL” cohort, the OS and PFS rates were higher in subjects who received rituximab-containing regimens and ASCT compared with those who received only the chemotherapy. The OS rates were 67% vs. 48% (P = .11); the PFS rates were 60% versus 30% (P = .02).

There was no evidence of an advantage in the CD-TIL cohort, the OS rates were 76% for the combined therapy versus 67% for those given rituximab-based chemo only (P = .66), and the PFS rates were 71% versus 36% (P = .54).

The sequential TIL cohort, however, saw improvements in both OS and PFS – 62% versus 36% (P = .07) and 53% versus 6% (P = .002), respectively – regardless of whether or not patients had previously received rituximab-based chemo.

Prospective clinical trials, specifically designed for TIL patients, should be encouraged to investigate the optimal treatment strategy for this still largely unmet clinical need, the researchers concluded.

The authors disclosed no conflicts of interest.

[email protected]

Autologous stem-cell transplantation can be highly effective in securing better long-term results for patients undergoing rituximab-based chemotherapy for transformed indolent lymphoma with high-grade histologies, according to a retrospective study published online in Annals of Oncology.

ASCT improved outcomes in patients with sequential TIL (S-TIL), but not in those with composite/discordant TIL (CD-TIL). The benefits of ASCT were greater in patients who were rituximab-naive at transformation, wrote Dr. Carsten Madsen of Denmark’s Aarhus University Hospital, and his coauthors (Ann. Oncol. 2014 Nov. 18 [doi: 10.1093/annonc/mdu537]).

Patients with “CD-TIL had a better outcome than [did those with] S-TIL regardless of treatment strategy at transformation. With regard to ASCT in particular, we found that it had a beneficial influence on outcome limited to S-TIL,” the investigators concluded.

In a multicenter cohort study, Dr. Madsen and his associates used the National Danish Pathology Registry to identify patients aged 18-68 years with histologically verified TIL diagnosed between 1999 and 2012 at the Aarhus, Odense, and Aalborg university hospitals in Denmark. Researchers looked for TIL, defined as “a biopsy proven IL in addition to a DLBCL [diffuse large B-cell lymphoma] lesion that was either coexisting at primary diagnosis or histologically ascertained over time through a subsequent biopsy.” In total, 85 patients were selected for the study – 72 subjects with follicular lymphoma at histological grades between 1 and 3A, and 13 subjects with otherwise unspecified forms of indolent lymphoma (IL).

Data for all patients were used to calculate 5-year overall survival (OS) and progression-free survival (PFS) rates. Calculations were done in three cohorts: an “all TIL” whole cohort, a CD-TIL cohort of subjects with “coexisting evidence of both indolent and aggressive histology at diagnosis,” and an S-TIL cohort of subjects who transformed after having indolent lymphoma for a prolonged period of time.

Of the 85 subjects, 54 (64%) received ASCT consolidation and 31 (36%) did not.

In the “all TIL” cohort, the OS and PFS rates were higher in subjects who received rituximab-containing regimens and ASCT compared with those who received only the chemotherapy. The OS rates were 67% vs. 48% (P = .11); the PFS rates were 60% versus 30% (P = .02).

There was no evidence of an advantage in the CD-TIL cohort, the OS rates were 76% for the combined therapy versus 67% for those given rituximab-based chemo only (P = .66), and the PFS rates were 71% versus 36% (P = .54).

The sequential TIL cohort, however, saw improvements in both OS and PFS – 62% versus 36% (P = .07) and 53% versus 6% (P = .002), respectively – regardless of whether or not patients had previously received rituximab-based chemo.

Prospective clinical trials, specifically designed for TIL patients, should be encouraged to investigate the optimal treatment strategy for this still largely unmet clinical need, the researchers concluded.

The authors disclosed no conflicts of interest.

[email protected]

SAN FRANCISCO—The anti-CD19 antibody M0R208 has demonstrated encouraging single-agent activity in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), according to a presenter at the 2014 ASH Annual Meeting.

“It is encouraging to see results in an NHL study that selects a different target than CD20,” said Kristie Blum, MD, of The Ohio State University in Columbus.

“In particular, it is good to see activity in elderly large-cell lymphoma patients.”

MOR208 is an Fc-engineered humanized monoclonal antibody that targets the CD19 antigen.

“It possesses significantly enhanced antibody-dependent cell-mediated cytotoxicity, a key mechanism for tumor cell killing,” Dr Blum explained. “We have seen previous responses in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).”

In fact, MOR208 recently received fast-track designation from the US Food and Drug Administration to treat DLBCL.

At ASH, Dr Blum reported on a non-randomized, phase 2a study designed to assess the efficacy and safety of single-agent MOR208 in adults with relapsed or refractory NHL (abstract 3089). The trial was sponsored by MorphoSys AG, the company developing MOR208.

The study included 89 patients—35 with DLBCL, 31 with FL, 12 with mantle cell lymphoma (MCL), and 11 with other indolent NHLs (iNHLs). The patients had a median age of 67 years, were previously treated with rituximab, and were not candidates for high-dose therapy with stem cell support.

The patients were treated over 56 days. MOR208 was given intravenously at 12 mg/kg as 8 weekly doses on days 1, 8, 15, and 22 of each cycle. Patients with at least stable disease continued treatment for another cycle.

After completing 12 weekly doses of treatment, responding patients received maintenance MOR208 every 2 or 4 weeks, depending on the investigator’s decision, until progression.

The results showed overall response rates of 26% for DLBCL patients, 23% for FL patients, and 36% in iNHL patients. No MCL patients responded.

There were 2 complete responses in the DLBCL cohort and 1 complete response each in the FL and iNHL cohorts. Response duration reached 13.8 months.

The drug was well-tolerated with an acceptable toxicity profile, Dr Blum said. The most frequently reported treatment-emergent adverse events of any grade were thrombocytopenia, anemia, and neutropenia, all at 9%.

Infusion-related reactions were reported in 9% of patients and were typically grade 1 or 2. There have been no treatment-related deaths.

Protocols are being developed for trials that combine MOR208 with other anti-lymphoma therapies, with plans to open phase 1/2 trials by mid-2015.

“We plan to take the drug forward in combination with bendamustine or lenalidomide plus rituximab,” Dr Blum said. “By adding the drug into a bendamustine-rituximab combination, we will hit 2 different targets and may see synergistic cell killing.”

SAN FRANCISCO—The anti-CD19 antibody M0R208 has demonstrated encouraging single-agent activity in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), according to a presenter at the 2014 ASH Annual Meeting.

“It is encouraging to see results in an NHL study that selects a different target than CD20,” said Kristie Blum, MD, of The Ohio State University in Columbus.

“In particular, it is good to see activity in elderly large-cell lymphoma patients.”

MOR208 is an Fc-engineered humanized monoclonal antibody that targets the CD19 antigen.

“It possesses significantly enhanced antibody-dependent cell-mediated cytotoxicity, a key mechanism for tumor cell killing,” Dr Blum explained. “We have seen previous responses in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).”

In fact, MOR208 recently received fast-track designation from the US Food and Drug Administration to treat DLBCL.

At ASH, Dr Blum reported on a non-randomized, phase 2a study designed to assess the efficacy and safety of single-agent MOR208 in adults with relapsed or refractory NHL (abstract 3089). The trial was sponsored by MorphoSys AG, the company developing MOR208.

The study included 89 patients—35 with DLBCL, 31 with FL, 12 with mantle cell lymphoma (MCL), and 11 with other indolent NHLs (iNHLs). The patients had a median age of 67 years, were previously treated with rituximab, and were not candidates for high-dose therapy with stem cell support.

The patients were treated over 56 days. MOR208 was given intravenously at 12 mg/kg as 8 weekly doses on days 1, 8, 15, and 22 of each cycle. Patients with at least stable disease continued treatment for another cycle.

After completing 12 weekly doses of treatment, responding patients received maintenance MOR208 every 2 or 4 weeks, depending on the investigator’s decision, until progression.

The results showed overall response rates of 26% for DLBCL patients, 23% for FL patients, and 36% in iNHL patients. No MCL patients responded.

There were 2 complete responses in the DLBCL cohort and 1 complete response each in the FL and iNHL cohorts. Response duration reached 13.8 months.

The drug was well-tolerated with an acceptable toxicity profile, Dr Blum said. The most frequently reported treatment-emergent adverse events of any grade were thrombocytopenia, anemia, and neutropenia, all at 9%.

Infusion-related reactions were reported in 9% of patients and were typically grade 1 or 2. There have been no treatment-related deaths.

Protocols are being developed for trials that combine MOR208 with other anti-lymphoma therapies, with plans to open phase 1/2 trials by mid-2015.

“We plan to take the drug forward in combination with bendamustine or lenalidomide plus rituximab,” Dr Blum said. “By adding the drug into a bendamustine-rituximab combination, we will hit 2 different targets and may see synergistic cell killing.”

SAN FRANCISCO—The anti-CD19 antibody M0R208 has demonstrated encouraging single-agent activity in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), according to a presenter at the 2014 ASH Annual Meeting.

“It is encouraging to see results in an NHL study that selects a different target than CD20,” said Kristie Blum, MD, of The Ohio State University in Columbus.

“In particular, it is good to see activity in elderly large-cell lymphoma patients.”

MOR208 is an Fc-engineered humanized monoclonal antibody that targets the CD19 antigen.

“It possesses significantly enhanced antibody-dependent cell-mediated cytotoxicity, a key mechanism for tumor cell killing,” Dr Blum explained. “We have seen previous responses in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).”

In fact, MOR208 recently received fast-track designation from the US Food and Drug Administration to treat DLBCL.

At ASH, Dr Blum reported on a non-randomized, phase 2a study designed to assess the efficacy and safety of single-agent MOR208 in adults with relapsed or refractory NHL (abstract 3089). The trial was sponsored by MorphoSys AG, the company developing MOR208.

The study included 89 patients—35 with DLBCL, 31 with FL, 12 with mantle cell lymphoma (MCL), and 11 with other indolent NHLs (iNHLs). The patients had a median age of 67 years, were previously treated with rituximab, and were not candidates for high-dose therapy with stem cell support.

The patients were treated over 56 days. MOR208 was given intravenously at 12 mg/kg as 8 weekly doses on days 1, 8, 15, and 22 of each cycle. Patients with at least stable disease continued treatment for another cycle.

After completing 12 weekly doses of treatment, responding patients received maintenance MOR208 every 2 or 4 weeks, depending on the investigator’s decision, until progression.

The results showed overall response rates of 26% for DLBCL patients, 23% for FL patients, and 36% in iNHL patients. No MCL patients responded.

There were 2 complete responses in the DLBCL cohort and 1 complete response each in the FL and iNHL cohorts. Response duration reached 13.8 months.

The drug was well-tolerated with an acceptable toxicity profile, Dr Blum said. The most frequently reported treatment-emergent adverse events of any grade were thrombocytopenia, anemia, and neutropenia, all at 9%.

Infusion-related reactions were reported in 9% of patients and were typically grade 1 or 2. There have been no treatment-related deaths.

Protocols are being developed for trials that combine MOR208 with other anti-lymphoma therapies, with plans to open phase 1/2 trials by mid-2015.

“We plan to take the drug forward in combination with bendamustine or lenalidomide plus rituximab,” Dr Blum said. “By adding the drug into a bendamustine-rituximab combination, we will hit 2 different targets and may see synergistic cell killing.”

SAN FRANCISCO – Ofatumumab maintenance therapy nearly doubled progression-free survival in patients with relapsed CLL, according to a preplanned interim analysis of the phase III PROLONG study.

At a median follow-up of 19.1 months, progression-free survival was 15.2 months with the standard approach of observation alone and 29.4 months with maintenance ofatumumab (Hazard ratio, 0.50; P < .0001).

Ofatumumab (Arzerra) also significantly increased the median time to next treatment from 31.1 months to 38 months (HR, 0.66; P = .0108), Dr. Marinus van Oers reported at the annual meeting of the American Society of Hematology.

The benefit in progression-free survival (PFS) with maintenance was “statistically significant and clinical relevant” and was present in all subgroups, he said. It was independent of age, gender, number and type of prior treatment, minimal residual disease status at study entry, and “response at study entry, although we have the impression that it’s more effective in patients on PR [partial response] than in patients on CR [complete response],” he added.

The rationale for the trial lies in the fact that despite recent advances, there is still no curative treatment for chronic lymphocytic leukemia (CLL). Ofatumumab, a type 1 CD20 monoclonal antibody, has a role as maintenance in follicular lymphoma (FL), which shares similarities in biological behavior with CLL. This role is debated, but a recent meta-analysis shows ofatumumab maintenance prolongs PFS and tends to prolong overall survival in relapsed patients with FL, Dr. van Oers of the Academic Medical Center in Amsterdam, The Netherlands, observed.

PROLONG randomized 474 patients with relapsed CLL to observation or ofatumumab 300 mg in week 1 and 1,000 mg in week 2, and every 8 weeks for 2 years. All patients were in second or third remission and within 3 months of response assessment after the last reinduction treatment. Patients with refractory disease or prior maintenance therapy or stem cell transplantation were excluded.

At baseline, the median age was about 65 years, 70% had at least two prior treatments, 80% were in partial remission from their last CLL treatment, and less than 10% had poor-risk cytogenetics 11p or 17p deletions. At the time of the analysis, 25% of patients had received all 13 cycles of ofatumumab.

Adverse events of any grade were increased with the addition of ofatumumab versus placebo (86% vs. 72%; P < .0001). Sixty percent were related to study treatment, but none resulted in study withdrawal, Dr. van Oers said. In all, 17 patients on the experimental arm dropped out due to physician decision or patient wish.

Among grade 3 events, neutropenia was significantly increased with maintenance therapy versus placebo (24% vs. 10%; P < .0001) and there was a non-significant increase in infections (13% vs. 8%). Five deaths occurred in the observation arm and two in the ofatumumab arm, one due to sepsis two months after the end of treatment and the other due to unrelated GI obstruction.

Median overall survival has not been reached for either arm (HR, 0.85; P = .487), he reported on behalf of HOVON and the NORDIC CLL group, co-developers of the study.

[email protected]

SAN FRANCISCO – Ofatumumab maintenance therapy nearly doubled progression-free survival in patients with relapsed CLL, according to a preplanned interim analysis of the phase III PROLONG study.

At a median follow-up of 19.1 months, progression-free survival was 15.2 months with the standard approach of observation alone and 29.4 months with maintenance ofatumumab (Hazard ratio, 0.50; P < .0001).

Ofatumumab (Arzerra) also significantly increased the median time to next treatment from 31.1 months to 38 months (HR, 0.66; P = .0108), Dr. Marinus van Oers reported at the annual meeting of the American Society of Hematology.

The benefit in progression-free survival (PFS) with maintenance was “statistically significant and clinical relevant” and was present in all subgroups, he said. It was independent of age, gender, number and type of prior treatment, minimal residual disease status at study entry, and “response at study entry, although we have the impression that it’s more effective in patients on PR [partial response] than in patients on CR [complete response],” he added.

The rationale for the trial lies in the fact that despite recent advances, there is still no curative treatment for chronic lymphocytic leukemia (CLL). Ofatumumab, a type 1 CD20 monoclonal antibody, has a role as maintenance in follicular lymphoma (FL), which shares similarities in biological behavior with CLL. This role is debated, but a recent meta-analysis shows ofatumumab maintenance prolongs PFS and tends to prolong overall survival in relapsed patients with FL, Dr. van Oers of the Academic Medical Center in Amsterdam, The Netherlands, observed.

PROLONG randomized 474 patients with relapsed CLL to observation or ofatumumab 300 mg in week 1 and 1,000 mg in week 2, and every 8 weeks for 2 years. All patients were in second or third remission and within 3 months of response assessment after the last reinduction treatment. Patients with refractory disease or prior maintenance therapy or stem cell transplantation were excluded.

At baseline, the median age was about 65 years, 70% had at least two prior treatments, 80% were in partial remission from their last CLL treatment, and less than 10% had poor-risk cytogenetics 11p or 17p deletions. At the time of the analysis, 25% of patients had received all 13 cycles of ofatumumab.

Adverse events of any grade were increased with the addition of ofatumumab versus placebo (86% vs. 72%; P < .0001). Sixty percent were related to study treatment, but none resulted in study withdrawal, Dr. van Oers said. In all, 17 patients on the experimental arm dropped out due to physician decision or patient wish.

Among grade 3 events, neutropenia was significantly increased with maintenance therapy versus placebo (24% vs. 10%; P < .0001) and there was a non-significant increase in infections (13% vs. 8%). Five deaths occurred in the observation arm and two in the ofatumumab arm, one due to sepsis two months after the end of treatment and the other due to unrelated GI obstruction.

Median overall survival has not been reached for either arm (HR, 0.85; P = .487), he reported on behalf of HOVON and the NORDIC CLL group, co-developers of the study.

[email protected]

SAN FRANCISCO – Ofatumumab maintenance therapy nearly doubled progression-free survival in patients with relapsed CLL, according to a preplanned interim analysis of the phase III PROLONG study.

At a median follow-up of 19.1 months, progression-free survival was 15.2 months with the standard approach of observation alone and 29.4 months with maintenance ofatumumab (Hazard ratio, 0.50; P < .0001).

Ofatumumab (Arzerra) also significantly increased the median time to next treatment from 31.1 months to 38 months (HR, 0.66; P = .0108), Dr. Marinus van Oers reported at the annual meeting of the American Society of Hematology.

The benefit in progression-free survival (PFS) with maintenance was “statistically significant and clinical relevant” and was present in all subgroups, he said. It was independent of age, gender, number and type of prior treatment, minimal residual disease status at study entry, and “response at study entry, although we have the impression that it’s more effective in patients on PR [partial response] than in patients on CR [complete response],” he added.

The rationale for the trial lies in the fact that despite recent advances, there is still no curative treatment for chronic lymphocytic leukemia (CLL). Ofatumumab, a type 1 CD20 monoclonal antibody, has a role as maintenance in follicular lymphoma (FL), which shares similarities in biological behavior with CLL. This role is debated, but a recent meta-analysis shows ofatumumab maintenance prolongs PFS and tends to prolong overall survival in relapsed patients with FL, Dr. van Oers of the Academic Medical Center in Amsterdam, The Netherlands, observed.

PROLONG randomized 474 patients with relapsed CLL to observation or ofatumumab 300 mg in week 1 and 1,000 mg in week 2, and every 8 weeks for 2 years. All patients were in second or third remission and within 3 months of response assessment after the last reinduction treatment. Patients with refractory disease or prior maintenance therapy or stem cell transplantation were excluded.

At baseline, the median age was about 65 years, 70% had at least two prior treatments, 80% were in partial remission from their last CLL treatment, and less than 10% had poor-risk cytogenetics 11p or 17p deletions. At the time of the analysis, 25% of patients had received all 13 cycles of ofatumumab.

Adverse events of any grade were increased with the addition of ofatumumab versus placebo (86% vs. 72%; P < .0001). Sixty percent were related to study treatment, but none resulted in study withdrawal, Dr. van Oers said. In all, 17 patients on the experimental arm dropped out due to physician decision or patient wish.

Among grade 3 events, neutropenia was significantly increased with maintenance therapy versus placebo (24% vs. 10%; P < .0001) and there was a non-significant increase in infections (13% vs. 8%). Five deaths occurred in the observation arm and two in the ofatumumab arm, one due to sepsis two months after the end of treatment and the other due to unrelated GI obstruction.

Median overall survival has not been reached for either arm (HR, 0.85; P = .487), he reported on behalf of HOVON and the NORDIC CLL group, co-developers of the study.

[email protected]

 

 

CLL cells

 

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.

 

 

CLL cells

 

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.

 

 

CLL cells

 

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.

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.