Multiple Myeloma

Anne Kirchoff, PhD

Photo courtesy of

Huntsman Cancer Institute

A new study indicates that childhood cancer survivors (CCSs) are more likely than individuals without a cancer history to enroll on federal programs that provide disability benefits.

CCSs diagnosed between 1970 and 1986 were about 2 to 5 times as likely as control subjects to utilize such a program.

“The long-term impact of cancer can affect other issues besides health outcomes,” said study author Anne Kirchhoff, PhD, of the Huntsman Cancer Institute at the University of Utah.

“We need to do a better job of helping people function throughout their lives, not just when they’re finishing their cancer therapy.”

Dr Kirchhoff and her colleagues conducted this research and detailed the results in the Journal of the National Cancer Institute.

The researchers looked at health insurance surveys completed in 2011 and 2012 by a random sample of 698 CCSs who were diagnosed between the ages of 0 and 20 years. Today, they range in age from 20s to early 60s.

The patients are part of a National Cancer Institute initiative, called the Childhood Cancer Survivor Study, which has followed more than 14,000 children and adolescents since 1994 who were diagnosed with cancer and survived at least 5 years after diagnosis. A comparison group of 210 siblings without cancer also responded to the survey and were used as controls.

Dr Kirchhoff and her colleagues looked at current or former enrollment on 2 federal disability programs:

• Supplemental security income (SSI), which is for people with limited income who have no prior work history
• Social security disability insurance (SSDI), which pays disability benefits to adults ages 18 years and older who have worked and paid social security taxes.

In all, 13.5% of CCSs reported being enrolled on SSI in the past or present, and 10% of survivors reported being enrolled on SSDI at some point. This was substantially higher than for the comparison group, in which 2.6% of patients reported SSI enrollment and 5.4% reported SSDI enrollment.

In addition, CCSs reported current enrollment in SSI more frequently than the US population, at rates of 7.3% and 2.5%, respectively.

Dr Kirchoff and her colleagues also identified survivor socio-demographic and treatment characteristics that were associated with a higher rate of enrollment in federal support programs.

“Survivors that were younger at diagnosis, age 4 or under, were about 7 times more likely to be on SSI than we see with survivors that were diagnosed in their adolescence,” she said.

SSI enrollment was more likely for female CCSs and for survivors with a history of cranial radiation treatment as well.

Dr Kirchhoff noted that, over the years, research on CCSs has caused hospitals to rethink how to better care for cancer survivors.

“There’s really a growing strategy to support survivors in the long-term,” she said. “For example, here at Huntsman Cancer Institute, we have a pediatric cancer late-effects clinic, which helps manage issues that might come up with childhood cancer survivors in the long term, including health-management support, health-behavior support, and access to providers to help them with other issues.”

Anne Kirchoff, PhD

Photo courtesy of

Huntsman Cancer Institute

A new study indicates that childhood cancer survivors (CCSs) are more likely than individuals without a cancer history to enroll on federal programs that provide disability benefits.

CCSs diagnosed between 1970 and 1986 were about 2 to 5 times as likely as control subjects to utilize such a program.

“The long-term impact of cancer can affect other issues besides health outcomes,” said study author Anne Kirchhoff, PhD, of the Huntsman Cancer Institute at the University of Utah.

“We need to do a better job of helping people function throughout their lives, not just when they’re finishing their cancer therapy.”

Dr Kirchhoff and her colleagues conducted this research and detailed the results in the Journal of the National Cancer Institute.

The researchers looked at health insurance surveys completed in 2011 and 2012 by a random sample of 698 CCSs who were diagnosed between the ages of 0 and 20 years. Today, they range in age from 20s to early 60s.

The patients are part of a National Cancer Institute initiative, called the Childhood Cancer Survivor Study, which has followed more than 14,000 children and adolescents since 1994 who were diagnosed with cancer and survived at least 5 years after diagnosis. A comparison group of 210 siblings without cancer also responded to the survey and were used as controls.

Dr Kirchhoff and her colleagues looked at current or former enrollment on 2 federal disability programs:

• Supplemental security income (SSI), which is for people with limited income who have no prior work history
• Social security disability insurance (SSDI), which pays disability benefits to adults ages 18 years and older who have worked and paid social security taxes.

In all, 13.5% of CCSs reported being enrolled on SSI in the past or present, and 10% of survivors reported being enrolled on SSDI at some point. This was substantially higher than for the comparison group, in which 2.6% of patients reported SSI enrollment and 5.4% reported SSDI enrollment.

In addition, CCSs reported current enrollment in SSI more frequently than the US population, at rates of 7.3% and 2.5%, respectively.

Dr Kirchoff and her colleagues also identified survivor socio-demographic and treatment characteristics that were associated with a higher rate of enrollment in federal support programs.

“Survivors that were younger at diagnosis, age 4 or under, were about 7 times more likely to be on SSI than we see with survivors that were diagnosed in their adolescence,” she said.

SSI enrollment was more likely for female CCSs and for survivors with a history of cranial radiation treatment as well.

Dr Kirchhoff noted that, over the years, research on CCSs has caused hospitals to rethink how to better care for cancer survivors.

“There’s really a growing strategy to support survivors in the long-term,” she said. “For example, here at Huntsman Cancer Institute, we have a pediatric cancer late-effects clinic, which helps manage issues that might come up with childhood cancer survivors in the long term, including health-management support, health-behavior support, and access to providers to help them with other issues.”

Anne Kirchoff, PhD

Photo courtesy of

Huntsman Cancer Institute

A new study indicates that childhood cancer survivors (CCSs) are more likely than individuals without a cancer history to enroll on federal programs that provide disability benefits.

CCSs diagnosed between 1970 and 1986 were about 2 to 5 times as likely as control subjects to utilize such a program.

“The long-term impact of cancer can affect other issues besides health outcomes,” said study author Anne Kirchhoff, PhD, of the Huntsman Cancer Institute at the University of Utah.

“We need to do a better job of helping people function throughout their lives, not just when they’re finishing their cancer therapy.”

Dr Kirchhoff and her colleagues conducted this research and detailed the results in the Journal of the National Cancer Institute.

The researchers looked at health insurance surveys completed in 2011 and 2012 by a random sample of 698 CCSs who were diagnosed between the ages of 0 and 20 years. Today, they range in age from 20s to early 60s.

The patients are part of a National Cancer Institute initiative, called the Childhood Cancer Survivor Study, which has followed more than 14,000 children and adolescents since 1994 who were diagnosed with cancer and survived at least 5 years after diagnosis. A comparison group of 210 siblings without cancer also responded to the survey and were used as controls.

Dr Kirchhoff and her colleagues looked at current or former enrollment on 2 federal disability programs:

• Supplemental security income (SSI), which is for people with limited income who have no prior work history
• Social security disability insurance (SSDI), which pays disability benefits to adults ages 18 years and older who have worked and paid social security taxes.

In all, 13.5% of CCSs reported being enrolled on SSI in the past or present, and 10% of survivors reported being enrolled on SSDI at some point. This was substantially higher than for the comparison group, in which 2.6% of patients reported SSI enrollment and 5.4% reported SSDI enrollment.

In addition, CCSs reported current enrollment in SSI more frequently than the US population, at rates of 7.3% and 2.5%, respectively.

Dr Kirchoff and her colleagues also identified survivor socio-demographic and treatment characteristics that were associated with a higher rate of enrollment in federal support programs.

“Survivors that were younger at diagnosis, age 4 or under, were about 7 times more likely to be on SSI than we see with survivors that were diagnosed in their adolescence,” she said.

SSI enrollment was more likely for female CCSs and for survivors with a history of cranial radiation treatment as well.

Dr Kirchhoff noted that, over the years, research on CCSs has caused hospitals to rethink how to better care for cancer survivors.

“There’s really a growing strategy to support survivors in the long-term,” she said. “For example, here at Huntsman Cancer Institute, we have a pediatric cancer late-effects clinic, which helps manage issues that might come up with childhood cancer survivors in the long term, including health-management support, health-behavior support, and access to providers to help them with other issues.”

In a population of patients with hematologic malignancies who refuse blood product transfusions, high-dose chemotherapy (HDC) followed by autologous stem-cell transplantation (ASCT) in the absence of hematopoietic support was shown to be relatively safe, according to a report published online April 13 in the Journal of Clinical Oncology.

From May of 1996 to March of 2014 at Pennsylvania Hospital, 125 Jehovah’s Witness patients with lymphoma (n = 55), multiple myeloma (n = 68), or amyloidosis (n = 2) were treated with HDC and ASCT without transfusion through the use of basic blood management techniques. These techniques included priming pretransplantation hemoglobin with erythropoiesis stimulating agents and intravenous iron, limiting iatrogenic blood loss by minimizing phlebotomy, and controlling or preventing bleeding with hemostatic agents, according to Dr. Patricia Ford and her colleagues at the hospital.

They described the low incidence of bleeding even in the absence of prophylactic platelet transfusions, which, they noted, challenges current American Society of Clinical Oncology guidelines that recommend transfusions at platelet counts less than 10 x 10³/mcL. “The absence of major bleeding events observed at platelet counts greater than 5 x 10³/mcL … suggests that a transfusion threshold trigger of 5 x 10³/mcL may be appropriate in a select patient population,” they wrote (J. Clin. Oncol. 2015 April 13 [doi: 10.1200/JCO.2014.57.9912]).

Among the patients treated with HDC and ASCT, those with multiple myeloma (n = 68) received melphalan 200 mg/m²,and those with lymphoma (n = 55) received carmustine 300mg/m² day 1, cyclophosphamide 1,500 mg/m² days 2-5, and VP16 700 mg/m² per day on days 2-4.

At 100 days post transplantation, 115 patients (92%) were still alive. Treatment-related mortality due to anemia, sepsis, pancytopenia, or cardiac events occurred in six patients (4.8%).

Out of 18 bleeding episodes, 2 were major (one grade 4 hemorrhagic temporal infarction with retinal hemorrhages and one grade 3 GI bleed) and 16 were minor. There were no bleeding-associated fatalities.

Cardiac complications occurred at an unexpectedly high rate of 32% (40 patients) and resulted in three treatment-related deaths. Subsequently, all candidates older than 50 years or at risk for cardiac disease were required to undergo cardiac consultation prior to transplantation. Given the cardiovascular risk associated with this population, in addition to ECHO testing, stress testing in patients with suspected coronary artery disease is recommended, the researchers wrote.

On the basis of the observed low mortality and morbidity, Dr. Ford and her associates suggested that HDC followed by ASCT be offered to certain patients who refuse or who have medical contraindications to transfusions, stating that simple blood management strategies were an effective alternative in select patients.

In a population of patients with hematologic malignancies who refuse blood product transfusions, high-dose chemotherapy (HDC) followed by autologous stem-cell transplantation (ASCT) in the absence of hematopoietic support was shown to be relatively safe, according to a report published online April 13 in the Journal of Clinical Oncology.

From May of 1996 to March of 2014 at Pennsylvania Hospital, 125 Jehovah’s Witness patients with lymphoma (n = 55), multiple myeloma (n = 68), or amyloidosis (n = 2) were treated with HDC and ASCT without transfusion through the use of basic blood management techniques. These techniques included priming pretransplantation hemoglobin with erythropoiesis stimulating agents and intravenous iron, limiting iatrogenic blood loss by minimizing phlebotomy, and controlling or preventing bleeding with hemostatic agents, according to Dr. Patricia Ford and her colleagues at the hospital.

They described the low incidence of bleeding even in the absence of prophylactic platelet transfusions, which, they noted, challenges current American Society of Clinical Oncology guidelines that recommend transfusions at platelet counts less than 10 x 10³/mcL. “The absence of major bleeding events observed at platelet counts greater than 5 x 10³/mcL … suggests that a transfusion threshold trigger of 5 x 10³/mcL may be appropriate in a select patient population,” they wrote (J. Clin. Oncol. 2015 April 13 [doi: 10.1200/JCO.2014.57.9912]).

Among the patients treated with HDC and ASCT, those with multiple myeloma (n = 68) received melphalan 200 mg/m²,and those with lymphoma (n = 55) received carmustine 300mg/m² day 1, cyclophosphamide 1,500 mg/m² days 2-5, and VP16 700 mg/m² per day on days 2-4.

At 100 days post transplantation, 115 patients (92%) were still alive. Treatment-related mortality due to anemia, sepsis, pancytopenia, or cardiac events occurred in six patients (4.8%).

Out of 18 bleeding episodes, 2 were major (one grade 4 hemorrhagic temporal infarction with retinal hemorrhages and one grade 3 GI bleed) and 16 were minor. There were no bleeding-associated fatalities.

Cardiac complications occurred at an unexpectedly high rate of 32% (40 patients) and resulted in three treatment-related deaths. Subsequently, all candidates older than 50 years or at risk for cardiac disease were required to undergo cardiac consultation prior to transplantation. Given the cardiovascular risk associated with this population, in addition to ECHO testing, stress testing in patients with suspected coronary artery disease is recommended, the researchers wrote.

On the basis of the observed low mortality and morbidity, Dr. Ford and her associates suggested that HDC followed by ASCT be offered to certain patients who refuse or who have medical contraindications to transfusions, stating that simple blood management strategies were an effective alternative in select patients.

In a population of patients with hematologic malignancies who refuse blood product transfusions, high-dose chemotherapy (HDC) followed by autologous stem-cell transplantation (ASCT) in the absence of hematopoietic support was shown to be relatively safe, according to a report published online April 13 in the Journal of Clinical Oncology.

From May of 1996 to March of 2014 at Pennsylvania Hospital, 125 Jehovah’s Witness patients with lymphoma (n = 55), multiple myeloma (n = 68), or amyloidosis (n = 2) were treated with HDC and ASCT without transfusion through the use of basic blood management techniques. These techniques included priming pretransplantation hemoglobin with erythropoiesis stimulating agents and intravenous iron, limiting iatrogenic blood loss by minimizing phlebotomy, and controlling or preventing bleeding with hemostatic agents, according to Dr. Patricia Ford and her colleagues at the hospital.

They described the low incidence of bleeding even in the absence of prophylactic platelet transfusions, which, they noted, challenges current American Society of Clinical Oncology guidelines that recommend transfusions at platelet counts less than 10 x 10³/mcL. “The absence of major bleeding events observed at platelet counts greater than 5 x 10³/mcL … suggests that a transfusion threshold trigger of 5 x 10³/mcL may be appropriate in a select patient population,” they wrote (J. Clin. Oncol. 2015 April 13 [doi: 10.1200/JCO.2014.57.9912]).

Among the patients treated with HDC and ASCT, those with multiple myeloma (n = 68) received melphalan 200 mg/m²,and those with lymphoma (n = 55) received carmustine 300mg/m² day 1, cyclophosphamide 1,500 mg/m² days 2-5, and VP16 700 mg/m² per day on days 2-4.

At 100 days post transplantation, 115 patients (92%) were still alive. Treatment-related mortality due to anemia, sepsis, pancytopenia, or cardiac events occurred in six patients (4.8%).

Out of 18 bleeding episodes, 2 were major (one grade 4 hemorrhagic temporal infarction with retinal hemorrhages and one grade 3 GI bleed) and 16 were minor. There were no bleeding-associated fatalities.

Cardiac complications occurred at an unexpectedly high rate of 32% (40 patients) and resulted in three treatment-related deaths. Subsequently, all candidates older than 50 years or at risk for cardiac disease were required to undergo cardiac consultation prior to transplantation. Given the cardiovascular risk associated with this population, in addition to ECHO testing, stress testing in patients with suspected coronary artery disease is recommended, the researchers wrote.

On the basis of the observed low mortality and morbidity, Dr. Ford and her associates suggested that HDC followed by ASCT be offered to certain patients who refuse or who have medical contraindications to transfusions, stating that simple blood management strategies were an effective alternative in select patients.

Fish oil capsules

Consuming certain types of fish and taking fish oil supplements may induce chemoresistance, according to research published in JAMA Oncology.

Researchers found that herring and mackerel, as well as 6 different types of fish oil supplements, raised blood levels of the fatty acid 16:4(n-3).

And experiments in mice showed that small amounts of either purified 16:4(n-3) or fish oil induced resistance to the chemotherapy drug cisplatin.

Emile E. Voest, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, and his colleagues conducted this multi-part study.

In one part, the team conducted a survey to determine the rate of fish oil use among patients undergoing cancer treatment (n=118). Thirty-five patients (30%) reported regular use of nutritional supplements, and 13 (11%) said they used supplements containing omega-3 fatty acids.

For another part of the study, the researchers evaluated 6 types of fish oil supplements. All of them contained relevant amounts of 16:4(n-3), ranging from 0.2 µM to 5.7 µM.

The team also recruited healthy volunteers to examine blood levels of 16:4(n-3) after the ingestion of fish oil supplements (n=30) and fish (n=20).

Volunteers had increased blood levels of 16:4(n-3) after the recommended daily amount of 10 mL of fish oil and after a 50 mL dose. Subjects had an almost-complete normalization of blood levels 8 hours after a 10 mL fish oil dose, but they had a more prolonged elevation of fatty acid levels after a 50 mL dose.

Eating 100 grams of herring and mackerel also increased blood levels of 16:4(n-3) compared with tuna, which did not affect blood levels, and salmon,

which resulted in a small, short-lived peak.

Finally, experiments in mice showed that as little as 2.5 pmol of purified 16:4(n-3) or 1 µL of fish oil was sufficient to induce resistance to the chemotherapy drug cisplatin.

The fish oil/cisplatin combination had no significant impact on mouse tumors when compared to vehicle control treatment. The estimated tumor volume difference was 44.1 mm³ (P >0.99).

When the researchers compared cisplatin alone to cisplatin plus 16:4(n-3), the estimated tumor volume difference was 95.5 mm³ (P=0 .04). When they compared vehicle control to cisplatin alone, there was an estimated tumor volume difference of 142.4 mm³ (P=0.001).

The team said these results suggest that simultaneous exposure to chemotherapy and fish oil may be detrimental to cancer patients. So until further data become available, patients should avoid consuming fish oil from the day before chemotherapy until the day after.

Fish oil capsules

Consuming certain types of fish and taking fish oil supplements may induce chemoresistance, according to research published in JAMA Oncology.

Researchers found that herring and mackerel, as well as 6 different types of fish oil supplements, raised blood levels of the fatty acid 16:4(n-3).

And experiments in mice showed that small amounts of either purified 16:4(n-3) or fish oil induced resistance to the chemotherapy drug cisplatin.

Emile E. Voest, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, and his colleagues conducted this multi-part study.

In one part, the team conducted a survey to determine the rate of fish oil use among patients undergoing cancer treatment (n=118). Thirty-five patients (30%) reported regular use of nutritional supplements, and 13 (11%) said they used supplements containing omega-3 fatty acids.

For another part of the study, the researchers evaluated 6 types of fish oil supplements. All of them contained relevant amounts of 16:4(n-3), ranging from 0.2 µM to 5.7 µM.

The team also recruited healthy volunteers to examine blood levels of 16:4(n-3) after the ingestion of fish oil supplements (n=30) and fish (n=20).

Volunteers had increased blood levels of 16:4(n-3) after the recommended daily amount of 10 mL of fish oil and after a 50 mL dose. Subjects had an almost-complete normalization of blood levels 8 hours after a 10 mL fish oil dose, but they had a more prolonged elevation of fatty acid levels after a 50 mL dose.

Eating 100 grams of herring and mackerel also increased blood levels of 16:4(n-3) compared with tuna, which did not affect blood levels, and salmon,

which resulted in a small, short-lived peak.

Finally, experiments in mice showed that as little as 2.5 pmol of purified 16:4(n-3) or 1 µL of fish oil was sufficient to induce resistance to the chemotherapy drug cisplatin.

The fish oil/cisplatin combination had no significant impact on mouse tumors when compared to vehicle control treatment. The estimated tumor volume difference was 44.1 mm³ (P >0.99).

When the researchers compared cisplatin alone to cisplatin plus 16:4(n-3), the estimated tumor volume difference was 95.5 mm³ (P=0 .04). When they compared vehicle control to cisplatin alone, there was an estimated tumor volume difference of 142.4 mm³ (P=0.001).

The team said these results suggest that simultaneous exposure to chemotherapy and fish oil may be detrimental to cancer patients. So until further data become available, patients should avoid consuming fish oil from the day before chemotherapy until the day after.

Fish oil capsules

Consuming certain types of fish and taking fish oil supplements may induce chemoresistance, according to research published in JAMA Oncology.

Researchers found that herring and mackerel, as well as 6 different types of fish oil supplements, raised blood levels of the fatty acid 16:4(n-3).

And experiments in mice showed that small amounts of either purified 16:4(n-3) or fish oil induced resistance to the chemotherapy drug cisplatin.

Emile E. Voest, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, and his colleagues conducted this multi-part study.

In one part, the team conducted a survey to determine the rate of fish oil use among patients undergoing cancer treatment (n=118). Thirty-five patients (30%) reported regular use of nutritional supplements, and 13 (11%) said they used supplements containing omega-3 fatty acids.

For another part of the study, the researchers evaluated 6 types of fish oil supplements. All of them contained relevant amounts of 16:4(n-3), ranging from 0.2 µM to 5.7 µM.

The team also recruited healthy volunteers to examine blood levels of 16:4(n-3) after the ingestion of fish oil supplements (n=30) and fish (n=20).

Volunteers had increased blood levels of 16:4(n-3) after the recommended daily amount of 10 mL of fish oil and after a 50 mL dose. Subjects had an almost-complete normalization of blood levels 8 hours after a 10 mL fish oil dose, but they had a more prolonged elevation of fatty acid levels after a 50 mL dose.

Eating 100 grams of herring and mackerel also increased blood levels of 16:4(n-3) compared with tuna, which did not affect blood levels, and salmon,

which resulted in a small, short-lived peak.

Finally, experiments in mice showed that as little as 2.5 pmol of purified 16:4(n-3) or 1 µL of fish oil was sufficient to induce resistance to the chemotherapy drug cisplatin.

The fish oil/cisplatin combination had no significant impact on mouse tumors when compared to vehicle control treatment. The estimated tumor volume difference was 44.1 mm³ (P >0.99).

When the researchers compared cisplatin alone to cisplatin plus 16:4(n-3), the estimated tumor volume difference was 95.5 mm³ (P=0 .04). When they compared vehicle control to cisplatin alone, there was an estimated tumor volume difference of 142.4 mm³ (P=0.001).

The team said these results suggest that simultaneous exposure to chemotherapy and fish oil may be detrimental to cancer patients. So until further data become available, patients should avoid consuming fish oil from the day before chemotherapy until the day after.

Prescription medications

Photo by Steven Harbour

Japan’s Ministry of Health, Labour and Welfare (MHLW) has granted full marketing authorization for pomalidomide (Pomalyst) to treat patients with relapsed or refractory multiple myeloma (MM) who have previously received lenalidomide and bortezomib.

Pomalidomide will be available in Japan through RevMate, a restricted distribution program that should ensure the proper use of pomalidomide and prevent fetal exposure to the drug.

The MHLW approved pomalidomide based on results of trials in patients with previously treated MM, including the phase 3 MM-003 trial and the phase 2 MM-011 trial.

Phase 2 trial

In the MM-011 trial, which has not yet been published, researchers evaluated the safety and efficacy of pomalidomide in combination with dexamethasone in 36 patients with relapsed/refractory MM.

The patients had received at least 2 prior therapies, including lenalidomide and bortezomib, and had disease progression within 60 days of completing their last therapy.

Twenty-five percent of patients responded to treatment with pomalidomide and dexamethasone, 1 with a complete response and 8 with a partial response.

About 89% of patients (32/36) experienced adverse events, including lab test abnormalities. The most common events were neutropenia (69.4%), thrombocytopenia (33.3%), rash (22.2%), leukocytopenia (13.9%), pyrexia (13.9%), anemia (11.1%), lymphopenia (11.1%), and constipation (11.1%).

Phase 3 trial

The MM-003 study included 455 patients with relapsed or refractory MM. They were randomized to receive either pomalidomide plus low-dose dexamethasone (POM-LoDEX, n=302) or high-dose dexamethasone (HiDEX, n=153). The median follow-up was 10 months.

The overall response rate was 31% (n=95) in the POM-LoDEX arm and 10% (n=15) in the HiDEX arm. The median duration of response was 7.0 months (range, 6 to 9 months) and 6.1 months (range, 1.4 to 8.5 months), respectively.

The median progression-free survival was 4.0 months in the POM-LoDEX arm and 1.9 months in the HiDEX arm (P<0.001). And the median overall survival was 12.7 months in the POM-LoDEX arm and 8.1 months in the HiDEX arm (P=0.028).

Patients in the POM-LoDEX arm experienced more grade 3/4 neutropenia than patients in the HiDEX arm. But rates of grade 3/4 anemia and thrombocytopenia were similar between the 2 arms.

Rates of grade 3/4 non-hematologic toxicities were also similar between the arms and included infection, pneumonia, hemorrhage, glucose intolerance, and fatigue. Other adverse events of note included venous thromboembolism and peripheral neuropathy, which occurred at similar rates in both arms.

Prescription medications

Photo by Steven Harbour

Japan’s Ministry of Health, Labour and Welfare (MHLW) has granted full marketing authorization for pomalidomide (Pomalyst) to treat patients with relapsed or refractory multiple myeloma (MM) who have previously received lenalidomide and bortezomib.

Pomalidomide will be available in Japan through RevMate, a restricted distribution program that should ensure the proper use of pomalidomide and prevent fetal exposure to the drug.

The MHLW approved pomalidomide based on results of trials in patients with previously treated MM, including the phase 3 MM-003 trial and the phase 2 MM-011 trial.

Phase 2 trial

In the MM-011 trial, which has not yet been published, researchers evaluated the safety and efficacy of pomalidomide in combination with dexamethasone in 36 patients with relapsed/refractory MM.

The patients had received at least 2 prior therapies, including lenalidomide and bortezomib, and had disease progression within 60 days of completing their last therapy.

Twenty-five percent of patients responded to treatment with pomalidomide and dexamethasone, 1 with a complete response and 8 with a partial response.

About 89% of patients (32/36) experienced adverse events, including lab test abnormalities. The most common events were neutropenia (69.4%), thrombocytopenia (33.3%), rash (22.2%), leukocytopenia (13.9%), pyrexia (13.9%), anemia (11.1%), lymphopenia (11.1%), and constipation (11.1%).

Phase 3 trial

The MM-003 study included 455 patients with relapsed or refractory MM. They were randomized to receive either pomalidomide plus low-dose dexamethasone (POM-LoDEX, n=302) or high-dose dexamethasone (HiDEX, n=153). The median follow-up was 10 months.

The overall response rate was 31% (n=95) in the POM-LoDEX arm and 10% (n=15) in the HiDEX arm. The median duration of response was 7.0 months (range, 6 to 9 months) and 6.1 months (range, 1.4 to 8.5 months), respectively.

The median progression-free survival was 4.0 months in the POM-LoDEX arm and 1.9 months in the HiDEX arm (P<0.001). And the median overall survival was 12.7 months in the POM-LoDEX arm and 8.1 months in the HiDEX arm (P=0.028).

Patients in the POM-LoDEX arm experienced more grade 3/4 neutropenia than patients in the HiDEX arm. But rates of grade 3/4 anemia and thrombocytopenia were similar between the 2 arms.

Rates of grade 3/4 non-hematologic toxicities were also similar between the arms and included infection, pneumonia, hemorrhage, glucose intolerance, and fatigue. Other adverse events of note included venous thromboembolism and peripheral neuropathy, which occurred at similar rates in both arms.

Prescription medications

Photo by Steven Harbour

Japan’s Ministry of Health, Labour and Welfare (MHLW) has granted full marketing authorization for pomalidomide (Pomalyst) to treat patients with relapsed or refractory multiple myeloma (MM) who have previously received lenalidomide and bortezomib.

Pomalidomide will be available in Japan through RevMate, a restricted distribution program that should ensure the proper use of pomalidomide and prevent fetal exposure to the drug.

The MHLW approved pomalidomide based on results of trials in patients with previously treated MM, including the phase 3 MM-003 trial and the phase 2 MM-011 trial.

Phase 2 trial

In the MM-011 trial, which has not yet been published, researchers evaluated the safety and efficacy of pomalidomide in combination with dexamethasone in 36 patients with relapsed/refractory MM.

The patients had received at least 2 prior therapies, including lenalidomide and bortezomib, and had disease progression within 60 days of completing their last therapy.

Twenty-five percent of patients responded to treatment with pomalidomide and dexamethasone, 1 with a complete response and 8 with a partial response.

About 89% of patients (32/36) experienced adverse events, including lab test abnormalities. The most common events were neutropenia (69.4%), thrombocytopenia (33.3%), rash (22.2%), leukocytopenia (13.9%), pyrexia (13.9%), anemia (11.1%), lymphopenia (11.1%), and constipation (11.1%).

Phase 3 trial

The MM-003 study included 455 patients with relapsed or refractory MM. They were randomized to receive either pomalidomide plus low-dose dexamethasone (POM-LoDEX, n=302) or high-dose dexamethasone (HiDEX, n=153). The median follow-up was 10 months.

The overall response rate was 31% (n=95) in the POM-LoDEX arm and 10% (n=15) in the HiDEX arm. The median duration of response was 7.0 months (range, 6 to 9 months) and 6.1 months (range, 1.4 to 8.5 months), respectively.

The median progression-free survival was 4.0 months in the POM-LoDEX arm and 1.9 months in the HiDEX arm (P<0.001). And the median overall survival was 12.7 months in the POM-LoDEX arm and 8.1 months in the HiDEX arm (P=0.028).

Patients in the POM-LoDEX arm experienced more grade 3/4 neutropenia than patients in the HiDEX arm. But rates of grade 3/4 anemia and thrombocytopenia were similar between the 2 arms.

Rates of grade 3/4 non-hematologic toxicities were also similar between the arms and included infection, pneumonia, hemorrhage, glucose intolerance, and fatigue. Other adverse events of note included venous thromboembolism and peripheral neuropathy, which occurred at similar rates in both arms.

Prescription drugs

Photo courtesy of CDC

The UK’s National Institute for Health and Care Excellence (NICE) has issued final guidance documents for rivaroxaban (Xarelto) and pomalidomide (Imnovid).

The agency is recommending rivaroxaban (in combination) as an option for preventing atherothrombotic events in patients with acute coronary syndrome (ACS).

But NICE said it cannot recommend pomalidomide (in combination) for the treatment of relapsed/refractory multiple myeloma (MM).

Rivaroxaban

Rivaroxaban is licensed in the European Union to prevent atherothrombotic events in adults who have an ACS severe enough to result in the release of cardiac biomarkers into the blood. The drug is given with aspirin and clopidogrel or aspirin alone.

Based on results of the ATLAS-ACS 2-TIMI 51 trial, an appraisal committee advising NICE concluded that rivaroxaban given at 2.5 mg twice daily in combination with aspirin plus clopidogrel or with aspirin alone was more effective than aspirin plus clopidogrel or aspirin alone for preventing further cardiovascular deaths and myocardial infarction in patients with ACS and raised cardiac biomarkers.

The committee also found rivaroxaban to be a cost-effective use of National Health Service (NHS) resources. They noted, however, that the drug can increase the risk of bleeding.

“Because rivaroxaban is associated with a higher risk of causing bleeding than clopidogrel in combination with aspirin or aspirin alone, the guidance recommends that, before starting treatment, doctors should carry out a careful assessment of a person’s bleeding risk,” said Carole Longson, NICE Health Technology Evaluation Centre Director.

“The decision to start treatment should be made after an informed discussion between the doctor and patient about the benefits and risks of rivaroxaban. Also, because there is limited experience of treatment with rivaroxaban up to 24 months, the guidance recommends careful consideration should be given to whether treatment is continued beyond 12 months.”

Pomalidomide

NICE’s final guidance on pomalidomide said the agency cannot recommend the drug as a treatment option for MM.

Pomalidomide is approved in the European Union for use in combination with dexamethasone to treat adults with relapsed and refractory MM who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on the last therapy.

“Unfortunately, we cannot recommend pomalidomide, as the analyses from Celgene, the company that markets the drug, showed that it does not offer enough benefit to justify its high price,” said Sir Andrew Dillon, NICE chief executive.

NICE said the appraisal committee could not judge with any confidence how effective pomalidomide is compared to current treatment options based on the available evidence provided before and after consultation.

Bearing in mind the magnitude of the differences in the overall survival estimates between pomalidomide and high-dose dexamethasone in the phase 3 MM-003 trial and all data presented to the committee for comparators, the committee was persuaded that pomalidomide extends life for at least 3 months on average when compared with standard NHS care.

However, considering the incremental cost-effectiveness ratios, the committee concluded that, even with the end-of-life criteria met, the weighting that would have to be placed on the quality-adjusted life-years gained would be too high to consider pomalidomide a cost-effective use of NHS resources.

The committee also said the uncertainty in the relative effectiveness of pomalidomide compared with established NHS practice would affect any weighting that could be placed on quality-adjusted life-years gained.

Prescription drugs

Photo courtesy of CDC

The UK’s National Institute for Health and Care Excellence (NICE) has issued final guidance documents for rivaroxaban (Xarelto) and pomalidomide (Imnovid).

The agency is recommending rivaroxaban (in combination) as an option for preventing atherothrombotic events in patients with acute coronary syndrome (ACS).

But NICE said it cannot recommend pomalidomide (in combination) for the treatment of relapsed/refractory multiple myeloma (MM).

Rivaroxaban

Rivaroxaban is licensed in the European Union to prevent atherothrombotic events in adults who have an ACS severe enough to result in the release of cardiac biomarkers into the blood. The drug is given with aspirin and clopidogrel or aspirin alone.

Based on results of the ATLAS-ACS 2-TIMI 51 trial, an appraisal committee advising NICE concluded that rivaroxaban given at 2.5 mg twice daily in combination with aspirin plus clopidogrel or with aspirin alone was more effective than aspirin plus clopidogrel or aspirin alone for preventing further cardiovascular deaths and myocardial infarction in patients with ACS and raised cardiac biomarkers.

The committee also found rivaroxaban to be a cost-effective use of National Health Service (NHS) resources. They noted, however, that the drug can increase the risk of bleeding.

“Because rivaroxaban is associated with a higher risk of causing bleeding than clopidogrel in combination with aspirin or aspirin alone, the guidance recommends that, before starting treatment, doctors should carry out a careful assessment of a person’s bleeding risk,” said Carole Longson, NICE Health Technology Evaluation Centre Director.

“The decision to start treatment should be made after an informed discussion between the doctor and patient about the benefits and risks of rivaroxaban. Also, because there is limited experience of treatment with rivaroxaban up to 24 months, the guidance recommends careful consideration should be given to whether treatment is continued beyond 12 months.”

Pomalidomide

NICE’s final guidance on pomalidomide said the agency cannot recommend the drug as a treatment option for MM.

Pomalidomide is approved in the European Union for use in combination with dexamethasone to treat adults with relapsed and refractory MM who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on the last therapy.

“Unfortunately, we cannot recommend pomalidomide, as the analyses from Celgene, the company that markets the drug, showed that it does not offer enough benefit to justify its high price,” said Sir Andrew Dillon, NICE chief executive.

NICE said the appraisal committee could not judge with any confidence how effective pomalidomide is compared to current treatment options based on the available evidence provided before and after consultation.

Bearing in mind the magnitude of the differences in the overall survival estimates between pomalidomide and high-dose dexamethasone in the phase 3 MM-003 trial and all data presented to the committee for comparators, the committee was persuaded that pomalidomide extends life for at least 3 months on average when compared with standard NHS care.

However, considering the incremental cost-effectiveness ratios, the committee concluded that, even with the end-of-life criteria met, the weighting that would have to be placed on the quality-adjusted life-years gained would be too high to consider pomalidomide a cost-effective use of NHS resources.

The committee also said the uncertainty in the relative effectiveness of pomalidomide compared with established NHS practice would affect any weighting that could be placed on quality-adjusted life-years gained.

Prescription drugs

Photo courtesy of CDC

The UK’s National Institute for Health and Care Excellence (NICE) has issued final guidance documents for rivaroxaban (Xarelto) and pomalidomide (Imnovid).

The agency is recommending rivaroxaban (in combination) as an option for preventing atherothrombotic events in patients with acute coronary syndrome (ACS).

But NICE said it cannot recommend pomalidomide (in combination) for the treatment of relapsed/refractory multiple myeloma (MM).

Rivaroxaban

Rivaroxaban is licensed in the European Union to prevent atherothrombotic events in adults who have an ACS severe enough to result in the release of cardiac biomarkers into the blood. The drug is given with aspirin and clopidogrel or aspirin alone.

Based on results of the ATLAS-ACS 2-TIMI 51 trial, an appraisal committee advising NICE concluded that rivaroxaban given at 2.5 mg twice daily in combination with aspirin plus clopidogrel or with aspirin alone was more effective than aspirin plus clopidogrel or aspirin alone for preventing further cardiovascular deaths and myocardial infarction in patients with ACS and raised cardiac biomarkers.

The committee also found rivaroxaban to be a cost-effective use of National Health Service (NHS) resources. They noted, however, that the drug can increase the risk of bleeding.

“Because rivaroxaban is associated with a higher risk of causing bleeding than clopidogrel in combination with aspirin or aspirin alone, the guidance recommends that, before starting treatment, doctors should carry out a careful assessment of a person’s bleeding risk,” said Carole Longson, NICE Health Technology Evaluation Centre Director.

“The decision to start treatment should be made after an informed discussion between the doctor and patient about the benefits and risks of rivaroxaban. Also, because there is limited experience of treatment with rivaroxaban up to 24 months, the guidance recommends careful consideration should be given to whether treatment is continued beyond 12 months.”

Pomalidomide

NICE’s final guidance on pomalidomide said the agency cannot recommend the drug as a treatment option for MM.

Pomalidomide is approved in the European Union for use in combination with dexamethasone to treat adults with relapsed and refractory MM who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on the last therapy.

“Unfortunately, we cannot recommend pomalidomide, as the analyses from Celgene, the company that markets the drug, showed that it does not offer enough benefit to justify its high price,” said Sir Andrew Dillon, NICE chief executive.

NICE said the appraisal committee could not judge with any confidence how effective pomalidomide is compared to current treatment options based on the available evidence provided before and after consultation.

Bearing in mind the magnitude of the differences in the overall survival estimates between pomalidomide and high-dose dexamethasone in the phase 3 MM-003 trial and all data presented to the committee for comparators, the committee was persuaded that pomalidomide extends life for at least 3 months on average when compared with standard NHS care.

However, considering the incremental cost-effectiveness ratios, the committee concluded that, even with the end-of-life criteria met, the weighting that would have to be placed on the quality-adjusted life-years gained would be too high to consider pomalidomide a cost-effective use of NHS resources.

The committee also said the uncertainty in the relative effectiveness of pomalidomide compared with established NHS practice would affect any weighting that could be placed on quality-adjusted life-years gained.

Red blood cells

Preclinical research suggests an enzyme found in hematopoietic stem cells (HSCs) is key to maintaining periods of inactivity, thereby decreasing the odds that HSCs will divide too often and acquire mutations or cell damage.

Experiments showed that animals lacking this enzyme, inositol trisphosphate 3-kinase B (Itpkb), experience dangerous HSC activation and ultimately succumb to lethal anemia.

“These HSCs remain active too long and then disappear,” said Karsten Sauer, PhD, of The Scripps Research Institute in La Jolla, California.

“As a consequence, the mice lose their red blood cells and die.”

With this new understanding of Itpkb, Dr Sauer and his colleagues believe they are closer to improving therapies for diseases such as bone marrow failure syndrome, anemia, leukemia, and lymphoma.

The team described their research in Blood.

The group set out to investigate the mechanisms that activate and deactivate HSCs. They focused on Itpkb because it is produced in HSCs, and the enzyme is known to dampen activating signaling in other cells.

“We hypothesized that Itpkb might do the same in HSCs to keep them at rest,” Dr Sauer said. “Moreover, Itpkb is an enzyme whose function can be controlled by small molecules. This might facilitate drug development if our hypothesis were true.”

The researchers started with a strain of mice that lacked the gene to produce Itpkb. As expected, these mice developed hyperactive HSCs. Eventually, the mutant HSCs exhausted themselves and stopped producing progenitor cells, so the mice developed severe anemia and died.

Dr Sauer and his colleagues linked the abnormal behavior of the mutant HSCs to a chain of events at the molecular level.

Itpkb’s job is to attach phosphates to molecules called inositols, which then send messages to other parts of the cell. The researchers found that Itpkb can turn one inositol, IP3, into another inositol known as IP4.

This is significant because IP4 controls cell proliferation, cellular metabolism, and aspects of the immune system. The study showed that IP4 also protects HSCs by dampening PI3K/Akt/mTOR signaling.

To confirm this finding, the researchers treated the animals with the mTOR inhibitor rapamycin. The drug halted the abnormal signaling process and prevented the excessive division of HSCs lacking Itpkb. This supported the notion that Itpkb maintains HSCs’ quiescence by dampening PI3K/Akt/mTOR signaling.

Dr Sauer said future research in his lab will focus on studying whether Itpkb has a similar function in human HSCs.

“A major question is whether we can translate our findings into innovative therapies,” he said. “If we can show that Itpkb also keeps human HSCs healthy, this could open avenues to target Itpkb to improve HSC function in bone marrow failure syndromes and immunodeficiencies or to increase the success rates of HSC transplantation therapies for leukemias and lymphomas.”

Red blood cells

Preclinical research suggests an enzyme found in hematopoietic stem cells (HSCs) is key to maintaining periods of inactivity, thereby decreasing the odds that HSCs will divide too often and acquire mutations or cell damage.

Experiments showed that animals lacking this enzyme, inositol trisphosphate 3-kinase B (Itpkb), experience dangerous HSC activation and ultimately succumb to lethal anemia.

“These HSCs remain active too long and then disappear,” said Karsten Sauer, PhD, of The Scripps Research Institute in La Jolla, California.

“As a consequence, the mice lose their red blood cells and die.”

With this new understanding of Itpkb, Dr Sauer and his colleagues believe they are closer to improving therapies for diseases such as bone marrow failure syndrome, anemia, leukemia, and lymphoma.

The team described their research in Blood.

The group set out to investigate the mechanisms that activate and deactivate HSCs. They focused on Itpkb because it is produced in HSCs, and the enzyme is known to dampen activating signaling in other cells.

“We hypothesized that Itpkb might do the same in HSCs to keep them at rest,” Dr Sauer said. “Moreover, Itpkb is an enzyme whose function can be controlled by small molecules. This might facilitate drug development if our hypothesis were true.”

The researchers started with a strain of mice that lacked the gene to produce Itpkb. As expected, these mice developed hyperactive HSCs. Eventually, the mutant HSCs exhausted themselves and stopped producing progenitor cells, so the mice developed severe anemia and died.

Dr Sauer and his colleagues linked the abnormal behavior of the mutant HSCs to a chain of events at the molecular level.

Itpkb’s job is to attach phosphates to molecules called inositols, which then send messages to other parts of the cell. The researchers found that Itpkb can turn one inositol, IP3, into another inositol known as IP4.

This is significant because IP4 controls cell proliferation, cellular metabolism, and aspects of the immune system. The study showed that IP4 also protects HSCs by dampening PI3K/Akt/mTOR signaling.

To confirm this finding, the researchers treated the animals with the mTOR inhibitor rapamycin. The drug halted the abnormal signaling process and prevented the excessive division of HSCs lacking Itpkb. This supported the notion that Itpkb maintains HSCs’ quiescence by dampening PI3K/Akt/mTOR signaling.

Dr Sauer said future research in his lab will focus on studying whether Itpkb has a similar function in human HSCs.

“A major question is whether we can translate our findings into innovative therapies,” he said. “If we can show that Itpkb also keeps human HSCs healthy, this could open avenues to target Itpkb to improve HSC function in bone marrow failure syndromes and immunodeficiencies or to increase the success rates of HSC transplantation therapies for leukemias and lymphomas.”

Red blood cells

Preclinical research suggests an enzyme found in hematopoietic stem cells (HSCs) is key to maintaining periods of inactivity, thereby decreasing the odds that HSCs will divide too often and acquire mutations or cell damage.

Experiments showed that animals lacking this enzyme, inositol trisphosphate 3-kinase B (Itpkb), experience dangerous HSC activation and ultimately succumb to lethal anemia.

“These HSCs remain active too long and then disappear,” said Karsten Sauer, PhD, of The Scripps Research Institute in La Jolla, California.

“As a consequence, the mice lose their red blood cells and die.”

With this new understanding of Itpkb, Dr Sauer and his colleagues believe they are closer to improving therapies for diseases such as bone marrow failure syndrome, anemia, leukemia, and lymphoma.

The team described their research in Blood.

The group set out to investigate the mechanisms that activate and deactivate HSCs. They focused on Itpkb because it is produced in HSCs, and the enzyme is known to dampen activating signaling in other cells.

“We hypothesized that Itpkb might do the same in HSCs to keep them at rest,” Dr Sauer said. “Moreover, Itpkb is an enzyme whose function can be controlled by small molecules. This might facilitate drug development if our hypothesis were true.”

The researchers started with a strain of mice that lacked the gene to produce Itpkb. As expected, these mice developed hyperactive HSCs. Eventually, the mutant HSCs exhausted themselves and stopped producing progenitor cells, so the mice developed severe anemia and died.

Dr Sauer and his colleagues linked the abnormal behavior of the mutant HSCs to a chain of events at the molecular level.

Itpkb’s job is to attach phosphates to molecules called inositols, which then send messages to other parts of the cell. The researchers found that Itpkb can turn one inositol, IP3, into another inositol known as IP4.

This is significant because IP4 controls cell proliferation, cellular metabolism, and aspects of the immune system. The study showed that IP4 also protects HSCs by dampening PI3K/Akt/mTOR signaling.

To confirm this finding, the researchers treated the animals with the mTOR inhibitor rapamycin. The drug halted the abnormal signaling process and prevented the excessive division of HSCs lacking Itpkb. This supported the notion that Itpkb maintains HSCs’ quiescence by dampening PI3K/Akt/mTOR signaling.

Dr Sauer said future research in his lab will focus on studying whether Itpkb has a similar function in human HSCs.

“A major question is whether we can translate our findings into innovative therapies,” he said. “If we can show that Itpkb also keeps human HSCs healthy, this could open avenues to target Itpkb to improve HSC function in bone marrow failure syndromes and immunodeficiencies or to increase the success rates of HSC transplantation therapies for leukemias and lymphomas.”

Lab mouse

Researchers say they have discovered a new way to target multiple myeloma (MM) and other cancer cells.

The investigators developed human T-cell receptors (TCRs) that have no tolerance toward human cancer antigens and specifically recognize the antigen MAGE-A1, which is present on MM and other cancer cells.

Matthias Obenaus, MD, of the Max-Delbrück-Center for Molecular Medicine in Berlin, Germany, and his colleagues described this work in Nature Biotechnology.

Instead of directly using human-derived TCRs, which do not mediate substantial anti-tumor effects, the researchers took a “detour” by employing a mouse model.

First, they transferred the genetic information for human TCRs into the mice, thereby creating an arsenal of human TCRs.

Then, the investigators isolated the TCRs from the mice and transferred them into human T cells. This “trained” the cells to recognize MM and other cancer cells (eg, melanoma and fibrosarcoma cells) as foreign.

The researchers noted that some people possess T cells that naturally recognize MAGE-A1 on tumor cells, but only in vitro.

In vivo experiments revealed that only the human TCRs derived from mice were effective against tumors. The TCRs derived directly from humans were too weak to recognize the tumor antigens sufficiently.

The investigators said the fact that their mouse-derived human TCRs were more effective is a strong indication that human T cells are tolerant toward MAGE-A1.

Using the TCRs they developed, the researchers are now planning a clinical trial of patients with MAGE-A1 positive MM.

Lab mouse

Researchers say they have discovered a new way to target multiple myeloma (MM) and other cancer cells.

The investigators developed human T-cell receptors (TCRs) that have no tolerance toward human cancer antigens and specifically recognize the antigen MAGE-A1, which is present on MM and other cancer cells.

Matthias Obenaus, MD, of the Max-Delbrück-Center for Molecular Medicine in Berlin, Germany, and his colleagues described this work in Nature Biotechnology.

Instead of directly using human-derived TCRs, which do not mediate substantial anti-tumor effects, the researchers took a “detour” by employing a mouse model.

First, they transferred the genetic information for human TCRs into the mice, thereby creating an arsenal of human TCRs.

Then, the investigators isolated the TCRs from the mice and transferred them into human T cells. This “trained” the cells to recognize MM and other cancer cells (eg, melanoma and fibrosarcoma cells) as foreign.

The researchers noted that some people possess T cells that naturally recognize MAGE-A1 on tumor cells, but only in vitro.

In vivo experiments revealed that only the human TCRs derived from mice were effective against tumors. The TCRs derived directly from humans were too weak to recognize the tumor antigens sufficiently.

The investigators said the fact that their mouse-derived human TCRs were more effective is a strong indication that human T cells are tolerant toward MAGE-A1.

Using the TCRs they developed, the researchers are now planning a clinical trial of patients with MAGE-A1 positive MM.

Lab mouse

Researchers say they have discovered a new way to target multiple myeloma (MM) and other cancer cells.

The investigators developed human T-cell receptors (TCRs) that have no tolerance toward human cancer antigens and specifically recognize the antigen MAGE-A1, which is present on MM and other cancer cells.

Matthias Obenaus, MD, of the Max-Delbrück-Center for Molecular Medicine in Berlin, Germany, and his colleagues described this work in Nature Biotechnology.

Instead of directly using human-derived TCRs, which do not mediate substantial anti-tumor effects, the researchers took a “detour” by employing a mouse model.

First, they transferred the genetic information for human TCRs into the mice, thereby creating an arsenal of human TCRs.

Then, the investigators isolated the TCRs from the mice and transferred them into human T cells. This “trained” the cells to recognize MM and other cancer cells (eg, melanoma and fibrosarcoma cells) as foreign.

The researchers noted that some people possess T cells that naturally recognize MAGE-A1 on tumor cells, but only in vitro.

In vivo experiments revealed that only the human TCRs derived from mice were effective against tumors. The TCRs derived directly from humans were too weak to recognize the tumor antigens sufficiently.

The investigators said the fact that their mouse-derived human TCRs were more effective is a strong indication that human T cells are tolerant toward MAGE-A1.

Using the TCRs they developed, the researchers are now planning a clinical trial of patients with MAGE-A1 positive MM.

Bone marrow aspirate

showing MM

The European Medicines Agency (EMA) has given a novel vaccine orphan designation as a treatment for multiple myeloma (MM).

The vaccine, known as ImMucin, targets the signal peptide domain of the MUC1 tumor antigen.

ImMucin works by “teaching” the immune system to identify and destroy cells that display a short, specific, 21-mer portion from MUC1, which appears on 90% of all cancer cells but not in patients’ blood.

Results of a phase 1/2 trial suggested that ImMucin was safe and active in MM patients. The trial included 15 MUC1-positive patients who had residual or biochemically progressive disease after autologous stem cell transplant.

The patients received 6 or 12 bi-weekly intradermal doses of ImMucin co-administered with human granulocyte-macrophage colony-stimulating factor.

The researchers said the vaccine was well-tolerated, as all adverse events were temporary, grade 1-2 in nature, and resolved spontaneously.

There was a significant decrease in soluble MUC1 levels in 9 patients, and 11 patients had stable disease or clinical improvement that persisted for 17.5 months to more than 41.3 months.

A follow-on study (which is ongoing) in patients who responded to ImMucin has shown that some patients can go more than 4 years without requiring any further treatment for their disease.

ImMucin is also being evaluated in a phase 1/2 study to treat patients with metastatic breast cancer who are receiving first-line hormone therapy.

ImMucin is under development by Vaxil Biotherapeutics Ltd.

About orphan designation

The EMA grants orphan designation to promote the clinical development of drugs that treat rare, life-threatening, or debilitating conditions and are expected to provide significant therapeutic advantage over existing treatments.

Orphan designation provides the company developing a drug with significant benefits, including 10 years of market exclusivity following approval, reductions in the fees and costs of the regulatory process, and scientific assistance from the EMA in clinical development.

Bone marrow aspirate

showing MM

The European Medicines Agency (EMA) has given a novel vaccine orphan designation as a treatment for multiple myeloma (MM).

The vaccine, known as ImMucin, targets the signal peptide domain of the MUC1 tumor antigen.

ImMucin works by “teaching” the immune system to identify and destroy cells that display a short, specific, 21-mer portion from MUC1, which appears on 90% of all cancer cells but not in patients’ blood.

Results of a phase 1/2 trial suggested that ImMucin was safe and active in MM patients. The trial included 15 MUC1-positive patients who had residual or biochemically progressive disease after autologous stem cell transplant.

The patients received 6 or 12 bi-weekly intradermal doses of ImMucin co-administered with human granulocyte-macrophage colony-stimulating factor.

The researchers said the vaccine was well-tolerated, as all adverse events were temporary, grade 1-2 in nature, and resolved spontaneously.

There was a significant decrease in soluble MUC1 levels in 9 patients, and 11 patients had stable disease or clinical improvement that persisted for 17.5 months to more than 41.3 months.

A follow-on study (which is ongoing) in patients who responded to ImMucin has shown that some patients can go more than 4 years without requiring any further treatment for their disease.

ImMucin is also being evaluated in a phase 1/2 study to treat patients with metastatic breast cancer who are receiving first-line hormone therapy.

ImMucin is under development by Vaxil Biotherapeutics Ltd.

About orphan designation

The EMA grants orphan designation to promote the clinical development of drugs that treat rare, life-threatening, or debilitating conditions and are expected to provide significant therapeutic advantage over existing treatments.

Orphan designation provides the company developing a drug with significant benefits, including 10 years of market exclusivity following approval, reductions in the fees and costs of the regulatory process, and scientific assistance from the EMA in clinical development.

Bone marrow aspirate

showing MM

The European Medicines Agency (EMA) has given a novel vaccine orphan designation as a treatment for multiple myeloma (MM).

The vaccine, known as ImMucin, targets the signal peptide domain of the MUC1 tumor antigen.

ImMucin works by “teaching” the immune system to identify and destroy cells that display a short, specific, 21-mer portion from MUC1, which appears on 90% of all cancer cells but not in patients’ blood.

Results of a phase 1/2 trial suggested that ImMucin was safe and active in MM patients. The trial included 15 MUC1-positive patients who had residual or biochemically progressive disease after autologous stem cell transplant.

The patients received 6 or 12 bi-weekly intradermal doses of ImMucin co-administered with human granulocyte-macrophage colony-stimulating factor.

The researchers said the vaccine was well-tolerated, as all adverse events were temporary, grade 1-2 in nature, and resolved spontaneously.

There was a significant decrease in soluble MUC1 levels in 9 patients, and 11 patients had stable disease or clinical improvement that persisted for 17.5 months to more than 41.3 months.

A follow-on study (which is ongoing) in patients who responded to ImMucin has shown that some patients can go more than 4 years without requiring any further treatment for their disease.

ImMucin is also being evaluated in a phase 1/2 study to treat patients with metastatic breast cancer who are receiving first-line hormone therapy.

ImMucin is under development by Vaxil Biotherapeutics Ltd.

About orphan designation

The EMA grants orphan designation to promote the clinical development of drugs that treat rare, life-threatening, or debilitating conditions and are expected to provide significant therapeutic advantage over existing treatments.

Orphan designation provides the company developing a drug with significant benefits, including 10 years of market exclusivity following approval, reductions in the fees and costs of the regulatory process, and scientific assistance from the EMA in clinical development.

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Zarxio (filgrastim-sndz), the first biosimilar product to be approved in the US.

A biosimilar product is approved based on data showing that it is highly similar to an already-approved biological product.

Sandoz Inc’s Zarxio is biosimilar to Amgen Inc’s Neupogen (filgrastim), which was originally licensed in 1991. Zarxio is now approved for the same indications as Neupogen.

Zarxio can be prescribed for:

• patients with cancer receiving myelosuppressive chemotherapy
• patients with acute myeloid leukemia receiving induction or consolidation chemotherapy
• patients with cancer undergoing bone marrow transplant
• patients undergoing autologous peripheral blood progenitor cell collection and therapy
• patients with severe chronic neutropenia.

Zarxio is marketed as Zarzio outside the US. The biosimilar is available in more than 60 countries worldwide.

“Biosimilars will provide access to important therapies for patients who need them,” said FDA Commissioner Margaret A. Hamburg, MD.

“Patients and the healthcare community can be confident that biosimilar products approved by the FDA meet the agency’s rigorous safety, efficacy, and quality standards.”

Zarxio data

The FDA’s approval of Zarxio is based on a review of evidence that included structural and functional characterization, in vivo data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen.

The PIONEER study was the final piece of data the FDA used to approve Zarxio as biosimilar to Neupogen. The data was sufficient to allow extrapolation of the use of Zarxio to all indications of Neupogen.

In the PIONEER study, Zarxio and Neupogen both produced the expected reduction in the duration of severe neutropenia in cancer patients undergoing myelosuppressive chemotherapy—1.17 and 1.20 days, respectively.

The mean time to absolute neutrophil count recovery in cycle 1 was also similar—1.8 ± 0.97 days in the Zarxio arm and 1.7 ± 0.81 days in the Neupogen arm. No immunogenicity or antibodies against rhG-CSF were detected throughout the study.

The most common side effects of Zarxio are aching in the bones or muscles and redness, swelling, or itching at the injection site. Serious side effects may include spleen rupture; serious allergic reactions that may cause rash, shortness of breath, wheezing and/or swelling around the mouth and eyes; fast pulse and sweating; and acute respiratory distress syndrome.

About biosimilar approval

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) was passed as part of the Affordable Care Act that President Barack Obama signed into law in March 2010. The BPCI Act created an abbreviated licensure pathway for biological products shown to be “biosimilar” to or “interchangeable” with an FDA-licensed biological product, known as the reference product.

This abbreviated licensure pathway under section 351(k) of the Public Health Service Act permits reliance on certain existing scientific knowledge about the safety and effectiveness of the reference product, and it enables a biosimilar biological product to be licensed based on less than a full complement of product-specific preclinical and clinical data.

A biosimilar product can only be approved by the FDA if it has the same mechanism(s) of action, route(s) of administration, dosage form(s) and strength(s) as the reference product, and only for the indication(s) and condition(s) of use that have been approved for the reference product. The facilities where biosimilars are manufactured must also meet the FDA’s standards.

There must be no clinically meaningful differences between the biosimilar and the reference product in terms of safety and effectiveness. Only minor differences in clinically inactive components are allowable.

Zarxio has been approved as a biosimilar, not an interchangeable product. Under the BPCI Act, a biological product that has been approved as “interchangeable” may be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product.

For Zarxio’s approval, the FDA has designated a placeholder nonproprietary name for this product as “filgrastim-sndz.” The provision of a placeholder nonproprietary name should not be viewed as reflective of the agency’s decision on a comprehensive naming policy for biosimilars and other biological products.

While the FDA has not yet issued draft guidance on how current and future biological products marketed in the US should be named, the agency intends to do so in the near future.

For more details on Zarxio, see the full prescribing information.

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Zarxio (filgrastim-sndz), the first biosimilar product to be approved in the US.

A biosimilar product is approved based on data showing that it is highly similar to an already-approved biological product.

Sandoz Inc’s Zarxio is biosimilar to Amgen Inc’s Neupogen (filgrastim), which was originally licensed in 1991. Zarxio is now approved for the same indications as Neupogen.

Zarxio can be prescribed for:

• patients with cancer receiving myelosuppressive chemotherapy
• patients with acute myeloid leukemia receiving induction or consolidation chemotherapy
• patients with cancer undergoing bone marrow transplant
• patients undergoing autologous peripheral blood progenitor cell collection and therapy
• patients with severe chronic neutropenia.

Zarxio is marketed as Zarzio outside the US. The biosimilar is available in more than 60 countries worldwide.

“Biosimilars will provide access to important therapies for patients who need them,” said FDA Commissioner Margaret A. Hamburg, MD.

“Patients and the healthcare community can be confident that biosimilar products approved by the FDA meet the agency’s rigorous safety, efficacy, and quality standards.”

Zarxio data

The FDA’s approval of Zarxio is based on a review of evidence that included structural and functional characterization, in vivo data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen.

The PIONEER study was the final piece of data the FDA used to approve Zarxio as biosimilar to Neupogen. The data was sufficient to allow extrapolation of the use of Zarxio to all indications of Neupogen.

In the PIONEER study, Zarxio and Neupogen both produced the expected reduction in the duration of severe neutropenia in cancer patients undergoing myelosuppressive chemotherapy—1.17 and 1.20 days, respectively.

The mean time to absolute neutrophil count recovery in cycle 1 was also similar—1.8 ± 0.97 days in the Zarxio arm and 1.7 ± 0.81 days in the Neupogen arm. No immunogenicity or antibodies against rhG-CSF were detected throughout the study.

The most common side effects of Zarxio are aching in the bones or muscles and redness, swelling, or itching at the injection site. Serious side effects may include spleen rupture; serious allergic reactions that may cause rash, shortness of breath, wheezing and/or swelling around the mouth and eyes; fast pulse and sweating; and acute respiratory distress syndrome.

About biosimilar approval

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) was passed as part of the Affordable Care Act that President Barack Obama signed into law in March 2010. The BPCI Act created an abbreviated licensure pathway for biological products shown to be “biosimilar” to or “interchangeable” with an FDA-licensed biological product, known as the reference product.

This abbreviated licensure pathway under section 351(k) of the Public Health Service Act permits reliance on certain existing scientific knowledge about the safety and effectiveness of the reference product, and it enables a biosimilar biological product to be licensed based on less than a full complement of product-specific preclinical and clinical data.

A biosimilar product can only be approved by the FDA if it has the same mechanism(s) of action, route(s) of administration, dosage form(s) and strength(s) as the reference product, and only for the indication(s) and condition(s) of use that have been approved for the reference product. The facilities where biosimilars are manufactured must also meet the FDA’s standards.

There must be no clinically meaningful differences between the biosimilar and the reference product in terms of safety and effectiveness. Only minor differences in clinically inactive components are allowable.

Zarxio has been approved as a biosimilar, not an interchangeable product. Under the BPCI Act, a biological product that has been approved as “interchangeable” may be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product.

For Zarxio’s approval, the FDA has designated a placeholder nonproprietary name for this product as “filgrastim-sndz.” The provision of a placeholder nonproprietary name should not be viewed as reflective of the agency’s decision on a comprehensive naming policy for biosimilars and other biological products.

While the FDA has not yet issued draft guidance on how current and future biological products marketed in the US should be named, the agency intends to do so in the near future.

For more details on Zarxio, see the full prescribing information.

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Zarxio (filgrastim-sndz), the first biosimilar product to be approved in the US.

A biosimilar product is approved based on data showing that it is highly similar to an already-approved biological product.

Sandoz Inc’s Zarxio is biosimilar to Amgen Inc’s Neupogen (filgrastim), which was originally licensed in 1991. Zarxio is now approved for the same indications as Neupogen.

Zarxio can be prescribed for:

• patients with cancer receiving myelosuppressive chemotherapy
• patients with acute myeloid leukemia receiving induction or consolidation chemotherapy
• patients with cancer undergoing bone marrow transplant
• patients undergoing autologous peripheral blood progenitor cell collection and therapy
• patients with severe chronic neutropenia.

Zarxio is marketed as Zarzio outside the US. The biosimilar is available in more than 60 countries worldwide.

“Biosimilars will provide access to important therapies for patients who need them,” said FDA Commissioner Margaret A. Hamburg, MD.

“Patients and the healthcare community can be confident that biosimilar products approved by the FDA meet the agency’s rigorous safety, efficacy, and quality standards.”

Zarxio data

The FDA’s approval of Zarxio is based on a review of evidence that included structural and functional characterization, in vivo data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen.

The PIONEER study was the final piece of data the FDA used to approve Zarxio as biosimilar to Neupogen. The data was sufficient to allow extrapolation of the use of Zarxio to all indications of Neupogen.

In the PIONEER study, Zarxio and Neupogen both produced the expected reduction in the duration of severe neutropenia in cancer patients undergoing myelosuppressive chemotherapy—1.17 and 1.20 days, respectively.

The mean time to absolute neutrophil count recovery in cycle 1 was also similar—1.8 ± 0.97 days in the Zarxio arm and 1.7 ± 0.81 days in the Neupogen arm. No immunogenicity or antibodies against rhG-CSF were detected throughout the study.

The most common side effects of Zarxio are aching in the bones or muscles and redness, swelling, or itching at the injection site. Serious side effects may include spleen rupture; serious allergic reactions that may cause rash, shortness of breath, wheezing and/or swelling around the mouth and eyes; fast pulse and sweating; and acute respiratory distress syndrome.

About biosimilar approval

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) was passed as part of the Affordable Care Act that President Barack Obama signed into law in March 2010. The BPCI Act created an abbreviated licensure pathway for biological products shown to be “biosimilar” to or “interchangeable” with an FDA-licensed biological product, known as the reference product.

This abbreviated licensure pathway under section 351(k) of the Public Health Service Act permits reliance on certain existing scientific knowledge about the safety and effectiveness of the reference product, and it enables a biosimilar biological product to be licensed based on less than a full complement of product-specific preclinical and clinical data.

A biosimilar product can only be approved by the FDA if it has the same mechanism(s) of action, route(s) of administration, dosage form(s) and strength(s) as the reference product, and only for the indication(s) and condition(s) of use that have been approved for the reference product. The facilities where biosimilars are manufactured must also meet the FDA’s standards.

There must be no clinically meaningful differences between the biosimilar and the reference product in terms of safety and effectiveness. Only minor differences in clinically inactive components are allowable.

Zarxio has been approved as a biosimilar, not an interchangeable product. Under the BPCI Act, a biological product that has been approved as “interchangeable” may be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product.

For Zarxio’s approval, the FDA has designated a placeholder nonproprietary name for this product as “filgrastim-sndz.” The provision of a placeholder nonproprietary name should not be viewed as reflective of the agency’s decision on a comprehensive naming policy for biosimilars and other biological products.

While the FDA has not yet issued draft guidance on how current and future biological products marketed in the US should be named, the agency intends to do so in the near future.

For more details on Zarxio, see the full prescribing information.

Micrograph showing MM

Patients with multiple myeloma (MM) appear to have better survival if they are first diagnosed with monoclonal gammopathy of undetermined significance (MGUS), according to a study published in JAMA Oncology.

The researchers think this may be because patients with MGUS are evaluated more often for signs of progression to MM. They may therefore be diagnosed with MM and started on therapy at an earlier stage than patients who have not been diagnosed with MGUS.

However, the study did not verify that MM patients initially diagnosed with MGUS were followed more closely than their peers.

So, as authors of a related editorial pointed out, it is difficult to confirm a causal relationship between closer follow-up and better prognosis.

Sigurdur Y. Kristinsson, MD, PhD, of the University of Iceland in Reykjavik, and his colleagues conducted this study, evaluating the impact of prior knowledge of MGUS diagnosis and coexisting illnesses on MM survival.

The study included all patients diagnosed with MM in Sweden (n=14,798) from 1976 to 2005. In all, 394 patients (2.7%) had previously been diagnosed with MGUS.

Patients with prior knowledge of MGUS had better overall survival than patients with MM who didn’t know when they had MGUS—a median survival of 2.8 years and 2.1 years, respectively (hazard ratio=0.86, P<0.01).

But patients with prior knowledge of their MGUS status had more coexisting illnesses, including systemic and organ-bound autoimmune diseases (P=0.02 for both), autoimmune diseases without auto-antibodies (P<0.001), infections (P<0.001), ischemic heart disease (P<0.001), heart failure (P=0.03), cerebrovascular diseases (P=0.04), and renal diseases (P<0.001).

Low M-protein concentration at MGUS diagnosis was associated with poorer survival among MM patients with prior knowledge of MGUS. Patients who had M-protein concentrations less than 0.5 g/dL had significantly worse survival than patients with concentrations of 0.5 to 3.0 g/dL (hazard ratio=1.86, P=0.01).

The researchers said the worse survival observed in these patients may be a result of less frequent clinical follow-up.

“Our results reflect the importance of lifelong follow-up for individuals diagnosed as having MGUS, independent of risk score, and highlight the need for better risk models based on the biology of the disease,” the researchers wrote.

“Patients should receive balanced information stressing not only the overall very low risk of progression to malignant neoplasm but also the symptoms that could signal such development and the need to consult their physician.”

Authors of a related editorial—Robert A. Kyle, MD, and S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota—expressed a somewhat different viewpoint.

“It cannot be determined whether MM patients with a known MGUS in the Icelandic study were followed more closely than those in whom a MGUS was not recognized, and, hence, it is difficult to attribute a causal relationship between follow-up and better prognosis,” they wrote.

“We also need studies to address the question of the possible merits of screening for the presence of MGUS in a normal, older population. The cost, inconvenience, and anxiety produced by the awareness of potential progression of a recognized MGUS, as well as the low absolute risk of progression (0.5% to 1%), probably override the possible potential benefit of screening for MGUS.”

Micrograph showing MM

Patients with multiple myeloma (MM) appear to have better survival if they are first diagnosed with monoclonal gammopathy of undetermined significance (MGUS), according to a study published in JAMA Oncology.

The researchers think this may be because patients with MGUS are evaluated more often for signs of progression to MM. They may therefore be diagnosed with MM and started on therapy at an earlier stage than patients who have not been diagnosed with MGUS.

However, the study did not verify that MM patients initially diagnosed with MGUS were followed more closely than their peers.

So, as authors of a related editorial pointed out, it is difficult to confirm a causal relationship between closer follow-up and better prognosis.

Sigurdur Y. Kristinsson, MD, PhD, of the University of Iceland in Reykjavik, and his colleagues conducted this study, evaluating the impact of prior knowledge of MGUS diagnosis and coexisting illnesses on MM survival.

The study included all patients diagnosed with MM in Sweden (n=14,798) from 1976 to 2005. In all, 394 patients (2.7%) had previously been diagnosed with MGUS.

Patients with prior knowledge of MGUS had better overall survival than patients with MM who didn’t know when they had MGUS—a median survival of 2.8 years and 2.1 years, respectively (hazard ratio=0.86, P<0.01).

But patients with prior knowledge of their MGUS status had more coexisting illnesses, including systemic and organ-bound autoimmune diseases (P=0.02 for both), autoimmune diseases without auto-antibodies (P<0.001), infections (P<0.001), ischemic heart disease (P<0.001), heart failure (P=0.03), cerebrovascular diseases (P=0.04), and renal diseases (P<0.001).

Low M-protein concentration at MGUS diagnosis was associated with poorer survival among MM patients with prior knowledge of MGUS. Patients who had M-protein concentrations less than 0.5 g/dL had significantly worse survival than patients with concentrations of 0.5 to 3.0 g/dL (hazard ratio=1.86, P=0.01).

The researchers said the worse survival observed in these patients may be a result of less frequent clinical follow-up.

“Our results reflect the importance of lifelong follow-up for individuals diagnosed as having MGUS, independent of risk score, and highlight the need for better risk models based on the biology of the disease,” the researchers wrote.

“Patients should receive balanced information stressing not only the overall very low risk of progression to malignant neoplasm but also the symptoms that could signal such development and the need to consult their physician.”

Authors of a related editorial—Robert A. Kyle, MD, and S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota—expressed a somewhat different viewpoint.

“It cannot be determined whether MM patients with a known MGUS in the Icelandic study were followed more closely than those in whom a MGUS was not recognized, and, hence, it is difficult to attribute a causal relationship between follow-up and better prognosis,” they wrote.

“We also need studies to address the question of the possible merits of screening for the presence of MGUS in a normal, older population. The cost, inconvenience, and anxiety produced by the awareness of potential progression of a recognized MGUS, as well as the low absolute risk of progression (0.5% to 1%), probably override the possible potential benefit of screening for MGUS.”

Micrograph showing MM

Patients with multiple myeloma (MM) appear to have better survival if they are first diagnosed with monoclonal gammopathy of undetermined significance (MGUS), according to a study published in JAMA Oncology.

The researchers think this may be because patients with MGUS are evaluated more often for signs of progression to MM. They may therefore be diagnosed with MM and started on therapy at an earlier stage than patients who have not been diagnosed with MGUS.

However, the study did not verify that MM patients initially diagnosed with MGUS were followed more closely than their peers.

So, as authors of a related editorial pointed out, it is difficult to confirm a causal relationship between closer follow-up and better prognosis.

Sigurdur Y. Kristinsson, MD, PhD, of the University of Iceland in Reykjavik, and his colleagues conducted this study, evaluating the impact of prior knowledge of MGUS diagnosis and coexisting illnesses on MM survival.

The study included all patients diagnosed with MM in Sweden (n=14,798) from 1976 to 2005. In all, 394 patients (2.7%) had previously been diagnosed with MGUS.

Patients with prior knowledge of MGUS had better overall survival than patients with MM who didn’t know when they had MGUS—a median survival of 2.8 years and 2.1 years, respectively (hazard ratio=0.86, P<0.01).

But patients with prior knowledge of their MGUS status had more coexisting illnesses, including systemic and organ-bound autoimmune diseases (P=0.02 for both), autoimmune diseases without auto-antibodies (P<0.001), infections (P<0.001), ischemic heart disease (P<0.001), heart failure (P=0.03), cerebrovascular diseases (P=0.04), and renal diseases (P<0.001).

Low M-protein concentration at MGUS diagnosis was associated with poorer survival among MM patients with prior knowledge of MGUS. Patients who had M-protein concentrations less than 0.5 g/dL had significantly worse survival than patients with concentrations of 0.5 to 3.0 g/dL (hazard ratio=1.86, P=0.01).

The researchers said the worse survival observed in these patients may be a result of less frequent clinical follow-up.

“Our results reflect the importance of lifelong follow-up for individuals diagnosed as having MGUS, independent of risk score, and highlight the need for better risk models based on the biology of the disease,” the researchers wrote.

“Patients should receive balanced information stressing not only the overall very low risk of progression to malignant neoplasm but also the symptoms that could signal such development and the need to consult their physician.”

Authors of a related editorial—Robert A. Kyle, MD, and S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota—expressed a somewhat different viewpoint.

“It cannot be determined whether MM patients with a known MGUS in the Icelandic study were followed more closely than those in whom a MGUS was not recognized, and, hence, it is difficult to attribute a causal relationship between follow-up and better prognosis,” they wrote.

“We also need studies to address the question of the possible merits of screening for the presence of MGUS in a normal, older population. The cost, inconvenience, and anxiety produced by the awareness of potential progression of a recognized MGUS, as well as the low absolute risk of progression (0.5% to 1%), probably override the possible potential benefit of screening for MGUS.”