Multiple Myeloma

 

 

Sodas and other sweetened

beverages at the supermarket

 

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

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

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

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

and mortality in the US.

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

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

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

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

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

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

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

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

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

 

 

Sodas and other sweetened

beverages at the supermarket

 

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

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

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

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

and mortality in the US.

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

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

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

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

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

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

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

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

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

 

 

Sodas and other sweetened

beverages at the supermarket

 

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

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

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

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

and mortality in the US.

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

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

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

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

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

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

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

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

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

The US Food and Drug Administration (FDA) has removed the full clinical hold placed on the investigational new drug application for the telomerase inhibitor imetelstat.

The hold, which was placed in March, suspended a phase 2 study of imetelstat in patients with essential thrombocythemia (ET) or polycythemia vera (PV), as well as a phase 2 study of the drug in patients with multiple myeloma (MM).

The hold also delayed a planned phase 2 trial in patients with myelofibrosis (MF).

And it temporarily suspended an investigator-sponsored trial of imetelstat in MF. The FDA lifted the hold on the investigator-sponsored trial in June.

The FDA halted these trials due to reports of persistent, low-grade liver function test (LFT) abnormalities observed in the phase 2 study of ET/PV patients and the potential risk of chronic liver injury following long-term exposure to imetelstat. The FDA expressed concern about whether these LFT abnormalities are reversible.

Now, data provided by the Geron Corporation, the company developing imetelstat, has convinced the FDA to lift the hold on all trials.

The FDA said the proposed clinical development plan for imetelstat, which is focused on high-risk myeloid disorders such as MF, is acceptable. Geron Corporation has said it does not intend to conduct further studies with, or develop imetelstat for, patients with ET or PV.

To address the clinical hold, the FDA required Geron to provide follow-up information from imetelstat-treated patients who experienced LFT abnormalities until such abnormalities resolved to normal or baseline.

Geron obtained follow-up information from patients in the previously ongoing company-sponsored phase 2 trials in ET/PV and MM. These data were submitted to the FDA as part of the company’s complete response.

The company’s analysis of these data showed that, in the ET/PV trial, LFT abnormalities resolved to normal or baseline in 14 of 18 follow-up patients. For the remaining 4 patients, at the time of the data cut-off, 3 patients showed improvement in LFT abnormalities, and 1 patient had unresolved LFT abnormalities. Two of the remaining 4 patients continue in follow-up.

In the MM trial, LFT abnormalities resolved to normal or baseline in all 9 follow-up patients. In addition, no emergent hepatic adverse events were reported during follow-up for either study.

The FDA also requested information regarding the reversibility of liver toxicity after chronic imetelstat administration in animals. Geron submitted data from its non-clinical toxicology studies, which included a 6-month study in mice and a 9-month study in cynomolgus monkeys.

In these studies, no clinical pathology changes indicative of hepatocellular injury were observed, and no clear signal of LFT abnormalities were identified.

With the clinical hold lifted, a multicenter phase 2 trial in MF is projected to begin in the first half of 2015.

The US Food and Drug Administration (FDA) has removed the full clinical hold placed on the investigational new drug application for the telomerase inhibitor imetelstat.

The hold, which was placed in March, suspended a phase 2 study of imetelstat in patients with essential thrombocythemia (ET) or polycythemia vera (PV), as well as a phase 2 study of the drug in patients with multiple myeloma (MM).

The hold also delayed a planned phase 2 trial in patients with myelofibrosis (MF).

And it temporarily suspended an investigator-sponsored trial of imetelstat in MF. The FDA lifted the hold on the investigator-sponsored trial in June.

The FDA halted these trials due to reports of persistent, low-grade liver function test (LFT) abnormalities observed in the phase 2 study of ET/PV patients and the potential risk of chronic liver injury following long-term exposure to imetelstat. The FDA expressed concern about whether these LFT abnormalities are reversible.

Now, data provided by the Geron Corporation, the company developing imetelstat, has convinced the FDA to lift the hold on all trials.

The FDA said the proposed clinical development plan for imetelstat, which is focused on high-risk myeloid disorders such as MF, is acceptable. Geron Corporation has said it does not intend to conduct further studies with, or develop imetelstat for, patients with ET or PV.

To address the clinical hold, the FDA required Geron to provide follow-up information from imetelstat-treated patients who experienced LFT abnormalities until such abnormalities resolved to normal or baseline.

Geron obtained follow-up information from patients in the previously ongoing company-sponsored phase 2 trials in ET/PV and MM. These data were submitted to the FDA as part of the company’s complete response.

The company’s analysis of these data showed that, in the ET/PV trial, LFT abnormalities resolved to normal or baseline in 14 of 18 follow-up patients. For the remaining 4 patients, at the time of the data cut-off, 3 patients showed improvement in LFT abnormalities, and 1 patient had unresolved LFT abnormalities. Two of the remaining 4 patients continue in follow-up.

In the MM trial, LFT abnormalities resolved to normal or baseline in all 9 follow-up patients. In addition, no emergent hepatic adverse events were reported during follow-up for either study.

The FDA also requested information regarding the reversibility of liver toxicity after chronic imetelstat administration in animals. Geron submitted data from its non-clinical toxicology studies, which included a 6-month study in mice and a 9-month study in cynomolgus monkeys.

In these studies, no clinical pathology changes indicative of hepatocellular injury were observed, and no clear signal of LFT abnormalities were identified.

With the clinical hold lifted, a multicenter phase 2 trial in MF is projected to begin in the first half of 2015.

The US Food and Drug Administration (FDA) has removed the full clinical hold placed on the investigational new drug application for the telomerase inhibitor imetelstat.

The hold, which was placed in March, suspended a phase 2 study of imetelstat in patients with essential thrombocythemia (ET) or polycythemia vera (PV), as well as a phase 2 study of the drug in patients with multiple myeloma (MM).

The hold also delayed a planned phase 2 trial in patients with myelofibrosis (MF).

And it temporarily suspended an investigator-sponsored trial of imetelstat in MF. The FDA lifted the hold on the investigator-sponsored trial in June.

The FDA halted these trials due to reports of persistent, low-grade liver function test (LFT) abnormalities observed in the phase 2 study of ET/PV patients and the potential risk of chronic liver injury following long-term exposure to imetelstat. The FDA expressed concern about whether these LFT abnormalities are reversible.

Now, data provided by the Geron Corporation, the company developing imetelstat, has convinced the FDA to lift the hold on all trials.

The FDA said the proposed clinical development plan for imetelstat, which is focused on high-risk myeloid disorders such as MF, is acceptable. Geron Corporation has said it does not intend to conduct further studies with, or develop imetelstat for, patients with ET or PV.

To address the clinical hold, the FDA required Geron to provide follow-up information from imetelstat-treated patients who experienced LFT abnormalities until such abnormalities resolved to normal or baseline.

Geron obtained follow-up information from patients in the previously ongoing company-sponsored phase 2 trials in ET/PV and MM. These data were submitted to the FDA as part of the company’s complete response.

The company’s analysis of these data showed that, in the ET/PV trial, LFT abnormalities resolved to normal or baseline in 14 of 18 follow-up patients. For the remaining 4 patients, at the time of the data cut-off, 3 patients showed improvement in LFT abnormalities, and 1 patient had unresolved LFT abnormalities. Two of the remaining 4 patients continue in follow-up.

In the MM trial, LFT abnormalities resolved to normal or baseline in all 9 follow-up patients. In addition, no emergent hepatic adverse events were reported during follow-up for either study.

The FDA also requested information regarding the reversibility of liver toxicity after chronic imetelstat administration in animals. Geron submitted data from its non-clinical toxicology studies, which included a 6-month study in mice and a 9-month study in cynomolgus monkeys.

In these studies, no clinical pathology changes indicative of hepatocellular injury were observed, and no clear signal of LFT abnormalities were identified.

With the clinical hold lifted, a multicenter phase 2 trial in MF is projected to begin in the first half of 2015.

Obese mouse

Immunotherapy that can be effective against tumors in young, thin mice can be lethal to obese ones, according to research published in The Journal of Experimental Medicine.

Investigators conducted experiments in mouse models to determine if there is a subset of cancer patients for whom certain immunotherapies might be especially toxic.

The group found a potential link between body fat and the risk of toxicity from some types of immunotherapy.

“Cancer is primarily considered a disease of the aged, and yet preclinical studies generally use young, lean animal models that may not be reflective of the ‘typical’ cancer patient,” said study author Annie Mirsoian, a PhD candidate at the University of California, Davis in Sacramento.

“Aging is a dynamic process that is characterized by increases in inflammatory factors, as well as a shift in body composition where there is a gradual loss of lean muscle mass and an increase in fat accumulation, which effect how the immune system functions.”

Mirsoian and her colleagues sought to determine if, by adjusting the mouse model to more closely reflect the cancer patient phenotype (advanced age and overweight), they could better understand the discrepancies between animal study outcomes and those in patients in the clinic.

So the team examined aged mice on standard diets and compared those to aged mice that were calorie-restricted throughout their lives.

The investigators found that calorie restriction plays a protective role against toxicity. When aged mice ate their standard diet freely throughout life, they became obese and ultimately experienced lethal adverse reactions after receiving a systemic immunotherapy regimen.

“We know that people who are obese in general are at higher risk for complications from surgery, radiation, and chemotherapy,” said study author Arta Monjazeb, MD, PhD, of the University of California, Davis.

“We know that obese people have higher levels of inflammatory markers in their blood, but there is a lack of data examining the effects of obesity on cancer treatment outcomes.”

In follow-up experiments, the investigators found that young mice that are obese also endure similar toxic consequences, demonstrating that fat is a critical factor in toxic responses to stimulatory anticancer immunotherapy regimens.

“It is important to note, however, that the aged mice on standard diets succumbed to lethality at a quicker rate than young obese mice,” Mirsoian said. “Although our data demonstrate that obesity plays a central role in the development of adverse effects, future studies will focus on examining the aged immune system and cellular characteristics that may have enhanced the sensitivity of these mice to inflammation.”

This study follows an earlier paper, which demonstrated that while young, lean mice tolerate immunotherapy regimens without toxicity, the same regimen for an aged cohort resulted in lethal consequences. The new paper takes a deeper look into how fat deposition throughout aging can be critical in determining treatment tolerance and efficacy.

“Obesity has become an epidemic in our society and is now also affecting younger populations,” Mirsoian said. “Therefore, it’s likely that what the ‘typical’ cancer patient looks like will change. Our findings demonstrate the importance of having preclinical animal models that reflect the clinical scenario.”

“Changing the characteristics of our mouse models allowed for a more accurate determination of possible adverse reactions to therapy and more closely modeled what has been reported in the clinic with stimulatory immunotherapies.”

The investigators said factors like age, fat content, and the types of infections experienced throughout life together shape how the immune system reacts, and they will continue to work on improving their modeling system to reflect these changes.

They project that improvements in mouse modeling may help produce data that can better modulate treatment choices for patients, as well as identify early which patients would benefit from the inclusion of drugs to prevent adverse reactions while maintaining anticancer efficacy.

Obese mouse

Immunotherapy that can be effective against tumors in young, thin mice can be lethal to obese ones, according to research published in The Journal of Experimental Medicine.

Investigators conducted experiments in mouse models to determine if there is a subset of cancer patients for whom certain immunotherapies might be especially toxic.

The group found a potential link between body fat and the risk of toxicity from some types of immunotherapy.

“Cancer is primarily considered a disease of the aged, and yet preclinical studies generally use young, lean animal models that may not be reflective of the ‘typical’ cancer patient,” said study author Annie Mirsoian, a PhD candidate at the University of California, Davis in Sacramento.

“Aging is a dynamic process that is characterized by increases in inflammatory factors, as well as a shift in body composition where there is a gradual loss of lean muscle mass and an increase in fat accumulation, which effect how the immune system functions.”

Mirsoian and her colleagues sought to determine if, by adjusting the mouse model to more closely reflect the cancer patient phenotype (advanced age and overweight), they could better understand the discrepancies between animal study outcomes and those in patients in the clinic.

So the team examined aged mice on standard diets and compared those to aged mice that were calorie-restricted throughout their lives.

The investigators found that calorie restriction plays a protective role against toxicity. When aged mice ate their standard diet freely throughout life, they became obese and ultimately experienced lethal adverse reactions after receiving a systemic immunotherapy regimen.

“We know that people who are obese in general are at higher risk for complications from surgery, radiation, and chemotherapy,” said study author Arta Monjazeb, MD, PhD, of the University of California, Davis.

“We know that obese people have higher levels of inflammatory markers in their blood, but there is a lack of data examining the effects of obesity on cancer treatment outcomes.”

In follow-up experiments, the investigators found that young mice that are obese also endure similar toxic consequences, demonstrating that fat is a critical factor in toxic responses to stimulatory anticancer immunotherapy regimens.

“It is important to note, however, that the aged mice on standard diets succumbed to lethality at a quicker rate than young obese mice,” Mirsoian said. “Although our data demonstrate that obesity plays a central role in the development of adverse effects, future studies will focus on examining the aged immune system and cellular characteristics that may have enhanced the sensitivity of these mice to inflammation.”

This study follows an earlier paper, which demonstrated that while young, lean mice tolerate immunotherapy regimens without toxicity, the same regimen for an aged cohort resulted in lethal consequences. The new paper takes a deeper look into how fat deposition throughout aging can be critical in determining treatment tolerance and efficacy.

“Obesity has become an epidemic in our society and is now also affecting younger populations,” Mirsoian said. “Therefore, it’s likely that what the ‘typical’ cancer patient looks like will change. Our findings demonstrate the importance of having preclinical animal models that reflect the clinical scenario.”

“Changing the characteristics of our mouse models allowed for a more accurate determination of possible adverse reactions to therapy and more closely modeled what has been reported in the clinic with stimulatory immunotherapies.”

The investigators said factors like age, fat content, and the types of infections experienced throughout life together shape how the immune system reacts, and they will continue to work on improving their modeling system to reflect these changes.

They project that improvements in mouse modeling may help produce data that can better modulate treatment choices for patients, as well as identify early which patients would benefit from the inclusion of drugs to prevent adverse reactions while maintaining anticancer efficacy.

Obese mouse

Immunotherapy that can be effective against tumors in young, thin mice can be lethal to obese ones, according to research published in The Journal of Experimental Medicine.

Investigators conducted experiments in mouse models to determine if there is a subset of cancer patients for whom certain immunotherapies might be especially toxic.

The group found a potential link between body fat and the risk of toxicity from some types of immunotherapy.

“Cancer is primarily considered a disease of the aged, and yet preclinical studies generally use young, lean animal models that may not be reflective of the ‘typical’ cancer patient,” said study author Annie Mirsoian, a PhD candidate at the University of California, Davis in Sacramento.

“Aging is a dynamic process that is characterized by increases in inflammatory factors, as well as a shift in body composition where there is a gradual loss of lean muscle mass and an increase in fat accumulation, which effect how the immune system functions.”

Mirsoian and her colleagues sought to determine if, by adjusting the mouse model to more closely reflect the cancer patient phenotype (advanced age and overweight), they could better understand the discrepancies between animal study outcomes and those in patients in the clinic.

So the team examined aged mice on standard diets and compared those to aged mice that were calorie-restricted throughout their lives.

The investigators found that calorie restriction plays a protective role against toxicity. When aged mice ate their standard diet freely throughout life, they became obese and ultimately experienced lethal adverse reactions after receiving a systemic immunotherapy regimen.

“We know that people who are obese in general are at higher risk for complications from surgery, radiation, and chemotherapy,” said study author Arta Monjazeb, MD, PhD, of the University of California, Davis.

“We know that obese people have higher levels of inflammatory markers in their blood, but there is a lack of data examining the effects of obesity on cancer treatment outcomes.”

In follow-up experiments, the investigators found that young mice that are obese also endure similar toxic consequences, demonstrating that fat is a critical factor in toxic responses to stimulatory anticancer immunotherapy regimens.

“It is important to note, however, that the aged mice on standard diets succumbed to lethality at a quicker rate than young obese mice,” Mirsoian said. “Although our data demonstrate that obesity plays a central role in the development of adverse effects, future studies will focus on examining the aged immune system and cellular characteristics that may have enhanced the sensitivity of these mice to inflammation.”

This study follows an earlier paper, which demonstrated that while young, lean mice tolerate immunotherapy regimens without toxicity, the same regimen for an aged cohort resulted in lethal consequences. The new paper takes a deeper look into how fat deposition throughout aging can be critical in determining treatment tolerance and efficacy.

“Obesity has become an epidemic in our society and is now also affecting younger populations,” Mirsoian said. “Therefore, it’s likely that what the ‘typical’ cancer patient looks like will change. Our findings demonstrate the importance of having preclinical animal models that reflect the clinical scenario.”

“Changing the characteristics of our mouse models allowed for a more accurate determination of possible adverse reactions to therapy and more closely modeled what has been reported in the clinic with stimulatory immunotherapies.”

The investigators said factors like age, fat content, and the types of infections experienced throughout life together shape how the immune system reacts, and they will continue to work on improving their modeling system to reflect these changes.

They project that improvements in mouse modeling may help produce data that can better modulate treatment choices for patients, as well as identify early which patients would benefit from the inclusion of drugs to prevent adverse reactions while maintaining anticancer efficacy.

Paul G. Richardson, MD

NEW YORK—Calling the synergy with the proteasome inhibitor “profound,” Paul G. Richardson, MD, presented results on the combination of the pan deacetylase inhibitor panobinostat with bortezomib and dexamethasone in relapsed/refractory multiple myeloma (MM).

The phase 3 PANORAMA 1 study confirmed data from the phase 1 and 2 trials, in which the triple combination demonstrated durable responses, even in bortezomib-refractory disease.

Dr Richardson, of the Dana-Farber Cancer Institute in Boston, presented updated data from the PANORAMA 1 trial, which received an award for the most clinically relevant myeloma abstract at the Lymphoma & Myeloma 2014 congress, held October 23–25.

Investigators randomized 768 patients with relapsed or relapsed and refractory MM to receive either panobinostat (n=387) or placebo (n=381) with bortezomib and dexamethasone. Bortezomib-refractory patients were excluded.

The study was conducted in 2 treatment phases, and patients with clinical benefit at the end of the first 24-week phase could proceed to the second treatment phase, consisting of four 42-day cycles.

The primary endpoint was progression-free survival (PFS) according to modified European Society for Blood and Marrow Transplantation criteria.

The key secondary endpoint was overall survival, and additional secondary endpoints included overall response rate, complete response/near complete response, duration of response, time to response, time to progression, quality of life, and safety.

Dr Richardson pointed out that in the first treatment phase, bortezomib was administered twice a week at 1.3 mg/m² intravenously, and, in the second phase, it was given once a week. The panobinostat dose was 20 mg orally 3 times a week, and oral dexamethasone was given at 20 mg on the same day and the day after bortezomib administration.

Patients were a median age of 63 years, and nearly half (48.4%) had received 2 or more prior therapies, including bortezomib, at 43.7% in the panobinostat arm and 42.3% in the placebo arm. Half the patients had prior exposure to thalidomide, and 1 in 4 patients had received bortezomib and an immunomodulator.

Approximately two-thirds of the patients had relapsed MM, and one-third had relapsed and refractory disease.

Twenty-six percent of patients in either arm completed treatment. Forty-four percent of patients in the panobinostat arm and 50% in the placebo arm entered treatment phase 2.

The dose intensity of panobinostat decreased to 78.2% at cycle 3 and remained stable through the rest of the trial. By cycle 3, the majority of patients were receiving 15 mg of panobinostat.

Results

The 3-drug combination met its primary endpoint, with a clinically relevant increase in median PFS of 3.9 months (P<0.0001).

The benefit with panobinostat was maintained regardless of prior treatment history or baseline characteristics.

“There was benefit across all subgroups,” Dr Richardson said, “but especially in the poor-risk group.”

He noted that the overall survival curve was holding between the 2 arms at about a 3-month difference.

And the complete response/near complete response rate in the panobinostat arm was nearly double that of the control arm, at 27.6% and 15.7%, respectively (P=0.00006).

While not significant, there were clinically meaningful improvements in overall response rate, duration of response, and time to progression. The overall response rate with panobinostat was 34.5%, the clinical benefit rate 52.7%, and the median PFS 5.4 months.

Safety

“Overall, side effects were relatively low,” Dr Richardson said, the major ones consisting of hematologic laboratory abnormalities.

Almost 98% of the patients receiving panobinostat and 83.5% of those in the placebo arm had thrombocytopenia of any grade. And 1.6% of patients on panobinostat discontinued due to thrombocytopenia, compared with 0.5% in the control arm.

Dr Richardson said the thrombocytopenia was reversible and not cumulative. Platelet levels rebounded to baseline by day 1 of each cycle.

Lymphopenia, neutropenia, and anemia were also more frequent in the panobinostat arm.

Nonhematologic adverse events, particularly diarrhea and fatigue, were, for the most part, increased over control, with 4.5% of patients on the panobinostat arm discontinuing due to diarrhea and 2.9% discontinuing due to fatigue.

The incidence of adverse events was lower in the second treatment phase, when bortezomib was administered once a week.

And deaths related to study drug were very low, Dr Richardson said, with 11 in the panobinostat arm and 7 in the control arm.

The triple drug combination is “a very important concept going forward,” Dr Richardson said.

Other combinations and additional histone deacetylase inhibitors are being evaluated for MM.

Paul G. Richardson, MD

NEW YORK—Calling the synergy with the proteasome inhibitor “profound,” Paul G. Richardson, MD, presented results on the combination of the pan deacetylase inhibitor panobinostat with bortezomib and dexamethasone in relapsed/refractory multiple myeloma (MM).

The phase 3 PANORAMA 1 study confirmed data from the phase 1 and 2 trials, in which the triple combination demonstrated durable responses, even in bortezomib-refractory disease.

Dr Richardson, of the Dana-Farber Cancer Institute in Boston, presented updated data from the PANORAMA 1 trial, which received an award for the most clinically relevant myeloma abstract at the Lymphoma & Myeloma 2014 congress, held October 23–25.

Investigators randomized 768 patients with relapsed or relapsed and refractory MM to receive either panobinostat (n=387) or placebo (n=381) with bortezomib and dexamethasone. Bortezomib-refractory patients were excluded.

The study was conducted in 2 treatment phases, and patients with clinical benefit at the end of the first 24-week phase could proceed to the second treatment phase, consisting of four 42-day cycles.

The primary endpoint was progression-free survival (PFS) according to modified European Society for Blood and Marrow Transplantation criteria.

The key secondary endpoint was overall survival, and additional secondary endpoints included overall response rate, complete response/near complete response, duration of response, time to response, time to progression, quality of life, and safety.

Dr Richardson pointed out that in the first treatment phase, bortezomib was administered twice a week at 1.3 mg/m² intravenously, and, in the second phase, it was given once a week. The panobinostat dose was 20 mg orally 3 times a week, and oral dexamethasone was given at 20 mg on the same day and the day after bortezomib administration.

Patients were a median age of 63 years, and nearly half (48.4%) had received 2 or more prior therapies, including bortezomib, at 43.7% in the panobinostat arm and 42.3% in the placebo arm. Half the patients had prior exposure to thalidomide, and 1 in 4 patients had received bortezomib and an immunomodulator.

Approximately two-thirds of the patients had relapsed MM, and one-third had relapsed and refractory disease.

Twenty-six percent of patients in either arm completed treatment. Forty-four percent of patients in the panobinostat arm and 50% in the placebo arm entered treatment phase 2.

The dose intensity of panobinostat decreased to 78.2% at cycle 3 and remained stable through the rest of the trial. By cycle 3, the majority of patients were receiving 15 mg of panobinostat.

Results

The 3-drug combination met its primary endpoint, with a clinically relevant increase in median PFS of 3.9 months (P<0.0001).

The benefit with panobinostat was maintained regardless of prior treatment history or baseline characteristics.

“There was benefit across all subgroups,” Dr Richardson said, “but especially in the poor-risk group.”

He noted that the overall survival curve was holding between the 2 arms at about a 3-month difference.

And the complete response/near complete response rate in the panobinostat arm was nearly double that of the control arm, at 27.6% and 15.7%, respectively (P=0.00006).

While not significant, there were clinically meaningful improvements in overall response rate, duration of response, and time to progression. The overall response rate with panobinostat was 34.5%, the clinical benefit rate 52.7%, and the median PFS 5.4 months.

Safety

“Overall, side effects were relatively low,” Dr Richardson said, the major ones consisting of hematologic laboratory abnormalities.

Almost 98% of the patients receiving panobinostat and 83.5% of those in the placebo arm had thrombocytopenia of any grade. And 1.6% of patients on panobinostat discontinued due to thrombocytopenia, compared with 0.5% in the control arm.

Dr Richardson said the thrombocytopenia was reversible and not cumulative. Platelet levels rebounded to baseline by day 1 of each cycle.

Lymphopenia, neutropenia, and anemia were also more frequent in the panobinostat arm.

Nonhematologic adverse events, particularly diarrhea and fatigue, were, for the most part, increased over control, with 4.5% of patients on the panobinostat arm discontinuing due to diarrhea and 2.9% discontinuing due to fatigue.

The incidence of adverse events was lower in the second treatment phase, when bortezomib was administered once a week.

And deaths related to study drug were very low, Dr Richardson said, with 11 in the panobinostat arm and 7 in the control arm.

The triple drug combination is “a very important concept going forward,” Dr Richardson said.

Other combinations and additional histone deacetylase inhibitors are being evaluated for MM.

Paul G. Richardson, MD

NEW YORK—Calling the synergy with the proteasome inhibitor “profound,” Paul G. Richardson, MD, presented results on the combination of the pan deacetylase inhibitor panobinostat with bortezomib and dexamethasone in relapsed/refractory multiple myeloma (MM).

The phase 3 PANORAMA 1 study confirmed data from the phase 1 and 2 trials, in which the triple combination demonstrated durable responses, even in bortezomib-refractory disease.

Dr Richardson, of the Dana-Farber Cancer Institute in Boston, presented updated data from the PANORAMA 1 trial, which received an award for the most clinically relevant myeloma abstract at the Lymphoma & Myeloma 2014 congress, held October 23–25.

Investigators randomized 768 patients with relapsed or relapsed and refractory MM to receive either panobinostat (n=387) or placebo (n=381) with bortezomib and dexamethasone. Bortezomib-refractory patients were excluded.

The study was conducted in 2 treatment phases, and patients with clinical benefit at the end of the first 24-week phase could proceed to the second treatment phase, consisting of four 42-day cycles.

The primary endpoint was progression-free survival (PFS) according to modified European Society for Blood and Marrow Transplantation criteria.

The key secondary endpoint was overall survival, and additional secondary endpoints included overall response rate, complete response/near complete response, duration of response, time to response, time to progression, quality of life, and safety.

Dr Richardson pointed out that in the first treatment phase, bortezomib was administered twice a week at 1.3 mg/m² intravenously, and, in the second phase, it was given once a week. The panobinostat dose was 20 mg orally 3 times a week, and oral dexamethasone was given at 20 mg on the same day and the day after bortezomib administration.

Patients were a median age of 63 years, and nearly half (48.4%) had received 2 or more prior therapies, including bortezomib, at 43.7% in the panobinostat arm and 42.3% in the placebo arm. Half the patients had prior exposure to thalidomide, and 1 in 4 patients had received bortezomib and an immunomodulator.

Approximately two-thirds of the patients had relapsed MM, and one-third had relapsed and refractory disease.

Twenty-six percent of patients in either arm completed treatment. Forty-four percent of patients in the panobinostat arm and 50% in the placebo arm entered treatment phase 2.

The dose intensity of panobinostat decreased to 78.2% at cycle 3 and remained stable through the rest of the trial. By cycle 3, the majority of patients were receiving 15 mg of panobinostat.

Results

The 3-drug combination met its primary endpoint, with a clinically relevant increase in median PFS of 3.9 months (P<0.0001).

The benefit with panobinostat was maintained regardless of prior treatment history or baseline characteristics.

“There was benefit across all subgroups,” Dr Richardson said, “but especially in the poor-risk group.”

He noted that the overall survival curve was holding between the 2 arms at about a 3-month difference.

And the complete response/near complete response rate in the panobinostat arm was nearly double that of the control arm, at 27.6% and 15.7%, respectively (P=0.00006).

While not significant, there were clinically meaningful improvements in overall response rate, duration of response, and time to progression. The overall response rate with panobinostat was 34.5%, the clinical benefit rate 52.7%, and the median PFS 5.4 months.

Safety

“Overall, side effects were relatively low,” Dr Richardson said, the major ones consisting of hematologic laboratory abnormalities.

Almost 98% of the patients receiving panobinostat and 83.5% of those in the placebo arm had thrombocytopenia of any grade. And 1.6% of patients on panobinostat discontinued due to thrombocytopenia, compared with 0.5% in the control arm.

Dr Richardson said the thrombocytopenia was reversible and not cumulative. Platelet levels rebounded to baseline by day 1 of each cycle.

Lymphopenia, neutropenia, and anemia were also more frequent in the panobinostat arm.

Nonhematologic adverse events, particularly diarrhea and fatigue, were, for the most part, increased over control, with 4.5% of patients on the panobinostat arm discontinuing due to diarrhea and 2.9% discontinuing due to fatigue.

The incidence of adverse events was lower in the second treatment phase, when bortezomib was administered once a week.

And deaths related to study drug were very low, Dr Richardson said, with 11 in the panobinostat arm and 7 in the control arm.

The triple drug combination is “a very important concept going forward,” Dr Richardson said.

Other combinations and additional histone deacetylase inhibitors are being evaluated for MM.

Bone marrow biopsy

Credit: Chad McNeeley

The International Myeloma Working Group (IMWG) has published new criteria for diagnosing multiple myeloma (MM) in The Lancet Oncology.

The group has added validated biomarkers to the current clinical symptoms used for MM diagnosis—hypercalcemia, renal failure, anemia, and bone lesions.

This addition will allow physicians to diagnose MM before patients become symptomatic and, therefore, before organ damage occurs, according to the IMWG.

Lead author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota, noted that MM is always preceded sequentially by two conditions—monoclonal gammopathy of undetermined significance and smoldering MM. Since both are asymptomatic, most MM patients are not diagnosed until organ damage occurs.

“The new IMWG criteria allow for the diagnosis of myeloma to be made in patients without symptoms and before organ damage occurs, using validated biomarkers that identify patients with [smoldering] MM who have an ‘ultra-high’ risk of progression to multiple myeloma,” Dr Rajkumar said.

“These biomarkers are associated with the near-inevitable development of clinical symptoms and are important for early diagnosis and treatment, which is very important for patients.”

Other updates to the criteria used to diagnose MM include the use of CT and PET-CT scans to identify bone lesions. According to the authors, this will enable more accurate diagnosis and intervention before fractures or other serious problems arise.

“We believe that the new criteria will rectify the situation where we were unable to use the considerable advances in multiple myeloma therapy prior to organ damage,” Dr Rajkumar said. “We can now initiate therapy in some patients early on in the course of their disease.”

The IMWG’s revised diagnostic criteria for MM and smoldering MM are as follows.

Definition of MM

Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma* and one or more of the following myeloma defining events:

• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:

  • Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL).
  • Renal insufficiency: creatinine clearance <40 mL per min (measured or estimated by validated equations) or serum creatinine >177 μmol/L (>2 mg/dL).
  • Anemia: hemoglobin value of >20 g/L below the lower limit of normal or a hemoglobin value <100 g/L.
  • Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT. If the bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement.

• One or more of the following biomarkers:

  • Clonal bone marrow plasma cell percentage ≥60%.
  • Involved:uninvolved serum free light chain ratio ≥100. These values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK). The involved free light chain must be ≥100 mg/L.
  • >1 focal lesions on MRI studies. Each focal lesion must be 5 mm or more in size.

*The IMWG said clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone

marrow plasma cell percentage should preferably be estimated from a core biopsy specimen. In case of a disparity between the aspirate and core biopsy, the highest value should be used.

Definition of smoldering MM

Both of the following criteria must be met:

• Serum monoclonal protein (IgG or IgA) ≥30 g/L or urinary monoclonal protein ≥500 mg per 24 hours and/or clonal bone marrow plasma cells 10%–60%.
• Absence of myeloma defining events or amyloidosis.
  

Bone marrow biopsy

Credit: Chad McNeeley

The International Myeloma Working Group (IMWG) has published new criteria for diagnosing multiple myeloma (MM) in The Lancet Oncology.

The group has added validated biomarkers to the current clinical symptoms used for MM diagnosis—hypercalcemia, renal failure, anemia, and bone lesions.

This addition will allow physicians to diagnose MM before patients become symptomatic and, therefore, before organ damage occurs, according to the IMWG.

Lead author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota, noted that MM is always preceded sequentially by two conditions—monoclonal gammopathy of undetermined significance and smoldering MM. Since both are asymptomatic, most MM patients are not diagnosed until organ damage occurs.

“The new IMWG criteria allow for the diagnosis of myeloma to be made in patients without symptoms and before organ damage occurs, using validated biomarkers that identify patients with [smoldering] MM who have an ‘ultra-high’ risk of progression to multiple myeloma,” Dr Rajkumar said.

“These biomarkers are associated with the near-inevitable development of clinical symptoms and are important for early diagnosis and treatment, which is very important for patients.”

Other updates to the criteria used to diagnose MM include the use of CT and PET-CT scans to identify bone lesions. According to the authors, this will enable more accurate diagnosis and intervention before fractures or other serious problems arise.

“We believe that the new criteria will rectify the situation where we were unable to use the considerable advances in multiple myeloma therapy prior to organ damage,” Dr Rajkumar said. “We can now initiate therapy in some patients early on in the course of their disease.”

The IMWG’s revised diagnostic criteria for MM and smoldering MM are as follows.

Definition of MM

Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma* and one or more of the following myeloma defining events:

• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:

  • Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL).
  • Renal insufficiency: creatinine clearance <40 mL per min (measured or estimated by validated equations) or serum creatinine >177 μmol/L (>2 mg/dL).
  • Anemia: hemoglobin value of >20 g/L below the lower limit of normal or a hemoglobin value <100 g/L.
  • Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT. If the bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement.

• One or more of the following biomarkers:

  • Clonal bone marrow plasma cell percentage ≥60%.
  • Involved:uninvolved serum free light chain ratio ≥100. These values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK). The involved free light chain must be ≥100 mg/L.
  • >1 focal lesions on MRI studies. Each focal lesion must be 5 mm or more in size.

*The IMWG said clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone

marrow plasma cell percentage should preferably be estimated from a core biopsy specimen. In case of a disparity between the aspirate and core biopsy, the highest value should be used.

Definition of smoldering MM

Both of the following criteria must be met:

• Serum monoclonal protein (IgG or IgA) ≥30 g/L or urinary monoclonal protein ≥500 mg per 24 hours and/or clonal bone marrow plasma cells 10%–60%.
• Absence of myeloma defining events or amyloidosis.
  

Bone marrow biopsy

Credit: Chad McNeeley

The International Myeloma Working Group (IMWG) has published new criteria for diagnosing multiple myeloma (MM) in The Lancet Oncology.

The group has added validated biomarkers to the current clinical symptoms used for MM diagnosis—hypercalcemia, renal failure, anemia, and bone lesions.

This addition will allow physicians to diagnose MM before patients become symptomatic and, therefore, before organ damage occurs, according to the IMWG.

Lead author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota, noted that MM is always preceded sequentially by two conditions—monoclonal gammopathy of undetermined significance and smoldering MM. Since both are asymptomatic, most MM patients are not diagnosed until organ damage occurs.

“The new IMWG criteria allow for the diagnosis of myeloma to be made in patients without symptoms and before organ damage occurs, using validated biomarkers that identify patients with [smoldering] MM who have an ‘ultra-high’ risk of progression to multiple myeloma,” Dr Rajkumar said.

“These biomarkers are associated with the near-inevitable development of clinical symptoms and are important for early diagnosis and treatment, which is very important for patients.”

Other updates to the criteria used to diagnose MM include the use of CT and PET-CT scans to identify bone lesions. According to the authors, this will enable more accurate diagnosis and intervention before fractures or other serious problems arise.

“We believe that the new criteria will rectify the situation where we were unable to use the considerable advances in multiple myeloma therapy prior to organ damage,” Dr Rajkumar said. “We can now initiate therapy in some patients early on in the course of their disease.”

The IMWG’s revised diagnostic criteria for MM and smoldering MM are as follows.

Definition of MM

Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma* and one or more of the following myeloma defining events:

• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:

  • Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL).
  • Renal insufficiency: creatinine clearance <40 mL per min (measured or estimated by validated equations) or serum creatinine >177 μmol/L (>2 mg/dL).
  • Anemia: hemoglobin value of >20 g/L below the lower limit of normal or a hemoglobin value <100 g/L.
  • Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT. If the bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement.

• One or more of the following biomarkers:

  • Clonal bone marrow plasma cell percentage ≥60%.
  • Involved:uninvolved serum free light chain ratio ≥100. These values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK). The involved free light chain must be ≥100 mg/L.
  • >1 focal lesions on MRI studies. Each focal lesion must be 5 mm or more in size.

*The IMWG said clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone

marrow plasma cell percentage should preferably be estimated from a core biopsy specimen. In case of a disparity between the aspirate and core biopsy, the highest value should be used.

Definition of smoldering MM

Both of the following criteria must be met:

• Serum monoclonal protein (IgG or IgA) ≥30 g/L or urinary monoclonal protein ≥500 mg per 24 hours and/or clonal bone marrow plasma cells 10%–60%.
• Absence of myeloma defining events or amyloidosis.
  

Cancer patient receiving

chemotherapy

Credit: Rhoda Baer

Many US cancer survivors may be experiencing financial or work-related hardship, a new survey suggests.

Twenty-seven percent of the nearly 1600 survivors surveyed reported at least one financial problem, such as debt or bankruptcy.

And 37% reported having to modify work plans, such as taking extended time off or delaying retirement.

Women, younger survivors, racial/ethnic minorities, and uninsured survivors were all disproportionally burdened by these challenges.

This research (abstract 238*) was presented in a presscast prior to the 2014 Palliative Care in Oncology Symposium, which is scheduled to take place October 24-25 at the Westin Boston Waterfront in Boston.

“We found that many cancer survivors, particularly those who are younger or from underserved populations, experience financial or work-related hardship—even when insured and years out from treatment,” said lead study author Robin Whitney, RN, a cancer survivor and PhD student at the Betty Irene Moore School of Nursing at the University of California, Davis.

“Addressing these challenges is an important aspect of providing quality cancer care, because they can substantially impact quality of life and health outcomes.”

Whitney and her colleagues focused this study on a subset of individuals surveyed in a larger study (2011 Medical Expenditures Panel Survey Experiences with Cancer Survivorship Supplement).

Among the 1592 survivors surveyed, 47% were younger than 65 years of age, 56% were female, 88% were white, and 4% were uninsured. Fourteen percent were in active treatment, 46% were less than 5 years post-treatment, and 39% were 5 years or more post-treatment.

Overall, 27% of those surveyed reported at least one financial difficulty, such as debt, bankruptcy, and worrying about medical bills. Patients in active treatment reported 120% more financial difficulties than survivors who were less than 5 years post-treatment.

Individuals younger than 65 reported 130% more financial difficulties than older survivors. Survivors without insurance had 67% more difficulties than those with insurance. And minorities had 42% more financial difficulties than whites.

In all, 37% of survivors reported making at least one work modification due to their cancer diagnosis, such as changing to a flexible schedule or less demanding job, early or delayed retirement, and extended or unpaid time off.

Women were significantly more likely than men to make at least one work modification. Patients in active treatment made 120% more work modifications than survivors who were less than 5 years post-treatment. And minorities made 57% more modifications than whites.

According to the researchers, these findings are generalizable to the US population and point to the urgent need for screening and support for financial and work challenges across the cancer survivorship trajectory, from diagnosis to long-term survivorship.

*Information presented differs from that in the abstract.

Cancer patient receiving

chemotherapy

Credit: Rhoda Baer

Many US cancer survivors may be experiencing financial or work-related hardship, a new survey suggests.

Twenty-seven percent of the nearly 1600 survivors surveyed reported at least one financial problem, such as debt or bankruptcy.

And 37% reported having to modify work plans, such as taking extended time off or delaying retirement.

Women, younger survivors, racial/ethnic minorities, and uninsured survivors were all disproportionally burdened by these challenges.

This research (abstract 238*) was presented in a presscast prior to the 2014 Palliative Care in Oncology Symposium, which is scheduled to take place October 24-25 at the Westin Boston Waterfront in Boston.

“We found that many cancer survivors, particularly those who are younger or from underserved populations, experience financial or work-related hardship—even when insured and years out from treatment,” said lead study author Robin Whitney, RN, a cancer survivor and PhD student at the Betty Irene Moore School of Nursing at the University of California, Davis.

“Addressing these challenges is an important aspect of providing quality cancer care, because they can substantially impact quality of life and health outcomes.”

Whitney and her colleagues focused this study on a subset of individuals surveyed in a larger study (2011 Medical Expenditures Panel Survey Experiences with Cancer Survivorship Supplement).

Among the 1592 survivors surveyed, 47% were younger than 65 years of age, 56% were female, 88% were white, and 4% were uninsured. Fourteen percent were in active treatment, 46% were less than 5 years post-treatment, and 39% were 5 years or more post-treatment.

Overall, 27% of those surveyed reported at least one financial difficulty, such as debt, bankruptcy, and worrying about medical bills. Patients in active treatment reported 120% more financial difficulties than survivors who were less than 5 years post-treatment.

Individuals younger than 65 reported 130% more financial difficulties than older survivors. Survivors without insurance had 67% more difficulties than those with insurance. And minorities had 42% more financial difficulties than whites.

In all, 37% of survivors reported making at least one work modification due to their cancer diagnosis, such as changing to a flexible schedule or less demanding job, early or delayed retirement, and extended or unpaid time off.

Women were significantly more likely than men to make at least one work modification. Patients in active treatment made 120% more work modifications than survivors who were less than 5 years post-treatment. And minorities made 57% more modifications than whites.

According to the researchers, these findings are generalizable to the US population and point to the urgent need for screening and support for financial and work challenges across the cancer survivorship trajectory, from diagnosis to long-term survivorship.

*Information presented differs from that in the abstract.

Cancer patient receiving

chemotherapy

Credit: Rhoda Baer

Many US cancer survivors may be experiencing financial or work-related hardship, a new survey suggests.

Twenty-seven percent of the nearly 1600 survivors surveyed reported at least one financial problem, such as debt or bankruptcy.

And 37% reported having to modify work plans, such as taking extended time off or delaying retirement.

Women, younger survivors, racial/ethnic minorities, and uninsured survivors were all disproportionally burdened by these challenges.

This research (abstract 238*) was presented in a presscast prior to the 2014 Palliative Care in Oncology Symposium, which is scheduled to take place October 24-25 at the Westin Boston Waterfront in Boston.

“We found that many cancer survivors, particularly those who are younger or from underserved populations, experience financial or work-related hardship—even when insured and years out from treatment,” said lead study author Robin Whitney, RN, a cancer survivor and PhD student at the Betty Irene Moore School of Nursing at the University of California, Davis.

“Addressing these challenges is an important aspect of providing quality cancer care, because they can substantially impact quality of life and health outcomes.”

Whitney and her colleagues focused this study on a subset of individuals surveyed in a larger study (2011 Medical Expenditures Panel Survey Experiences with Cancer Survivorship Supplement).

Among the 1592 survivors surveyed, 47% were younger than 65 years of age, 56% were female, 88% were white, and 4% were uninsured. Fourteen percent were in active treatment, 46% were less than 5 years post-treatment, and 39% were 5 years or more post-treatment.

Overall, 27% of those surveyed reported at least one financial difficulty, such as debt, bankruptcy, and worrying about medical bills. Patients in active treatment reported 120% more financial difficulties than survivors who were less than 5 years post-treatment.

Individuals younger than 65 reported 130% more financial difficulties than older survivors. Survivors without insurance had 67% more difficulties than those with insurance. And minorities had 42% more financial difficulties than whites.

In all, 37% of survivors reported making at least one work modification due to their cancer diagnosis, such as changing to a flexible schedule or less demanding job, early or delayed retirement, and extended or unpaid time off.

Women were significantly more likely than men to make at least one work modification. Patients in active treatment made 120% more work modifications than survivors who were less than 5 years post-treatment. And minorities made 57% more modifications than whites.

According to the researchers, these findings are generalizable to the US population and point to the urgent need for screening and support for financial and work challenges across the cancer survivorship trajectory, from diagnosis to long-term survivorship.

*Information presented differs from that in the abstract.

Prescription medications

Credit: CDC

The UK’s National Institute for Health and Care Excellence (NICE) has issued a preliminary draft guidance rejecting the use of pomalidomide

(Imnovid) to treat patients with relapsed or refractory multiple myeloma (MM).

NICE said the drug’s maker, Celgene, did not provide sufficient evidence of pomalidomide’s effectiveness as compared to current treatment.

Furthermore, the drug did not offer enough of a benefit to justify its high price.

“We are disappointed not to be able to recommend pomalidomide in this preliminary guidance, but the analyses submitted by Celgene, the company that makes the drug, did not show how well the drug works compared to the other treatments available,” said Sir Andrew Dillon, NICE chief executive.

Specifically, NICE said it cannot recommend pomalidomide in combination with dexamethasone for treating relapsed and refractory MM in adults who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.

A committee advising NICE concluded that, because of the design of the MM-003 study, the extent of the benefits associated with pomalidomide was uncertain. In addition, the MM-003 results were of limited value in comparing pomalidomide with “established practice without pomalidomide.”

The recommended dose of pomalidomide is 4 mg once daily, taken on days 1 to 21 of repeated 28-day cycles. Treatment should continue until disease progression.

The price of a pack (21 tablets) of 1 mg, 2 mg, 3 mg, or 4 mg tablets is £8884 (excluding value-added tax). Costs may vary in different settings because of negotiated procurement discounts.

The cost per quality-adjusted life-year (QALY) gained presented by Celgene was over £50,000 compared with bortezomib.

The committee heard from a clinical expert that, although there is no standard of care for people with relapsed or refractory MM, bendamustine was likely to be the most commonly used therapy in this setting in England.

When comparing pomalidomide with bendamustine plus thalidomide and dexamethasone, all costs per QALYs presented were over £70,000.

The committee was not persuaded that the estimates of the extension to life were robust, objective, or plausible based on the company’s economic modeling. It therefore concluded that pomalidomide did not fulfill the criteria for being a life-extending, end-of-life treatment.

The committee further concluded that, even if pomalidomide fulfilled these criteria, the weight that would have to be placed on the QALYs would be too high for pomalidomide to be considered a cost-effective use of National Health Service resources.

Consultees, including the manufacturer, healthcare professionals, and members of the public are now able to comment on these preliminary recommendations.

Until a final guidance is issued, National Health Service bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.

Prescription medications

Credit: CDC

The UK’s National Institute for Health and Care Excellence (NICE) has issued a preliminary draft guidance rejecting the use of pomalidomide

(Imnovid) to treat patients with relapsed or refractory multiple myeloma (MM).

NICE said the drug’s maker, Celgene, did not provide sufficient evidence of pomalidomide’s effectiveness as compared to current treatment.

Furthermore, the drug did not offer enough of a benefit to justify its high price.

“We are disappointed not to be able to recommend pomalidomide in this preliminary guidance, but the analyses submitted by Celgene, the company that makes the drug, did not show how well the drug works compared to the other treatments available,” said Sir Andrew Dillon, NICE chief executive.

Specifically, NICE said it cannot recommend pomalidomide in combination with dexamethasone for treating relapsed and refractory MM in adults who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.

A committee advising NICE concluded that, because of the design of the MM-003 study, the extent of the benefits associated with pomalidomide was uncertain. In addition, the MM-003 results were of limited value in comparing pomalidomide with “established practice without pomalidomide.”

The recommended dose of pomalidomide is 4 mg once daily, taken on days 1 to 21 of repeated 28-day cycles. Treatment should continue until disease progression.

The price of a pack (21 tablets) of 1 mg, 2 mg, 3 mg, or 4 mg tablets is £8884 (excluding value-added tax). Costs may vary in different settings because of negotiated procurement discounts.

The cost per quality-adjusted life-year (QALY) gained presented by Celgene was over £50,000 compared with bortezomib.

The committee heard from a clinical expert that, although there is no standard of care for people with relapsed or refractory MM, bendamustine was likely to be the most commonly used therapy in this setting in England.

When comparing pomalidomide with bendamustine plus thalidomide and dexamethasone, all costs per QALYs presented were over £70,000.

The committee was not persuaded that the estimates of the extension to life were robust, objective, or plausible based on the company’s economic modeling. It therefore concluded that pomalidomide did not fulfill the criteria for being a life-extending, end-of-life treatment.

The committee further concluded that, even if pomalidomide fulfilled these criteria, the weight that would have to be placed on the QALYs would be too high for pomalidomide to be considered a cost-effective use of National Health Service resources.

Consultees, including the manufacturer, healthcare professionals, and members of the public are now able to comment on these preliminary recommendations.

Until a final guidance is issued, National Health Service bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.

Prescription medications

Credit: CDC

The UK’s National Institute for Health and Care Excellence (NICE) has issued a preliminary draft guidance rejecting the use of pomalidomide

(Imnovid) to treat patients with relapsed or refractory multiple myeloma (MM).

NICE said the drug’s maker, Celgene, did not provide sufficient evidence of pomalidomide’s effectiveness as compared to current treatment.

Furthermore, the drug did not offer enough of a benefit to justify its high price.

“We are disappointed not to be able to recommend pomalidomide in this preliminary guidance, but the analyses submitted by Celgene, the company that makes the drug, did not show how well the drug works compared to the other treatments available,” said Sir Andrew Dillon, NICE chief executive.

Specifically, NICE said it cannot recommend pomalidomide in combination with dexamethasone for treating relapsed and refractory MM in adults who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.

A committee advising NICE concluded that, because of the design of the MM-003 study, the extent of the benefits associated with pomalidomide was uncertain. In addition, the MM-003 results were of limited value in comparing pomalidomide with “established practice without pomalidomide.”

The recommended dose of pomalidomide is 4 mg once daily, taken on days 1 to 21 of repeated 28-day cycles. Treatment should continue until disease progression.

The price of a pack (21 tablets) of 1 mg, 2 mg, 3 mg, or 4 mg tablets is £8884 (excluding value-added tax). Costs may vary in different settings because of negotiated procurement discounts.

The cost per quality-adjusted life-year (QALY) gained presented by Celgene was over £50,000 compared with bortezomib.

The committee heard from a clinical expert that, although there is no standard of care for people with relapsed or refractory MM, bendamustine was likely to be the most commonly used therapy in this setting in England.

When comparing pomalidomide with bendamustine plus thalidomide and dexamethasone, all costs per QALYs presented were over £70,000.

The committee was not persuaded that the estimates of the extension to life were robust, objective, or plausible based on the company’s economic modeling. It therefore concluded that pomalidomide did not fulfill the criteria for being a life-extending, end-of-life treatment.

The committee further concluded that, even if pomalidomide fulfilled these criteria, the weight that would have to be placed on the QALYs would be too high for pomalidomide to be considered a cost-effective use of National Health Service resources.

Consultees, including the manufacturer, healthcare professionals, and members of the public are now able to comment on these preliminary recommendations.

Until a final guidance is issued, National Health Service bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.

Dictyostelium discoideum

Experiments in a soil-dwelling amoeba have provided insight that could help us treat cancers characterized by PTEN mutations, researchers have reported in PLOS ONE.

The team discovered that this amoeba has two genes that function like the human tumor suppressor PTEN.

And increasing expression of one of these genes compensated for a mutation in the other gene.

If the same method works in humans with mutated PTEN, this finding could have implications for a range of cancers.

PTEN mutations are thought to be involved in nearly half of all leukemia cases, 40% of breast cancer cases, and up to 70% of prostate cancer cases.

“If you look at tumors across the board . . . , you find that PTEN is the most generally mutated gene, and, when you mutate PTEN in mice, you cause tumors,” said study author David Soll, PhD, of the University of Iowa in Iowa City.

He and his colleagues found that the amoeba Dictyostelium discoideum has the gene ptenA, which mutates similarly to the human PTEN gene and causes behavioral defects in the cell.

They also found a close relative of ptenA in the amoeba, called lpten, that performs the same functions of ptenA but to a lesser degree.

The researchers hypothesized that ramping up the presence of lpten could compensate for the mutated ptenA.

They tested this theory by placing lpten in a plasmid behind a powerful promoter designed to overexpress the gene. They then introduced the super-charged lpten into a cell with the mutated ptenA gene.

The team found that the overexpressed lpten gene fully compensated for all of the defects in the ptenA mutant.

If this method works in human cells, it could lead to a new way to treat cancers, the researchers said. They are now aiming to identify a drug that would activate the promoter for one of PTEN’s close relatives.

Once a patient is diagnosed with cancer caused by a PTEN mutation, the patient could take the drug, overexpress the PTEN replacement gene, and potentially stop cancer in its tracks, Dr Soll said.

This research has also led Dr Soll and his colleagues to study other human genes that may be able to step in for the mutated PTEN gene and perform the same tumor-suppressing role. The team is currently studying 2 close relatives of PTEN.

“And nature might have put them there just for that; that’s the curious thing,” Dr Soll said. “Somewhere, there may be a backup system, what we call ‘redundancy,’ that might be the basis for better identifying tumors and possibly creating cancer-fighting drugs. You have another gene which might be able to step in for the broken gene to keep things normal, and that’s what we’re playing with here. It’s very sophisticated.”

Dictyostelium discoideum

Experiments in a soil-dwelling amoeba have provided insight that could help us treat cancers characterized by PTEN mutations, researchers have reported in PLOS ONE.

The team discovered that this amoeba has two genes that function like the human tumor suppressor PTEN.

And increasing expression of one of these genes compensated for a mutation in the other gene.

If the same method works in humans with mutated PTEN, this finding could have implications for a range of cancers.

PTEN mutations are thought to be involved in nearly half of all leukemia cases, 40% of breast cancer cases, and up to 70% of prostate cancer cases.

“If you look at tumors across the board . . . , you find that PTEN is the most generally mutated gene, and, when you mutate PTEN in mice, you cause tumors,” said study author David Soll, PhD, of the University of Iowa in Iowa City.

He and his colleagues found that the amoeba Dictyostelium discoideum has the gene ptenA, which mutates similarly to the human PTEN gene and causes behavioral defects in the cell.

They also found a close relative of ptenA in the amoeba, called lpten, that performs the same functions of ptenA but to a lesser degree.

The researchers hypothesized that ramping up the presence of lpten could compensate for the mutated ptenA.

They tested this theory by placing lpten in a plasmid behind a powerful promoter designed to overexpress the gene. They then introduced the super-charged lpten into a cell with the mutated ptenA gene.

The team found that the overexpressed lpten gene fully compensated for all of the defects in the ptenA mutant.

If this method works in human cells, it could lead to a new way to treat cancers, the researchers said. They are now aiming to identify a drug that would activate the promoter for one of PTEN’s close relatives.

Once a patient is diagnosed with cancer caused by a PTEN mutation, the patient could take the drug, overexpress the PTEN replacement gene, and potentially stop cancer in its tracks, Dr Soll said.

This research has also led Dr Soll and his colleagues to study other human genes that may be able to step in for the mutated PTEN gene and perform the same tumor-suppressing role. The team is currently studying 2 close relatives of PTEN.

“And nature might have put them there just for that; that’s the curious thing,” Dr Soll said. “Somewhere, there may be a backup system, what we call ‘redundancy,’ that might be the basis for better identifying tumors and possibly creating cancer-fighting drugs. You have another gene which might be able to step in for the broken gene to keep things normal, and that’s what we’re playing with here. It’s very sophisticated.”

Dictyostelium discoideum

Experiments in a soil-dwelling amoeba have provided insight that could help us treat cancers characterized by PTEN mutations, researchers have reported in PLOS ONE.

The team discovered that this amoeba has two genes that function like the human tumor suppressor PTEN.

And increasing expression of one of these genes compensated for a mutation in the other gene.

If the same method works in humans with mutated PTEN, this finding could have implications for a range of cancers.

PTEN mutations are thought to be involved in nearly half of all leukemia cases, 40% of breast cancer cases, and up to 70% of prostate cancer cases.

“If you look at tumors across the board . . . , you find that PTEN is the most generally mutated gene, and, when you mutate PTEN in mice, you cause tumors,” said study author David Soll, PhD, of the University of Iowa in Iowa City.

He and his colleagues found that the amoeba Dictyostelium discoideum has the gene ptenA, which mutates similarly to the human PTEN gene and causes behavioral defects in the cell.

They also found a close relative of ptenA in the amoeba, called lpten, that performs the same functions of ptenA but to a lesser degree.

The researchers hypothesized that ramping up the presence of lpten could compensate for the mutated ptenA.

They tested this theory by placing lpten in a plasmid behind a powerful promoter designed to overexpress the gene. They then introduced the super-charged lpten into a cell with the mutated ptenA gene.

The team found that the overexpressed lpten gene fully compensated for all of the defects in the ptenA mutant.

If this method works in human cells, it could lead to a new way to treat cancers, the researchers said. They are now aiming to identify a drug that would activate the promoter for one of PTEN’s close relatives.

Once a patient is diagnosed with cancer caused by a PTEN mutation, the patient could take the drug, overexpress the PTEN replacement gene, and potentially stop cancer in its tracks, Dr Soll said.

This research has also led Dr Soll and his colleagues to study other human genes that may be able to step in for the mutated PTEN gene and perform the same tumor-suppressing role. The team is currently studying 2 close relatives of PTEN.

“And nature might have put them there just for that; that’s the curious thing,” Dr Soll said. “Somewhere, there may be a backup system, what we call ‘redundancy,’ that might be the basis for better identifying tumors and possibly creating cancer-fighting drugs. You have another gene which might be able to step in for the broken gene to keep things normal, and that’s what we’re playing with here. It’s very sophisticated.”

Researchers in the lab

Credit: Rhoda Baer

A new drug can safely target the NF-κB pathway in multiple myeloma (MM), according to research published in Cancer Cell.

The investigators identified an interaction between the NF-κB-regulated antiapoptotic factor GADD45β and the JNK kinase MKK7 as a  therapeutic target in MM.

They then developed a drug known as DTP3, which disrupts the GADD45β/MKK7 complex, thereby killing MM cells in vitro and in vivo, without harming normal cells.

“Lab studies suggest that DTP3 could have therapeutic benefit for patients with multiple myeloma and potentially several other types of cancer, but we will need to confirm this in our clinical trials, the first of which will start next year,” said study author Guido Franzoso, MD, PhD, of Imperial College London in the UK.

Dr Franzoso and his colleagues knew that NF-κB is overactive in MM and other malignancies, but targeting NF-κB can have detrimental effects on healthy cells. So they looked for target genes downstream of NF-kB that might be responsible for its role in cancers.

By studying cells from MM patients, the investigators identified the protein complex GADD45β/MKK7, which appeared to play a critical role in allowing MM cells to survive.

Searching for a safe way to target the NF-kB pathway, the team screened more than 20,000 molecules and found 2 that disrupted GADD45β/MKK7. Further refinements led to the development of DTP3.

In human MM cells, DTP3 had a similar anticancer potency to that of bortezomib, but with a more than 100-fold higher cancer-cell specificity. DTP3 also retained full therapeutic efficacy in cell lines that were resistant to standard MM treatments.

In mice, DTP3 eradicated MM, with no apparent side effects at the effective doses.

In an orthotopic xenograft model of MM, control mice had a median overall survival of 26 days. But mice treated with DTP3 had a median overall survival that extended past the experimental endpoint on day 161.

“We had known for many years that NF-kB is very important for cancer cells, but because it is also needed by healthy cells, we did not know how to block it specifically,” Dr Franzoso said.

“The discovery that blocking the GADD45β/MKK7 segment of the NF-kB pathway with our DTP3 peptide therapeutic selectively kills myeloma cells could offer a completely new approach to treating patients with certain cancers, such as multiple myeloma.”

A spinout company, Kesios Therapeutics, was formed to commercialize DTP3 and other drug candidates based on Dr Franzoso’s research, with support from Imperial Innovations, a technology commercialization company focused on developing academic research in the UK.

Researchers in the lab

Credit: Rhoda Baer

A new drug can safely target the NF-κB pathway in multiple myeloma (MM), according to research published in Cancer Cell.

The investigators identified an interaction between the NF-κB-regulated antiapoptotic factor GADD45β and the JNK kinase MKK7 as a  therapeutic target in MM.

They then developed a drug known as DTP3, which disrupts the GADD45β/MKK7 complex, thereby killing MM cells in vitro and in vivo, without harming normal cells.

“Lab studies suggest that DTP3 could have therapeutic benefit for patients with multiple myeloma and potentially several other types of cancer, but we will need to confirm this in our clinical trials, the first of which will start next year,” said study author Guido Franzoso, MD, PhD, of Imperial College London in the UK.

Dr Franzoso and his colleagues knew that NF-κB is overactive in MM and other malignancies, but targeting NF-κB can have detrimental effects on healthy cells. So they looked for target genes downstream of NF-kB that might be responsible for its role in cancers.

By studying cells from MM patients, the investigators identified the protein complex GADD45β/MKK7, which appeared to play a critical role in allowing MM cells to survive.

Searching for a safe way to target the NF-kB pathway, the team screened more than 20,000 molecules and found 2 that disrupted GADD45β/MKK7. Further refinements led to the development of DTP3.

In human MM cells, DTP3 had a similar anticancer potency to that of bortezomib, but with a more than 100-fold higher cancer-cell specificity. DTP3 also retained full therapeutic efficacy in cell lines that were resistant to standard MM treatments.

In mice, DTP3 eradicated MM, with no apparent side effects at the effective doses.

In an orthotopic xenograft model of MM, control mice had a median overall survival of 26 days. But mice treated with DTP3 had a median overall survival that extended past the experimental endpoint on day 161.

“We had known for many years that NF-kB is very important for cancer cells, but because it is also needed by healthy cells, we did not know how to block it specifically,” Dr Franzoso said.

“The discovery that blocking the GADD45β/MKK7 segment of the NF-kB pathway with our DTP3 peptide therapeutic selectively kills myeloma cells could offer a completely new approach to treating patients with certain cancers, such as multiple myeloma.”

A spinout company, Kesios Therapeutics, was formed to commercialize DTP3 and other drug candidates based on Dr Franzoso’s research, with support from Imperial Innovations, a technology commercialization company focused on developing academic research in the UK.

Researchers in the lab

Credit: Rhoda Baer

A new drug can safely target the NF-κB pathway in multiple myeloma (MM), according to research published in Cancer Cell.

The investigators identified an interaction between the NF-κB-regulated antiapoptotic factor GADD45β and the JNK kinase MKK7 as a  therapeutic target in MM.

They then developed a drug known as DTP3, which disrupts the GADD45β/MKK7 complex, thereby killing MM cells in vitro and in vivo, without harming normal cells.

“Lab studies suggest that DTP3 could have therapeutic benefit for patients with multiple myeloma and potentially several other types of cancer, but we will need to confirm this in our clinical trials, the first of which will start next year,” said study author Guido Franzoso, MD, PhD, of Imperial College London in the UK.

Dr Franzoso and his colleagues knew that NF-κB is overactive in MM and other malignancies, but targeting NF-κB can have detrimental effects on healthy cells. So they looked for target genes downstream of NF-kB that might be responsible for its role in cancers.

By studying cells from MM patients, the investigators identified the protein complex GADD45β/MKK7, which appeared to play a critical role in allowing MM cells to survive.

Searching for a safe way to target the NF-kB pathway, the team screened more than 20,000 molecules and found 2 that disrupted GADD45β/MKK7. Further refinements led to the development of DTP3.

In human MM cells, DTP3 had a similar anticancer potency to that of bortezomib, but with a more than 100-fold higher cancer-cell specificity. DTP3 also retained full therapeutic efficacy in cell lines that were resistant to standard MM treatments.

In mice, DTP3 eradicated MM, with no apparent side effects at the effective doses.

In an orthotopic xenograft model of MM, control mice had a median overall survival of 26 days. But mice treated with DTP3 had a median overall survival that extended past the experimental endpoint on day 161.

“We had known for many years that NF-kB is very important for cancer cells, but because it is also needed by healthy cells, we did not know how to block it specifically,” Dr Franzoso said.

“The discovery that blocking the GADD45β/MKK7 segment of the NF-kB pathway with our DTP3 peptide therapeutic selectively kills myeloma cells could offer a completely new approach to treating patients with certain cancers, such as multiple myeloma.”

A spinout company, Kesios Therapeutics, was formed to commercialize DTP3 and other drug candidates based on Dr Franzoso’s research, with support from Imperial Innovations, a technology commercialization company focused on developing academic research in the UK.

The sea mollusk Aplysia

californica

releasing ink

after being disturbed

Results of preclinical research appear to explain how the anticancer agent doxorubicin can cause chemo brain.

Neuroscientists conducted experiments in cells from rats and Aplysia californica, a marine mollusk that has many of the same memory mechanisms as humans.

This revealed memory mechanisms that are inhibited by doxorubicin, as well as a method of unblocking these mechanisms—administering a drug known as SB203580.

“Our research has implications in the care of people given to cognitive deficits following drug treatment for cancer,” said John H. Byrne, PhD, of the University of Texas Health Medical School.

He added that understanding how drugs like doxorubicin impact the brain is an important first step in alleviating chemo brain, which is characterized by forgetfulness, trouble concentrating, and difficulty multitasking.

Dr Byrne and his colleagues explained this first step in The Journal of Neuroscience.

The researchers knew that, in non-neuronal cells, doxorubicin inhibits the expression of MAPK phosphatases, thereby inhibiting the dephosphorylation of ERK and p38 MAPK, 2 MAPK isoforms that are important for long-term memory.

To evaluate doxorubicin’s effects on levels of phosphorylated ERK and p38 MAPK, the team used cultures of cortical neurons from rats and sensory neurons from Aplysia californica.

Experiments showed that doxorubicin elevated levels of phosphorylated ERK and phosphorylated p38 MAPK in sensory neurons and cortical neurons. In addition, the drug increased phosphorylation of the downstream transcriptional repressor CREB2 in sensory neurons.

The researchers also assessed doxorubicin’s effects on long-term enhanced excitability, long-term synaptic facilitation, and long-term

synaptic depression.

They found that doxorubicin enhanced long-term synaptic depression induced by the neuropeptide Phe-Met-Arg-Phe-NH2. And the drug inhibited long-term synaptic facilitation induced by serotonin.

However, the researchers were able to restore long-term synaptic facilitation with SB203580, an inhibitor of p38 MAPK.

Unfortunately, SB203580 would not be appropriate for human use, Dr Byrne noted, adding that his team would like to identify other drugs that might have the same effect as SB203580.

The researchers also hope to determine if doxorubicin works the same way in humans as it did in these experiments.

The sea mollusk Aplysia

californica

releasing ink

after being disturbed

Results of preclinical research appear to explain how the anticancer agent doxorubicin can cause chemo brain.

Neuroscientists conducted experiments in cells from rats and Aplysia californica, a marine mollusk that has many of the same memory mechanisms as humans.

This revealed memory mechanisms that are inhibited by doxorubicin, as well as a method of unblocking these mechanisms—administering a drug known as SB203580.

“Our research has implications in the care of people given to cognitive deficits following drug treatment for cancer,” said John H. Byrne, PhD, of the University of Texas Health Medical School.

He added that understanding how drugs like doxorubicin impact the brain is an important first step in alleviating chemo brain, which is characterized by forgetfulness, trouble concentrating, and difficulty multitasking.

Dr Byrne and his colleagues explained this first step in The Journal of Neuroscience.

The researchers knew that, in non-neuronal cells, doxorubicin inhibits the expression of MAPK phosphatases, thereby inhibiting the dephosphorylation of ERK and p38 MAPK, 2 MAPK isoforms that are important for long-term memory.

To evaluate doxorubicin’s effects on levels of phosphorylated ERK and p38 MAPK, the team used cultures of cortical neurons from rats and sensory neurons from Aplysia californica.

Experiments showed that doxorubicin elevated levels of phosphorylated ERK and phosphorylated p38 MAPK in sensory neurons and cortical neurons. In addition, the drug increased phosphorylation of the downstream transcriptional repressor CREB2 in sensory neurons.

The researchers also assessed doxorubicin’s effects on long-term enhanced excitability, long-term synaptic facilitation, and long-term

synaptic depression.

They found that doxorubicin enhanced long-term synaptic depression induced by the neuropeptide Phe-Met-Arg-Phe-NH2. And the drug inhibited long-term synaptic facilitation induced by serotonin.

However, the researchers were able to restore long-term synaptic facilitation with SB203580, an inhibitor of p38 MAPK.

Unfortunately, SB203580 would not be appropriate for human use, Dr Byrne noted, adding that his team would like to identify other drugs that might have the same effect as SB203580.

The researchers also hope to determine if doxorubicin works the same way in humans as it did in these experiments.

The sea mollusk Aplysia

californica

releasing ink

after being disturbed

Results of preclinical research appear to explain how the anticancer agent doxorubicin can cause chemo brain.

Neuroscientists conducted experiments in cells from rats and Aplysia californica, a marine mollusk that has many of the same memory mechanisms as humans.

This revealed memory mechanisms that are inhibited by doxorubicin, as well as a method of unblocking these mechanisms—administering a drug known as SB203580.

“Our research has implications in the care of people given to cognitive deficits following drug treatment for cancer,” said John H. Byrne, PhD, of the University of Texas Health Medical School.

He added that understanding how drugs like doxorubicin impact the brain is an important first step in alleviating chemo brain, which is characterized by forgetfulness, trouble concentrating, and difficulty multitasking.

Dr Byrne and his colleagues explained this first step in The Journal of Neuroscience.

The researchers knew that, in non-neuronal cells, doxorubicin inhibits the expression of MAPK phosphatases, thereby inhibiting the dephosphorylation of ERK and p38 MAPK, 2 MAPK isoforms that are important for long-term memory.

To evaluate doxorubicin’s effects on levels of phosphorylated ERK and p38 MAPK, the team used cultures of cortical neurons from rats and sensory neurons from Aplysia californica.

Experiments showed that doxorubicin elevated levels of phosphorylated ERK and phosphorylated p38 MAPK in sensory neurons and cortical neurons. In addition, the drug increased phosphorylation of the downstream transcriptional repressor CREB2 in sensory neurons.

The researchers also assessed doxorubicin’s effects on long-term enhanced excitability, long-term synaptic facilitation, and long-term

synaptic depression.

They found that doxorubicin enhanced long-term synaptic depression induced by the neuropeptide Phe-Met-Arg-Phe-NH2. And the drug inhibited long-term synaptic facilitation induced by serotonin.

However, the researchers were able to restore long-term synaptic facilitation with SB203580, an inhibitor of p38 MAPK.

Unfortunately, SB203580 would not be appropriate for human use, Dr Byrne noted, adding that his team would like to identify other drugs that might have the same effect as SB203580.

The researchers also hope to determine if doxorubicin works the same way in humans as it did in these experiments.