Multiple Myeloma

Elena Fidarova, MD

Photo courtesy of ASTRO

BOSTON—A new study suggests that roughly half of cancer patients in developing countries need radiation therapy (RT) to treat their disease, but many of these patients do not have access to it.

Examining 9 developing countries, investigators found that between 18% and 82% of patients who can benefit from RT do not receive the treatment.

These findings were presented at ASTRO’s 58th Annual Meeting (abstract 82).

“Access to radiation therapy remains limited in low-and middle-income countries,” said study investigator Elena Fidarova, MD, of the International Atomic Energy Agency in Vienna, Austria.

“In Ghana and the Philippines, for example, about 8 in 10 cancer patients who need radiation therapy will not receive needed treatment.”

Dr Fidarova and her colleagues conducted this study to assess levels of optimal and actual RT utilization (RTU) and calculate unmet RT need in 9 developing countries—Costa Rica, Ghana, Malaysia, the Philippines, Romania, Serbia, Slovenia, Tunisia, and Uruguay.

The investigators determined the optimal and actual RTU rates for each country. The optimal RTU rate is the proportion of all newly diagnosed cancer patients who have an indication for RT at least once in their lifetime.

An indication for RT was defined as a clinical scenario for which RT is recommended as the treatment of choice because there is evidence of its superiority to alternative modalities and/or no treatment (eg, better survival, local control, or quality of life profiles).

In clinical situations where RT was equivalent to other treatment options, all comparable modalities were included in the model, and a subsequent sensitivity analysis was conducted to determine the proportion of these patients for whom RT was indicated.

Results

The median optimal RTU for all countries was 52%. Optimal RTU rates ranged from a low of 47% for Costa Rica to a high of 56% for Tunisia. Differences in optimal RTU rates are attributable to varying incidence rates of cancer types in each country.

The median actual RTU rate was roughly half of optimal utilization, suggesting that nearly half of cancer patients across these 9 countries combined may not be receiving adequate care for their disease.

The median actual RTU rate was 28%. The lowest rates of utilization were in Ghana (9%) and the Philippines (10.3%), while the highest utilization rates were in Tunisia (46%) and Uruguay (37%).

Actual RTU rates were lower than optimal RTU rates for all 9 countries, with the smallest difference in Tunisia and the widest gap in Ghana—at nearly 43 percentage points.

The median level of unmet need was 47% for all countries combined.

Ghana and the Philippines had the highest levels of unmet need, at 82.3% and 80.5%, respectively. Costa Rica and Tunisia had the lowest levels of unmet need, at 25.5% and 18%, respectively.

The unmet need was especially high in countries with limited resources and a large population. The number of teletherapy machines per 1000 cancer cases ranged from a high of 1.3 in Tunisia to a low of 0.19 in Ghana.

The strong correlation between the actual RTU rates and the number of teletherapy machines per 1000 cancer cases/year in each country confirms that, although other access factors may be at play, the availability of RT machines is an important factor in RT utilization.

“Differences between optimal and actual RTU rates and the high percentage of unmet RT need likely stem from a number of complex reasons, although inadequate capacity for radiation therapy is the most obvious factor,” Dr Fidarova said.

“As obstacles in access to existing RT services—such as inadequate referral patterns, affordability of treatment, and geographical distribution of centers—differ by country, so does the ideal mix of solutions.”

Elena Fidarova, MD

Photo courtesy of ASTRO

BOSTON—A new study suggests that roughly half of cancer patients in developing countries need radiation therapy (RT) to treat their disease, but many of these patients do not have access to it.

Examining 9 developing countries, investigators found that between 18% and 82% of patients who can benefit from RT do not receive the treatment.

These findings were presented at ASTRO’s 58th Annual Meeting (abstract 82).

“Access to radiation therapy remains limited in low-and middle-income countries,” said study investigator Elena Fidarova, MD, of the International Atomic Energy Agency in Vienna, Austria.

“In Ghana and the Philippines, for example, about 8 in 10 cancer patients who need radiation therapy will not receive needed treatment.”

Dr Fidarova and her colleagues conducted this study to assess levels of optimal and actual RT utilization (RTU) and calculate unmet RT need in 9 developing countries—Costa Rica, Ghana, Malaysia, the Philippines, Romania, Serbia, Slovenia, Tunisia, and Uruguay.

The investigators determined the optimal and actual RTU rates for each country. The optimal RTU rate is the proportion of all newly diagnosed cancer patients who have an indication for RT at least once in their lifetime.

An indication for RT was defined as a clinical scenario for which RT is recommended as the treatment of choice because there is evidence of its superiority to alternative modalities and/or no treatment (eg, better survival, local control, or quality of life profiles).

In clinical situations where RT was equivalent to other treatment options, all comparable modalities were included in the model, and a subsequent sensitivity analysis was conducted to determine the proportion of these patients for whom RT was indicated.

Results

The median optimal RTU for all countries was 52%. Optimal RTU rates ranged from a low of 47% for Costa Rica to a high of 56% for Tunisia. Differences in optimal RTU rates are attributable to varying incidence rates of cancer types in each country.

The median actual RTU rate was roughly half of optimal utilization, suggesting that nearly half of cancer patients across these 9 countries combined may not be receiving adequate care for their disease.

The median actual RTU rate was 28%. The lowest rates of utilization were in Ghana (9%) and the Philippines (10.3%), while the highest utilization rates were in Tunisia (46%) and Uruguay (37%).

Actual RTU rates were lower than optimal RTU rates for all 9 countries, with the smallest difference in Tunisia and the widest gap in Ghana—at nearly 43 percentage points.

The median level of unmet need was 47% for all countries combined.

Ghana and the Philippines had the highest levels of unmet need, at 82.3% and 80.5%, respectively. Costa Rica and Tunisia had the lowest levels of unmet need, at 25.5% and 18%, respectively.

The unmet need was especially high in countries with limited resources and a large population. The number of teletherapy machines per 1000 cancer cases ranged from a high of 1.3 in Tunisia to a low of 0.19 in Ghana.

The strong correlation between the actual RTU rates and the number of teletherapy machines per 1000 cancer cases/year in each country confirms that, although other access factors may be at play, the availability of RT machines is an important factor in RT utilization.

“Differences between optimal and actual RTU rates and the high percentage of unmet RT need likely stem from a number of complex reasons, although inadequate capacity for radiation therapy is the most obvious factor,” Dr Fidarova said.

“As obstacles in access to existing RT services—such as inadequate referral patterns, affordability of treatment, and geographical distribution of centers—differ by country, so does the ideal mix of solutions.”

Elena Fidarova, MD

Photo courtesy of ASTRO

BOSTON—A new study suggests that roughly half of cancer patients in developing countries need radiation therapy (RT) to treat their disease, but many of these patients do not have access to it.

Examining 9 developing countries, investigators found that between 18% and 82% of patients who can benefit from RT do not receive the treatment.

These findings were presented at ASTRO’s 58th Annual Meeting (abstract 82).

“Access to radiation therapy remains limited in low-and middle-income countries,” said study investigator Elena Fidarova, MD, of the International Atomic Energy Agency in Vienna, Austria.

“In Ghana and the Philippines, for example, about 8 in 10 cancer patients who need radiation therapy will not receive needed treatment.”

Dr Fidarova and her colleagues conducted this study to assess levels of optimal and actual RT utilization (RTU) and calculate unmet RT need in 9 developing countries—Costa Rica, Ghana, Malaysia, the Philippines, Romania, Serbia, Slovenia, Tunisia, and Uruguay.

The investigators determined the optimal and actual RTU rates for each country. The optimal RTU rate is the proportion of all newly diagnosed cancer patients who have an indication for RT at least once in their lifetime.

An indication for RT was defined as a clinical scenario for which RT is recommended as the treatment of choice because there is evidence of its superiority to alternative modalities and/or no treatment (eg, better survival, local control, or quality of life profiles).

In clinical situations where RT was equivalent to other treatment options, all comparable modalities were included in the model, and a subsequent sensitivity analysis was conducted to determine the proportion of these patients for whom RT was indicated.

Results

The median optimal RTU for all countries was 52%. Optimal RTU rates ranged from a low of 47% for Costa Rica to a high of 56% for Tunisia. Differences in optimal RTU rates are attributable to varying incidence rates of cancer types in each country.

The median actual RTU rate was roughly half of optimal utilization, suggesting that nearly half of cancer patients across these 9 countries combined may not be receiving adequate care for their disease.

The median actual RTU rate was 28%. The lowest rates of utilization were in Ghana (9%) and the Philippines (10.3%), while the highest utilization rates were in Tunisia (46%) and Uruguay (37%).

Actual RTU rates were lower than optimal RTU rates for all 9 countries, with the smallest difference in Tunisia and the widest gap in Ghana—at nearly 43 percentage points.

The median level of unmet need was 47% for all countries combined.

Ghana and the Philippines had the highest levels of unmet need, at 82.3% and 80.5%, respectively. Costa Rica and Tunisia had the lowest levels of unmet need, at 25.5% and 18%, respectively.

The unmet need was especially high in countries with limited resources and a large population. The number of teletherapy machines per 1000 cancer cases ranged from a high of 1.3 in Tunisia to a low of 0.19 in Ghana.

The strong correlation between the actual RTU rates and the number of teletherapy machines per 1000 cancer cases/year in each country confirms that, although other access factors may be at play, the availability of RT machines is an important factor in RT utilization.

“Differences between optimal and actual RTU rates and the high percentage of unmet RT need likely stem from a number of complex reasons, although inadequate capacity for radiation therapy is the most obvious factor,” Dr Fidarova said.

“As obstacles in access to existing RT services—such as inadequate referral patterns, affordability of treatment, and geographical distribution of centers—differ by country, so does the ideal mix of solutions.”

Micrograph showing MM

Top-line results from the phase 3 CLARION trial suggest that treatment with carfilzomib, melphalan, and prednisone (KMP) is not superior to treatment with bortezomib, melphalan, and prednisone (VMP).

The trial was designed to compare KMP and VMP in patients with newly diagnosed multiple myeloma (MM) who were ineligible for hematopoietic stem cell transplant.

The results showed that progression-free survival (PFS) rates were similar with the 2 regimens.

And although overall survival data are not yet mature, there seems to be a trend favoring the VMP regimen.

Amgen, the company developing carfilzomib, released these results yesterday.

“The CLARION results, generated in the context of a melphalan-containing regimen, are disappointing, especially given the robust data we’ve seen in the second-line setting,” said Sean E. Harper, MD, executive vice president of Research and Development at Amgen.

“However, the myeloma landscape has changed dramatically since the design of the CLARION study, with very few newly diagnosed patients treated with

melphalan-based regimens, particularly in the US. We remain committed to exploring Kyprolis in combination with other agents to advance the treatment of multiple myeloma.”

Dr Harper said he could not comment on whether the CLARION trial will continue, as Amgen hopes to present data from the trial at the 2016 ASH Annual Meeting.

The CLARION trial is a head-to-head, randomized study in transplant-ineligible patients with newly diagnosed MM. A total of 955 patients were randomized 1:1 to receive KMP or VMP for 54 weeks. The median patient age was 72.

The trial did not meet the primary endpoint of superiority in PFS. The median PFS was 22.3 months in the KMP arm and 22.1 months in the VMP arm. The hazard ratio was 0.91 (95% CI, 0.75-1.10), and the difference between the arms was not statistically significant.

The data for overall survival, a secondary endpoint, are not yet mature. But the observed hazard ratio was 1.21 (95% CI, 0.90-1.64), and there was no significant difference between the treatment arms.

The incidence of grade 3 or higher adverse events was 74.7% in the KMP arm and 76.2% in the VMP arm.

The incidence of grade 2 or higher peripheral neuropathy, a secondary endpoint, was 2.5% in the KMP arm and 35.1% in the VMP arm.

Fatal treatment-emergent adverse events occurred in 6.5% of patients in the KMP arm and 4.3% of those in the VMP arm.

Micrograph showing MM

Top-line results from the phase 3 CLARION trial suggest that treatment with carfilzomib, melphalan, and prednisone (KMP) is not superior to treatment with bortezomib, melphalan, and prednisone (VMP).

The trial was designed to compare KMP and VMP in patients with newly diagnosed multiple myeloma (MM) who were ineligible for hematopoietic stem cell transplant.

The results showed that progression-free survival (PFS) rates were similar with the 2 regimens.

And although overall survival data are not yet mature, there seems to be a trend favoring the VMP regimen.

Amgen, the company developing carfilzomib, released these results yesterday.

“The CLARION results, generated in the context of a melphalan-containing regimen, are disappointing, especially given the robust data we’ve seen in the second-line setting,” said Sean E. Harper, MD, executive vice president of Research and Development at Amgen.

“However, the myeloma landscape has changed dramatically since the design of the CLARION study, with very few newly diagnosed patients treated with

melphalan-based regimens, particularly in the US. We remain committed to exploring Kyprolis in combination with other agents to advance the treatment of multiple myeloma.”

Dr Harper said he could not comment on whether the CLARION trial will continue, as Amgen hopes to present data from the trial at the 2016 ASH Annual Meeting.

The CLARION trial is a head-to-head, randomized study in transplant-ineligible patients with newly diagnosed MM. A total of 955 patients were randomized 1:1 to receive KMP or VMP for 54 weeks. The median patient age was 72.

The trial did not meet the primary endpoint of superiority in PFS. The median PFS was 22.3 months in the KMP arm and 22.1 months in the VMP arm. The hazard ratio was 0.91 (95% CI, 0.75-1.10), and the difference between the arms was not statistically significant.

The data for overall survival, a secondary endpoint, are not yet mature. But the observed hazard ratio was 1.21 (95% CI, 0.90-1.64), and there was no significant difference between the treatment arms.

The incidence of grade 3 or higher adverse events was 74.7% in the KMP arm and 76.2% in the VMP arm.

The incidence of grade 2 or higher peripheral neuropathy, a secondary endpoint, was 2.5% in the KMP arm and 35.1% in the VMP arm.

Fatal treatment-emergent adverse events occurred in 6.5% of patients in the KMP arm and 4.3% of those in the VMP arm.

Micrograph showing MM

Top-line results from the phase 3 CLARION trial suggest that treatment with carfilzomib, melphalan, and prednisone (KMP) is not superior to treatment with bortezomib, melphalan, and prednisone (VMP).

The trial was designed to compare KMP and VMP in patients with newly diagnosed multiple myeloma (MM) who were ineligible for hematopoietic stem cell transplant.

The results showed that progression-free survival (PFS) rates were similar with the 2 regimens.

And although overall survival data are not yet mature, there seems to be a trend favoring the VMP regimen.

Amgen, the company developing carfilzomib, released these results yesterday.

“The CLARION results, generated in the context of a melphalan-containing regimen, are disappointing, especially given the robust data we’ve seen in the second-line setting,” said Sean E. Harper, MD, executive vice president of Research and Development at Amgen.

“However, the myeloma landscape has changed dramatically since the design of the CLARION study, with very few newly diagnosed patients treated with

melphalan-based regimens, particularly in the US. We remain committed to exploring Kyprolis in combination with other agents to advance the treatment of multiple myeloma.”

Dr Harper said he could not comment on whether the CLARION trial will continue, as Amgen hopes to present data from the trial at the 2016 ASH Annual Meeting.

The CLARION trial is a head-to-head, randomized study in transplant-ineligible patients with newly diagnosed MM. A total of 955 patients were randomized 1:1 to receive KMP or VMP for 54 weeks. The median patient age was 72.

The trial did not meet the primary endpoint of superiority in PFS. The median PFS was 22.3 months in the KMP arm and 22.1 months in the VMP arm. The hazard ratio was 0.91 (95% CI, 0.75-1.10), and the difference between the arms was not statistically significant.

The data for overall survival, a secondary endpoint, are not yet mature. But the observed hazard ratio was 1.21 (95% CI, 0.90-1.64), and there was no significant difference between the treatment arms.

The incidence of grade 3 or higher adverse events was 74.7% in the KMP arm and 76.2% in the VMP arm.

The incidence of grade 2 or higher peripheral neuropathy, a secondary endpoint, was 2.5% in the KMP arm and 35.1% in the VMP arm.

Fatal treatment-emergent adverse events occurred in 6.5% of patients in the KMP arm and 4.3% of those in the VMP arm.

Patients with relapsed multiple myeloma treated with carfilzomib, lenalidomide, and dexamethasone (KRd) experienced improved Global Health Status/Quality of Life scale scores, compared with similar patients who received lenalidomide and dexamethasone (Rd) in the open-label, randomized, phase III ASPIRE trial.

In addition to the improved progression-free survival with KRd vs. Rd, which was previously reported (N Engl J Med. 2015 Jan 8;372[3]:142-52), 396 patients randomized to receive KRd had higher scores on the Global Health Status/Quality of Life (GHS/QoL) scale across 18 28-day treatment cycles, as compared with 396 patients randomized to receive Rd. Statistically significant differences were seen at cycle 12 when 25.5% of KRd-treated patients and 17.4% of Rd patients met the responder definition of at least a 5-point improvement on the GHS/QoL scale. At cycle 18, 24.2% vs. 12.9% of patients in the groups, respectively, met the responder definition, A. Keith Stewart, MD, of the Mayo Clinic in Scottsdale, Ariz., and his colleagues reported online ahead of print (J Clin Oncol. 2016 Sep. 6. doi: 10.1200/JCO.2016.66.9648).

At least a 15-point improvement was seen in 19.9% of KRd-treated patients and 12.4% of Rd-treated patients at cycle 12, and in 17.7% and 10.6%, respectively, at cycle 18. The minimal important difference of 5.6 points on the GHS/QoL scale was met at cycle 12 and was approached (4.8) at cycle 18, the researchers said.

The addition of carfilzomib to Rd improved health-related quality of life without negatively affecting patient-reported symptoms or increasing adverse treatment effects, they concluded.

Dr. Stewart reported consulting or advisory roles with several drug companies including Amgen, the maker of carfilzomib. Detailed disclosures for all authors are available with the full text of the article at JCO.org.

[email protected]

Patients with relapsed multiple myeloma treated with carfilzomib, lenalidomide, and dexamethasone (KRd) experienced improved Global Health Status/Quality of Life scale scores, compared with similar patients who received lenalidomide and dexamethasone (Rd) in the open-label, randomized, phase III ASPIRE trial.

In addition to the improved progression-free survival with KRd vs. Rd, which was previously reported (N Engl J Med. 2015 Jan 8;372[3]:142-52), 396 patients randomized to receive KRd had higher scores on the Global Health Status/Quality of Life (GHS/QoL) scale across 18 28-day treatment cycles, as compared with 396 patients randomized to receive Rd. Statistically significant differences were seen at cycle 12 when 25.5% of KRd-treated patients and 17.4% of Rd patients met the responder definition of at least a 5-point improvement on the GHS/QoL scale. At cycle 18, 24.2% vs. 12.9% of patients in the groups, respectively, met the responder definition, A. Keith Stewart, MD, of the Mayo Clinic in Scottsdale, Ariz., and his colleagues reported online ahead of print (J Clin Oncol. 2016 Sep. 6. doi: 10.1200/JCO.2016.66.9648).

At least a 15-point improvement was seen in 19.9% of KRd-treated patients and 12.4% of Rd-treated patients at cycle 12, and in 17.7% and 10.6%, respectively, at cycle 18. The minimal important difference of 5.6 points on the GHS/QoL scale was met at cycle 12 and was approached (4.8) at cycle 18, the researchers said.

The addition of carfilzomib to Rd improved health-related quality of life without negatively affecting patient-reported symptoms or increasing adverse treatment effects, they concluded.

Dr. Stewart reported consulting or advisory roles with several drug companies including Amgen, the maker of carfilzomib. Detailed disclosures for all authors are available with the full text of the article at JCO.org.

[email protected]

Patients with relapsed multiple myeloma treated with carfilzomib, lenalidomide, and dexamethasone (KRd) experienced improved Global Health Status/Quality of Life scale scores, compared with similar patients who received lenalidomide and dexamethasone (Rd) in the open-label, randomized, phase III ASPIRE trial.

In addition to the improved progression-free survival with KRd vs. Rd, which was previously reported (N Engl J Med. 2015 Jan 8;372[3]:142-52), 396 patients randomized to receive KRd had higher scores on the Global Health Status/Quality of Life (GHS/QoL) scale across 18 28-day treatment cycles, as compared with 396 patients randomized to receive Rd. Statistically significant differences were seen at cycle 12 when 25.5% of KRd-treated patients and 17.4% of Rd patients met the responder definition of at least a 5-point improvement on the GHS/QoL scale. At cycle 18, 24.2% vs. 12.9% of patients in the groups, respectively, met the responder definition, A. Keith Stewart, MD, of the Mayo Clinic in Scottsdale, Ariz., and his colleagues reported online ahead of print (J Clin Oncol. 2016 Sep. 6. doi: 10.1200/JCO.2016.66.9648).

At least a 15-point improvement was seen in 19.9% of KRd-treated patients and 12.4% of Rd-treated patients at cycle 12, and in 17.7% and 10.6%, respectively, at cycle 18. The minimal important difference of 5.6 points on the GHS/QoL scale was met at cycle 12 and was approached (4.8) at cycle 18, the researchers said.

The addition of carfilzomib to Rd improved health-related quality of life without negatively affecting patient-reported symptoms or increasing adverse treatment effects, they concluded.

Dr. Stewart reported consulting or advisory roles with several drug companies including Amgen, the maker of carfilzomib. Detailed disclosures for all authors are available with the full text of the article at JCO.org.

[email protected]

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

Researchers say they have discovered a type of macrophage that may protect against lung infections during chemotherapy.

These macrophages, found in the lungs of mice, were able to survive chemotherapy.

The macrophages could remove bacteria when activated by a vaccine, which improved survival in mice with lethal bacterial pneumonia that had received chemotherapy and were therefore depleted of neutrophils.

The researchers said these results suggest the cells—known as vaccine-induced macrophages (ViMs)— might be able to protect cancer patients from life-threatening infections.

“We have identified a new form of housekeeping macrophage in mice that may, in future, be harnessed to protect against lung infections—like bacterial pneumonia—that remain one of the greatest threats to survival of cancer patients during chemotherapy,” said Peter Murray, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

Dr Murray and his colleagues detailed this discovery in PNAS.

Working in a mouse model that mimics infection in chemotherapy-treated patients, the researchers found that vaccination protected mice from Pseudomonas aeruginosa pneumonia.

The quest to understand how such protection was possible in the absence of neutrophils led the team to discover ViMs.

The researchers found that ViMs were produced in the lungs following vaccination, proliferated locally, and could persist for at least a month.

Analyses suggested ViMs are closely related to alveolar macrophages, which originate in the embryo, reside in the air-exposed surfaces of alveoli, and are self-maintained in adults.

“All lines of cellular and molecular evidence in this study point to alveolar macrophages as the source of ViMs,” Dr Murray said.

However, unlike alveolar macrophages, the population of ViMs remained stable during chemotherapy and exhibited enhanced phagocytic activity.

When ViMs were transferred to unvaccinated mice depleted of neutrophils via chemotherapy, the animals were protected from lethal Pseudomonas infections.

“We now know that increasing the number of ViMs in the tissue can compensate for the immune deficit caused by chemotherapy,” said study author Akinobu Kamei, MD, of St. Jude Children’s Research Hospital.

“In this study, we relied on vaccination prior to chemotherapy. Going forward, we will explore other, more practical methods for use at the bedside to effectively induce tissue-resident macrophages like ViMs.”

The possible approaches include using drugs or cytokines to induce protection in the immune-compromised host.

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

Researchers say they have discovered a type of macrophage that may protect against lung infections during chemotherapy.

These macrophages, found in the lungs of mice, were able to survive chemotherapy.

The macrophages could remove bacteria when activated by a vaccine, which improved survival in mice with lethal bacterial pneumonia that had received chemotherapy and were therefore depleted of neutrophils.

The researchers said these results suggest the cells—known as vaccine-induced macrophages (ViMs)— might be able to protect cancer patients from life-threatening infections.

“We have identified a new form of housekeeping macrophage in mice that may, in future, be harnessed to protect against lung infections—like bacterial pneumonia—that remain one of the greatest threats to survival of cancer patients during chemotherapy,” said Peter Murray, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

Dr Murray and his colleagues detailed this discovery in PNAS.

Working in a mouse model that mimics infection in chemotherapy-treated patients, the researchers found that vaccination protected mice from Pseudomonas aeruginosa pneumonia.

The quest to understand how such protection was possible in the absence of neutrophils led the team to discover ViMs.

The researchers found that ViMs were produced in the lungs following vaccination, proliferated locally, and could persist for at least a month.

Analyses suggested ViMs are closely related to alveolar macrophages, which originate in the embryo, reside in the air-exposed surfaces of alveoli, and are self-maintained in adults.

“All lines of cellular and molecular evidence in this study point to alveolar macrophages as the source of ViMs,” Dr Murray said.

However, unlike alveolar macrophages, the population of ViMs remained stable during chemotherapy and exhibited enhanced phagocytic activity.

When ViMs were transferred to unvaccinated mice depleted of neutrophils via chemotherapy, the animals were protected from lethal Pseudomonas infections.

“We now know that increasing the number of ViMs in the tissue can compensate for the immune deficit caused by chemotherapy,” said study author Akinobu Kamei, MD, of St. Jude Children’s Research Hospital.

“In this study, we relied on vaccination prior to chemotherapy. Going forward, we will explore other, more practical methods for use at the bedside to effectively induce tissue-resident macrophages like ViMs.”

The possible approaches include using drugs or cytokines to induce protection in the immune-compromised host.

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

Researchers say they have discovered a type of macrophage that may protect against lung infections during chemotherapy.

These macrophages, found in the lungs of mice, were able to survive chemotherapy.

The macrophages could remove bacteria when activated by a vaccine, which improved survival in mice with lethal bacterial pneumonia that had received chemotherapy and were therefore depleted of neutrophils.

The researchers said these results suggest the cells—known as vaccine-induced macrophages (ViMs)— might be able to protect cancer patients from life-threatening infections.

“We have identified a new form of housekeeping macrophage in mice that may, in future, be harnessed to protect against lung infections—like bacterial pneumonia—that remain one of the greatest threats to survival of cancer patients during chemotherapy,” said Peter Murray, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

Dr Murray and his colleagues detailed this discovery in PNAS.

Working in a mouse model that mimics infection in chemotherapy-treated patients, the researchers found that vaccination protected mice from Pseudomonas aeruginosa pneumonia.

The quest to understand how such protection was possible in the absence of neutrophils led the team to discover ViMs.

The researchers found that ViMs were produced in the lungs following vaccination, proliferated locally, and could persist for at least a month.

Analyses suggested ViMs are closely related to alveolar macrophages, which originate in the embryo, reside in the air-exposed surfaces of alveoli, and are self-maintained in adults.

“All lines of cellular and molecular evidence in this study point to alveolar macrophages as the source of ViMs,” Dr Murray said.

However, unlike alveolar macrophages, the population of ViMs remained stable during chemotherapy and exhibited enhanced phagocytic activity.

When ViMs were transferred to unvaccinated mice depleted of neutrophils via chemotherapy, the animals were protected from lethal Pseudomonas infections.

“We now know that increasing the number of ViMs in the tissue can compensate for the immune deficit caused by chemotherapy,” said study author Akinobu Kamei, MD, of St. Jude Children’s Research Hospital.

“In this study, we relied on vaccination prior to chemotherapy. Going forward, we will explore other, more practical methods for use at the bedside to effectively induce tissue-resident macrophages like ViMs.”

The possible approaches include using drugs or cytokines to induce protection in the immune-compromised host.

Clinician and cancer patient

Photo courtesy of NCI Clinical

Center/Mathews Media Group

Expectations may not correspond to reality for cancer patients considering enrollment in phase 1 trials, according to a study published in Cancer.

The study showed that, even after consulting with clinicians, nearly half of patients expected their tumors would shrink during the trial, and some patients expected to be cured.

In reality, the typical response rates of phase 1 cancer trials range from 4% to 20%, and patients survive for a median of 6 months.

Udai Banerji, MD, PhD, of The Institute of Cancer Research in London, England, and his colleagues conducted this study.

The team explored patients’ motivations for considering participation in phase 1 trials and assessed their expectations both before and after they consulted with clinicians.

The study included 396 patients who were considering enrollment in a phase 1 trial. All of these patients completed questionnaires prior to a consultation with a clinician, and 301 completed an abbreviated follow-up questionnaire after their consultation.

A majority of the patients said they were willing to enroll in a trial—72% pre-consultation and 84% after.

Before their consultation, 84% of patients ranked the possibility of tumor shrinkage as the most important reason for considering a phase 1 trial.

Fifty-six percent of patients said the most important reason was a lack of alternative treatments, 44% said it was their physician’s recommendation, and 38% said it was the possibility that the research might benefit others. (Patients could give the same rank to multiple reasons.)

Before their consultation, 43% of patients predicted their tumors would shrink if they participated in a trial. After the consultation, this increased to 47%, and 14% of patients thought they would be cured by participating in the trial. (Patients were not asked about the possibility of cure in the pre-consultation questionnaire.)

Before their consultation, 71% of patients said they expected moderate side effects related to the treatment being tested. This increased to 77% after the consultation. Only 11% of patients expected severe side effects pre-consultation, a figure that decreased to 7% after consultation.

Before consultation, about half of patients did not expect that weekly hospital visits would be required for participation in the trial. After the consultation, 93% of patients expected weekly visits.

“There is a positive message in this [study], which is that 84% of patients are willing to participate in phase 1 oncology studies after a discussion with clinical and nursing staff who lay out the conservative estimates of benefit and requirements of hospital visits,” Dr Banerji said.

“This is good for current and future patients and cancer medicine in general. [However,] the high percentage of patients expecting their tumors to shrink was a sobering finding. This creates a challenge for healthcare professionals to manage expectations but to do so without being patronizing or dismissing human hope.”

Clinician and cancer patient

Photo courtesy of NCI Clinical

Center/Mathews Media Group

Expectations may not correspond to reality for cancer patients considering enrollment in phase 1 trials, according to a study published in Cancer.

The study showed that, even after consulting with clinicians, nearly half of patients expected their tumors would shrink during the trial, and some patients expected to be cured.

In reality, the typical response rates of phase 1 cancer trials range from 4% to 20%, and patients survive for a median of 6 months.

Udai Banerji, MD, PhD, of The Institute of Cancer Research in London, England, and his colleagues conducted this study.

The team explored patients’ motivations for considering participation in phase 1 trials and assessed their expectations both before and after they consulted with clinicians.

The study included 396 patients who were considering enrollment in a phase 1 trial. All of these patients completed questionnaires prior to a consultation with a clinician, and 301 completed an abbreviated follow-up questionnaire after their consultation.

A majority of the patients said they were willing to enroll in a trial—72% pre-consultation and 84% after.

Before their consultation, 84% of patients ranked the possibility of tumor shrinkage as the most important reason for considering a phase 1 trial.

Fifty-six percent of patients said the most important reason was a lack of alternative treatments, 44% said it was their physician’s recommendation, and 38% said it was the possibility that the research might benefit others. (Patients could give the same rank to multiple reasons.)

Before their consultation, 43% of patients predicted their tumors would shrink if they participated in a trial. After the consultation, this increased to 47%, and 14% of patients thought they would be cured by participating in the trial. (Patients were not asked about the possibility of cure in the pre-consultation questionnaire.)

Before their consultation, 71% of patients said they expected moderate side effects related to the treatment being tested. This increased to 77% after the consultation. Only 11% of patients expected severe side effects pre-consultation, a figure that decreased to 7% after consultation.

Before consultation, about half of patients did not expect that weekly hospital visits would be required for participation in the trial. After the consultation, 93% of patients expected weekly visits.

“There is a positive message in this [study], which is that 84% of patients are willing to participate in phase 1 oncology studies after a discussion with clinical and nursing staff who lay out the conservative estimates of benefit and requirements of hospital visits,” Dr Banerji said.

“This is good for current and future patients and cancer medicine in general. [However,] the high percentage of patients expecting their tumors to shrink was a sobering finding. This creates a challenge for healthcare professionals to manage expectations but to do so without being patronizing or dismissing human hope.”

Clinician and cancer patient

Photo courtesy of NCI Clinical

Center/Mathews Media Group

Expectations may not correspond to reality for cancer patients considering enrollment in phase 1 trials, according to a study published in Cancer.

The study showed that, even after consulting with clinicians, nearly half of patients expected their tumors would shrink during the trial, and some patients expected to be cured.

In reality, the typical response rates of phase 1 cancer trials range from 4% to 20%, and patients survive for a median of 6 months.

Udai Banerji, MD, PhD, of The Institute of Cancer Research in London, England, and his colleagues conducted this study.

The team explored patients’ motivations for considering participation in phase 1 trials and assessed their expectations both before and after they consulted with clinicians.

The study included 396 patients who were considering enrollment in a phase 1 trial. All of these patients completed questionnaires prior to a consultation with a clinician, and 301 completed an abbreviated follow-up questionnaire after their consultation.

A majority of the patients said they were willing to enroll in a trial—72% pre-consultation and 84% after.

Before their consultation, 84% of patients ranked the possibility of tumor shrinkage as the most important reason for considering a phase 1 trial.

Fifty-six percent of patients said the most important reason was a lack of alternative treatments, 44% said it was their physician’s recommendation, and 38% said it was the possibility that the research might benefit others. (Patients could give the same rank to multiple reasons.)

Before their consultation, 43% of patients predicted their tumors would shrink if they participated in a trial. After the consultation, this increased to 47%, and 14% of patients thought they would be cured by participating in the trial. (Patients were not asked about the possibility of cure in the pre-consultation questionnaire.)

Before their consultation, 71% of patients said they expected moderate side effects related to the treatment being tested. This increased to 77% after the consultation. Only 11% of patients expected severe side effects pre-consultation, a figure that decreased to 7% after consultation.

Before consultation, about half of patients did not expect that weekly hospital visits would be required for participation in the trial. After the consultation, 93% of patients expected weekly visits.

“There is a positive message in this [study], which is that 84% of patients are willing to participate in phase 1 oncology studies after a discussion with clinical and nursing staff who lay out the conservative estimates of benefit and requirements of hospital visits,” Dr Banerji said.

“This is good for current and future patients and cancer medicine in general. [However,] the high percentage of patients expecting their tumors to shrink was a sobering finding. This creates a challenge for healthcare professionals to manage expectations but to do so without being patronizing or dismissing human hope.”

Prescription medications

Photo courtesy of CDC

Results of a retrospective study suggest statins may decrease the risk of death in patients with multiple myeloma (MM).

Researchers analyzed data from nearly 5000 patients with MM and found that patients who took statins had a significant reduction in all-cause mortality and MM-specific mortality when compared to patients who did not take these drugs.

Kristen Marie Sanfilippo, MD, of Washington University School of Medicine in St Louis, Missouri, and her colleagues reported these findings in the Journal of Clinical Oncology.

The researchers analyzed data from the Veterans Administration Central Cancer Registry and identified 4957 patients who were diagnosed with MM between 1999 and 2013.

Of these patients, 2294 were classified as statin users. The researchers defined statin use as the presence of any prescription for a statin within 3 months before MM diagnosis or any time thereafter.

The data showed that statin users had a longer median survival than non-users—39.5 months and 27 months, respectively.

When the researchers adjusted for potential confounders, they found that statin users had a 21% reduction in the risk of all-cause mortality (adjusted hazard ratio [aHR]=0.79, P<0.001) and a 24% reduction in the risk of MM-specific mortality (aHR=0.76, P<0.001).

In addition, statin users had a 31% reduction in the risk of developing a skeletal-related event (aHR=0.69, P<0.001).

In a 12-month landmark analysis, statin use was associated with a significant reduction in the risk of all-cause mortality (aHR=0.86, P=0.001) and MM-specific mortality (aHR=0.83, P=0.01).

The reduction in all-cause mortality was 12% (P=0.004) for patients taking statins for at least 3 months, 16% (P<0.001) for patients taking statins for at least 6 months, and 18% (P=0.003) for patients taking statins for at least 9 months.

Patients with less than 365 daily defined doses (DDDs) of statins had a 20% reduction in the risk of all-cause mortality (aHR=0.80, P<0.001). And patients with ≥ 365 DDDs had a 22% reduction in the risk of all-cause mortality (aHR=0.78, P<0.001).

The reductions in MM-specific mortality according to DDDs were 22% (aHR=0.78, P=0.001) and 28% (aHR=0.72, P<0.001), respectively.

The researchers further adjusted for baseline differences between statin users and non-users with propensity-score matching. And statin use was still associated with a reduction in all-cause mortality (aHR=0.78, P<0.001) and MM-specific mortality (aHR=0.79, P=0.007).

The researchers said these results suggest a potential role for statin therapy in patients with MM, although the findings should be corroborated in prospective studies.

Prescription medications

Photo courtesy of CDC

Results of a retrospective study suggest statins may decrease the risk of death in patients with multiple myeloma (MM).

Researchers analyzed data from nearly 5000 patients with MM and found that patients who took statins had a significant reduction in all-cause mortality and MM-specific mortality when compared to patients who did not take these drugs.

Kristen Marie Sanfilippo, MD, of Washington University School of Medicine in St Louis, Missouri, and her colleagues reported these findings in the Journal of Clinical Oncology.

The researchers analyzed data from the Veterans Administration Central Cancer Registry and identified 4957 patients who were diagnosed with MM between 1999 and 2013.

Of these patients, 2294 were classified as statin users. The researchers defined statin use as the presence of any prescription for a statin within 3 months before MM diagnosis or any time thereafter.

The data showed that statin users had a longer median survival than non-users—39.5 months and 27 months, respectively.

When the researchers adjusted for potential confounders, they found that statin users had a 21% reduction in the risk of all-cause mortality (adjusted hazard ratio [aHR]=0.79, P<0.001) and a 24% reduction in the risk of MM-specific mortality (aHR=0.76, P<0.001).

In addition, statin users had a 31% reduction in the risk of developing a skeletal-related event (aHR=0.69, P<0.001).

In a 12-month landmark analysis, statin use was associated with a significant reduction in the risk of all-cause mortality (aHR=0.86, P=0.001) and MM-specific mortality (aHR=0.83, P=0.01).

The reduction in all-cause mortality was 12% (P=0.004) for patients taking statins for at least 3 months, 16% (P<0.001) for patients taking statins for at least 6 months, and 18% (P=0.003) for patients taking statins for at least 9 months.

Patients with less than 365 daily defined doses (DDDs) of statins had a 20% reduction in the risk of all-cause mortality (aHR=0.80, P<0.001). And patients with ≥ 365 DDDs had a 22% reduction in the risk of all-cause mortality (aHR=0.78, P<0.001).

The reductions in MM-specific mortality according to DDDs were 22% (aHR=0.78, P=0.001) and 28% (aHR=0.72, P<0.001), respectively.

The researchers further adjusted for baseline differences between statin users and non-users with propensity-score matching. And statin use was still associated with a reduction in all-cause mortality (aHR=0.78, P<0.001) and MM-specific mortality (aHR=0.79, P=0.007).

The researchers said these results suggest a potential role for statin therapy in patients with MM, although the findings should be corroborated in prospective studies.

Prescription medications

Photo courtesy of CDC

Results of a retrospective study suggest statins may decrease the risk of death in patients with multiple myeloma (MM).

Researchers analyzed data from nearly 5000 patients with MM and found that patients who took statins had a significant reduction in all-cause mortality and MM-specific mortality when compared to patients who did not take these drugs.

Kristen Marie Sanfilippo, MD, of Washington University School of Medicine in St Louis, Missouri, and her colleagues reported these findings in the Journal of Clinical Oncology.

The researchers analyzed data from the Veterans Administration Central Cancer Registry and identified 4957 patients who were diagnosed with MM between 1999 and 2013.

Of these patients, 2294 were classified as statin users. The researchers defined statin use as the presence of any prescription for a statin within 3 months before MM diagnosis or any time thereafter.

The data showed that statin users had a longer median survival than non-users—39.5 months and 27 months, respectively.

When the researchers adjusted for potential confounders, they found that statin users had a 21% reduction in the risk of all-cause mortality (adjusted hazard ratio [aHR]=0.79, P<0.001) and a 24% reduction in the risk of MM-specific mortality (aHR=0.76, P<0.001).

In addition, statin users had a 31% reduction in the risk of developing a skeletal-related event (aHR=0.69, P<0.001).

In a 12-month landmark analysis, statin use was associated with a significant reduction in the risk of all-cause mortality (aHR=0.86, P=0.001) and MM-specific mortality (aHR=0.83, P=0.01).

The reduction in all-cause mortality was 12% (P=0.004) for patients taking statins for at least 3 months, 16% (P<0.001) for patients taking statins for at least 6 months, and 18% (P=0.003) for patients taking statins for at least 9 months.

Patients with less than 365 daily defined doses (DDDs) of statins had a 20% reduction in the risk of all-cause mortality (aHR=0.80, P<0.001). And patients with ≥ 365 DDDs had a 22% reduction in the risk of all-cause mortality (aHR=0.78, P<0.001).

The reductions in MM-specific mortality according to DDDs were 22% (aHR=0.78, P=0.001) and 28% (aHR=0.72, P<0.001), respectively.

The researchers further adjusted for baseline differences between statin users and non-users with propensity-score matching. And statin use was still associated with a reduction in all-cause mortality (aHR=0.78, P<0.001) and MM-specific mortality (aHR=0.79, P=0.007).

The researchers said these results suggest a potential role for statin therapy in patients with MM, although the findings should be corroborated in prospective studies.

 

 

Cancer patient receives therapy

Photo by Rhoda Baer

 

A new report highlights recent advances made in the fight against cancer but suggests the burden of cancer in the US is still on the rise.

The AACR Cancer Progress Report 2016 states that the number of cancer survivors in the US rose by 1 million from 2014 to 2016, reaching an estimated 15.5 million.

Meanwhile, the US Food and Drug Administration (FDA) approved new treatments for a range of cancers.

Between August 1, 2015, and July 31, 2016, the FDA approved 13 new anticancer therapies and new uses for 11 previously approved anticancer therapies.

Six of these drugs were approved to treat hematologic malignancies:

• Venetoclax for chronic lymphocytic leukemia
• Daratumumab for multiple myeloma
• Elotuzumab for multiple myeloma
• Ixazomib for multiple myeloma
• Obinutuzumab for follicular lymphoma
• Nivolumab for classical Hodgkin lymphoma.

The report notes that the use of immunotherapy, in particular, is on the rise. For example, on August 1, 2015, checkpoint inhibitors were approved for just 2 cancers—melanoma and lung cancer.

As of September 1, 2016, checkpoint inhibitors have been approved for 6 cancers—Hodgkin lymphoma, bladder cancer, head and neck cancer, kidney cancer, lung cancer, and melanoma.

“The promise of immunotherapy for cancer therapy has never been greater, and the opportunity to make significant progress in this critical area is real,” said Nancy E. Davidson, MD, president of the AACR and director of the University of Pittsburgh Cancer Institute in Pennsylvania.

“However, continued progress is going to require a sustained federal commitment to the research agenda. And in fact, if the necessary funding is provided, we will accelerate the pace of progress and, in turn, markedly reduce morbidity and mortality from cancer.”

Growing burden of cancer

The report emphasizes that although advances are being made against cancers, these diseases continue to exert an immense personal and economic toll, and the burden of cancer is expected to grow in the coming decades.

According to the report:

• More than 595,000 people in the US are projected to die from cancer in 2016
• Cancer is the number one cause of disease-related death among US children
• The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035
• It is estimated that the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs will rise to $156 billion in 2020.

The report states that the increasing economic and personal burden of cancer underscores the need for more research to develop new approaches to cancer prevention and treatment.

The report also highlights the recommendations of the National Cancer Moonshot Initiative Blue Ribbon Panel for accelerating the pace of progress in cancer research.

“Research has made tremendous advances against cancer,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, we need to accelerate the pace of progress because it is unacceptable that 1 American will die of cancer every minute of every day this year.”

 

 

Cancer patient receives therapy

Photo by Rhoda Baer

 

A new report highlights recent advances made in the fight against cancer but suggests the burden of cancer in the US is still on the rise.

The AACR Cancer Progress Report 2016 states that the number of cancer survivors in the US rose by 1 million from 2014 to 2016, reaching an estimated 15.5 million.

Meanwhile, the US Food and Drug Administration (FDA) approved new treatments for a range of cancers.

Between August 1, 2015, and July 31, 2016, the FDA approved 13 new anticancer therapies and new uses for 11 previously approved anticancer therapies.

Six of these drugs were approved to treat hematologic malignancies:

• Venetoclax for chronic lymphocytic leukemia
• Daratumumab for multiple myeloma
• Elotuzumab for multiple myeloma
• Ixazomib for multiple myeloma
• Obinutuzumab for follicular lymphoma
• Nivolumab for classical Hodgkin lymphoma.

The report notes that the use of immunotherapy, in particular, is on the rise. For example, on August 1, 2015, checkpoint inhibitors were approved for just 2 cancers—melanoma and lung cancer.

As of September 1, 2016, checkpoint inhibitors have been approved for 6 cancers—Hodgkin lymphoma, bladder cancer, head and neck cancer, kidney cancer, lung cancer, and melanoma.

“The promise of immunotherapy for cancer therapy has never been greater, and the opportunity to make significant progress in this critical area is real,” said Nancy E. Davidson, MD, president of the AACR and director of the University of Pittsburgh Cancer Institute in Pennsylvania.

“However, continued progress is going to require a sustained federal commitment to the research agenda. And in fact, if the necessary funding is provided, we will accelerate the pace of progress and, in turn, markedly reduce morbidity and mortality from cancer.”

Growing burden of cancer

The report emphasizes that although advances are being made against cancers, these diseases continue to exert an immense personal and economic toll, and the burden of cancer is expected to grow in the coming decades.

According to the report:

• More than 595,000 people in the US are projected to die from cancer in 2016
• Cancer is the number one cause of disease-related death among US children
• The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035
• It is estimated that the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs will rise to $156 billion in 2020.

The report states that the increasing economic and personal burden of cancer underscores the need for more research to develop new approaches to cancer prevention and treatment.

The report also highlights the recommendations of the National Cancer Moonshot Initiative Blue Ribbon Panel for accelerating the pace of progress in cancer research.

“Research has made tremendous advances against cancer,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, we need to accelerate the pace of progress because it is unacceptable that 1 American will die of cancer every minute of every day this year.”

 

 

Cancer patient receives therapy

Photo by Rhoda Baer

 

A new report highlights recent advances made in the fight against cancer but suggests the burden of cancer in the US is still on the rise.

The AACR Cancer Progress Report 2016 states that the number of cancer survivors in the US rose by 1 million from 2014 to 2016, reaching an estimated 15.5 million.

Meanwhile, the US Food and Drug Administration (FDA) approved new treatments for a range of cancers.

Between August 1, 2015, and July 31, 2016, the FDA approved 13 new anticancer therapies and new uses for 11 previously approved anticancer therapies.

Six of these drugs were approved to treat hematologic malignancies:

• Venetoclax for chronic lymphocytic leukemia
• Daratumumab for multiple myeloma
• Elotuzumab for multiple myeloma
• Ixazomib for multiple myeloma
• Obinutuzumab for follicular lymphoma
• Nivolumab for classical Hodgkin lymphoma.

The report notes that the use of immunotherapy, in particular, is on the rise. For example, on August 1, 2015, checkpoint inhibitors were approved for just 2 cancers—melanoma and lung cancer.

As of September 1, 2016, checkpoint inhibitors have been approved for 6 cancers—Hodgkin lymphoma, bladder cancer, head and neck cancer, kidney cancer, lung cancer, and melanoma.

“The promise of immunotherapy for cancer therapy has never been greater, and the opportunity to make significant progress in this critical area is real,” said Nancy E. Davidson, MD, president of the AACR and director of the University of Pittsburgh Cancer Institute in Pennsylvania.

“However, continued progress is going to require a sustained federal commitment to the research agenda. And in fact, if the necessary funding is provided, we will accelerate the pace of progress and, in turn, markedly reduce morbidity and mortality from cancer.”

Growing burden of cancer

The report emphasizes that although advances are being made against cancers, these diseases continue to exert an immense personal and economic toll, and the burden of cancer is expected to grow in the coming decades.

According to the report:

• More than 595,000 people in the US are projected to die from cancer in 2016
• Cancer is the number one cause of disease-related death among US children
• The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035
• It is estimated that the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs will rise to $156 billion in 2020.

The report states that the increasing economic and personal burden of cancer underscores the need for more research to develop new approaches to cancer prevention and treatment.

The report also highlights the recommendations of the National Cancer Moonshot Initiative Blue Ribbon Panel for accelerating the pace of progress in cancer research.

“Research has made tremendous advances against cancer,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, we need to accelerate the pace of progress because it is unacceptable that 1 American will die of cancer every minute of every day this year.”

Doctor and patient in hospital

Photo courtesy of CDC

New research suggests that many patients who die of cancer do not receive strong opioid medications in their last year of life, despite the fact that these drugs are the recommended treatment for cancer-related pain.

Researchers used UK Cancer Registry Data to study more than 6000 cancer patients who died over a 7-year period.

Less than half of these patients received prescriptions for strong opioid medications in their last year of life.

Among those patients who did receive such prescriptions, many received them late.

Lucy Ziegler, PhD, of the University of Leeds in the UK, and her colleagues conducted this study and reported the results in PAIN.

The study included 6080 cancer patients who died between 2005 and 2012.

About 76% (n=4610) of these patients had received one or more prescriptions for analgesics, including 48% (n=2919) who received a strong opioid and 28% (n=1691) who received a non-opioid or weak opioid. The remaining 24% (n=1470) did not receive any prescription analgesic.

The chance of receiving strong opioids was not affected by patients’ age or sex.

However, patients who died in a hospital were 60% less likely to have a prescription for strong opioids during the last year of life, when compared with those who died in hospice.

And patients who received chemotherapy in the last year of life were 30% more likely to receive a strong opioid than patients who did not receive chemotherapy.

Timing of therapy

Among the patients who did receive strong opioids, the median time between receiving the medication and death was 9 weeks. By 6 weeks before death, just 30% of patients had been prescribed a strong opioid.

The researchers noted that these figures don’t match up with previous studies reporting that severe pain can occur “much earlier in the cancer trajectory.”

Older patients were more likely to receive their strong opioid prescription late (defined as later than 9 weeks before death). After other factors were taken into account, patients age 60 or older were about 2 to 4 times more likely to be in the late-prescribing group, compared with those age 50 or younger.

Compared to patients who died in hospice, patients who died in a hospital were 40% more likely to receive a late prescription for a strong opioid. Patients who died in their own home were 2.6 times more likely to receive a late prescription, and patients who died in a care home were 2.8 times more likely to receive a late prescription.

Patients who had surgery were 40% more likely to receive a late prescription than patients who did not undergo surgery.

But patients who received chemotherapy and/or radiotherapy were 30% more likely to have received an early prescription for a strong opioid than patients who did not receive chemo/radiotherapy.

Dr Ziegler and her colleagues noted that this study had its limitations; in particular, the lack of data on pain severity.

Still, the researchers believe their results support the hypothesis of potential under-treatment of cancer pain and suggest that many more patients with advanced cancer and pain may benefit from a strong opioid analgesic.

Doctor and patient in hospital

Photo courtesy of CDC

New research suggests that many patients who die of cancer do not receive strong opioid medications in their last year of life, despite the fact that these drugs are the recommended treatment for cancer-related pain.

Researchers used UK Cancer Registry Data to study more than 6000 cancer patients who died over a 7-year period.

Less than half of these patients received prescriptions for strong opioid medications in their last year of life.

Among those patients who did receive such prescriptions, many received them late.

Lucy Ziegler, PhD, of the University of Leeds in the UK, and her colleagues conducted this study and reported the results in PAIN.

The study included 6080 cancer patients who died between 2005 and 2012.

About 76% (n=4610) of these patients had received one or more prescriptions for analgesics, including 48% (n=2919) who received a strong opioid and 28% (n=1691) who received a non-opioid or weak opioid. The remaining 24% (n=1470) did not receive any prescription analgesic.

The chance of receiving strong opioids was not affected by patients’ age or sex.

However, patients who died in a hospital were 60% less likely to have a prescription for strong opioids during the last year of life, when compared with those who died in hospice.

And patients who received chemotherapy in the last year of life were 30% more likely to receive a strong opioid than patients who did not receive chemotherapy.

Timing of therapy

Among the patients who did receive strong opioids, the median time between receiving the medication and death was 9 weeks. By 6 weeks before death, just 30% of patients had been prescribed a strong opioid.

The researchers noted that these figures don’t match up with previous studies reporting that severe pain can occur “much earlier in the cancer trajectory.”

Older patients were more likely to receive their strong opioid prescription late (defined as later than 9 weeks before death). After other factors were taken into account, patients age 60 or older were about 2 to 4 times more likely to be in the late-prescribing group, compared with those age 50 or younger.

Compared to patients who died in hospice, patients who died in a hospital were 40% more likely to receive a late prescription for a strong opioid. Patients who died in their own home were 2.6 times more likely to receive a late prescription, and patients who died in a care home were 2.8 times more likely to receive a late prescription.

Patients who had surgery were 40% more likely to receive a late prescription than patients who did not undergo surgery.

But patients who received chemotherapy and/or radiotherapy were 30% more likely to have received an early prescription for a strong opioid than patients who did not receive chemo/radiotherapy.

Dr Ziegler and her colleagues noted that this study had its limitations; in particular, the lack of data on pain severity.

Still, the researchers believe their results support the hypothesis of potential under-treatment of cancer pain and suggest that many more patients with advanced cancer and pain may benefit from a strong opioid analgesic.

Doctor and patient in hospital

Photo courtesy of CDC

New research suggests that many patients who die of cancer do not receive strong opioid medications in their last year of life, despite the fact that these drugs are the recommended treatment for cancer-related pain.

Researchers used UK Cancer Registry Data to study more than 6000 cancer patients who died over a 7-year period.

Less than half of these patients received prescriptions for strong opioid medications in their last year of life.

Among those patients who did receive such prescriptions, many received them late.

Lucy Ziegler, PhD, of the University of Leeds in the UK, and her colleagues conducted this study and reported the results in PAIN.

The study included 6080 cancer patients who died between 2005 and 2012.

About 76% (n=4610) of these patients had received one or more prescriptions for analgesics, including 48% (n=2919) who received a strong opioid and 28% (n=1691) who received a non-opioid or weak opioid. The remaining 24% (n=1470) did not receive any prescription analgesic.

The chance of receiving strong opioids was not affected by patients’ age or sex.

However, patients who died in a hospital were 60% less likely to have a prescription for strong opioids during the last year of life, when compared with those who died in hospice.

And patients who received chemotherapy in the last year of life were 30% more likely to receive a strong opioid than patients who did not receive chemotherapy.

Timing of therapy

Among the patients who did receive strong opioids, the median time between receiving the medication and death was 9 weeks. By 6 weeks before death, just 30% of patients had been prescribed a strong opioid.

The researchers noted that these figures don’t match up with previous studies reporting that severe pain can occur “much earlier in the cancer trajectory.”

Older patients were more likely to receive their strong opioid prescription late (defined as later than 9 weeks before death). After other factors were taken into account, patients age 60 or older were about 2 to 4 times more likely to be in the late-prescribing group, compared with those age 50 or younger.

Compared to patients who died in hospice, patients who died in a hospital were 40% more likely to receive a late prescription for a strong opioid. Patients who died in their own home were 2.6 times more likely to receive a late prescription, and patients who died in a care home were 2.8 times more likely to receive a late prescription.

Patients who had surgery were 40% more likely to receive a late prescription than patients who did not undergo surgery.

But patients who received chemotherapy and/or radiotherapy were 30% more likely to have received an early prescription for a strong opioid than patients who did not receive chemo/radiotherapy.

Dr Ziegler and her colleagues noted that this study had its limitations; in particular, the lack of data on pain severity.

Still, the researchers believe their results support the hypothesis of potential under-treatment of cancer pain and suggest that many more patients with advanced cancer and pain may benefit from a strong opioid analgesic.

Micrograph showing MM

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that ixazomib (Ninlaro^TM) receive conditional marketing authorization.

The recommendation is for ixazomib in combination with lenalidomide and dexamethasone as a treatment for adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission (EC).

If the EC grants the authorization, ixazomib will be the first oral proteasome inhibitor approved for use across the European Economic Area.

Ixazomib is being developed by Takeda Pharmaceutical Company Limited.

Phase 3 trial

The CHMP’s positive opinion of ixazomib is based on results from the phase 3 TOURMALINE-MM1 trial, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. The incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

About conditional authorization

Conditional marketing authorization represents an expedited path for approval. The EC grants this type of authorization before pivotal registration studies are completed.

Conditional marketing authorization is granted to products whose benefits are thought to outweigh their risks, products that address unmet needs, and products that are expected to provide a significant public health benefit.

If ixazomib receives conditional marketing authorization, Takeda will be required to provide post-approval updates on safety and efficacy analyses for TOURMALINE-MM1 and some other ongoing studies to demonstrate the treatment’s long-term effects.

Micrograph showing MM

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that ixazomib (Ninlaro^TM) receive conditional marketing authorization.

The recommendation is for ixazomib in combination with lenalidomide and dexamethasone as a treatment for adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission (EC).

If the EC grants the authorization, ixazomib will be the first oral proteasome inhibitor approved for use across the European Economic Area.

Ixazomib is being developed by Takeda Pharmaceutical Company Limited.

Phase 3 trial

The CHMP’s positive opinion of ixazomib is based on results from the phase 3 TOURMALINE-MM1 trial, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. The incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

About conditional authorization

Conditional marketing authorization represents an expedited path for approval. The EC grants this type of authorization before pivotal registration studies are completed.

Conditional marketing authorization is granted to products whose benefits are thought to outweigh their risks, products that address unmet needs, and products that are expected to provide a significant public health benefit.

If ixazomib receives conditional marketing authorization, Takeda will be required to provide post-approval updates on safety and efficacy analyses for TOURMALINE-MM1 and some other ongoing studies to demonstrate the treatment’s long-term effects.

Micrograph showing MM

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that ixazomib (Ninlaro^TM) receive conditional marketing authorization.

The recommendation is for ixazomib in combination with lenalidomide and dexamethasone as a treatment for adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission (EC).

If the EC grants the authorization, ixazomib will be the first oral proteasome inhibitor approved for use across the European Economic Area.

Ixazomib is being developed by Takeda Pharmaceutical Company Limited.

Phase 3 trial

The CHMP’s positive opinion of ixazomib is based on results from the phase 3 TOURMALINE-MM1 trial, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. The incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

About conditional authorization

Conditional marketing authorization represents an expedited path for approval. The EC grants this type of authorization before pivotal registration studies are completed.

Conditional marketing authorization is granted to products whose benefits are thought to outweigh their risks, products that address unmet needs, and products that are expected to provide a significant public health benefit.

If ixazomib receives conditional marketing authorization, Takeda will be required to provide post-approval updates on safety and efficacy analyses for TOURMALINE-MM1 and some other ongoing studies to demonstrate the treatment’s long-term effects.

Nikhil C. Munshi, MD

Photo courtesy of the

Dana-Farber Cancer Institute

Patients with newly diagnosed multiple myeloma (MM) have better survival outcomes if they are minimal residual disease (MRD)-negative after treatment, according to research published in JAMA Oncology.

MRD negativity was significantly associated with better progression-free survival (PFS) and overall survival (OS).

Researchers therefore concluded that MRD status after treatment should be considered as an endpoint in clinical trials of MM.

Nikhil C. Munshi, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues conducted this study.

The team evaluated the prognostic value of MRD in patients with MM by performing a meta-analysis of 21 studies published between January 1990 and January 2016.

The impact of MRD on PFS was assessed in 14 of the studies (n=1273), and the impact of MRD on OS was assessed in 12 studies (n=1100).

Five of the PFS studies (n=574) had results reported specifically in patients with a complete response (CR), as did 6 of the OS studies (n=616).

Dr Munchi and his colleagues found that MRD negativity was associated with significantly better PFS—both overall and in studies looking specifically at patients with CRs. The hazard ratios were 0.41 (95% CI, 0.36-0.48) and 0.44 (95% CI, 0.34-0.56), respectively (P<0.001 for both).

Likewise, MRD negativity was associated with significantly better OS—both overall and in studies looking at patients with CRs. The hazard ratios were 0.57 (95% CI, 0.46-0.71) and 0.47 (95% CI, 0.33-0.67), respectively (P<0.001 for both).

The researchers said there were no significant differences among the studies for PFS and OS.

The team therefore concluded that this study provides quantitative evidence to support the integration of MRD assessment as an endpoint in trials of MM patients.

Nikhil C. Munshi, MD

Photo courtesy of the

Dana-Farber Cancer Institute

Patients with newly diagnosed multiple myeloma (MM) have better survival outcomes if they are minimal residual disease (MRD)-negative after treatment, according to research published in JAMA Oncology.

MRD negativity was significantly associated with better progression-free survival (PFS) and overall survival (OS).

Researchers therefore concluded that MRD status after treatment should be considered as an endpoint in clinical trials of MM.

Nikhil C. Munshi, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues conducted this study.

The team evaluated the prognostic value of MRD in patients with MM by performing a meta-analysis of 21 studies published between January 1990 and January 2016.

The impact of MRD on PFS was assessed in 14 of the studies (n=1273), and the impact of MRD on OS was assessed in 12 studies (n=1100).

Five of the PFS studies (n=574) had results reported specifically in patients with a complete response (CR), as did 6 of the OS studies (n=616).

Dr Munchi and his colleagues found that MRD negativity was associated with significantly better PFS—both overall and in studies looking specifically at patients with CRs. The hazard ratios were 0.41 (95% CI, 0.36-0.48) and 0.44 (95% CI, 0.34-0.56), respectively (P<0.001 for both).

Likewise, MRD negativity was associated with significantly better OS—both overall and in studies looking at patients with CRs. The hazard ratios were 0.57 (95% CI, 0.46-0.71) and 0.47 (95% CI, 0.33-0.67), respectively (P<0.001 for both).

The researchers said there were no significant differences among the studies for PFS and OS.

The team therefore concluded that this study provides quantitative evidence to support the integration of MRD assessment as an endpoint in trials of MM patients.

Nikhil C. Munshi, MD

Photo courtesy of the

Dana-Farber Cancer Institute

Patients with newly diagnosed multiple myeloma (MM) have better survival outcomes if they are minimal residual disease (MRD)-negative after treatment, according to research published in JAMA Oncology.

MRD negativity was significantly associated with better progression-free survival (PFS) and overall survival (OS).

Researchers therefore concluded that MRD status after treatment should be considered as an endpoint in clinical trials of MM.

Nikhil C. Munshi, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues conducted this study.

The team evaluated the prognostic value of MRD in patients with MM by performing a meta-analysis of 21 studies published between January 1990 and January 2016.

The impact of MRD on PFS was assessed in 14 of the studies (n=1273), and the impact of MRD on OS was assessed in 12 studies (n=1100).

Five of the PFS studies (n=574) had results reported specifically in patients with a complete response (CR), as did 6 of the OS studies (n=616).

Dr Munchi and his colleagues found that MRD negativity was associated with significantly better PFS—both overall and in studies looking specifically at patients with CRs. The hazard ratios were 0.41 (95% CI, 0.36-0.48) and 0.44 (95% CI, 0.34-0.56), respectively (P<0.001 for both).

Likewise, MRD negativity was associated with significantly better OS—both overall and in studies looking at patients with CRs. The hazard ratios were 0.57 (95% CI, 0.46-0.71) and 0.47 (95% CI, 0.33-0.67), respectively (P<0.001 for both).

The researchers said there were no significant differences among the studies for PFS and OS.

The team therefore concluded that this study provides quantitative evidence to support the integration of MRD assessment as an endpoint in trials of MM patients.