Multiple Myeloma

Vials of drugs

Credit: Bill Branson

In a new draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) has recommended bortezomib (Velcade) for certain patients with newly diagnosed multiple myeloma (MM).

NICE is recommending the drug in combination with dexamethasone, or with dexamethasone and thalidomide, as induction treatment for adults with previously untreated MM who are eligible for high-dose chemotherapy with hematopoietic stem cell transplant (HSCT).

An appraisal committee said these regimens are clinically effective for this patient population. Trial data suggest the regimens confer a “clear advantage” over standard therapy with respect to induction response.

And it’s plausible that this may translate to improved survival, the committee said. (Standard treatment in the UK is a combination of cyclophosphamide, thalidomide, and dexamethasone.)

“Clinical specialists told the committee that induction treatment with bortezomib would enable a greater number of patients to proceed to [HSCT] and, consequently, prevent the disease from progressing for longer,” said Sir Andrew Dillon, NICE Chief Executive.

In addition, the committee said the bortezomib regimens are cost-effective for this patient population. The cost of bortezomib is £762.38 per 3.5 mg vial.

On average, a course of treatment with bortezomib given with dexamethasone costs £12,260.91. And a course of bortezomib given with dexamethasone and thalidomide costs £24,840.10.

The cost for bortezomib, thalidomide, and dexamethasone compared to thalidomide and dexamethasone is likely to be below £30,000 per quality-adjusted life-year gained.

The same is true when comparing bortezomib and dexamethasone to cyclophosphamide, thalidomide, and dexamethasone as well as vincristine, doxorubicin, and dexamethasone.

This draft guidance is now with consultees, who have the opportunity to appeal against it.

Other NICE recommendations for MM

NICE already recommends bortezomib monotherapy as a treatment option for MM patients at first relapse who have received one prior therapy and who have undergone, or are unsuitable for, HSCT.

Thalidomide in combination with an alkylating agent and a corticosteroid is recommended as a first-line treatment option in MM patients for whom high-dose chemotherapy with HSCT is considered inappropriate.

Bortezomib is also recommended under these circumstances, if the patient is unable to tolerate or has contraindications to thalidomide.

Lenalidomide in combination with dexamethasone is recommended as a treatment option for people with MM who have received 2 or more prior therapies.

Vials of drugs

Credit: Bill Branson

In a new draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) has recommended bortezomib (Velcade) for certain patients with newly diagnosed multiple myeloma (MM).

NICE is recommending the drug in combination with dexamethasone, or with dexamethasone and thalidomide, as induction treatment for adults with previously untreated MM who are eligible for high-dose chemotherapy with hematopoietic stem cell transplant (HSCT).

An appraisal committee said these regimens are clinically effective for this patient population. Trial data suggest the regimens confer a “clear advantage” over standard therapy with respect to induction response.

And it’s plausible that this may translate to improved survival, the committee said. (Standard treatment in the UK is a combination of cyclophosphamide, thalidomide, and dexamethasone.)

“Clinical specialists told the committee that induction treatment with bortezomib would enable a greater number of patients to proceed to [HSCT] and, consequently, prevent the disease from progressing for longer,” said Sir Andrew Dillon, NICE Chief Executive.

In addition, the committee said the bortezomib regimens are cost-effective for this patient population. The cost of bortezomib is £762.38 per 3.5 mg vial.

On average, a course of treatment with bortezomib given with dexamethasone costs £12,260.91. And a course of bortezomib given with dexamethasone and thalidomide costs £24,840.10.

The cost for bortezomib, thalidomide, and dexamethasone compared to thalidomide and dexamethasone is likely to be below £30,000 per quality-adjusted life-year gained.

The same is true when comparing bortezomib and dexamethasone to cyclophosphamide, thalidomide, and dexamethasone as well as vincristine, doxorubicin, and dexamethasone.

This draft guidance is now with consultees, who have the opportunity to appeal against it.

Other NICE recommendations for MM

NICE already recommends bortezomib monotherapy as a treatment option for MM patients at first relapse who have received one prior therapy and who have undergone, or are unsuitable for, HSCT.

Thalidomide in combination with an alkylating agent and a corticosteroid is recommended as a first-line treatment option in MM patients for whom high-dose chemotherapy with HSCT is considered inappropriate.

Bortezomib is also recommended under these circumstances, if the patient is unable to tolerate or has contraindications to thalidomide.

Lenalidomide in combination with dexamethasone is recommended as a treatment option for people with MM who have received 2 or more prior therapies.

Vials of drugs

Credit: Bill Branson

In a new draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) has recommended bortezomib (Velcade) for certain patients with newly diagnosed multiple myeloma (MM).

NICE is recommending the drug in combination with dexamethasone, or with dexamethasone and thalidomide, as induction treatment for adults with previously untreated MM who are eligible for high-dose chemotherapy with hematopoietic stem cell transplant (HSCT).

An appraisal committee said these regimens are clinically effective for this patient population. Trial data suggest the regimens confer a “clear advantage” over standard therapy with respect to induction response.

And it’s plausible that this may translate to improved survival, the committee said. (Standard treatment in the UK is a combination of cyclophosphamide, thalidomide, and dexamethasone.)

“Clinical specialists told the committee that induction treatment with bortezomib would enable a greater number of patients to proceed to [HSCT] and, consequently, prevent the disease from progressing for longer,” said Sir Andrew Dillon, NICE Chief Executive.

In addition, the committee said the bortezomib regimens are cost-effective for this patient population. The cost of bortezomib is £762.38 per 3.5 mg vial.

On average, a course of treatment with bortezomib given with dexamethasone costs £12,260.91. And a course of bortezomib given with dexamethasone and thalidomide costs £24,840.10.

The cost for bortezomib, thalidomide, and dexamethasone compared to thalidomide and dexamethasone is likely to be below £30,000 per quality-adjusted life-year gained.

The same is true when comparing bortezomib and dexamethasone to cyclophosphamide, thalidomide, and dexamethasone as well as vincristine, doxorubicin, and dexamethasone.

This draft guidance is now with consultees, who have the opportunity to appeal against it.

Other NICE recommendations for MM

NICE already recommends bortezomib monotherapy as a treatment option for MM patients at first relapse who have received one prior therapy and who have undergone, or are unsuitable for, HSCT.

Thalidomide in combination with an alkylating agent and a corticosteroid is recommended as a first-line treatment option in MM patients for whom high-dose chemotherapy with HSCT is considered inappropriate.

Bortezomib is also recommended under these circumstances, if the patient is unable to tolerate or has contraindications to thalidomide.

Lenalidomide in combination with dexamethasone is recommended as a treatment option for people with MM who have received 2 or more prior therapies.

Nurse treating a cancer patient

Credit: Rhoda Baer

New research indicates that less than 2% of trials funded by the National Cancer Institute focus on racial and ethnic minorities, and minority participation in adult cancer trials is not representative of the US population.

The researchers said these findings suggest we must do more to promote minority-focused research and clinical trial recruitment, beyond the National Institutes of Health (NIH) Revitalization Act of 1993, which mandated the appropriate inclusion of minorities in all NIH-funded research.

“What is needed is deliberate effort,” said study author Moon Chen, Jr, PhD, of the University of California, Davis. “Minorities are not hard to reach. They are hardly reached.”

To assess minority inclusion in clinical trials, Dr Chen and his colleagues searched ClinicalTrials.gov, looking for trials sponsored by the National Cancer Institute that were available in January 2013.

They searched using terms for different minority groups, then counted the number of clinical trials with a primary focus on a particular ethnic or minority population. Roughly 150 trials out of 10,000—or less than 2%—met the criteria.

The researchers also reviewed abstracts and articles accessed from January through March 2013 on PubMed to find those that specifically examined minority accrual in clinical trials.

Of the 42 citations found, 5 included reports explicitly discussing participation levels by race and ethnicity. Those reports revealed an “encouraging but less than optimal” increase in specification of race or ethnicity in published results of clinical trials.

Dr Chen and his colleagues also reported that participation of adult minorities is not proportional to their representation in the US population.

For example, African Americans experience the highest cancer incidence of any racial group (593.7 cases per 100,000), but they have the lowest rates of cancer trial participation (tied with Hispanics), at 1.3%. It’s important to note, however, that clinical trial participation is low for all adult cancer patients, at 3% to 5%.

In contrast, the researchers pointed out that 60% of all patients under age 15 are enrolled in clinical trials. And minority representation among children is excellent, either equal to or greater than their proportion of the population.

To put the adult population on par with the pediatric population, researchers should design trials to include and focus on specific populations, Dr Chen said. Furthermore, scientific journals should insist on appropriate representation and analyses of NIH research by race and ethnicity.

“Whatever happens in the laboratory or in the clinic needs to be applied to solving real-world problems,” Dr Chen said. “And those relate to the disproportionate effects of cancer and other diseases on racial and ethnic minorities.”

Dr Chen and his colleagues reported this research in Cancer.

Nurse treating a cancer patient

Credit: Rhoda Baer

New research indicates that less than 2% of trials funded by the National Cancer Institute focus on racial and ethnic minorities, and minority participation in adult cancer trials is not representative of the US population.

The researchers said these findings suggest we must do more to promote minority-focused research and clinical trial recruitment, beyond the National Institutes of Health (NIH) Revitalization Act of 1993, which mandated the appropriate inclusion of minorities in all NIH-funded research.

“What is needed is deliberate effort,” said study author Moon Chen, Jr, PhD, of the University of California, Davis. “Minorities are not hard to reach. They are hardly reached.”

To assess minority inclusion in clinical trials, Dr Chen and his colleagues searched ClinicalTrials.gov, looking for trials sponsored by the National Cancer Institute that were available in January 2013.

They searched using terms for different minority groups, then counted the number of clinical trials with a primary focus on a particular ethnic or minority population. Roughly 150 trials out of 10,000—or less than 2%—met the criteria.

The researchers also reviewed abstracts and articles accessed from January through March 2013 on PubMed to find those that specifically examined minority accrual in clinical trials.

Of the 42 citations found, 5 included reports explicitly discussing participation levels by race and ethnicity. Those reports revealed an “encouraging but less than optimal” increase in specification of race or ethnicity in published results of clinical trials.

Dr Chen and his colleagues also reported that participation of adult minorities is not proportional to their representation in the US population.

For example, African Americans experience the highest cancer incidence of any racial group (593.7 cases per 100,000), but they have the lowest rates of cancer trial participation (tied with Hispanics), at 1.3%. It’s important to note, however, that clinical trial participation is low for all adult cancer patients, at 3% to 5%.

In contrast, the researchers pointed out that 60% of all patients under age 15 are enrolled in clinical trials. And minority representation among children is excellent, either equal to or greater than their proportion of the population.

To put the adult population on par with the pediatric population, researchers should design trials to include and focus on specific populations, Dr Chen said. Furthermore, scientific journals should insist on appropriate representation and analyses of NIH research by race and ethnicity.

“Whatever happens in the laboratory or in the clinic needs to be applied to solving real-world problems,” Dr Chen said. “And those relate to the disproportionate effects of cancer and other diseases on racial and ethnic minorities.”

Dr Chen and his colleagues reported this research in Cancer.

Nurse treating a cancer patient

Credit: Rhoda Baer

New research indicates that less than 2% of trials funded by the National Cancer Institute focus on racial and ethnic minorities, and minority participation in adult cancer trials is not representative of the US population.

The researchers said these findings suggest we must do more to promote minority-focused research and clinical trial recruitment, beyond the National Institutes of Health (NIH) Revitalization Act of 1993, which mandated the appropriate inclusion of minorities in all NIH-funded research.

“What is needed is deliberate effort,” said study author Moon Chen, Jr, PhD, of the University of California, Davis. “Minorities are not hard to reach. They are hardly reached.”

To assess minority inclusion in clinical trials, Dr Chen and his colleagues searched ClinicalTrials.gov, looking for trials sponsored by the National Cancer Institute that were available in January 2013.

They searched using terms for different minority groups, then counted the number of clinical trials with a primary focus on a particular ethnic or minority population. Roughly 150 trials out of 10,000—or less than 2%—met the criteria.

The researchers also reviewed abstracts and articles accessed from January through March 2013 on PubMed to find those that specifically examined minority accrual in clinical trials.

Of the 42 citations found, 5 included reports explicitly discussing participation levels by race and ethnicity. Those reports revealed an “encouraging but less than optimal” increase in specification of race or ethnicity in published results of clinical trials.

Dr Chen and his colleagues also reported that participation of adult minorities is not proportional to their representation in the US population.

For example, African Americans experience the highest cancer incidence of any racial group (593.7 cases per 100,000), but they have the lowest rates of cancer trial participation (tied with Hispanics), at 1.3%. It’s important to note, however, that clinical trial participation is low for all adult cancer patients, at 3% to 5%.

In contrast, the researchers pointed out that 60% of all patients under age 15 are enrolled in clinical trials. And minority representation among children is excellent, either equal to or greater than their proportion of the population.

To put the adult population on par with the pediatric population, researchers should design trials to include and focus on specific populations, Dr Chen said. Furthermore, scientific journals should insist on appropriate representation and analyses of NIH research by race and ethnicity.

“Whatever happens in the laboratory or in the clinic needs to be applied to solving real-world problems,” Dr Chen said. “And those relate to the disproportionate effects of cancer and other diseases on racial and ethnic minorities.”

Dr Chen and his colleagues reported this research in Cancer.

Prescription medications

Credit: CDC

The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending against the use of lenalidomide (Revlimid) in multiple myeloma (MM) patients who have previously received bortezomib.

Based on current information, NICE has said it cannot recommend the drug for patients who have received bortezomib once and are unable to receive thalidomide or undergo hematopoietic stem cell transplant.

NICE’s previous recommendation regarding lenalidomide in MM has not changed. The drug will still be available through the National Health Service (NHS) for MM patients who have received 2 or more prior therapies.

“We are now looking specifically at how well lenalidomide works after someone has received bortezomib, and whether it provides value for money,” said Sir Andrew Dillon, NICE Chief Executive.

“However, from the information provided by the manufacturer, it was unclear if lenalidomide was as effective as re-treatment with bortezomib, and the manufacturer’s own economic model showed that the drug would not be cost effective at this stage.”

“Because of this, we are unable to recommend the drug in preliminary recommendations. We hope that the manufacturer, Celgene, will look again at their submission.”

NICE also pointed out that, since the organization recommended lenalidomide for MM in 2009, there have been no studies comparing lenalidomide to other treatments in these patients. Celgene has only provided data comparing lenalidomide to placebo.

In addition, for the 2009 guidance, Celgene submitted a patient access scheme, where they bear the costs of the drug beyond 26 cycles (normally for a period of 2 years). And this enabled NICE to recommend the drug. But Celgene has not submitted a patient access scheme for the current appraisal.

NICE considered all the cost effectiveness models Celgene submitted to be fundamentally flawed.

NICE concluded that the most plausible costs per quality-adjusted life-year for lenalidomide compared with bortezomib or standard chemotherapies were more than £30,000, whether bortezomib re-treatment was appropriate or not.

Lenalidomide is available as a 21-capsule pack. The cost per pack varies according to capsule size: £3570 (5 mg), £3780 (10 mg), £3969 (15 mg), and £4368 (25 mg). The recommended starting dose is 25 mg orally, once daily on days 1-21 of repeated 28-day cycles.

The draft guidance is open for public comment until April 4. Until a final guidance is issued, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance, it replaces local recommendations.

Prescription medications

Credit: CDC

The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending against the use of lenalidomide (Revlimid) in multiple myeloma (MM) patients who have previously received bortezomib.

Based on current information, NICE has said it cannot recommend the drug for patients who have received bortezomib once and are unable to receive thalidomide or undergo hematopoietic stem cell transplant.

NICE’s previous recommendation regarding lenalidomide in MM has not changed. The drug will still be available through the National Health Service (NHS) for MM patients who have received 2 or more prior therapies.

“We are now looking specifically at how well lenalidomide works after someone has received bortezomib, and whether it provides value for money,” said Sir Andrew Dillon, NICE Chief Executive.

“However, from the information provided by the manufacturer, it was unclear if lenalidomide was as effective as re-treatment with bortezomib, and the manufacturer’s own economic model showed that the drug would not be cost effective at this stage.”

“Because of this, we are unable to recommend the drug in preliminary recommendations. We hope that the manufacturer, Celgene, will look again at their submission.”

NICE also pointed out that, since the organization recommended lenalidomide for MM in 2009, there have been no studies comparing lenalidomide to other treatments in these patients. Celgene has only provided data comparing lenalidomide to placebo.

In addition, for the 2009 guidance, Celgene submitted a patient access scheme, where they bear the costs of the drug beyond 26 cycles (normally for a period of 2 years). And this enabled NICE to recommend the drug. But Celgene has not submitted a patient access scheme for the current appraisal.

NICE considered all the cost effectiveness models Celgene submitted to be fundamentally flawed.

NICE concluded that the most plausible costs per quality-adjusted life-year for lenalidomide compared with bortezomib or standard chemotherapies were more than £30,000, whether bortezomib re-treatment was appropriate or not.

Lenalidomide is available as a 21-capsule pack. The cost per pack varies according to capsule size: £3570 (5 mg), £3780 (10 mg), £3969 (15 mg), and £4368 (25 mg). The recommended starting dose is 25 mg orally, once daily on days 1-21 of repeated 28-day cycles.

The draft guidance is open for public comment until April 4. Until a final guidance is issued, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance, it replaces local recommendations.

Prescription medications

Credit: CDC

The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending against the use of lenalidomide (Revlimid) in multiple myeloma (MM) patients who have previously received bortezomib.

Based on current information, NICE has said it cannot recommend the drug for patients who have received bortezomib once and are unable to receive thalidomide or undergo hematopoietic stem cell transplant.

NICE’s previous recommendation regarding lenalidomide in MM has not changed. The drug will still be available through the National Health Service (NHS) for MM patients who have received 2 or more prior therapies.

“We are now looking specifically at how well lenalidomide works after someone has received bortezomib, and whether it provides value for money,” said Sir Andrew Dillon, NICE Chief Executive.

“However, from the information provided by the manufacturer, it was unclear if lenalidomide was as effective as re-treatment with bortezomib, and the manufacturer’s own economic model showed that the drug would not be cost effective at this stage.”

“Because of this, we are unable to recommend the drug in preliminary recommendations. We hope that the manufacturer, Celgene, will look again at their submission.”

NICE also pointed out that, since the organization recommended lenalidomide for MM in 2009, there have been no studies comparing lenalidomide to other treatments in these patients. Celgene has only provided data comparing lenalidomide to placebo.

In addition, for the 2009 guidance, Celgene submitted a patient access scheme, where they bear the costs of the drug beyond 26 cycles (normally for a period of 2 years). And this enabled NICE to recommend the drug. But Celgene has not submitted a patient access scheme for the current appraisal.

NICE considered all the cost effectiveness models Celgene submitted to be fundamentally flawed.

NICE concluded that the most plausible costs per quality-adjusted life-year for lenalidomide compared with bortezomib or standard chemotherapies were more than £30,000, whether bortezomib re-treatment was appropriate or not.

Lenalidomide is available as a 21-capsule pack. The cost per pack varies according to capsule size: £3570 (5 mg), £3780 (10 mg), £3969 (15 mg), and £4368 (25 mg). The recommended starting dose is 25 mg orally, once daily on days 1-21 of repeated 28-day cycles.

The draft guidance is open for public comment until April 4. Until a final guidance is issued, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance, it replaces local recommendations.

Candida albicans

The US Food and Drug Administration has approved an intravenous formulation of posaconazole (Noxafil), which is expected to be available at wholesalers in mid-April.

The antifungal agent is already available as delayed-release tablets and in an oral suspension formulation.

In any formulation, posaconazole is indicated for prophylaxis of invasive Aspergillus and Candida infections in immunocompromised patients who are at high risk of developing these infections.

This includes patients who have developed graft-vs-host disease after hematopoietic stem cell transplant and patients with hematologic malignancies who have prolonged neutropenia resulting from chemotherapy.

Posaconazole injection is indicated for use in patients 18 years of age and older. The delayed-release tablets and oral suspension are indicated for patients 13 years of age and older.

Posaconazole injection is administered with a loading dose of 300 mg (one 300 mg vial) twice a day on the first day of therapy, then 300 mg once a day thereafter. It is given through a central venous line by slow intravenous infusion over approximately 90 minutes.

Once combined with a mixture of intravenous solution (150 mL of 5% dextrose in water or sodium chloride 0.9%), posaconazole injection should be administered immediately. If not used immediately, the solution can be stored up to 24 hours if refrigerated at 2-8 degrees C (36-46 degrees F).

Co-administration of drugs that can decrease the plasma concentration of posaconazole should be avoided unless the benefit outweighs the risk. If such drugs are necessary, patients should be monitored closely for breakthrough fungal infections.

In clinical trials, the adverse reactions reported for posaconazole injection were generally similar to those reported in trials of posaconazole oral suspension. The most frequently reported adverse reactions with an onset during the posaconazole intravenous phase of dosing 300 mg once-daily therapy were diarrhea (32%), hypokalemia (22%), fever (21%), and nausea (19%).

Patients who are allergic to posaconazole or other azole antifungal medicines should not receive posaconazole. The drug should not be given along with sirolimus, pimozide, quinidine, atorvastatin, lovastatin, simvastatin, or ergot alkaloids.

Drugs such as cyclosporine and tacrolimus require dose adjustments and frequent blood monitoring when administered with posaconazole. Serious side effects, including nephrotoxicity, leukoencephalopathy, and death, have been reported in patients with increased cyclosporine or tacrolimus blood levels.

Healthcare professionals should use caution when administering posaconazole to patients at risk of developing an irregular heart rhythm, as the drug has been shown to prolong the QT interval, and cases of potentially fatal irregular heart rhythm (torsades de pointes) have been reported in patients taking posaconazole.

For more details, see the complete prescribing information. Posaconazole is marketed as Noxafil by Merck.

Candida albicans

The US Food and Drug Administration has approved an intravenous formulation of posaconazole (Noxafil), which is expected to be available at wholesalers in mid-April.

The antifungal agent is already available as delayed-release tablets and in an oral suspension formulation.

In any formulation, posaconazole is indicated for prophylaxis of invasive Aspergillus and Candida infections in immunocompromised patients who are at high risk of developing these infections.

This includes patients who have developed graft-vs-host disease after hematopoietic stem cell transplant and patients with hematologic malignancies who have prolonged neutropenia resulting from chemotherapy.

Posaconazole injection is indicated for use in patients 18 years of age and older. The delayed-release tablets and oral suspension are indicated for patients 13 years of age and older.

Posaconazole injection is administered with a loading dose of 300 mg (one 300 mg vial) twice a day on the first day of therapy, then 300 mg once a day thereafter. It is given through a central venous line by slow intravenous infusion over approximately 90 minutes.

Once combined with a mixture of intravenous solution (150 mL of 5% dextrose in water or sodium chloride 0.9%), posaconazole injection should be administered immediately. If not used immediately, the solution can be stored up to 24 hours if refrigerated at 2-8 degrees C (36-46 degrees F).

Co-administration of drugs that can decrease the plasma concentration of posaconazole should be avoided unless the benefit outweighs the risk. If such drugs are necessary, patients should be monitored closely for breakthrough fungal infections.

In clinical trials, the adverse reactions reported for posaconazole injection were generally similar to those reported in trials of posaconazole oral suspension. The most frequently reported adverse reactions with an onset during the posaconazole intravenous phase of dosing 300 mg once-daily therapy were diarrhea (32%), hypokalemia (22%), fever (21%), and nausea (19%).

Patients who are allergic to posaconazole or other azole antifungal medicines should not receive posaconazole. The drug should not be given along with sirolimus, pimozide, quinidine, atorvastatin, lovastatin, simvastatin, or ergot alkaloids.

Drugs such as cyclosporine and tacrolimus require dose adjustments and frequent blood monitoring when administered with posaconazole. Serious side effects, including nephrotoxicity, leukoencephalopathy, and death, have been reported in patients with increased cyclosporine or tacrolimus blood levels.

Healthcare professionals should use caution when administering posaconazole to patients at risk of developing an irregular heart rhythm, as the drug has been shown to prolong the QT interval, and cases of potentially fatal irregular heart rhythm (torsades de pointes) have been reported in patients taking posaconazole.

For more details, see the complete prescribing information. Posaconazole is marketed as Noxafil by Merck.

Candida albicans

The US Food and Drug Administration has approved an intravenous formulation of posaconazole (Noxafil), which is expected to be available at wholesalers in mid-April.

The antifungal agent is already available as delayed-release tablets and in an oral suspension formulation.

In any formulation, posaconazole is indicated for prophylaxis of invasive Aspergillus and Candida infections in immunocompromised patients who are at high risk of developing these infections.

This includes patients who have developed graft-vs-host disease after hematopoietic stem cell transplant and patients with hematologic malignancies who have prolonged neutropenia resulting from chemotherapy.

Posaconazole injection is indicated for use in patients 18 years of age and older. The delayed-release tablets and oral suspension are indicated for patients 13 years of age and older.

Posaconazole injection is administered with a loading dose of 300 mg (one 300 mg vial) twice a day on the first day of therapy, then 300 mg once a day thereafter. It is given through a central venous line by slow intravenous infusion over approximately 90 minutes.

Once combined with a mixture of intravenous solution (150 mL of 5% dextrose in water or sodium chloride 0.9%), posaconazole injection should be administered immediately. If not used immediately, the solution can be stored up to 24 hours if refrigerated at 2-8 degrees C (36-46 degrees F).

Co-administration of drugs that can decrease the plasma concentration of posaconazole should be avoided unless the benefit outweighs the risk. If such drugs are necessary, patients should be monitored closely for breakthrough fungal infections.

In clinical trials, the adverse reactions reported for posaconazole injection were generally similar to those reported in trials of posaconazole oral suspension. The most frequently reported adverse reactions with an onset during the posaconazole intravenous phase of dosing 300 mg once-daily therapy were diarrhea (32%), hypokalemia (22%), fever (21%), and nausea (19%).

Patients who are allergic to posaconazole or other azole antifungal medicines should not receive posaconazole. The drug should not be given along with sirolimus, pimozide, quinidine, atorvastatin, lovastatin, simvastatin, or ergot alkaloids.

Drugs such as cyclosporine and tacrolimus require dose adjustments and frequent blood monitoring when administered with posaconazole. Serious side effects, including nephrotoxicity, leukoencephalopathy, and death, have been reported in patients with increased cyclosporine or tacrolimus blood levels.

Healthcare professionals should use caution when administering posaconazole to patients at risk of developing an irregular heart rhythm, as the drug has been shown to prolong the QT interval, and cases of potentially fatal irregular heart rhythm (torsades de pointes) have been reported in patients taking posaconazole.

For more details, see the complete prescribing information. Posaconazole is marketed as Noxafil by Merck.

Drug release in a cancer cell

Credit: PNAS

Researchers say they’ve discovered how a class of diabetes drugs known as biguanides exerts anticancer properties in certain malignancies.

The team identified a mitochondrial pathway that imbues cancer cells with the ability to survive in low-glucose environments.

By finding cancer cells with defects in this pathway or impaired glucose utilization, the researchers found they could predict which cancers would be sensitive to drugs that inhibit this pathway.

And follow-up experiments confirmed that lymphoma, leukemia, and myeloma tumors were among those sensitive to treatment.

Kivanç Birsoy, PhD, of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, and his colleagues reported these findings in Nature.

To study how cancer cells survive in the kind of low-glucose environment found within cancerous tumors, the researchers developed a system that circulates low-nutrient media continuously around cells.

Of the 30 cancer cell lines the team tested within this system, most appeared unaffected by a lack of glucose. However, a few of the cells lines thrived and reproduced rapidly, while others struggled.

Specifically, a low-glucose environment prompted an increase in proliferation for the Burkitt lymphoma cell line Raji, as well as in medulloblastoma, lung, and stomach cancer cell lines.

However, the lymphoma cell lines U-937 and MC116, as well as the myeloma cell lines NCI-H929 and KMS-26, saw significant decreases in proliferation in a low-glucose environment. The leukemia cell line Jurkat was moderately sensitive to a low-glucose environment.

“No one really understood why cancer cells had these responses or whether they were important for the formation of the tumor,” said study author Richard Possemato, PhD, also of the Whitehead Institute.

To gain more insight, the researchers screened overly distressed cells for genes whose suppression improved or further hindered the cells’ survival rates. The screen flagged genes involved in glucose transportation and oxidative phosphorylation.

The team hypothesized that cancer cells with mutations in these genes are over-taxing their mitochondria under normal conditions. When placed in a harsh, low-glucose environment, the mitochondria are maxed out, and the cells suffer.

If true, the hypothesis would suggest that further impairing mitochondrial function with biguanides, which are known oxidative phosphorylation inhibitors, could push the mitochondria beyond their limits, to the detriment of the cancer cells.

The researchers first tested this hypothesis in vitro on cell lines with glucose utilization defects (NCI-H929, KMS-26, LP-1, L-363, MOLP-8, D341Med, and KMS-28BM) or mitochondrial DNA (mtDNA) mutations (U-937, BxPC3, Cal-62, HCC-1438, HCC-827, and NU-DHL-1).

They found that, in a low-glucose environment, cell lines with mtDNA mutations or impaired glucose utilization were 5 to 20 times more susceptible to phenformin, a more potent biguanide than metformin, when compared to control cancer cell lines or an immortalized B-cell line.

The team then tested phenformin in mice implanted with tumors derived from low-glucose-sensitive cancer cells. The drug inhibited the growth of tumors derived from cancer cells with mtDNA mutations (Cal-62 and U-937) or poor glucose consumption (KMS-26 and NCI-H929) but not from cells lacking these defects (NCI-H2171 and NCI-H82).

“These results show that mitochondrial DNA mutations and glucose import defects can be used as biomarkers for biguanide sensitivity to determine if a cancer patient might benefit from these drugs,” Dr Birsoy said.

“And this is the first time that anyone has shown that the direct cytotoxic effects of this class of drugs, including metformin and phenformin, on cancer cells are mediated through their effect on mitochondria.”

To confirm the accuracy of their proposed biomarkers, the researchers now want to analyze previous clinical trials to see if cancer patients with the proposed biomarkers fared better with metformin treatment than patients without the biomarkers.

Drug release in a cancer cell

Credit: PNAS

Researchers say they’ve discovered how a class of diabetes drugs known as biguanides exerts anticancer properties in certain malignancies.

The team identified a mitochondrial pathway that imbues cancer cells with the ability to survive in low-glucose environments.

By finding cancer cells with defects in this pathway or impaired glucose utilization, the researchers found they could predict which cancers would be sensitive to drugs that inhibit this pathway.

And follow-up experiments confirmed that lymphoma, leukemia, and myeloma tumors were among those sensitive to treatment.

Kivanç Birsoy, PhD, of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, and his colleagues reported these findings in Nature.

To study how cancer cells survive in the kind of low-glucose environment found within cancerous tumors, the researchers developed a system that circulates low-nutrient media continuously around cells.

Of the 30 cancer cell lines the team tested within this system, most appeared unaffected by a lack of glucose. However, a few of the cells lines thrived and reproduced rapidly, while others struggled.

Specifically, a low-glucose environment prompted an increase in proliferation for the Burkitt lymphoma cell line Raji, as well as in medulloblastoma, lung, and stomach cancer cell lines.

However, the lymphoma cell lines U-937 and MC116, as well as the myeloma cell lines NCI-H929 and KMS-26, saw significant decreases in proliferation in a low-glucose environment. The leukemia cell line Jurkat was moderately sensitive to a low-glucose environment.

“No one really understood why cancer cells had these responses or whether they were important for the formation of the tumor,” said study author Richard Possemato, PhD, also of the Whitehead Institute.

To gain more insight, the researchers screened overly distressed cells for genes whose suppression improved or further hindered the cells’ survival rates. The screen flagged genes involved in glucose transportation and oxidative phosphorylation.

The team hypothesized that cancer cells with mutations in these genes are over-taxing their mitochondria under normal conditions. When placed in a harsh, low-glucose environment, the mitochondria are maxed out, and the cells suffer.

If true, the hypothesis would suggest that further impairing mitochondrial function with biguanides, which are known oxidative phosphorylation inhibitors, could push the mitochondria beyond their limits, to the detriment of the cancer cells.

The researchers first tested this hypothesis in vitro on cell lines with glucose utilization defects (NCI-H929, KMS-26, LP-1, L-363, MOLP-8, D341Med, and KMS-28BM) or mitochondrial DNA (mtDNA) mutations (U-937, BxPC3, Cal-62, HCC-1438, HCC-827, and NU-DHL-1).

They found that, in a low-glucose environment, cell lines with mtDNA mutations or impaired glucose utilization were 5 to 20 times more susceptible to phenformin, a more potent biguanide than metformin, when compared to control cancer cell lines or an immortalized B-cell line.

The team then tested phenformin in mice implanted with tumors derived from low-glucose-sensitive cancer cells. The drug inhibited the growth of tumors derived from cancer cells with mtDNA mutations (Cal-62 and U-937) or poor glucose consumption (KMS-26 and NCI-H929) but not from cells lacking these defects (NCI-H2171 and NCI-H82).

“These results show that mitochondrial DNA mutations and glucose import defects can be used as biomarkers for biguanide sensitivity to determine if a cancer patient might benefit from these drugs,” Dr Birsoy said.

“And this is the first time that anyone has shown that the direct cytotoxic effects of this class of drugs, including metformin and phenformin, on cancer cells are mediated through their effect on mitochondria.”

To confirm the accuracy of their proposed biomarkers, the researchers now want to analyze previous clinical trials to see if cancer patients with the proposed biomarkers fared better with metformin treatment than patients without the biomarkers.

Drug release in a cancer cell

Credit: PNAS

Researchers say they’ve discovered how a class of diabetes drugs known as biguanides exerts anticancer properties in certain malignancies.

The team identified a mitochondrial pathway that imbues cancer cells with the ability to survive in low-glucose environments.

By finding cancer cells with defects in this pathway or impaired glucose utilization, the researchers found they could predict which cancers would be sensitive to drugs that inhibit this pathway.

And follow-up experiments confirmed that lymphoma, leukemia, and myeloma tumors were among those sensitive to treatment.

Kivanç Birsoy, PhD, of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, and his colleagues reported these findings in Nature.

To study how cancer cells survive in the kind of low-glucose environment found within cancerous tumors, the researchers developed a system that circulates low-nutrient media continuously around cells.

Of the 30 cancer cell lines the team tested within this system, most appeared unaffected by a lack of glucose. However, a few of the cells lines thrived and reproduced rapidly, while others struggled.

Specifically, a low-glucose environment prompted an increase in proliferation for the Burkitt lymphoma cell line Raji, as well as in medulloblastoma, lung, and stomach cancer cell lines.

However, the lymphoma cell lines U-937 and MC116, as well as the myeloma cell lines NCI-H929 and KMS-26, saw significant decreases in proliferation in a low-glucose environment. The leukemia cell line Jurkat was moderately sensitive to a low-glucose environment.

“No one really understood why cancer cells had these responses or whether they were important for the formation of the tumor,” said study author Richard Possemato, PhD, also of the Whitehead Institute.

To gain more insight, the researchers screened overly distressed cells for genes whose suppression improved or further hindered the cells’ survival rates. The screen flagged genes involved in glucose transportation and oxidative phosphorylation.

The team hypothesized that cancer cells with mutations in these genes are over-taxing their mitochondria under normal conditions. When placed in a harsh, low-glucose environment, the mitochondria are maxed out, and the cells suffer.

If true, the hypothesis would suggest that further impairing mitochondrial function with biguanides, which are known oxidative phosphorylation inhibitors, could push the mitochondria beyond their limits, to the detriment of the cancer cells.

The researchers first tested this hypothesis in vitro on cell lines with glucose utilization defects (NCI-H929, KMS-26, LP-1, L-363, MOLP-8, D341Med, and KMS-28BM) or mitochondrial DNA (mtDNA) mutations (U-937, BxPC3, Cal-62, HCC-1438, HCC-827, and NU-DHL-1).

They found that, in a low-glucose environment, cell lines with mtDNA mutations or impaired glucose utilization were 5 to 20 times more susceptible to phenformin, a more potent biguanide than metformin, when compared to control cancer cell lines or an immortalized B-cell line.

The team then tested phenformin in mice implanted with tumors derived from low-glucose-sensitive cancer cells. The drug inhibited the growth of tumors derived from cancer cells with mtDNA mutations (Cal-62 and U-937) or poor glucose consumption (KMS-26 and NCI-H929) but not from cells lacking these defects (NCI-H2171 and NCI-H82).

“These results show that mitochondrial DNA mutations and glucose import defects can be used as biomarkers for biguanide sensitivity to determine if a cancer patient might benefit from these drugs,” Dr Birsoy said.

“And this is the first time that anyone has shown that the direct cytotoxic effects of this class of drugs, including metformin and phenformin, on cancer cells are mediated through their effect on mitochondria.”

To confirm the accuracy of their proposed biomarkers, the researchers now want to analyze previous clinical trials to see if cancer patients with the proposed biomarkers fared better with metformin treatment than patients without the biomarkers.

The US Food and Drug Administration (FDA) has issued a full clinical hold for the telomerase inhibitor imetelstat, citing concerns that long-term exposure to the drug may pose a risk of chronic liver injury.

The hold temporarily suspends all ongoing clinical trials of imetelstat sponsored by the drug’s maker, Geron Corporation.

It’s possible that other studies of imetelstat, such as ongoing investigator-sponsored trials, may be placed on hold as well.

At present, the hold affects the remaining 8 patients enrolled on Geron’s phase 2 study of imetelstat in essential thrombocythemia and polycythemia vera.

It also affects the remaining 2 patients in the company’s phase 2 study of the drug in previously treated multiple myeloma. And Geron believes its planned phase 2 trial of imetelstat in myelofibrosis will likely be delayed as well.

The FDA has not yet issued a written notice of the hold but has given Geron verbal notice.

The agency indicated that the hold is due to persistent low-grade liver function test abnormalities observed in the study of imetelstat in patients with essential thrombocythemia or polycythemia vera and the potential risk of chronic liver injury following long-term exposure to imetelstat.

The FDA expressed concerns about whether these abnormalities are reversible. Geron said it plans to work with the FDA to put an end to the hold.

The US Food and Drug Administration (FDA) has issued a full clinical hold for the telomerase inhibitor imetelstat, citing concerns that long-term exposure to the drug may pose a risk of chronic liver injury.

The hold temporarily suspends all ongoing clinical trials of imetelstat sponsored by the drug’s maker, Geron Corporation.

It’s possible that other studies of imetelstat, such as ongoing investigator-sponsored trials, may be placed on hold as well.

At present, the hold affects the remaining 8 patients enrolled on Geron’s phase 2 study of imetelstat in essential thrombocythemia and polycythemia vera.

It also affects the remaining 2 patients in the company’s phase 2 study of the drug in previously treated multiple myeloma. And Geron believes its planned phase 2 trial of imetelstat in myelofibrosis will likely be delayed as well.

The FDA has not yet issued a written notice of the hold but has given Geron verbal notice.

The agency indicated that the hold is due to persistent low-grade liver function test abnormalities observed in the study of imetelstat in patients with essential thrombocythemia or polycythemia vera and the potential risk of chronic liver injury following long-term exposure to imetelstat.

The FDA expressed concerns about whether these abnormalities are reversible. Geron said it plans to work with the FDA to put an end to the hold.

The US Food and Drug Administration (FDA) has issued a full clinical hold for the telomerase inhibitor imetelstat, citing concerns that long-term exposure to the drug may pose a risk of chronic liver injury.

The hold temporarily suspends all ongoing clinical trials of imetelstat sponsored by the drug’s maker, Geron Corporation.

It’s possible that other studies of imetelstat, such as ongoing investigator-sponsored trials, may be placed on hold as well.

At present, the hold affects the remaining 8 patients enrolled on Geron’s phase 2 study of imetelstat in essential thrombocythemia and polycythemia vera.

It also affects the remaining 2 patients in the company’s phase 2 study of the drug in previously treated multiple myeloma. And Geron believes its planned phase 2 trial of imetelstat in myelofibrosis will likely be delayed as well.

The FDA has not yet issued a written notice of the hold but has given Geron verbal notice.

The agency indicated that the hold is due to persistent low-grade liver function test abnormalities observed in the study of imetelstat in patients with essential thrombocythemia or polycythemia vera and the potential risk of chronic liver injury following long-term exposure to imetelstat.

The FDA expressed concerns about whether these abnormalities are reversible. Geron said it plans to work with the FDA to put an end to the hold.

Patient consulting pharmacist

Credit: Rhoda Baer

Cancer patients in England are more likely to receive prescriptions for expensive drugs than patients in Wales, according to a study published in the British Journal of Cancer.

The research suggests this disparity is associated with the Cancer Drugs Fund (CDF), money set aside by the English government to pay for drugs that haven’t been approved by the National Institute for Health and Care Excellence (NICE) and aren’t available within the National Health Service (NHS).

The governments of Wales, Scotland, and Northern Ireland do not have access to the CDF or have similar programs of their own.

“There’s been much debate surrounding the Cancer Drugs Fund,” said study author Charlotte Chamberlain, MBBS, of the University of Bristol in the UK.

“The vast majority of Cancer Drugs Fund drugs do not cure the cancer but may extend life or improve symptoms in some people. The high cost of these drugs means that the NHS cannot afford other treatments, and, therefore, critics argue that public money is being spent inefficiently.”

To assess the impact of the CDF, Dr Chamberlain and her colleagues analyzed data from hospital pharmacies in England and Wales from August 2007 to December 2012. (The CDF was established in 2010, and the researchers wanted to capture data from before and after its introduction.)

The team evaluated 15 drugs that represent different categories of NICE approval—recommended, not recommended, and not yet appraised.

The results showed that, after the CDF was established, drugs recommended by NICE were not prescribed any more in England than in Wales.

However, drugs that were rejected by NICE because they were not cost-effective were prescribed up to 7 times more often in England than in Wales. For example, in the year before the CDF was introduced, prescription rates of imatinib (which is not recommended by NICE) were substantially higher in England than in Wales.

Immediately before the introduction of the CDF, following the first NICE rejection, imatinib prescribing declined in both countries. But it declined more slowly in England than in Wales, despite 2 additional NICE rejections. Regression analysis showed evidence of an association between the CDF and increased prescribing in England compared to Wales (P<0.001).

The research also revealed surprising information regarding the 3 most recently launched drugs—bendamustine, pazopanib, and abiraterone, which were awaiting NICE appraisal when the CDF was established but have since been approved.

These drugs were prescribed less often in England than in Wales. For instance, prescription rates of bendamustine were 25% lower in England.

This finding suggests that physicians in England have been slower to adopt newer drugs that are cost-effective, the researchers said.

“Our research has highlighted that the CDF has created an inequality between cancer sufferers in England and those in Wales,” Dr Chamberlain noted. “This raises ethical, moral, financial, and policy concerns.”

Patient consulting pharmacist

Credit: Rhoda Baer

Cancer patients in England are more likely to receive prescriptions for expensive drugs than patients in Wales, according to a study published in the British Journal of Cancer.

The research suggests this disparity is associated with the Cancer Drugs Fund (CDF), money set aside by the English government to pay for drugs that haven’t been approved by the National Institute for Health and Care Excellence (NICE) and aren’t available within the National Health Service (NHS).

The governments of Wales, Scotland, and Northern Ireland do not have access to the CDF or have similar programs of their own.

“There’s been much debate surrounding the Cancer Drugs Fund,” said study author Charlotte Chamberlain, MBBS, of the University of Bristol in the UK.

“The vast majority of Cancer Drugs Fund drugs do not cure the cancer but may extend life or improve symptoms in some people. The high cost of these drugs means that the NHS cannot afford other treatments, and, therefore, critics argue that public money is being spent inefficiently.”

To assess the impact of the CDF, Dr Chamberlain and her colleagues analyzed data from hospital pharmacies in England and Wales from August 2007 to December 2012. (The CDF was established in 2010, and the researchers wanted to capture data from before and after its introduction.)

The team evaluated 15 drugs that represent different categories of NICE approval—recommended, not recommended, and not yet appraised.

The results showed that, after the CDF was established, drugs recommended by NICE were not prescribed any more in England than in Wales.

However, drugs that were rejected by NICE because they were not cost-effective were prescribed up to 7 times more often in England than in Wales. For example, in the year before the CDF was introduced, prescription rates of imatinib (which is not recommended by NICE) were substantially higher in England than in Wales.

Immediately before the introduction of the CDF, following the first NICE rejection, imatinib prescribing declined in both countries. But it declined more slowly in England than in Wales, despite 2 additional NICE rejections. Regression analysis showed evidence of an association between the CDF and increased prescribing in England compared to Wales (P<0.001).

The research also revealed surprising information regarding the 3 most recently launched drugs—bendamustine, pazopanib, and abiraterone, which were awaiting NICE appraisal when the CDF was established but have since been approved.

These drugs were prescribed less often in England than in Wales. For instance, prescription rates of bendamustine were 25% lower in England.

This finding suggests that physicians in England have been slower to adopt newer drugs that are cost-effective, the researchers said.

“Our research has highlighted that the CDF has created an inequality between cancer sufferers in England and those in Wales,” Dr Chamberlain noted. “This raises ethical, moral, financial, and policy concerns.”

Patient consulting pharmacist

Credit: Rhoda Baer

Cancer patients in England are more likely to receive prescriptions for expensive drugs than patients in Wales, according to a study published in the British Journal of Cancer.

The research suggests this disparity is associated with the Cancer Drugs Fund (CDF), money set aside by the English government to pay for drugs that haven’t been approved by the National Institute for Health and Care Excellence (NICE) and aren’t available within the National Health Service (NHS).

The governments of Wales, Scotland, and Northern Ireland do not have access to the CDF or have similar programs of their own.

“There’s been much debate surrounding the Cancer Drugs Fund,” said study author Charlotte Chamberlain, MBBS, of the University of Bristol in the UK.

“The vast majority of Cancer Drugs Fund drugs do not cure the cancer but may extend life or improve symptoms in some people. The high cost of these drugs means that the NHS cannot afford other treatments, and, therefore, critics argue that public money is being spent inefficiently.”

To assess the impact of the CDF, Dr Chamberlain and her colleagues analyzed data from hospital pharmacies in England and Wales from August 2007 to December 2012. (The CDF was established in 2010, and the researchers wanted to capture data from before and after its introduction.)

The team evaluated 15 drugs that represent different categories of NICE approval—recommended, not recommended, and not yet appraised.

The results showed that, after the CDF was established, drugs recommended by NICE were not prescribed any more in England than in Wales.

However, drugs that were rejected by NICE because they were not cost-effective were prescribed up to 7 times more often in England than in Wales. For example, in the year before the CDF was introduced, prescription rates of imatinib (which is not recommended by NICE) were substantially higher in England than in Wales.

Immediately before the introduction of the CDF, following the first NICE rejection, imatinib prescribing declined in both countries. But it declined more slowly in England than in Wales, despite 2 additional NICE rejections. Regression analysis showed evidence of an association between the CDF and increased prescribing in England compared to Wales (P<0.001).

The research also revealed surprising information regarding the 3 most recently launched drugs—bendamustine, pazopanib, and abiraterone, which were awaiting NICE appraisal when the CDF was established but have since been approved.

These drugs were prescribed less often in England than in Wales. For instance, prescription rates of bendamustine were 25% lower in England.

This finding suggests that physicians in England have been slower to adopt newer drugs that are cost-effective, the researchers said.

“Our research has highlighted that the CDF has created an inequality between cancer sufferers in England and those in Wales,” Dr Chamberlain noted. “This raises ethical, moral, financial, and policy concerns.”

Lab mouse

An experimental nanoparticle therapy has shown preclinical activity against a range of B-cell malignancies, researchers have reported.

The therapy, SNS01-T, inhibited tumor growth and improved survival in mouse models of multiple myeloma, mantle cell lymphoma, and diffuse large B-cell lymphoma.

The treatment exhibited single-agent activity in these mice but also demonstrated synergy with lenalidomide and bortezomib.

Sarah Francis, PhD, of the University of Waterloo in Ontario, Canada, and her colleagues conducted this research and recounted the results in Molecular Therapy.

SNS01-T consists of 3 components: small interfering RNA targeting the native eukaryotic translation initiation factor 5A (eIF5A), plasmids expressing a pro-apoptotic mutant of elF5A under the control of a B-cell specific promoter, and a synthetic cationic polymer polyethylenimine, which serves as the delivery vehicle.

The small interfering RNA component of SNS01-T suppresses elF5A expression, thereby interfering with translation of eIF5A and reducing levels of hypusinated elF5A in cancer cells. This inhibits activation of NF-kB and induces apoptosis.

The B-cell specific plasmid component of SNS01-T expresses an arginine substituted form of eIF5A—eIF5AK50R—that cannot be hypusinated, which leads to selective induction of apoptosis in B cells.

Dr Francis and her colleagues found that SNS01-T is preferentially taken up by malignant B cells. In myeloma cells, uptake of SNS01-T was up to 5-fold higher than uptake by normal, naïve B cells.

Uptake into myeloma cells induced 45% cell death within 24 hours, but there was almost no measureable death of normal, naïve B cells.

SNS01-T also prompted dose-dependent inhibition of tumor growth in mouse models of multiple myeloma, mantle cell lymphoma, and diffuse large B-cell lymphoma, with up to 90% inhibition at the highest doses.

When administered at doses of 0.18 mg/kg or more, SNS01-T significantly extended the life span of treated mice. The researchers observed a reduction in the pro-survival form of the eIF5A protein in tumor tissue, which was consistent with drug activity.

SNS01-T also demonstrated synergy with bortezomib and lenalidomide. Mice that received SNS01-T and lenalidomide in combination had a 100% survival rate, compared to 60% for mice that received SNS01-T alone and 20% for mice that received lenalidomide alone.

A single 6-week cycle of SNS01-T and lenalidomide eradicated tumors in 67% of mice, and there was no regrowth after an additional 8 weeks without further treatment.

Similarly, combination SNS01-T and bortezomib inhibited tumor growth by 89%, compared to 59% for SNS01-T alone and 39% for bortezomib alone.

This research was supported by Senesco Technologies, Inc., the company developing SNS01-T.

Lab mouse

An experimental nanoparticle therapy has shown preclinical activity against a range of B-cell malignancies, researchers have reported.

The therapy, SNS01-T, inhibited tumor growth and improved survival in mouse models of multiple myeloma, mantle cell lymphoma, and diffuse large B-cell lymphoma.

The treatment exhibited single-agent activity in these mice but also demonstrated synergy with lenalidomide and bortezomib.

Sarah Francis, PhD, of the University of Waterloo in Ontario, Canada, and her colleagues conducted this research and recounted the results in Molecular Therapy.

SNS01-T consists of 3 components: small interfering RNA targeting the native eukaryotic translation initiation factor 5A (eIF5A), plasmids expressing a pro-apoptotic mutant of elF5A under the control of a B-cell specific promoter, and a synthetic cationic polymer polyethylenimine, which serves as the delivery vehicle.

The small interfering RNA component of SNS01-T suppresses elF5A expression, thereby interfering with translation of eIF5A and reducing levels of hypusinated elF5A in cancer cells. This inhibits activation of NF-kB and induces apoptosis.

The B-cell specific plasmid component of SNS01-T expresses an arginine substituted form of eIF5A—eIF5AK50R—that cannot be hypusinated, which leads to selective induction of apoptosis in B cells.

Dr Francis and her colleagues found that SNS01-T is preferentially taken up by malignant B cells. In myeloma cells, uptake of SNS01-T was up to 5-fold higher than uptake by normal, naïve B cells.

Uptake into myeloma cells induced 45% cell death within 24 hours, but there was almost no measureable death of normal, naïve B cells.

SNS01-T also prompted dose-dependent inhibition of tumor growth in mouse models of multiple myeloma, mantle cell lymphoma, and diffuse large B-cell lymphoma, with up to 90% inhibition at the highest doses.

When administered at doses of 0.18 mg/kg or more, SNS01-T significantly extended the life span of treated mice. The researchers observed a reduction in the pro-survival form of the eIF5A protein in tumor tissue, which was consistent with drug activity.

SNS01-T also demonstrated synergy with bortezomib and lenalidomide. Mice that received SNS01-T and lenalidomide in combination had a 100% survival rate, compared to 60% for mice that received SNS01-T alone and 20% for mice that received lenalidomide alone.

A single 6-week cycle of SNS01-T and lenalidomide eradicated tumors in 67% of mice, and there was no regrowth after an additional 8 weeks without further treatment.

Similarly, combination SNS01-T and bortezomib inhibited tumor growth by 89%, compared to 59% for SNS01-T alone and 39% for bortezomib alone.

This research was supported by Senesco Technologies, Inc., the company developing SNS01-T.

Lab mouse

An experimental nanoparticle therapy has shown preclinical activity against a range of B-cell malignancies, researchers have reported.

The therapy, SNS01-T, inhibited tumor growth and improved survival in mouse models of multiple myeloma, mantle cell lymphoma, and diffuse large B-cell lymphoma.

The treatment exhibited single-agent activity in these mice but also demonstrated synergy with lenalidomide and bortezomib.

Sarah Francis, PhD, of the University of Waterloo in Ontario, Canada, and her colleagues conducted this research and recounted the results in Molecular Therapy.

SNS01-T consists of 3 components: small interfering RNA targeting the native eukaryotic translation initiation factor 5A (eIF5A), plasmids expressing a pro-apoptotic mutant of elF5A under the control of a B-cell specific promoter, and a synthetic cationic polymer polyethylenimine, which serves as the delivery vehicle.

The small interfering RNA component of SNS01-T suppresses elF5A expression, thereby interfering with translation of eIF5A and reducing levels of hypusinated elF5A in cancer cells. This inhibits activation of NF-kB and induces apoptosis.

The B-cell specific plasmid component of SNS01-T expresses an arginine substituted form of eIF5A—eIF5AK50R—that cannot be hypusinated, which leads to selective induction of apoptosis in B cells.

Dr Francis and her colleagues found that SNS01-T is preferentially taken up by malignant B cells. In myeloma cells, uptake of SNS01-T was up to 5-fold higher than uptake by normal, naïve B cells.

Uptake into myeloma cells induced 45% cell death within 24 hours, but there was almost no measureable death of normal, naïve B cells.

SNS01-T also prompted dose-dependent inhibition of tumor growth in mouse models of multiple myeloma, mantle cell lymphoma, and diffuse large B-cell lymphoma, with up to 90% inhibition at the highest doses.

When administered at doses of 0.18 mg/kg or more, SNS01-T significantly extended the life span of treated mice. The researchers observed a reduction in the pro-survival form of the eIF5A protein in tumor tissue, which was consistent with drug activity.

SNS01-T also demonstrated synergy with bortezomib and lenalidomide. Mice that received SNS01-T and lenalidomide in combination had a 100% survival rate, compared to 60% for mice that received SNS01-T alone and 20% for mice that received lenalidomide alone.

A single 6-week cycle of SNS01-T and lenalidomide eradicated tumors in 67% of mice, and there was no regrowth after an additional 8 weeks without further treatment.

Similarly, combination SNS01-T and bortezomib inhibited tumor growth by 89%, compared to 59% for SNS01-T alone and 39% for bortezomib alone.

This research was supported by Senesco Technologies, Inc., the company developing SNS01-T.

Patient receiving chemotherapy

Credit: Rhoda Baer

Palliative chemotherapy can negatively impact the end of life for terminally ill cancer patients, according to a paper published in BMJ.

Investigators found that patients who received palliative chemotherapy in their last months of life had an increased risk of requiring intensive medical care, such as resuscitation, and dying in a place they did not choose, such as an intensive care unit.

The researchers therefore suggested that end-of-life discussions may be particularly important for patients who want to receive palliative chemotherapy.

“The results highlight the need for more effective communication by doctors of terminal prognoses and the likely outcomes of chemotherapy for these patients,” said study author Holly Prigerson, PhD, of Weill Cornell Medical College in New York.

“For patients to make informed choices about their care, they need to know if they are incurable and understand what their life expectancy is, that palliative chemotherapy is not intended to cure them, that it may not appreciably prolong their life, and that it may result in the receipt of very aggressive, life-prolonging care at the expense of their quality of life.”

Data have suggested that between 20% and 50% of patients with incurable cancers undergo palliative chemotherapy within 30 days of death. But it has not been clear whether the use of chemotherapy in a patient’s last months is associated with the need for intensive medical care in the last week of life or with the patient’s death.

So Dr Prigerson and her colleagues decided to study the use of palliative chemotherapy in patients with 6 or fewer months to live. The researchers used data from “Coping with Cancer,” a 6-year study of 386 terminally ill patients.

The patients were interviewed around the time of their decision regarding palliative chemotherapy. In the month after each patient died, caregivers were asked to rate their loved ones’ care, quality of life, and place of death as being where the patient would have wanted to die. The investigators then reviewed patients’ medical charts to determine the type of care they actually received in their last week.

Effects of palliative chemo

In all, 56% of patients opted to receive palliative chemotherapy. They were more likely to be younger, married, and better educated than patients not on the treatment.

Patients on chemotherapy also had better performance status, overall quality of life, physical functioning, and psychological well-being at study enrollment.

However, patients who received palliative chemotherapy had a greater risk of requiring cardiopulmonary resuscitation and/or mechanical ventilation (14% vs 2%), and they were more likely to need a feeding tube (11% vs 5%) in their last weeks of life.

Patients on chemotherapy had a greater risk of being admitted to an intensive care unit (14% vs 8%) and of having a late hospice referral (54% vs 37%).

They were also less likely to die where they wanted to (65% vs 80%). They had a greater risk of dying in an intensive care unit (11% vs 2%) and were less likely than their peers to die at home (47% vs 66%).

“It’s hard to see in these data much of a silver lining to palliative chemotherapy for patients in the terminal stage of their cancer,” Dr Prigerson said. “Until now, there hasn’t been evidence of harmful effects of palliative chemotherapy in the last few months of life.”

“This study is a first step in providing evidence that specifically demonstrates what negative outcomes may result. Additional studies are needed to confirm these troubling findings.”

Explaining the negative effects

Dr Prigerson said the harmful effects of palliative chemotherapy may be a result of misunderstanding, a lack of communication, and denial. Patients may not comprehend the purpose and likely consequences of palliative chemotherapy, and they may not fully acknowledge their own prognoses.

In the study, patients receiving palliative chemotherapy were less likely than their peers to talk to their oncologists about end-of-life care (37% vs 48%), to complete Do-Not-Resuscitate orders (36% vs 49%), or to acknowledge that they were terminally ill (35% vs 47%).

“Our finding that patients with terminal cancers were at higher risk of receiving intensive end-of-life care if they were treated with palliative chemotherapy months earlier underscores the importance of oncologists asking patients about their end-of-life wishes,” said Alexi Wright, MD, of the Dana-Farber Cancer Institute in Boston.

“We often wait until patients stop chemotherapy before asking them about where and how they want to die, but this study shows we need to ask patients about their preferences while they are receiving chemotherapy to ensure they receive the kind of care they want near death.”

Moving forward

The investigators stressed that the study results do not suggest patients should be denied palliative chemotherapy.

“The vast majority of patients in this study wanted palliative chemotherapy if it might increase their survival by as little as a week,” Dr Wright said. “This study is a step towards understanding some of the human costs and benefits of palliative chemotherapy.”

The researchers said additional studies should examine whether patients who are aware that chemotherapy is not intended to cure them still want to receive the treatment, confirm the negative outcomes of palliative chemotherapy, and determine if end-of-life discussions promote more informed decision-making and receipt of value-consistent care.

In a related editorial, Mike Rabow, MD, of the University of California, San Francisco, noted that although most patients with metastatic cancer choose to receive chemotherapy, evidence suggests most do not understand its intent.

He said Dr Prigerson’s study suggests the need to “better identify patients who are likely to benefit from chemotherapy near the end of life.” And he encouraged oncologists to discuss with patients the broader implications of chemotherapy when making decisions about treatment.

Patient receiving chemotherapy

Credit: Rhoda Baer

Palliative chemotherapy can negatively impact the end of life for terminally ill cancer patients, according to a paper published in BMJ.

Investigators found that patients who received palliative chemotherapy in their last months of life had an increased risk of requiring intensive medical care, such as resuscitation, and dying in a place they did not choose, such as an intensive care unit.

The researchers therefore suggested that end-of-life discussions may be particularly important for patients who want to receive palliative chemotherapy.

“The results highlight the need for more effective communication by doctors of terminal prognoses and the likely outcomes of chemotherapy for these patients,” said study author Holly Prigerson, PhD, of Weill Cornell Medical College in New York.

“For patients to make informed choices about their care, they need to know if they are incurable and understand what their life expectancy is, that palliative chemotherapy is not intended to cure them, that it may not appreciably prolong their life, and that it may result in the receipt of very aggressive, life-prolonging care at the expense of their quality of life.”

Data have suggested that between 20% and 50% of patients with incurable cancers undergo palliative chemotherapy within 30 days of death. But it has not been clear whether the use of chemotherapy in a patient’s last months is associated with the need for intensive medical care in the last week of life or with the patient’s death.

So Dr Prigerson and her colleagues decided to study the use of palliative chemotherapy in patients with 6 or fewer months to live. The researchers used data from “Coping with Cancer,” a 6-year study of 386 terminally ill patients.

The patients were interviewed around the time of their decision regarding palliative chemotherapy. In the month after each patient died, caregivers were asked to rate their loved ones’ care, quality of life, and place of death as being where the patient would have wanted to die. The investigators then reviewed patients’ medical charts to determine the type of care they actually received in their last week.

Effects of palliative chemo

In all, 56% of patients opted to receive palliative chemotherapy. They were more likely to be younger, married, and better educated than patients not on the treatment.

Patients on chemotherapy also had better performance status, overall quality of life, physical functioning, and psychological well-being at study enrollment.

However, patients who received palliative chemotherapy had a greater risk of requiring cardiopulmonary resuscitation and/or mechanical ventilation (14% vs 2%), and they were more likely to need a feeding tube (11% vs 5%) in their last weeks of life.

Patients on chemotherapy had a greater risk of being admitted to an intensive care unit (14% vs 8%) and of having a late hospice referral (54% vs 37%).

They were also less likely to die where they wanted to (65% vs 80%). They had a greater risk of dying in an intensive care unit (11% vs 2%) and were less likely than their peers to die at home (47% vs 66%).

“It’s hard to see in these data much of a silver lining to palliative chemotherapy for patients in the terminal stage of their cancer,” Dr Prigerson said. “Until now, there hasn’t been evidence of harmful effects of palliative chemotherapy in the last few months of life.”

“This study is a first step in providing evidence that specifically demonstrates what negative outcomes may result. Additional studies are needed to confirm these troubling findings.”

Explaining the negative effects

Dr Prigerson said the harmful effects of palliative chemotherapy may be a result of misunderstanding, a lack of communication, and denial. Patients may not comprehend the purpose and likely consequences of palliative chemotherapy, and they may not fully acknowledge their own prognoses.

In the study, patients receiving palliative chemotherapy were less likely than their peers to talk to their oncologists about end-of-life care (37% vs 48%), to complete Do-Not-Resuscitate orders (36% vs 49%), or to acknowledge that they were terminally ill (35% vs 47%).

“Our finding that patients with terminal cancers were at higher risk of receiving intensive end-of-life care if they were treated with palliative chemotherapy months earlier underscores the importance of oncologists asking patients about their end-of-life wishes,” said Alexi Wright, MD, of the Dana-Farber Cancer Institute in Boston.

“We often wait until patients stop chemotherapy before asking them about where and how they want to die, but this study shows we need to ask patients about their preferences while they are receiving chemotherapy to ensure they receive the kind of care they want near death.”

Moving forward

The investigators stressed that the study results do not suggest patients should be denied palliative chemotherapy.

“The vast majority of patients in this study wanted palliative chemotherapy if it might increase their survival by as little as a week,” Dr Wright said. “This study is a step towards understanding some of the human costs and benefits of palliative chemotherapy.”

The researchers said additional studies should examine whether patients who are aware that chemotherapy is not intended to cure them still want to receive the treatment, confirm the negative outcomes of palliative chemotherapy, and determine if end-of-life discussions promote more informed decision-making and receipt of value-consistent care.

In a related editorial, Mike Rabow, MD, of the University of California, San Francisco, noted that although most patients with metastatic cancer choose to receive chemotherapy, evidence suggests most do not understand its intent.

He said Dr Prigerson’s study suggests the need to “better identify patients who are likely to benefit from chemotherapy near the end of life.” And he encouraged oncologists to discuss with patients the broader implications of chemotherapy when making decisions about treatment.

Patient receiving chemotherapy

Credit: Rhoda Baer

Palliative chemotherapy can negatively impact the end of life for terminally ill cancer patients, according to a paper published in BMJ.

Investigators found that patients who received palliative chemotherapy in their last months of life had an increased risk of requiring intensive medical care, such as resuscitation, and dying in a place they did not choose, such as an intensive care unit.

The researchers therefore suggested that end-of-life discussions may be particularly important for patients who want to receive palliative chemotherapy.

“The results highlight the need for more effective communication by doctors of terminal prognoses and the likely outcomes of chemotherapy for these patients,” said study author Holly Prigerson, PhD, of Weill Cornell Medical College in New York.

“For patients to make informed choices about their care, they need to know if they are incurable and understand what their life expectancy is, that palliative chemotherapy is not intended to cure them, that it may not appreciably prolong their life, and that it may result in the receipt of very aggressive, life-prolonging care at the expense of their quality of life.”

Data have suggested that between 20% and 50% of patients with incurable cancers undergo palliative chemotherapy within 30 days of death. But it has not been clear whether the use of chemotherapy in a patient’s last months is associated with the need for intensive medical care in the last week of life or with the patient’s death.

So Dr Prigerson and her colleagues decided to study the use of palliative chemotherapy in patients with 6 or fewer months to live. The researchers used data from “Coping with Cancer,” a 6-year study of 386 terminally ill patients.

The patients were interviewed around the time of their decision regarding palliative chemotherapy. In the month after each patient died, caregivers were asked to rate their loved ones’ care, quality of life, and place of death as being where the patient would have wanted to die. The investigators then reviewed patients’ medical charts to determine the type of care they actually received in their last week.

Effects of palliative chemo

In all, 56% of patients opted to receive palliative chemotherapy. They were more likely to be younger, married, and better educated than patients not on the treatment.

Patients on chemotherapy also had better performance status, overall quality of life, physical functioning, and psychological well-being at study enrollment.

However, patients who received palliative chemotherapy had a greater risk of requiring cardiopulmonary resuscitation and/or mechanical ventilation (14% vs 2%), and they were more likely to need a feeding tube (11% vs 5%) in their last weeks of life.

Patients on chemotherapy had a greater risk of being admitted to an intensive care unit (14% vs 8%) and of having a late hospice referral (54% vs 37%).

They were also less likely to die where they wanted to (65% vs 80%). They had a greater risk of dying in an intensive care unit (11% vs 2%) and were less likely than their peers to die at home (47% vs 66%).

“It’s hard to see in these data much of a silver lining to palliative chemotherapy for patients in the terminal stage of their cancer,” Dr Prigerson said. “Until now, there hasn’t been evidence of harmful effects of palliative chemotherapy in the last few months of life.”

“This study is a first step in providing evidence that specifically demonstrates what negative outcomes may result. Additional studies are needed to confirm these troubling findings.”

Explaining the negative effects

Dr Prigerson said the harmful effects of palliative chemotherapy may be a result of misunderstanding, a lack of communication, and denial. Patients may not comprehend the purpose and likely consequences of palliative chemotherapy, and they may not fully acknowledge their own prognoses.

In the study, patients receiving palliative chemotherapy were less likely than their peers to talk to their oncologists about end-of-life care (37% vs 48%), to complete Do-Not-Resuscitate orders (36% vs 49%), or to acknowledge that they were terminally ill (35% vs 47%).

“Our finding that patients with terminal cancers were at higher risk of receiving intensive end-of-life care if they were treated with palliative chemotherapy months earlier underscores the importance of oncologists asking patients about their end-of-life wishes,” said Alexi Wright, MD, of the Dana-Farber Cancer Institute in Boston.

“We often wait until patients stop chemotherapy before asking them about where and how they want to die, but this study shows we need to ask patients about their preferences while they are receiving chemotherapy to ensure they receive the kind of care they want near death.”

Moving forward

The investigators stressed that the study results do not suggest patients should be denied palliative chemotherapy.

“The vast majority of patients in this study wanted palliative chemotherapy if it might increase their survival by as little as a week,” Dr Wright said. “This study is a step towards understanding some of the human costs and benefits of palliative chemotherapy.”

The researchers said additional studies should examine whether patients who are aware that chemotherapy is not intended to cure them still want to receive the treatment, confirm the negative outcomes of palliative chemotherapy, and determine if end-of-life discussions promote more informed decision-making and receipt of value-consistent care.

In a related editorial, Mike Rabow, MD, of the University of California, San Francisco, noted that although most patients with metastatic cancer choose to receive chemotherapy, evidence suggests most do not understand its intent.

He said Dr Prigerson’s study suggests the need to “better identify patients who are likely to benefit from chemotherapy near the end of life.” And he encouraged oncologists to discuss with patients the broader implications of chemotherapy when making decisions about treatment.

Pill production

Credit: FDA

The US Food and Drug Administration (FDA) has granted orphan designation for the histone deacetylase (HDAC) inhibitor pracinostat to treat acute myeloid leukemia (AML) and the proteasome inhibitor marizomib to treat multiple myeloma (MM).

Orphan designation is available for drugs that treat or prevent rare diseases affecting fewer than 200,000 people in the US.

The designation qualifies the sponsor of a drug for development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions, and 7-year marketing exclusivity upon FDA approval.

About pracinostat

The oral HDAC inhibitor pracinostat has been tested in phase 1 and 2 trials of adult and pediatric patients with advanced hematologic disorders and solid tumors.

The drug has been generally well tolerated in more than 200 patients to date, according to the drug’s maker, MEI Pharma.

In a dose-escalation phase 1 trial, pracinostat demonstrated single-agent activity in elderly AML patients. Two of 14 patients (14%) achieved a complete remission, with responses persisting more than 206 days and 362 days.

Researchers are currently conducting a phase 2 trial of pracinostat in combination with azacitidine in elderly patients with newly diagnosed AML. Preliminary data from this trial are expected to be available by December 2014.

About marizomib

The proteasome inhibitor marizomib is under development for the treatment of MM and other malignancies.

Intravenous marizomib has been evaluated in more than 230 patients across 4 phase 1/2 studies, as a single agent or in combination with dexamethasone or an HDAC inhibitor.

Researchers are currently evaluating marizomib in combination with dexamethasone in an ongoing phase 2 trial of highly refractory MM patients, including those who are refractory to carfilzomib.

Marizomib is also being tested in combination with pomalidomide and dexamethasone in a phase 1/2 study of patients with relapsed and refractory MM.

The drug’s maker, Triphase Accelerator Corporation, is currently developing an oral formulation of marizomib.

Pill production

Credit: FDA

The US Food and Drug Administration (FDA) has granted orphan designation for the histone deacetylase (HDAC) inhibitor pracinostat to treat acute myeloid leukemia (AML) and the proteasome inhibitor marizomib to treat multiple myeloma (MM).

Orphan designation is available for drugs that treat or prevent rare diseases affecting fewer than 200,000 people in the US.

The designation qualifies the sponsor of a drug for development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions, and 7-year marketing exclusivity upon FDA approval.

About pracinostat

The oral HDAC inhibitor pracinostat has been tested in phase 1 and 2 trials of adult and pediatric patients with advanced hematologic disorders and solid tumors.

The drug has been generally well tolerated in more than 200 patients to date, according to the drug’s maker, MEI Pharma.

In a dose-escalation phase 1 trial, pracinostat demonstrated single-agent activity in elderly AML patients. Two of 14 patients (14%) achieved a complete remission, with responses persisting more than 206 days and 362 days.

Researchers are currently conducting a phase 2 trial of pracinostat in combination with azacitidine in elderly patients with newly diagnosed AML. Preliminary data from this trial are expected to be available by December 2014.

About marizomib

The proteasome inhibitor marizomib is under development for the treatment of MM and other malignancies.

Intravenous marizomib has been evaluated in more than 230 patients across 4 phase 1/2 studies, as a single agent or in combination with dexamethasone or an HDAC inhibitor.

Researchers are currently evaluating marizomib in combination with dexamethasone in an ongoing phase 2 trial of highly refractory MM patients, including those who are refractory to carfilzomib.

Marizomib is also being tested in combination with pomalidomide and dexamethasone in a phase 1/2 study of patients with relapsed and refractory MM.

The drug’s maker, Triphase Accelerator Corporation, is currently developing an oral formulation of marizomib.

Pill production

Credit: FDA

The US Food and Drug Administration (FDA) has granted orphan designation for the histone deacetylase (HDAC) inhibitor pracinostat to treat acute myeloid leukemia (AML) and the proteasome inhibitor marizomib to treat multiple myeloma (MM).

Orphan designation is available for drugs that treat or prevent rare diseases affecting fewer than 200,000 people in the US.

The designation qualifies the sponsor of a drug for development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions, and 7-year marketing exclusivity upon FDA approval.

About pracinostat

The oral HDAC inhibitor pracinostat has been tested in phase 1 and 2 trials of adult and pediatric patients with advanced hematologic disorders and solid tumors.

The drug has been generally well tolerated in more than 200 patients to date, according to the drug’s maker, MEI Pharma.

In a dose-escalation phase 1 trial, pracinostat demonstrated single-agent activity in elderly AML patients. Two of 14 patients (14%) achieved a complete remission, with responses persisting more than 206 days and 362 days.

Researchers are currently conducting a phase 2 trial of pracinostat in combination with azacitidine in elderly patients with newly diagnosed AML. Preliminary data from this trial are expected to be available by December 2014.

About marizomib

The proteasome inhibitor marizomib is under development for the treatment of MM and other malignancies.

Intravenous marizomib has been evaluated in more than 230 patients across 4 phase 1/2 studies, as a single agent or in combination with dexamethasone or an HDAC inhibitor.

Researchers are currently evaluating marizomib in combination with dexamethasone in an ongoing phase 2 trial of highly refractory MM patients, including those who are refractory to carfilzomib.

Marizomib is also being tested in combination with pomalidomide and dexamethasone in a phase 1/2 study of patients with relapsed and refractory MM.

The drug’s maker, Triphase Accelerator Corporation, is currently developing an oral formulation of marizomib.