Multiple Myeloma

Lab mouse

Researchers say they have developed an animal model that allows them to better understand the mechanisms leading to multiple myeloma (MM) and other plasma cell neoplasms.

The group described this model in Scientific Reports.

“So far, there have not been animal models of malignant plasma cell diseases that allow us to study their stepwise progression and fully understand the complex cellular mechanisms,” said study author Stephen D. Nimer, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami in Florida.

“Now that we have a proper model of the disease, we’ll be able to more effectively study multiple myeloma as well as potential treatments.”

To create this model, the researchers crossed 2 genetically modified mice: mice lacking the Mef gene and mice with a Rad50 gene mutation (Rad50s).

Mef, also called Elf4, is a transcription factor known to both promote and suppress cancer formation. Rad50 is a component of a sensor of DNA damage induced by various stresses, and it regulates the DNA damage response pathways in cells.

The researchers found that Mef^−/−Rad50^s/s mice initially had abnormal plasma cell proliferation and monoclonal protein production.

Then, they developed anemia and a decreased bone mineral density. And 70% of these mice died from MM or other plasma cell neoplasms.

“We also found that the phenotype of these mice is not linked to activation of a specific oncogene or inactivation of a specific tumor suppressor, other than Mef,” said study author Takashi Asai, MD, PhD, also of the Sylvester Comprehensive Cancer Center.

Considering their findings together, the researchers said this model recapitulates the systemic manifestations of human MM and other plasma cell neoplasms. And their work suggests the Rad50s and Mef/Elf4 pathways cooperate to initiate myelomagenic mutations that promote plasma cell transformation.

“Although outcomes for multiple myeloma patients have greatly improved, it remains an incurable disease, despite the availability of newer treatments,” Dr Nimer noted.

“Several animal models of multiple myeloma have been reported, including models of human myeloma cells. However, these models imperfectly mimic the human disease. Developing more reliable and accurate animal models that help us better understand myeloma and test new treatments will take us to the next level on the long and challenging road to a cure.”

Lab mouse

Researchers say they have developed an animal model that allows them to better understand the mechanisms leading to multiple myeloma (MM) and other plasma cell neoplasms.

The group described this model in Scientific Reports.

“So far, there have not been animal models of malignant plasma cell diseases that allow us to study their stepwise progression and fully understand the complex cellular mechanisms,” said study author Stephen D. Nimer, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami in Florida.

“Now that we have a proper model of the disease, we’ll be able to more effectively study multiple myeloma as well as potential treatments.”

To create this model, the researchers crossed 2 genetically modified mice: mice lacking the Mef gene and mice with a Rad50 gene mutation (Rad50s).

Mef, also called Elf4, is a transcription factor known to both promote and suppress cancer formation. Rad50 is a component of a sensor of DNA damage induced by various stresses, and it regulates the DNA damage response pathways in cells.

The researchers found that Mef^−/−Rad50^s/s mice initially had abnormal plasma cell proliferation and monoclonal protein production.

Then, they developed anemia and a decreased bone mineral density. And 70% of these mice died from MM or other plasma cell neoplasms.

“We also found that the phenotype of these mice is not linked to activation of a specific oncogene or inactivation of a specific tumor suppressor, other than Mef,” said study author Takashi Asai, MD, PhD, also of the Sylvester Comprehensive Cancer Center.

Considering their findings together, the researchers said this model recapitulates the systemic manifestations of human MM and other plasma cell neoplasms. And their work suggests the Rad50s and Mef/Elf4 pathways cooperate to initiate myelomagenic mutations that promote plasma cell transformation.

“Although outcomes for multiple myeloma patients have greatly improved, it remains an incurable disease, despite the availability of newer treatments,” Dr Nimer noted.

“Several animal models of multiple myeloma have been reported, including models of human myeloma cells. However, these models imperfectly mimic the human disease. Developing more reliable and accurate animal models that help us better understand myeloma and test new treatments will take us to the next level on the long and challenging road to a cure.”

Lab mouse

Researchers say they have developed an animal model that allows them to better understand the mechanisms leading to multiple myeloma (MM) and other plasma cell neoplasms.

The group described this model in Scientific Reports.

“So far, there have not been animal models of malignant plasma cell diseases that allow us to study their stepwise progression and fully understand the complex cellular mechanisms,” said study author Stephen D. Nimer, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami in Florida.

“Now that we have a proper model of the disease, we’ll be able to more effectively study multiple myeloma as well as potential treatments.”

To create this model, the researchers crossed 2 genetically modified mice: mice lacking the Mef gene and mice with a Rad50 gene mutation (Rad50s).

Mef, also called Elf4, is a transcription factor known to both promote and suppress cancer formation. Rad50 is a component of a sensor of DNA damage induced by various stresses, and it regulates the DNA damage response pathways in cells.

The researchers found that Mef^−/−Rad50^s/s mice initially had abnormal plasma cell proliferation and monoclonal protein production.

Then, they developed anemia and a decreased bone mineral density. And 70% of these mice died from MM or other plasma cell neoplasms.

“We also found that the phenotype of these mice is not linked to activation of a specific oncogene or inactivation of a specific tumor suppressor, other than Mef,” said study author Takashi Asai, MD, PhD, also of the Sylvester Comprehensive Cancer Center.

Considering their findings together, the researchers said this model recapitulates the systemic manifestations of human MM and other plasma cell neoplasms. And their work suggests the Rad50s and Mef/Elf4 pathways cooperate to initiate myelomagenic mutations that promote plasma cell transformation.

“Although outcomes for multiple myeloma patients have greatly improved, it remains an incurable disease, despite the availability of newer treatments,” Dr Nimer noted.

“Several animal models of multiple myeloma have been reported, including models of human myeloma cells. However, these models imperfectly mimic the human disease. Developing more reliable and accurate animal models that help us better understand myeloma and test new treatments will take us to the next level on the long and challenging road to a cure.”

Doctor evaluating patient

Photo courtesy of the CDC

WASHINGTON, DC—The American Society of Hematology (ASH) has created a toolkit to help hematologists aid patients who are transitioning from pediatric to adult practices.

The toolkit contains general resources for all hematologic conditions, as well as specific resources for patients with hemophilia and sickle cell disease.

It includes 2 types of forms—a transition-readiness assessment and a clinical summary.

The toolkit was presented at the American College of Physicians (ACP) Internal Medicine Meeting 2016.

“Transitioning from pediatric to adult healthcare practices is often a challenge for patients with chronic medical issues because it can be difficult to adhere to a treatment regimen or attend regular appointments without the assistance of a parent or guardian,” said ASH President Charles S. Abrams, MD, of the University of Pennsylvania in Philadelphia.

“ASH recognizes that understanding a patient’s preparedness to take control of his or her medical condition in adulthood can make a huge difference in quality of care, which is why we are pleased to join the American College of Physicians and partner societies in this important initiative.”

ASH joined more than 2 dozen groups to participate in the ACP’s Pediatric to Adult Care Transition Initiative. The goal of this initiative was to develop guidance and tools that both primary care internal medicine and subspecialty practices can use for patients who are transitioning from pediatric/adolescent practices to adult care.

An ASH Transitions Work Group, made up of society members from pediatric and adult practices, developed 3 segments of the hematology-specific toolkit:

• generic forms for patients with any hematologic condition, with an addendum that includes links to additional condition-specific guidelines and resources
• specific forms for hemophilia
• specific forms for sickle cell disease.

For each segment, there are 2 types of forms— a transition-readiness assessment and a clinical summary.

The transition-readiness assessment should be completed by the patient. It assesses the patient’s readiness for the transition to adult care by evaluating the patient’s understanding of his or her condition and ability to manage medications, appointments, insurance, and medical privacy issues.

This assessment should be used by the adult care team to assess any remaining gaps in the patient’s self-care knowledge or additional issues that should be addressed to ensure optimal care.

The clinical summary is a medical record summary to be completed by the referring provider and the patient. The summary contains essential clinical information regarding the patient’s condition that is to be included in the patient’s medical record upon transfer to the adult practice.

More information on the ACP Pediatric to Adult Care Transitions Initiative is available on the ACP website. The forms for the ASH transitions toolkit are available in the “Hematology” section of the Condition-Specific Tools page.

Doctor evaluating patient

Photo courtesy of the CDC

WASHINGTON, DC—The American Society of Hematology (ASH) has created a toolkit to help hematologists aid patients who are transitioning from pediatric to adult practices.

The toolkit contains general resources for all hematologic conditions, as well as specific resources for patients with hemophilia and sickle cell disease.

It includes 2 types of forms—a transition-readiness assessment and a clinical summary.

The toolkit was presented at the American College of Physicians (ACP) Internal Medicine Meeting 2016.

“Transitioning from pediatric to adult healthcare practices is often a challenge for patients with chronic medical issues because it can be difficult to adhere to a treatment regimen or attend regular appointments without the assistance of a parent or guardian,” said ASH President Charles S. Abrams, MD, of the University of Pennsylvania in Philadelphia.

“ASH recognizes that understanding a patient’s preparedness to take control of his or her medical condition in adulthood can make a huge difference in quality of care, which is why we are pleased to join the American College of Physicians and partner societies in this important initiative.”

ASH joined more than 2 dozen groups to participate in the ACP’s Pediatric to Adult Care Transition Initiative. The goal of this initiative was to develop guidance and tools that both primary care internal medicine and subspecialty practices can use for patients who are transitioning from pediatric/adolescent practices to adult care.

An ASH Transitions Work Group, made up of society members from pediatric and adult practices, developed 3 segments of the hematology-specific toolkit:

• generic forms for patients with any hematologic condition, with an addendum that includes links to additional condition-specific guidelines and resources
• specific forms for hemophilia
• specific forms for sickle cell disease.

For each segment, there are 2 types of forms— a transition-readiness assessment and a clinical summary.

The transition-readiness assessment should be completed by the patient. It assesses the patient’s readiness for the transition to adult care by evaluating the patient’s understanding of his or her condition and ability to manage medications, appointments, insurance, and medical privacy issues.

This assessment should be used by the adult care team to assess any remaining gaps in the patient’s self-care knowledge or additional issues that should be addressed to ensure optimal care.

The clinical summary is a medical record summary to be completed by the referring provider and the patient. The summary contains essential clinical information regarding the patient’s condition that is to be included in the patient’s medical record upon transfer to the adult practice.

More information on the ACP Pediatric to Adult Care Transitions Initiative is available on the ACP website. The forms for the ASH transitions toolkit are available in the “Hematology” section of the Condition-Specific Tools page.

Doctor evaluating patient

Photo courtesy of the CDC

WASHINGTON, DC—The American Society of Hematology (ASH) has created a toolkit to help hematologists aid patients who are transitioning from pediatric to adult practices.

The toolkit contains general resources for all hematologic conditions, as well as specific resources for patients with hemophilia and sickle cell disease.

It includes 2 types of forms—a transition-readiness assessment and a clinical summary.

The toolkit was presented at the American College of Physicians (ACP) Internal Medicine Meeting 2016.

“Transitioning from pediatric to adult healthcare practices is often a challenge for patients with chronic medical issues because it can be difficult to adhere to a treatment regimen or attend regular appointments without the assistance of a parent or guardian,” said ASH President Charles S. Abrams, MD, of the University of Pennsylvania in Philadelphia.

“ASH recognizes that understanding a patient’s preparedness to take control of his or her medical condition in adulthood can make a huge difference in quality of care, which is why we are pleased to join the American College of Physicians and partner societies in this important initiative.”

ASH joined more than 2 dozen groups to participate in the ACP’s Pediatric to Adult Care Transition Initiative. The goal of this initiative was to develop guidance and tools that both primary care internal medicine and subspecialty practices can use for patients who are transitioning from pediatric/adolescent practices to adult care.

An ASH Transitions Work Group, made up of society members from pediatric and adult practices, developed 3 segments of the hematology-specific toolkit:

• generic forms for patients with any hematologic condition, with an addendum that includes links to additional condition-specific guidelines and resources
• specific forms for hemophilia
• specific forms for sickle cell disease.

For each segment, there are 2 types of forms— a transition-readiness assessment and a clinical summary.

The transition-readiness assessment should be completed by the patient. It assesses the patient’s readiness for the transition to adult care by evaluating the patient’s understanding of his or her condition and ability to manage medications, appointments, insurance, and medical privacy issues.

This assessment should be used by the adult care team to assess any remaining gaps in the patient’s self-care knowledge or additional issues that should be addressed to ensure optimal care.

The clinical summary is a medical record summary to be completed by the referring provider and the patient. The summary contains essential clinical information regarding the patient’s condition that is to be included in the patient’s medical record upon transfer to the adult practice.

More information on the ACP Pediatric to Adult Care Transitions Initiative is available on the ACP website. The forms for the ASH transitions toolkit are available in the “Hematology” section of the Condition-Specific Tools page.

 

 

Three generations of women

 

New research suggests there is a significant positive association between high levels of residential radon and the risk of hematologic malignancies in women.

The study is the first prospective, population-based study of residential radon exposure and hematologic malignancy risk.

Therefore, the researchers caution that it requires replication to better understand the association and whether it truly differs by sex.

Lauren Teras, PhD, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in Environmental Research.

Radon is a naturally occurring byproduct of the decay of radium and is a known human lung carcinogen. It is the second-leading cause of lung cancer in the US.

Modeling studies have shown that radon delivers a non-negligible dose of alpha radiation to the bone marrow and therefore could increase the risk of hematologic malignancies. However, studies investigating the link between radon and hematologic malignancies have produced inconsistent results.

For the current study, Dr Teras and her colleagues used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort to examine the association between county-level residential radon exposure and the risk of hematologic cancer.

The analysis included 140,652 participants, including 3019 who had hematologic malignancies during 19 years of follow-up (1992 to 2011).

The researchers found that women living in counties with the highest mean radon concentration (> 148 Bq/m³) had a significantly higher risk of developing a hematologic malignancy than women living in counties with the lowest radon levels (< 74 Bq/m³).

The adjusted hazard ratio (adjusted for age, race, family history of hematologic malignancy, etc.) was 1.63 (P=0.0010).

The researchers also found evidence of a dose-response relationship, with an adjusted hazard ratio of 1.38 (P=0.001).

The team said there was evidence of a positive exposure-response relationship between radon concentration and the risk of all lymphoid malignancy subtypes in women. But the highest risk was observed for follicular lymphoma, with an adjusted hazard ratio of 2.74 (P=0.02).

On the other hand, there was a non-significant inverse association between radon and myeloid leukemias in women.

There was no association between hematologic malignancy and radon exposure among the men.

The researchers said a possible explanation for this finding is that men may have a higher baseline risk of hematologic malignancy, possibly because of more exposure to occupational or other risk factors, which would reduce the impact of any additional risk from residential radon.

In women, who have a smaller baseline risk, residential radon exposure might be a larger contributor to overall risk.

Another reason for the sex difference observed in this study may be that the women of this generation spent more time in their homes, so they had more residential exposure than men.

“The overall lifetime risk of hematological cancers in the United States is about 2%, so even a 60% relative increase would still mean a relatively small absolute risk,” Dr Teras noted.

“Nonetheless, radon is already associated with lung cancer, and if other studies confirm the link to blood cancers, we think it would warrant strengthened public health efforts to mitigate residential radon risks.”

 

 

Three generations of women

 

New research suggests there is a significant positive association between high levels of residential radon and the risk of hematologic malignancies in women.

The study is the first prospective, population-based study of residential radon exposure and hematologic malignancy risk.

Therefore, the researchers caution that it requires replication to better understand the association and whether it truly differs by sex.

Lauren Teras, PhD, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in Environmental Research.

Radon is a naturally occurring byproduct of the decay of radium and is a known human lung carcinogen. It is the second-leading cause of lung cancer in the US.

Modeling studies have shown that radon delivers a non-negligible dose of alpha radiation to the bone marrow and therefore could increase the risk of hematologic malignancies. However, studies investigating the link between radon and hematologic malignancies have produced inconsistent results.

For the current study, Dr Teras and her colleagues used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort to examine the association between county-level residential radon exposure and the risk of hematologic cancer.

The analysis included 140,652 participants, including 3019 who had hematologic malignancies during 19 years of follow-up (1992 to 2011).

The researchers found that women living in counties with the highest mean radon concentration (> 148 Bq/m³) had a significantly higher risk of developing a hematologic malignancy than women living in counties with the lowest radon levels (< 74 Bq/m³).

The adjusted hazard ratio (adjusted for age, race, family history of hematologic malignancy, etc.) was 1.63 (P=0.0010).

The researchers also found evidence of a dose-response relationship, with an adjusted hazard ratio of 1.38 (P=0.001).

The team said there was evidence of a positive exposure-response relationship between radon concentration and the risk of all lymphoid malignancy subtypes in women. But the highest risk was observed for follicular lymphoma, with an adjusted hazard ratio of 2.74 (P=0.02).

On the other hand, there was a non-significant inverse association between radon and myeloid leukemias in women.

There was no association between hematologic malignancy and radon exposure among the men.

The researchers said a possible explanation for this finding is that men may have a higher baseline risk of hematologic malignancy, possibly because of more exposure to occupational or other risk factors, which would reduce the impact of any additional risk from residential radon.

In women, who have a smaller baseline risk, residential radon exposure might be a larger contributor to overall risk.

Another reason for the sex difference observed in this study may be that the women of this generation spent more time in their homes, so they had more residential exposure than men.

“The overall lifetime risk of hematological cancers in the United States is about 2%, so even a 60% relative increase would still mean a relatively small absolute risk,” Dr Teras noted.

“Nonetheless, radon is already associated with lung cancer, and if other studies confirm the link to blood cancers, we think it would warrant strengthened public health efforts to mitigate residential radon risks.”

 

 

Three generations of women

 

New research suggests there is a significant positive association between high levels of residential radon and the risk of hematologic malignancies in women.

The study is the first prospective, population-based study of residential radon exposure and hematologic malignancy risk.

Therefore, the researchers caution that it requires replication to better understand the association and whether it truly differs by sex.

Lauren Teras, PhD, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in Environmental Research.

Radon is a naturally occurring byproduct of the decay of radium and is a known human lung carcinogen. It is the second-leading cause of lung cancer in the US.

Modeling studies have shown that radon delivers a non-negligible dose of alpha radiation to the bone marrow and therefore could increase the risk of hematologic malignancies. However, studies investigating the link between radon and hematologic malignancies have produced inconsistent results.

For the current study, Dr Teras and her colleagues used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort to examine the association between county-level residential radon exposure and the risk of hematologic cancer.

The analysis included 140,652 participants, including 3019 who had hematologic malignancies during 19 years of follow-up (1992 to 2011).

The researchers found that women living in counties with the highest mean radon concentration (> 148 Bq/m³) had a significantly higher risk of developing a hematologic malignancy than women living in counties with the lowest radon levels (< 74 Bq/m³).

The adjusted hazard ratio (adjusted for age, race, family history of hematologic malignancy, etc.) was 1.63 (P=0.0010).

The researchers also found evidence of a dose-response relationship, with an adjusted hazard ratio of 1.38 (P=0.001).

The team said there was evidence of a positive exposure-response relationship between radon concentration and the risk of all lymphoid malignancy subtypes in women. But the highest risk was observed for follicular lymphoma, with an adjusted hazard ratio of 2.74 (P=0.02).

On the other hand, there was a non-significant inverse association between radon and myeloid leukemias in women.

There was no association between hematologic malignancy and radon exposure among the men.

The researchers said a possible explanation for this finding is that men may have a higher baseline risk of hematologic malignancy, possibly because of more exposure to occupational or other risk factors, which would reduce the impact of any additional risk from residential radon.

In women, who have a smaller baseline risk, residential radon exposure might be a larger contributor to overall risk.

Another reason for the sex difference observed in this study may be that the women of this generation spent more time in their homes, so they had more residential exposure than men.

“The overall lifetime risk of hematological cancers in the United States is about 2%, so even a 60% relative increase would still mean a relatively small absolute risk,” Dr Teras noted.

“Nonetheless, radon is already associated with lung cancer, and if other studies confirm the link to blood cancers, we think it would warrant strengthened public health efforts to mitigate residential radon risks.”

Treating multiple myeloma cells with panobinostat and FK506 reduced their viability by inhibiting expression of the PPP3CA catalytic subunit of calcineurin, according to researchers.

“The development of new calcineurin-targeted therapies, which inhibit PPP3CA–NF-kappaB signaling by small molecules, is expected to profoundly improve the treatment of multiple myeloma. This will overcome drug resistance and improve osteolytic lesions in a wide range of patients, including those receiving reduced intensity–conditioned allogeneic stem cell transplantation, who may be treated with panobinostat and FK506,” wrote Dr. Yoichi Imai of Tokyo Women’s Medical University in Japan, and his associates (JCI Insight 2016 doi: 10.1172/jci.insight.85061). .

Adding panobinostat to bortezomib and dexamethasone has been shown to improve progression-free survival in relapsed and refractory multiple myeloma, the researchers noted. Other studies have linked calcineurin activation to the pathogenesis of T-cell cancers, and calcineurin inhibition seems to be involved in defective B-cell activation, they added.

Eight candidate oncogenes were identified by use of the Gene Expression Omnibus. PPP3CA was expressed at significantly higher levels in multiple myeloma cells from patients with stage III disease compared with those with stage I disease (P = .016). Furthermore, levels of serum lactate dehydrogenase correlated with PPP3CA expression and with poor overall and progression-free survival. Patients with high PPP3CA expression also had high levels of alpha₄ integrins, which mediate resistance to bortezomib and conventional chemotherapy, the researchers noted.

When multiple myeloma cells were exposed to either panobinostat or a control agent, PPP3CA dropped in the panobinostat-treated cells. Adding the proteasome inhibitor lactacystin to the mixture counteracted this effect, “supporting the possibility that PPP3CA expression was reduced through protein degradation by panobinostat,” they said.

Levels of PPP3CA expression were lower in multiple myeloma cells that were cotreated with an HDAC inhibitor (panobinostat or ACY-1215) and the immunosuppressive agent FK506 than in multiple myeloma cells that were exposed only to an HDAC inhibitor. In addition, the combination regimen blocked the formation of osteoclasts, which are involved in osteolytic lesions, the researchers noted.

Also, significantly higher PPP3CA expression, which correlated with worse progression-free survival, was noted in bortezomib-resistant patients, compared with bortezomib-sensitive patients.

“The cytotoxic effect exerted by panobinostat on CD20+ cells was subtle, while the addition of FK506 did not increase their viability,” the researchers reported. “Moreover, development of T and B lineage cells was normal in PPP3CA-deficient mice, and panobinostat did not compromise donor lymphocyte reconstitution in a mouse BM transplantation model. These results suggest that calcineurin-targeting therapy exerts an antimyeloma effect without inducing significant side effects in normal lymphoid systems.”

The Japan Society for the Promotion of Science, the Takeda Science Foundation, the International Myeloma Foundation, and the Japan Leukemia Research Fund funded the study. The investigators had no disclosures.

Treating multiple myeloma cells with panobinostat and FK506 reduced their viability by inhibiting expression of the PPP3CA catalytic subunit of calcineurin, according to researchers.

“The development of new calcineurin-targeted therapies, which inhibit PPP3CA–NF-kappaB signaling by small molecules, is expected to profoundly improve the treatment of multiple myeloma. This will overcome drug resistance and improve osteolytic lesions in a wide range of patients, including those receiving reduced intensity–conditioned allogeneic stem cell transplantation, who may be treated with panobinostat and FK506,” wrote Dr. Yoichi Imai of Tokyo Women’s Medical University in Japan, and his associates (JCI Insight 2016 doi: 10.1172/jci.insight.85061). .

Adding panobinostat to bortezomib and dexamethasone has been shown to improve progression-free survival in relapsed and refractory multiple myeloma, the researchers noted. Other studies have linked calcineurin activation to the pathogenesis of T-cell cancers, and calcineurin inhibition seems to be involved in defective B-cell activation, they added.

Eight candidate oncogenes were identified by use of the Gene Expression Omnibus. PPP3CA was expressed at significantly higher levels in multiple myeloma cells from patients with stage III disease compared with those with stage I disease (P = .016). Furthermore, levels of serum lactate dehydrogenase correlated with PPP3CA expression and with poor overall and progression-free survival. Patients with high PPP3CA expression also had high levels of alpha₄ integrins, which mediate resistance to bortezomib and conventional chemotherapy, the researchers noted.

When multiple myeloma cells were exposed to either panobinostat or a control agent, PPP3CA dropped in the panobinostat-treated cells. Adding the proteasome inhibitor lactacystin to the mixture counteracted this effect, “supporting the possibility that PPP3CA expression was reduced through protein degradation by panobinostat,” they said.

Levels of PPP3CA expression were lower in multiple myeloma cells that were cotreated with an HDAC inhibitor (panobinostat or ACY-1215) and the immunosuppressive agent FK506 than in multiple myeloma cells that were exposed only to an HDAC inhibitor. In addition, the combination regimen blocked the formation of osteoclasts, which are involved in osteolytic lesions, the researchers noted.

Also, significantly higher PPP3CA expression, which correlated with worse progression-free survival, was noted in bortezomib-resistant patients, compared with bortezomib-sensitive patients.

“The cytotoxic effect exerted by panobinostat on CD20+ cells was subtle, while the addition of FK506 did not increase their viability,” the researchers reported. “Moreover, development of T and B lineage cells was normal in PPP3CA-deficient mice, and panobinostat did not compromise donor lymphocyte reconstitution in a mouse BM transplantation model. These results suggest that calcineurin-targeting therapy exerts an antimyeloma effect without inducing significant side effects in normal lymphoid systems.”

The Japan Society for the Promotion of Science, the Takeda Science Foundation, the International Myeloma Foundation, and the Japan Leukemia Research Fund funded the study. The investigators had no disclosures.

Treating multiple myeloma cells with panobinostat and FK506 reduced their viability by inhibiting expression of the PPP3CA catalytic subunit of calcineurin, according to researchers.

“The development of new calcineurin-targeted therapies, which inhibit PPP3CA–NF-kappaB signaling by small molecules, is expected to profoundly improve the treatment of multiple myeloma. This will overcome drug resistance and improve osteolytic lesions in a wide range of patients, including those receiving reduced intensity–conditioned allogeneic stem cell transplantation, who may be treated with panobinostat and FK506,” wrote Dr. Yoichi Imai of Tokyo Women’s Medical University in Japan, and his associates (JCI Insight 2016 doi: 10.1172/jci.insight.85061). .

Adding panobinostat to bortezomib and dexamethasone has been shown to improve progression-free survival in relapsed and refractory multiple myeloma, the researchers noted. Other studies have linked calcineurin activation to the pathogenesis of T-cell cancers, and calcineurin inhibition seems to be involved in defective B-cell activation, they added.

Eight candidate oncogenes were identified by use of the Gene Expression Omnibus. PPP3CA was expressed at significantly higher levels in multiple myeloma cells from patients with stage III disease compared with those with stage I disease (P = .016). Furthermore, levels of serum lactate dehydrogenase correlated with PPP3CA expression and with poor overall and progression-free survival. Patients with high PPP3CA expression also had high levels of alpha₄ integrins, which mediate resistance to bortezomib and conventional chemotherapy, the researchers noted.

When multiple myeloma cells were exposed to either panobinostat or a control agent, PPP3CA dropped in the panobinostat-treated cells. Adding the proteasome inhibitor lactacystin to the mixture counteracted this effect, “supporting the possibility that PPP3CA expression was reduced through protein degradation by panobinostat,” they said.

Levels of PPP3CA expression were lower in multiple myeloma cells that were cotreated with an HDAC inhibitor (panobinostat or ACY-1215) and the immunosuppressive agent FK506 than in multiple myeloma cells that were exposed only to an HDAC inhibitor. In addition, the combination regimen blocked the formation of osteoclasts, which are involved in osteolytic lesions, the researchers noted.

Also, significantly higher PPP3CA expression, which correlated with worse progression-free survival, was noted in bortezomib-resistant patients, compared with bortezomib-sensitive patients.

“The cytotoxic effect exerted by panobinostat on CD20+ cells was subtle, while the addition of FK506 did not increase their viability,” the researchers reported. “Moreover, development of T and B lineage cells was normal in PPP3CA-deficient mice, and panobinostat did not compromise donor lymphocyte reconstitution in a mouse BM transplantation model. These results suggest that calcineurin-targeting therapy exerts an antimyeloma effect without inducing significant side effects in normal lymphoid systems.”

The Japan Society for the Promotion of Science, the Takeda Science Foundation, the International Myeloma Foundation, and the Japan Leukemia Research Fund funded the study. The investigators had no disclosures.

Philippe Moreau, MD

Photo courtesy of ASH

In the phase 3 TOURMALINE-MM1 trial, adding the oral proteasome inhibitor ixazomib to treatment with lenalidomide and dexamethasone significantly extended progression-free survival (PFS), with limited additional toxicity, in patients with relapsed/refractory multiple myeloma (MM).

The median PFS was about 21 months for patients who received ixazomib, lenalidomide, and dexamethasone (IRd) and about 15 months for those who received placebo, lenalidomide, and dexamethasone (Rd).

Gastrointestinal adverse events (AEs), rash, and grade 3/4 thrombocytopenia were more common in the IRd arm than the Rd arm.

These results were published in NEJM. The study was sponsored by Millennium Pharmaceuticals, Inc. Results from this trial were previously presented at ASH 2015, but the data in NEJM differ slightly from that presentation.

“NEJM has published the results of the first phase 3 study supporting an all-oral triplet regimen containing a proteasome inhibitor in multiple myeloma,” said study author Philippe Moreau, MD, of University of Nantes in France.

“The TOURMALINE-MM1 results demonstrated that ixazomib in combination with lenalidomide and dexamethasone is an effective and tolerable oral regimen with a manageable safety profile for patients with relapsed and/or refractory multiple myeloma.”

TOURMALINE-MM1 enrolled 722 patients with relapsed (77%), refractory (11%), relapsed and refractory (12%), or primary refractory (6%) MM.

The patients were randomized to receive IRd (n=360) or Rd (n=362). Baseline patient characteristics were similar between the treatment arms. The median age was 66 in both arms (overall range, 30-91), and nearly 60% of patients were male.

About 60% of patients in both arms had received 1 prior therapy, roughly 30% had received 2, and about 10% had received 3. Seventy percent of patients in both arms had received prior treatment with a proteasome inhibitor, and about 55% had received an immunomodulatory drug.

Efficacy

The study’s primary endpoint was PFS. And the researchers saw a significant improvement in PFS for the IRd arm compared to the Rd arm. The median PFS was 20.6 months and 14.7 months, respectively. The hazard ratio was 0.74 (P=0.01).

There was a benefit in PFS in the IRd arm across pre-specified patient subgroups, including patients with poor prognosis, such as elderly patients, those who had received 2 or 3 prior therapies, those with advanced stage disease, and those with high-risk cytogenetic abnormalities.

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

The overall response rates were 78% in the IRd arm and 72% in the Rd arm. The complete response rates were 12% and 7%, respectively, and the stringent complete response rates were 2% and <1%, respectively.

The median time to response was 1.1 months in the IRd arm and 1.9 months in the Rd arm. The median duration of response was 20.5 months and 15.0 months, respectively.

Safety

AEs occurred in 98% of patients in the IRd arm and 99% in the Rd arm. Grade 3 or higher AEs occurred in 74% and 69% of patients, respectively, serious AEs occurred in 47% and 49%, respectively, and on-study deaths occurred in 4% and 6%, respectively.

Grade 3 and 4 thrombocytopenia was more frequent in the IRd arm (12% and 7%, respectively) than in the Rd arm (5% and 4%, respectively). Rash also occurred more frequently in the IRd arm than in the Rd arm (36% and 23%, respectively).

Gastrointestinal AEs were more frequent in the IRd arm than the Rd arm, including diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), and vomiting (23% vs 12%).

The incidence of peripheral neuropathy was 27% in the IRd arm and 22% in the Rd arm. Grade 3 events occurred in 2% of patients in each arm, and no grade 4 events were reported.

Roughly the same percentage of patients developed new primary malignant tumors—5% in the IRd arm and 4% in the Rd arm.

Philippe Moreau, MD

Photo courtesy of ASH

In the phase 3 TOURMALINE-MM1 trial, adding the oral proteasome inhibitor ixazomib to treatment with lenalidomide and dexamethasone significantly extended progression-free survival (PFS), with limited additional toxicity, in patients with relapsed/refractory multiple myeloma (MM).

The median PFS was about 21 months for patients who received ixazomib, lenalidomide, and dexamethasone (IRd) and about 15 months for those who received placebo, lenalidomide, and dexamethasone (Rd).

Gastrointestinal adverse events (AEs), rash, and grade 3/4 thrombocytopenia were more common in the IRd arm than the Rd arm.

These results were published in NEJM. The study was sponsored by Millennium Pharmaceuticals, Inc. Results from this trial were previously presented at ASH 2015, but the data in NEJM differ slightly from that presentation.

“NEJM has published the results of the first phase 3 study supporting an all-oral triplet regimen containing a proteasome inhibitor in multiple myeloma,” said study author Philippe Moreau, MD, of University of Nantes in France.

“The TOURMALINE-MM1 results demonstrated that ixazomib in combination with lenalidomide and dexamethasone is an effective and tolerable oral regimen with a manageable safety profile for patients with relapsed and/or refractory multiple myeloma.”

TOURMALINE-MM1 enrolled 722 patients with relapsed (77%), refractory (11%), relapsed and refractory (12%), or primary refractory (6%) MM.

The patients were randomized to receive IRd (n=360) or Rd (n=362). Baseline patient characteristics were similar between the treatment arms. The median age was 66 in both arms (overall range, 30-91), and nearly 60% of patients were male.

About 60% of patients in both arms had received 1 prior therapy, roughly 30% had received 2, and about 10% had received 3. Seventy percent of patients in both arms had received prior treatment with a proteasome inhibitor, and about 55% had received an immunomodulatory drug.

Efficacy

The study’s primary endpoint was PFS. And the researchers saw a significant improvement in PFS for the IRd arm compared to the Rd arm. The median PFS was 20.6 months and 14.7 months, respectively. The hazard ratio was 0.74 (P=0.01).

There was a benefit in PFS in the IRd arm across pre-specified patient subgroups, including patients with poor prognosis, such as elderly patients, those who had received 2 or 3 prior therapies, those with advanced stage disease, and those with high-risk cytogenetic abnormalities.

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

The overall response rates were 78% in the IRd arm and 72% in the Rd arm. The complete response rates were 12% and 7%, respectively, and the stringent complete response rates were 2% and <1%, respectively.

The median time to response was 1.1 months in the IRd arm and 1.9 months in the Rd arm. The median duration of response was 20.5 months and 15.0 months, respectively.

Safety

AEs occurred in 98% of patients in the IRd arm and 99% in the Rd arm. Grade 3 or higher AEs occurred in 74% and 69% of patients, respectively, serious AEs occurred in 47% and 49%, respectively, and on-study deaths occurred in 4% and 6%, respectively.

Grade 3 and 4 thrombocytopenia was more frequent in the IRd arm (12% and 7%, respectively) than in the Rd arm (5% and 4%, respectively). Rash also occurred more frequently in the IRd arm than in the Rd arm (36% and 23%, respectively).

Gastrointestinal AEs were more frequent in the IRd arm than the Rd arm, including diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), and vomiting (23% vs 12%).

The incidence of peripheral neuropathy was 27% in the IRd arm and 22% in the Rd arm. Grade 3 events occurred in 2% of patients in each arm, and no grade 4 events were reported.

Roughly the same percentage of patients developed new primary malignant tumors—5% in the IRd arm and 4% in the Rd arm.

Philippe Moreau, MD

Photo courtesy of ASH

In the phase 3 TOURMALINE-MM1 trial, adding the oral proteasome inhibitor ixazomib to treatment with lenalidomide and dexamethasone significantly extended progression-free survival (PFS), with limited additional toxicity, in patients with relapsed/refractory multiple myeloma (MM).

The median PFS was about 21 months for patients who received ixazomib, lenalidomide, and dexamethasone (IRd) and about 15 months for those who received placebo, lenalidomide, and dexamethasone (Rd).

Gastrointestinal adverse events (AEs), rash, and grade 3/4 thrombocytopenia were more common in the IRd arm than the Rd arm.

These results were published in NEJM. The study was sponsored by Millennium Pharmaceuticals, Inc. Results from this trial were previously presented at ASH 2015, but the data in NEJM differ slightly from that presentation.

“NEJM has published the results of the first phase 3 study supporting an all-oral triplet regimen containing a proteasome inhibitor in multiple myeloma,” said study author Philippe Moreau, MD, of University of Nantes in France.

“The TOURMALINE-MM1 results demonstrated that ixazomib in combination with lenalidomide and dexamethasone is an effective and tolerable oral regimen with a manageable safety profile for patients with relapsed and/or refractory multiple myeloma.”

TOURMALINE-MM1 enrolled 722 patients with relapsed (77%), refractory (11%), relapsed and refractory (12%), or primary refractory (6%) MM.

The patients were randomized to receive IRd (n=360) or Rd (n=362). Baseline patient characteristics were similar between the treatment arms. The median age was 66 in both arms (overall range, 30-91), and nearly 60% of patients were male.

About 60% of patients in both arms had received 1 prior therapy, roughly 30% had received 2, and about 10% had received 3. Seventy percent of patients in both arms had received prior treatment with a proteasome inhibitor, and about 55% had received an immunomodulatory drug.

Efficacy

The study’s primary endpoint was PFS. And the researchers saw a significant improvement in PFS for the IRd arm compared to the Rd arm. The median PFS was 20.6 months and 14.7 months, respectively. The hazard ratio was 0.74 (P=0.01).

There was a benefit in PFS in the IRd arm across pre-specified patient subgroups, including patients with poor prognosis, such as elderly patients, those who had received 2 or 3 prior therapies, those with advanced stage disease, and those with high-risk cytogenetic abnormalities.

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

The overall response rates were 78% in the IRd arm and 72% in the Rd arm. The complete response rates were 12% and 7%, respectively, and the stringent complete response rates were 2% and <1%, respectively.

The median time to response was 1.1 months in the IRd arm and 1.9 months in the Rd arm. The median duration of response was 20.5 months and 15.0 months, respectively.

Safety

AEs occurred in 98% of patients in the IRd arm and 99% in the Rd arm. Grade 3 or higher AEs occurred in 74% and 69% of patients, respectively, serious AEs occurred in 47% and 49%, respectively, and on-study deaths occurred in 4% and 6%, respectively.

Grade 3 and 4 thrombocytopenia was more frequent in the IRd arm (12% and 7%, respectively) than in the Rd arm (5% and 4%, respectively). Rash also occurred more frequently in the IRd arm than in the Rd arm (36% and 23%, respectively).

Gastrointestinal AEs were more frequent in the IRd arm than the Rd arm, including diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), and vomiting (23% vs 12%).

The incidence of peripheral neuropathy was 27% in the IRd arm and 22% in the Rd arm. Grade 3 events occurred in 2% of patients in each arm, and no grade 4 events were reported.

Roughly the same percentage of patients developed new primary malignant tumors—5% in the IRd arm and 4% in the Rd arm.

Researcher placing PCR tubes

in a thermal cycler

Photo by Karl Mumm

Measuring expression of the gene TJP1 could help determine which multiple myeloma (MM) patients are most likely to benefit from treatment with proteasome inhibitors (PIs), according to a study published in Cancer Cell.

Investigators found that TJP1 enhanced PI sensitivity in vitro and in vivo.

When they analyzed patient data, the team found that high TJP1 expression in patients’ MM cells was associated with a significantly higher likelihood of responding to bortezomib and a longer response duration.

“Proteasome inhibitors form the cornerstone of our standard therapy for multiple myeloma,” said study author Robert Orlowski, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston.

“However, no biomarkers have been clinically validated that can identify patients most likely to respond to this treatment. Our findings provide a rationale for use of TJP1 as the first biomarker to select patients who are most and least likely to benefit from proteasome inhibitors.”

At the start of this study, Dr Orlowski and his colleagues examined gene-expression profiles of ANBL-6 and KAS-6/1 wild-type and bortezomib-resistant MM cells and found that TJP1 was downregulated in the resistant cells.

To further study the role of TJP1 in PI resistance, the investigators conducted experiments with RPMI 8226 and U266 MM cell lines (models that expressed high TJP1 levels) and MOLP-8 (a model that expressed low levels).

They found that knocking down TJP1 in RPMI 8226 and U266 cells with short hairpin RNA (shRNA) preserved the cells’ viability after exposure to bortezomib or carfilzomib. On the other hand, TJP1 overexpression sensitized MOLP-8 cells to the PIs.

In mice, RPMI 8226/TJP1 shRNA tumors were less sensitive to bortezomib than RPMI 8226/control tumors. And mice with MOLP-8/TJP1 shRNA tumors had a greater reduction in tumor growth after bortezomib treatment than MOLP-8/control mice.

Further investigation revealed that TJP1 modulates signaling through a pathway involving EGFR, JAK1, and STAT3. This finding supports the hypothesis that plasma cells expressing low TJP1 levels have both high EGFR/JAK1/STAT3 activity and high proteasome content.

“Therefore, these plasma cells were resistant to proteasome inhibitors,” Dr Orlowski explained. “Moreover, they demonstrated a previously unknown role for EGFR signaling in myeloma and for STAT3 in controlling the level of proteasomes in cells and, therefore, the cell’s ability to break down proteins.”

“This study allows us to identify promising future directions to overcome proteasome inhibitor resistance in patients with high signaling through the EGFR/JAK1/STAT3 pathway by offering combination therapies such as bortezomib with either the EGFR inhibitor erlotinib or a JAK1 inhibitor such as ruxolitinib.”

Finally, Dr Orlowski and his colleagues found that patients whose MM cells expressed low TJP1 levels were significantly less likely to achieve a response or benefit from bortezomib.

Patients who achieved a response after bortezomib across multiple studies had significantly higher TJP1 expression than nonresponders. And patients with the highest TJP1 expression levels had the longest time to progression.

Researcher placing PCR tubes

in a thermal cycler

Photo by Karl Mumm

Measuring expression of the gene TJP1 could help determine which multiple myeloma (MM) patients are most likely to benefit from treatment with proteasome inhibitors (PIs), according to a study published in Cancer Cell.

Investigators found that TJP1 enhanced PI sensitivity in vitro and in vivo.

When they analyzed patient data, the team found that high TJP1 expression in patients’ MM cells was associated with a significantly higher likelihood of responding to bortezomib and a longer response duration.

“Proteasome inhibitors form the cornerstone of our standard therapy for multiple myeloma,” said study author Robert Orlowski, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston.

“However, no biomarkers have been clinically validated that can identify patients most likely to respond to this treatment. Our findings provide a rationale for use of TJP1 as the first biomarker to select patients who are most and least likely to benefit from proteasome inhibitors.”

At the start of this study, Dr Orlowski and his colleagues examined gene-expression profiles of ANBL-6 and KAS-6/1 wild-type and bortezomib-resistant MM cells and found that TJP1 was downregulated in the resistant cells.

To further study the role of TJP1 in PI resistance, the investigators conducted experiments with RPMI 8226 and U266 MM cell lines (models that expressed high TJP1 levels) and MOLP-8 (a model that expressed low levels).

They found that knocking down TJP1 in RPMI 8226 and U266 cells with short hairpin RNA (shRNA) preserved the cells’ viability after exposure to bortezomib or carfilzomib. On the other hand, TJP1 overexpression sensitized MOLP-8 cells to the PIs.

In mice, RPMI 8226/TJP1 shRNA tumors were less sensitive to bortezomib than RPMI 8226/control tumors. And mice with MOLP-8/TJP1 shRNA tumors had a greater reduction in tumor growth after bortezomib treatment than MOLP-8/control mice.

Further investigation revealed that TJP1 modulates signaling through a pathway involving EGFR, JAK1, and STAT3. This finding supports the hypothesis that plasma cells expressing low TJP1 levels have both high EGFR/JAK1/STAT3 activity and high proteasome content.

“Therefore, these plasma cells were resistant to proteasome inhibitors,” Dr Orlowski explained. “Moreover, they demonstrated a previously unknown role for EGFR signaling in myeloma and for STAT3 in controlling the level of proteasomes in cells and, therefore, the cell’s ability to break down proteins.”

“This study allows us to identify promising future directions to overcome proteasome inhibitor resistance in patients with high signaling through the EGFR/JAK1/STAT3 pathway by offering combination therapies such as bortezomib with either the EGFR inhibitor erlotinib or a JAK1 inhibitor such as ruxolitinib.”

Finally, Dr Orlowski and his colleagues found that patients whose MM cells expressed low TJP1 levels were significantly less likely to achieve a response or benefit from bortezomib.

Patients who achieved a response after bortezomib across multiple studies had significantly higher TJP1 expression than nonresponders. And patients with the highest TJP1 expression levels had the longest time to progression.

Researcher placing PCR tubes

in a thermal cycler

Photo by Karl Mumm

Measuring expression of the gene TJP1 could help determine which multiple myeloma (MM) patients are most likely to benefit from treatment with proteasome inhibitors (PIs), according to a study published in Cancer Cell.

Investigators found that TJP1 enhanced PI sensitivity in vitro and in vivo.

When they analyzed patient data, the team found that high TJP1 expression in patients’ MM cells was associated with a significantly higher likelihood of responding to bortezomib and a longer response duration.

“Proteasome inhibitors form the cornerstone of our standard therapy for multiple myeloma,” said study author Robert Orlowski, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston.

“However, no biomarkers have been clinically validated that can identify patients most likely to respond to this treatment. Our findings provide a rationale for use of TJP1 as the first biomarker to select patients who are most and least likely to benefit from proteasome inhibitors.”

At the start of this study, Dr Orlowski and his colleagues examined gene-expression profiles of ANBL-6 and KAS-6/1 wild-type and bortezomib-resistant MM cells and found that TJP1 was downregulated in the resistant cells.

To further study the role of TJP1 in PI resistance, the investigators conducted experiments with RPMI 8226 and U266 MM cell lines (models that expressed high TJP1 levels) and MOLP-8 (a model that expressed low levels).

They found that knocking down TJP1 in RPMI 8226 and U266 cells with short hairpin RNA (shRNA) preserved the cells’ viability after exposure to bortezomib or carfilzomib. On the other hand, TJP1 overexpression sensitized MOLP-8 cells to the PIs.

In mice, RPMI 8226/TJP1 shRNA tumors were less sensitive to bortezomib than RPMI 8226/control tumors. And mice with MOLP-8/TJP1 shRNA tumors had a greater reduction in tumor growth after bortezomib treatment than MOLP-8/control mice.

Further investigation revealed that TJP1 modulates signaling through a pathway involving EGFR, JAK1, and STAT3. This finding supports the hypothesis that plasma cells expressing low TJP1 levels have both high EGFR/JAK1/STAT3 activity and high proteasome content.

“Therefore, these plasma cells were resistant to proteasome inhibitors,” Dr Orlowski explained. “Moreover, they demonstrated a previously unknown role for EGFR signaling in myeloma and for STAT3 in controlling the level of proteasomes in cells and, therefore, the cell’s ability to break down proteins.”

“This study allows us to identify promising future directions to overcome proteasome inhibitor resistance in patients with high signaling through the EGFR/JAK1/STAT3 pathway by offering combination therapies such as bortezomib with either the EGFR inhibitor erlotinib or a JAK1 inhibitor such as ruxolitinib.”

Finally, Dr Orlowski and his colleagues found that patients whose MM cells expressed low TJP1 levels were significantly less likely to achieve a response or benefit from bortezomib.

Patients who achieved a response after bortezomib across multiple studies had significantly higher TJP1 expression than nonresponders. And patients with the highest TJP1 expression levels had the longest time to progression.

Doctor with a clipboard

A recent cancer diagnosis is associated with an increased risk for mental health disorders and increased use of psychiatric medications, according to a large, nationwide study conducted in Sweden.

Overall, there was an increased risk of mental health disorders from 10 months before a cancer diagnosis that peaked during the first week after diagnosis and decreased after that, although the risk remained elevated at 10 years after diagnosis.

In addition, there was an increased use of psychiatric medications from 1 month before cancer diagnosis that peaked at about 3 months after diagnosis and remained elevated 2 years after diagnosis.

Donghao Lu, MD, of the Karolinska Institutet in Stockholm, Sweden and colleagues conducted this study and reported the results in JAMA Oncology.

The study included 304,118 patients with cancer and 3,041,174 cancer-free individuals randomly selected from the Swedish population for comparison.

The researchers investigated changes in risk for several common and potentially stress-related mental disorders—including depression, anxiety, substance abuse, somatoform/conversion disorder, and stress reaction/adjustment disorder—from the cancer diagnostic workup through to post-diagnosis.

They found the relative rate for all of the mental disorders studied started to increase from 10 months before cancer diagnosis, with a hazard ratio [HR] of 1.1 (95%CI, 1.1-1.2).

The rate peaked during the first week after diagnosis, with an HR of 6.7 (95%CI, 6.1-7.4). It decreased rapidly thereafter but was still elevated 10 years after diagnosis, with an HR of 1.1 (95%CI, 1.1-1.2).

The rate elevation was clear for all of the main cancers, including hematologic malignancies, except for nonmelanoma skin cancer.

Among the cancer patients, the mental disorder with the highest cumulative incidence was depression. This was followed by anxiety and stress reaction/adjustment disorder.

When compared to controls, the cancer patients had a higher cumulative incidence of most of the mental disorders. The exception was somatoform/conversion disorder.

The researchers also examined the use of psychiatric medications for patients with cancer to assess milder mental health conditions and symptoms.

The team found an increased use of psychiatric medications in cancer patients compared to controls, from 1 month before diagnosis—12.2% vs 11.7% (P=0.04)—that peaked at about 3 months after diagnosis—18.1% vs 11.9% (P<0.001)—and was still elevated 2 years after diagnosis—15.4% vs 12.7% (P<0.001).

The researchers said the results of this study support the existing guidelines of integrating psychological management into cancer care and call for extended vigilance for multiple mental disorders starting from the time of the cancer diagnostic workup.

Doctor with a clipboard

A recent cancer diagnosis is associated with an increased risk for mental health disorders and increased use of psychiatric medications, according to a large, nationwide study conducted in Sweden.

Overall, there was an increased risk of mental health disorders from 10 months before a cancer diagnosis that peaked during the first week after diagnosis and decreased after that, although the risk remained elevated at 10 years after diagnosis.

In addition, there was an increased use of psychiatric medications from 1 month before cancer diagnosis that peaked at about 3 months after diagnosis and remained elevated 2 years after diagnosis.

Donghao Lu, MD, of the Karolinska Institutet in Stockholm, Sweden and colleagues conducted this study and reported the results in JAMA Oncology.

The study included 304,118 patients with cancer and 3,041,174 cancer-free individuals randomly selected from the Swedish population for comparison.

The researchers investigated changes in risk for several common and potentially stress-related mental disorders—including depression, anxiety, substance abuse, somatoform/conversion disorder, and stress reaction/adjustment disorder—from the cancer diagnostic workup through to post-diagnosis.

They found the relative rate for all of the mental disorders studied started to increase from 10 months before cancer diagnosis, with a hazard ratio [HR] of 1.1 (95%CI, 1.1-1.2).

The rate peaked during the first week after diagnosis, with an HR of 6.7 (95%CI, 6.1-7.4). It decreased rapidly thereafter but was still elevated 10 years after diagnosis, with an HR of 1.1 (95%CI, 1.1-1.2).

The rate elevation was clear for all of the main cancers, including hematologic malignancies, except for nonmelanoma skin cancer.

Among the cancer patients, the mental disorder with the highest cumulative incidence was depression. This was followed by anxiety and stress reaction/adjustment disorder.

When compared to controls, the cancer patients had a higher cumulative incidence of most of the mental disorders. The exception was somatoform/conversion disorder.

The researchers also examined the use of psychiatric medications for patients with cancer to assess milder mental health conditions and symptoms.

The team found an increased use of psychiatric medications in cancer patients compared to controls, from 1 month before diagnosis—12.2% vs 11.7% (P=0.04)—that peaked at about 3 months after diagnosis—18.1% vs 11.9% (P<0.001)—and was still elevated 2 years after diagnosis—15.4% vs 12.7% (P<0.001).

The researchers said the results of this study support the existing guidelines of integrating psychological management into cancer care and call for extended vigilance for multiple mental disorders starting from the time of the cancer diagnostic workup.

Doctor with a clipboard

A recent cancer diagnosis is associated with an increased risk for mental health disorders and increased use of psychiatric medications, according to a large, nationwide study conducted in Sweden.

Overall, there was an increased risk of mental health disorders from 10 months before a cancer diagnosis that peaked during the first week after diagnosis and decreased after that, although the risk remained elevated at 10 years after diagnosis.

In addition, there was an increased use of psychiatric medications from 1 month before cancer diagnosis that peaked at about 3 months after diagnosis and remained elevated 2 years after diagnosis.

Donghao Lu, MD, of the Karolinska Institutet in Stockholm, Sweden and colleagues conducted this study and reported the results in JAMA Oncology.

The study included 304,118 patients with cancer and 3,041,174 cancer-free individuals randomly selected from the Swedish population for comparison.

The researchers investigated changes in risk for several common and potentially stress-related mental disorders—including depression, anxiety, substance abuse, somatoform/conversion disorder, and stress reaction/adjustment disorder—from the cancer diagnostic workup through to post-diagnosis.

They found the relative rate for all of the mental disorders studied started to increase from 10 months before cancer diagnosis, with a hazard ratio [HR] of 1.1 (95%CI, 1.1-1.2).

The rate peaked during the first week after diagnosis, with an HR of 6.7 (95%CI, 6.1-7.4). It decreased rapidly thereafter but was still elevated 10 years after diagnosis, with an HR of 1.1 (95%CI, 1.1-1.2).

The rate elevation was clear for all of the main cancers, including hematologic malignancies, except for nonmelanoma skin cancer.

Among the cancer patients, the mental disorder with the highest cumulative incidence was depression. This was followed by anxiety and stress reaction/adjustment disorder.

When compared to controls, the cancer patients had a higher cumulative incidence of most of the mental disorders. The exception was somatoform/conversion disorder.

The researchers also examined the use of psychiatric medications for patients with cancer to assess milder mental health conditions and symptoms.

The team found an increased use of psychiatric medications in cancer patients compared to controls, from 1 month before diagnosis—12.2% vs 11.7% (P=0.04)—that peaked at about 3 months after diagnosis—18.1% vs 11.9% (P<0.001)—and was still elevated 2 years after diagnosis—15.4% vs 12.7% (P<0.001).

The researchers said the results of this study support the existing guidelines of integrating psychological management into cancer care and call for extended vigilance for multiple mental disorders starting from the time of the cancer diagnostic workup.

Prescription medications

Photo courtesy of the CDC

New orally administered cancer drugs are much more expensive in their first year on the market than such drugs launched about 15 years ago, according to a study published in JAMA Oncology.

The research showed that a month of treatment with orally administered cancer drugs introduced in 2014 was, on average, 6 times more expensive at launch than monthly treatment costs for such drugs introduced in 2000, after adjusting for inflation.

In addition, most existing therapies had substantial price increases from the time they were launched to 2014.

“The major trend here is that these products are just getting more expensive over time,” said study author Stacie Dusetzina, PhD, of the University of North Carolina at Chapel Hill.

For this study, Dr Dusetzina evaluated what commercial health insurance companies and patients paid for prescription fills—before rebates and discounts—for 32 orally administered cancer drugs from 2000 to 2014. The information came from the TruvenHealth MarketScan Commercial Claims and Encounters database.

The data showed that orally administered drugs approved in 2000 cost an average of $1869 (95% CI, $1648-$2121) per month, compared to $11,325 (95% CI, $10 989-$11 671) for those approved in 2014.

When Dr Dusetzina compared changes in spending by year from a product’s launch to 2014, she observed increases in most of the drugs studied.

The drugs with the largest increases in monthly spending were thalidomide, which increased from $1869 to $7564 ($5695) and imatinib, which increased from $3346 to $8479 ($5133).

However, 2 drugs showed decreases in mean monthly spending between their launch and 2014. Monthly spending for lenalidomide decreased from $10,109 to $9640 ($469), and monthly spending for vorinostat decreased from $9755 to $7592 ($2163).

Dr Dusetzina pointed out that the amount patients pay for these drugs depends on their healthcare benefits. However, the high prices are being passed along to patients more and more, potentially affecting the patients’ access to these drugs.

“Patients are increasingly taking on the burden of paying for these high-cost specialty drugs as plans move toward use of higher deductibles and co-insurance—where a patient will pay a percentage of the drug cost rather than a flat copay,” Dr Dusetzina said.

She noted that while this study did account for payments by commercial health plans, it did not account for spending by Medicaid and Medicare, which may differ. In addition, only the products that were dispensed and reimbursed by commercial health plans were included, which may have excluded rarely used or recently approved products.

Prescription medications

Photo courtesy of the CDC

New orally administered cancer drugs are much more expensive in their first year on the market than such drugs launched about 15 years ago, according to a study published in JAMA Oncology.

The research showed that a month of treatment with orally administered cancer drugs introduced in 2014 was, on average, 6 times more expensive at launch than monthly treatment costs for such drugs introduced in 2000, after adjusting for inflation.

In addition, most existing therapies had substantial price increases from the time they were launched to 2014.

“The major trend here is that these products are just getting more expensive over time,” said study author Stacie Dusetzina, PhD, of the University of North Carolina at Chapel Hill.

For this study, Dr Dusetzina evaluated what commercial health insurance companies and patients paid for prescription fills—before rebates and discounts—for 32 orally administered cancer drugs from 2000 to 2014. The information came from the TruvenHealth MarketScan Commercial Claims and Encounters database.

The data showed that orally administered drugs approved in 2000 cost an average of $1869 (95% CI, $1648-$2121) per month, compared to $11,325 (95% CI, $10 989-$11 671) for those approved in 2014.

When Dr Dusetzina compared changes in spending by year from a product’s launch to 2014, she observed increases in most of the drugs studied.

The drugs with the largest increases in monthly spending were thalidomide, which increased from $1869 to $7564 ($5695) and imatinib, which increased from $3346 to $8479 ($5133).

However, 2 drugs showed decreases in mean monthly spending between their launch and 2014. Monthly spending for lenalidomide decreased from $10,109 to $9640 ($469), and monthly spending for vorinostat decreased from $9755 to $7592 ($2163).

Dr Dusetzina pointed out that the amount patients pay for these drugs depends on their healthcare benefits. However, the high prices are being passed along to patients more and more, potentially affecting the patients’ access to these drugs.

“Patients are increasingly taking on the burden of paying for these high-cost specialty drugs as plans move toward use of higher deductibles and co-insurance—where a patient will pay a percentage of the drug cost rather than a flat copay,” Dr Dusetzina said.

She noted that while this study did account for payments by commercial health plans, it did not account for spending by Medicaid and Medicare, which may differ. In addition, only the products that were dispensed and reimbursed by commercial health plans were included, which may have excluded rarely used or recently approved products.

Prescription medications

Photo courtesy of the CDC

New orally administered cancer drugs are much more expensive in their first year on the market than such drugs launched about 15 years ago, according to a study published in JAMA Oncology.

The research showed that a month of treatment with orally administered cancer drugs introduced in 2014 was, on average, 6 times more expensive at launch than monthly treatment costs for such drugs introduced in 2000, after adjusting for inflation.

In addition, most existing therapies had substantial price increases from the time they were launched to 2014.

“The major trend here is that these products are just getting more expensive over time,” said study author Stacie Dusetzina, PhD, of the University of North Carolina at Chapel Hill.

For this study, Dr Dusetzina evaluated what commercial health insurance companies and patients paid for prescription fills—before rebates and discounts—for 32 orally administered cancer drugs from 2000 to 2014. The information came from the TruvenHealth MarketScan Commercial Claims and Encounters database.

The data showed that orally administered drugs approved in 2000 cost an average of $1869 (95% CI, $1648-$2121) per month, compared to $11,325 (95% CI, $10 989-$11 671) for those approved in 2014.

When Dr Dusetzina compared changes in spending by year from a product’s launch to 2014, she observed increases in most of the drugs studied.

The drugs with the largest increases in monthly spending were thalidomide, which increased from $1869 to $7564 ($5695) and imatinib, which increased from $3346 to $8479 ($5133).

However, 2 drugs showed decreases in mean monthly spending between their launch and 2014. Monthly spending for lenalidomide decreased from $10,109 to $9640 ($469), and monthly spending for vorinostat decreased from $9755 to $7592 ($2163).

Dr Dusetzina pointed out that the amount patients pay for these drugs depends on their healthcare benefits. However, the high prices are being passed along to patients more and more, potentially affecting the patients’ access to these drugs.

“Patients are increasingly taking on the burden of paying for these high-cost specialty drugs as plans move toward use of higher deductibles and co-insurance—where a patient will pay a percentage of the drug cost rather than a flat copay,” Dr Dusetzina said.

She noted that while this study did account for payments by commercial health plans, it did not account for spending by Medicaid and Medicare, which may differ. In addition, only the products that were dispensed and reimbursed by commercial health plans were included, which may have excluded rarely used or recently approved products.

Adding ixazomib to lenalidomide and dexamethasone was associated with longer progression-free survival and limited additional toxic effects in patients with multiple myeloma, based on the published phase 3 results of the TOURMALINE trial.

The double-blind, placebo-controlled trial included 722 patients who had relapsed, refractory, or relapsed and refractory multiple myeloma and were randomly assigned to receive the oral proteasome inhibitor plus lenalidomide-dexamethasone or placebo plus lenalidomide-dexamethasone (len-dex), according to Dr. Philippe Moreau of University Hospital Hôtel

Dieu, Nantes, France, and his colleagues in the TOURMALINE-MM1 Study Group.

At a median follow-up of nearly 14.7 months, median progression-free survival was 20.6 months in the ixazomib plus len-dex group and 14.7 months in the placebo plus len-dex group, a significant difference for ixazomib with a 0.74 hazard ratio for disease progression or death (P = .01). The benefit was noted for all prespecified patient subgroups, including patients with high-risk cytogenetic abnormalities. The overall rates of response were 78% in the ixazomib plus len-dex group and 72% in the placebo plus len-dex group, and the corresponding rates of complete response plus very good partial response were 48% and 39%, respectively. At a median follow-up of approximately 23 months, the median duration of response was 20.5 months for ixazomib plus len-dex and 15 months for len-dex alone, the researchers reported (N Engl J Med. 2016;374:1621-34. doi: 10.1056/NEJMoa1516282).

The rates of serious adverse events were 47% in the ixazomib plus len-dex group and 49% in the placebo plus len-dex group; the rates of death during the study period were 4% and 6%, respectively.

The results of the trial also were presented at the annual meeting of the American Society of Hematology, where Dr. Shaji Kumar, one the study investigators, discussed the implications of the TOURMALINE results in a video interview.

The study was sponsored by Millennium Pharmaceuticals, the makers of ixazomib (Ninlaro). Dr. Moreau reports receiving fees for serving on advisory boards for Millennium Pharmaceuticals and several other drug companies.

[email protected]

On Twitter @maryjodales

Adding ixazomib to lenalidomide and dexamethasone was associated with longer progression-free survival and limited additional toxic effects in patients with multiple myeloma, based on the published phase 3 results of the TOURMALINE trial.

The double-blind, placebo-controlled trial included 722 patients who had relapsed, refractory, or relapsed and refractory multiple myeloma and were randomly assigned to receive the oral proteasome inhibitor plus lenalidomide-dexamethasone or placebo plus lenalidomide-dexamethasone (len-dex), according to Dr. Philippe Moreau of University Hospital Hôtel

Dieu, Nantes, France, and his colleagues in the TOURMALINE-MM1 Study Group.

At a median follow-up of nearly 14.7 months, median progression-free survival was 20.6 months in the ixazomib plus len-dex group and 14.7 months in the placebo plus len-dex group, a significant difference for ixazomib with a 0.74 hazard ratio for disease progression or death (P = .01). The benefit was noted for all prespecified patient subgroups, including patients with high-risk cytogenetic abnormalities. The overall rates of response were 78% in the ixazomib plus len-dex group and 72% in the placebo plus len-dex group, and the corresponding rates of complete response plus very good partial response were 48% and 39%, respectively. At a median follow-up of approximately 23 months, the median duration of response was 20.5 months for ixazomib plus len-dex and 15 months for len-dex alone, the researchers reported (N Engl J Med. 2016;374:1621-34. doi: 10.1056/NEJMoa1516282).

The rates of serious adverse events were 47% in the ixazomib plus len-dex group and 49% in the placebo plus len-dex group; the rates of death during the study period were 4% and 6%, respectively.

The results of the trial also were presented at the annual meeting of the American Society of Hematology, where Dr. Shaji Kumar, one the study investigators, discussed the implications of the TOURMALINE results in a video interview.

The study was sponsored by Millennium Pharmaceuticals, the makers of ixazomib (Ninlaro). Dr. Moreau reports receiving fees for serving on advisory boards for Millennium Pharmaceuticals and several other drug companies.

[email protected]

On Twitter @maryjodales

Adding ixazomib to lenalidomide and dexamethasone was associated with longer progression-free survival and limited additional toxic effects in patients with multiple myeloma, based on the published phase 3 results of the TOURMALINE trial.

The double-blind, placebo-controlled trial included 722 patients who had relapsed, refractory, or relapsed and refractory multiple myeloma and were randomly assigned to receive the oral proteasome inhibitor plus lenalidomide-dexamethasone or placebo plus lenalidomide-dexamethasone (len-dex), according to Dr. Philippe Moreau of University Hospital Hôtel

Dieu, Nantes, France, and his colleagues in the TOURMALINE-MM1 Study Group.

At a median follow-up of nearly 14.7 months, median progression-free survival was 20.6 months in the ixazomib plus len-dex group and 14.7 months in the placebo plus len-dex group, a significant difference for ixazomib with a 0.74 hazard ratio for disease progression or death (P = .01). The benefit was noted for all prespecified patient subgroups, including patients with high-risk cytogenetic abnormalities. The overall rates of response were 78% in the ixazomib plus len-dex group and 72% in the placebo plus len-dex group, and the corresponding rates of complete response plus very good partial response were 48% and 39%, respectively. At a median follow-up of approximately 23 months, the median duration of response was 20.5 months for ixazomib plus len-dex and 15 months for len-dex alone, the researchers reported (N Engl J Med. 2016;374:1621-34. doi: 10.1056/NEJMoa1516282).

The rates of serious adverse events were 47% in the ixazomib plus len-dex group and 49% in the placebo plus len-dex group; the rates of death during the study period were 4% and 6%, respectively.

The results of the trial also were presented at the annual meeting of the American Society of Hematology, where Dr. Shaji Kumar, one the study investigators, discussed the implications of the TOURMALINE results in a video interview.

The study was sponsored by Millennium Pharmaceuticals, the makers of ixazomib (Ninlaro). Dr. Moreau reports receiving fees for serving on advisory boards for Millennium Pharmaceuticals and several other drug companies.

[email protected]

On Twitter @maryjodales

Gurmukh Singh, MD, PhD

Photo by Phil Jones

A series of tests used to diagnose and monitor monoclonal gammopathies may fail to benefit patients while increasing healthcare costs, according to research published in The American Journal of Clinical Pathology.

Researchers conducted a review of all tests for investigating monoclonal gammopathies at a single institution and found that fewer than half of the serum immunofixation and serum free light chain assays performed were actually warranted.

According to the researchers, these results suggest that, instead of ordering individual tests, physicians should request an initial workup for monoclonal gammopathy.

Once pathologists interpret results of a screening serum protein electrophoresis (SPEP) and examine the patient’s medical record, they can decide what, if any, additional tests are needed.

“These are stepwise things,” said study author Gurmukh Singh, MD, PhD, of the Medical College of Georgia at Augusta University.

“If it’s a new patient, do this. If it’s a known patient, do that. Results drive it. That will reduce the number of tests that are done without in any way being of detriment to the patient or the quality of care.”

To conduct this study, Dr Singh and his colleagues reviewed the history of 237 patients, ages 19 to 87, who had a total of 1503 episodes of testing.

In addition to SPEP, many patients had serum immunofixation electrophoresis and/or serum free light chain assays.

But the researchers found that only 46% of the serum immunofixation and 42% of the serum free light chain assays were warranted.

The 2 tests were ordered multiple times in patients in whom M-protein was easily detected with SPEP. In fact, for most patients with measurable levels of M-protein, SPEP can be used to follow the course of the disease and treatment, the researchers said.

“About 40% to 50% of the second tests are not needed or adding value,” Dr Sing stressed.

In fact, he and his colleagues estimated that putting an end to unnecessary testing would have saved $64,182.95 per year in healthcare costs at this institution.

Therefore, the researchers propose using an algorithm that would put more of the decision-making in the hands of pathologists interpreting the tests.

An example of when serum immunofixation and serum free light chain assays should be done at least once is in a new patient when M-protein is first found, Dr Singh said. The additional tests might also be beneficial for patients under treatment for multiple myeloma, to ensure there are no trace amounts left of the abnormal protein.

Dr Singh added that testing patterns similar to those observed in this study are in play in hospitals across the US. However, a protocol similar to the one he is proposing has safely enabled up to a 60% reduction in the volume of second tests at a Missouri hospital where it has been in use for about 8 years.

“It’s better for patients and for healthcare delivery in general,” Dr Singh said. “Why spend money that you don’t need to spend when you are not gaining information that will benefit the patient’s outcome?”

Gurmukh Singh, MD, PhD

Photo by Phil Jones

A series of tests used to diagnose and monitor monoclonal gammopathies may fail to benefit patients while increasing healthcare costs, according to research published in The American Journal of Clinical Pathology.

Researchers conducted a review of all tests for investigating monoclonal gammopathies at a single institution and found that fewer than half of the serum immunofixation and serum free light chain assays performed were actually warranted.

According to the researchers, these results suggest that, instead of ordering individual tests, physicians should request an initial workup for monoclonal gammopathy.

Once pathologists interpret results of a screening serum protein electrophoresis (SPEP) and examine the patient’s medical record, they can decide what, if any, additional tests are needed.

“These are stepwise things,” said study author Gurmukh Singh, MD, PhD, of the Medical College of Georgia at Augusta University.

“If it’s a new patient, do this. If it’s a known patient, do that. Results drive it. That will reduce the number of tests that are done without in any way being of detriment to the patient or the quality of care.”

To conduct this study, Dr Singh and his colleagues reviewed the history of 237 patients, ages 19 to 87, who had a total of 1503 episodes of testing.

In addition to SPEP, many patients had serum immunofixation electrophoresis and/or serum free light chain assays.

But the researchers found that only 46% of the serum immunofixation and 42% of the serum free light chain assays were warranted.

The 2 tests were ordered multiple times in patients in whom M-protein was easily detected with SPEP. In fact, for most patients with measurable levels of M-protein, SPEP can be used to follow the course of the disease and treatment, the researchers said.

“About 40% to 50% of the second tests are not needed or adding value,” Dr Sing stressed.

In fact, he and his colleagues estimated that putting an end to unnecessary testing would have saved $64,182.95 per year in healthcare costs at this institution.

Therefore, the researchers propose using an algorithm that would put more of the decision-making in the hands of pathologists interpreting the tests.

An example of when serum immunofixation and serum free light chain assays should be done at least once is in a new patient when M-protein is first found, Dr Singh said. The additional tests might also be beneficial for patients under treatment for multiple myeloma, to ensure there are no trace amounts left of the abnormal protein.

Dr Singh added that testing patterns similar to those observed in this study are in play in hospitals across the US. However, a protocol similar to the one he is proposing has safely enabled up to a 60% reduction in the volume of second tests at a Missouri hospital where it has been in use for about 8 years.

“It’s better for patients and for healthcare delivery in general,” Dr Singh said. “Why spend money that you don’t need to spend when you are not gaining information that will benefit the patient’s outcome?”

Gurmukh Singh, MD, PhD

Photo by Phil Jones

A series of tests used to diagnose and monitor monoclonal gammopathies may fail to benefit patients while increasing healthcare costs, according to research published in The American Journal of Clinical Pathology.

Researchers conducted a review of all tests for investigating monoclonal gammopathies at a single institution and found that fewer than half of the serum immunofixation and serum free light chain assays performed were actually warranted.

According to the researchers, these results suggest that, instead of ordering individual tests, physicians should request an initial workup for monoclonal gammopathy.

Once pathologists interpret results of a screening serum protein electrophoresis (SPEP) and examine the patient’s medical record, they can decide what, if any, additional tests are needed.

“These are stepwise things,” said study author Gurmukh Singh, MD, PhD, of the Medical College of Georgia at Augusta University.

“If it’s a new patient, do this. If it’s a known patient, do that. Results drive it. That will reduce the number of tests that are done without in any way being of detriment to the patient or the quality of care.”

To conduct this study, Dr Singh and his colleagues reviewed the history of 237 patients, ages 19 to 87, who had a total of 1503 episodes of testing.

In addition to SPEP, many patients had serum immunofixation electrophoresis and/or serum free light chain assays.

But the researchers found that only 46% of the serum immunofixation and 42% of the serum free light chain assays were warranted.

The 2 tests were ordered multiple times in patients in whom M-protein was easily detected with SPEP. In fact, for most patients with measurable levels of M-protein, SPEP can be used to follow the course of the disease and treatment, the researchers said.

“About 40% to 50% of the second tests are not needed or adding value,” Dr Sing stressed.

In fact, he and his colleagues estimated that putting an end to unnecessary testing would have saved $64,182.95 per year in healthcare costs at this institution.

Therefore, the researchers propose using an algorithm that would put more of the decision-making in the hands of pathologists interpreting the tests.

An example of when serum immunofixation and serum free light chain assays should be done at least once is in a new patient when M-protein is first found, Dr Singh said. The additional tests might also be beneficial for patients under treatment for multiple myeloma, to ensure there are no trace amounts left of the abnormal protein.

Dr Singh added that testing patterns similar to those observed in this study are in play in hospitals across the US. However, a protocol similar to the one he is proposing has safely enabled up to a 60% reduction in the volume of second tests at a Missouri hospital where it has been in use for about 8 years.

“It’s better for patients and for healthcare delivery in general,” Dr Singh said. “Why spend money that you don’t need to spend when you are not gaining information that will benefit the patient’s outcome?”