Multiple Myeloma

Doctor and cancer patient

Credit: NCI and

Mathews Media Group

A new study suggests many patients in cancer centers do not experience a dignified death.

Study investigators surveyed physicians and nurses in 16 hospitals belonging to 10 cancer centers in Baden-Württemberg, Germany.

The results revealed a need for cancer centers to invest more in palliative care services, adequate rooms for dying patients, staff training in end-of-life care, and advance-care-planning standards.

Karin Jors, of the University Medical Center Freiburg, and her colleagues reported these findings in Cancer.

Previous research has shown that hospitals are often ill-prepared to provide care for dying patients.

To investigate whether the circumstances for dying on cancer center wards allow for a dignified death, Jors and her colleagues surveyed physicians and nurses in German cancer centers.

Among 1131 survey respondents, 57% believed that patients could die with dignity on their ward.

Half of the surveyed staff members indicated that they rarely have enough time to care for dying patients, and 55% found the rooms available for dying patients unsatisfactory.

Only 19% of respondents felt they had been well-prepared to care for dying patients, and only 6% of physicians felt that way.

On the other hand, physicians perceived the circumstances for dying patients much more positively than nurses, especially regarding communication and life-prolonging measures.

While 72% of physicians reported that patients can usually die a dignified death on their ward, only 52% of nurses shared this opinion.

Palliative care staff reported much better conditions for dying patients than staff from other wards, with 95% of palliative care staff indicating that patients die with dignity on their wards.

“In our aging society, it is predicted that the number of hospital deaths will continue to rise in the coming years, and many of these deaths will be attributable to cancer,” Jors said.

“For this reason, it is particularly important that cancer centers strive to create a comfortable, dignified experience for dying patients and their families. Above all, this requires that staff members are provided with the adequate resources to care for these patients.”

The investigators therefore encourage the integration of palliative care into standard oncology care, beginning as early as diagnosis. They also believe physicians and nurses would benefit from increased education and training in end-of-life care.

Doctor and cancer patient

Credit: NCI and

Mathews Media Group

A new study suggests many patients in cancer centers do not experience a dignified death.

Study investigators surveyed physicians and nurses in 16 hospitals belonging to 10 cancer centers in Baden-Württemberg, Germany.

The results revealed a need for cancer centers to invest more in palliative care services, adequate rooms for dying patients, staff training in end-of-life care, and advance-care-planning standards.

Karin Jors, of the University Medical Center Freiburg, and her colleagues reported these findings in Cancer.

Previous research has shown that hospitals are often ill-prepared to provide care for dying patients.

To investigate whether the circumstances for dying on cancer center wards allow for a dignified death, Jors and her colleagues surveyed physicians and nurses in German cancer centers.

Among 1131 survey respondents, 57% believed that patients could die with dignity on their ward.

Half of the surveyed staff members indicated that they rarely have enough time to care for dying patients, and 55% found the rooms available for dying patients unsatisfactory.

Only 19% of respondents felt they had been well-prepared to care for dying patients, and only 6% of physicians felt that way.

On the other hand, physicians perceived the circumstances for dying patients much more positively than nurses, especially regarding communication and life-prolonging measures.

While 72% of physicians reported that patients can usually die a dignified death on their ward, only 52% of nurses shared this opinion.

Palliative care staff reported much better conditions for dying patients than staff from other wards, with 95% of palliative care staff indicating that patients die with dignity on their wards.

“In our aging society, it is predicted that the number of hospital deaths will continue to rise in the coming years, and many of these deaths will be attributable to cancer,” Jors said.

“For this reason, it is particularly important that cancer centers strive to create a comfortable, dignified experience for dying patients and their families. Above all, this requires that staff members are provided with the adequate resources to care for these patients.”

The investigators therefore encourage the integration of palliative care into standard oncology care, beginning as early as diagnosis. They also believe physicians and nurses would benefit from increased education and training in end-of-life care.

Doctor and cancer patient

Credit: NCI and

Mathews Media Group

A new study suggests many patients in cancer centers do not experience a dignified death.

Study investigators surveyed physicians and nurses in 16 hospitals belonging to 10 cancer centers in Baden-Württemberg, Germany.

The results revealed a need for cancer centers to invest more in palliative care services, adequate rooms for dying patients, staff training in end-of-life care, and advance-care-planning standards.

Karin Jors, of the University Medical Center Freiburg, and her colleagues reported these findings in Cancer.

Previous research has shown that hospitals are often ill-prepared to provide care for dying patients.

To investigate whether the circumstances for dying on cancer center wards allow for a dignified death, Jors and her colleagues surveyed physicians and nurses in German cancer centers.

Among 1131 survey respondents, 57% believed that patients could die with dignity on their ward.

Half of the surveyed staff members indicated that they rarely have enough time to care for dying patients, and 55% found the rooms available for dying patients unsatisfactory.

Only 19% of respondents felt they had been well-prepared to care for dying patients, and only 6% of physicians felt that way.

On the other hand, physicians perceived the circumstances for dying patients much more positively than nurses, especially regarding communication and life-prolonging measures.

While 72% of physicians reported that patients can usually die a dignified death on their ward, only 52% of nurses shared this opinion.

Palliative care staff reported much better conditions for dying patients than staff from other wards, with 95% of palliative care staff indicating that patients die with dignity on their wards.

“In our aging society, it is predicted that the number of hospital deaths will continue to rise in the coming years, and many of these deaths will be attributable to cancer,” Jors said.

“For this reason, it is particularly important that cancer centers strive to create a comfortable, dignified experience for dying patients and their families. Above all, this requires that staff members are provided with the adequate resources to care for these patients.”

The investigators therefore encourage the integration of palliative care into standard oncology care, beginning as early as diagnosis. They also believe physicians and nurses would benefit from increased education and training in end-of-life care.

A drug that targets mitochondrial function is largely safe and can be active in heavily pretreated patients with hematologic malignancies, a phase 1 trial indicates.

The drug, CPI-613, prompted responses in only 4 of 21 evaluable patients. However, 2 of those responses lasted more than 2 years.

CPI-613 was generally well-tolerated and did not induce bone marrow suppression. Four patients experienced renal failure, but it was reversed in 3 of them.

These results appear in Clinical Cancer Research.

“This drug is selectively taken up by cancer cells and then shuts down the production of energy in the mitochondria,” said study author Timothy Pardee, MD, PhD, of the Comprehensive Cancer Center of Wake Forest University in Winston-Salem, North Carolina.

“This is the first drug to inhibit mitochondria in this way, and, if it proves effective in further clinical trials, it will open up a whole new approach to fighting cancer.”

Dr Pardee and his colleagues evaluated CPI-613 in 26 patients with relapsed or refractory hematologic malignancies—11 with acute myeloid leukemia, 6 with non-Hodgkin lymphoma, 4 with multiple myeloma, 4 with myelodysplastic syndrome (MDS), and 1 with Hodgkin lymphoma.

The median patient age was 65 years (range, 19-81), and the median number of prior therapies was 3 (range, 1-9).

Treatment dosing and toxicity

Patients received CPI-613 as a 2-hour infusion on days 1 and 4 for 3 weeks every 28 days.

When the infusion time was shortened to 1 hour, renal failure occurred in 2 patients. At 3780 mg/m², there were 2 dose-limiting toxicities. There were no such toxicities at a dose of 2940 mg/m² over 2 hours, so this was considered the maximum-tolerated dose.

The following grade 2 or higher toxicities were probably or definitely related to treatment: nausea (1 grade 2), vomiting (1 grade 3), diarrhea (3 grade 2), proteinuria (1 grade 2), renal failure (4 grade 3), hypotension (1 grade 2), hypocalcemia (1 grade 2), hypoalbuminemia (1 grade 2), and hyperkalemia (1 grade 3).

Renal failure was resolved in 3 of the 4 patients. The remaining patient chose hospice care.

Response data

Five patients discontinued treatment—1 refused therapy, 1 acquired an infection, and 3 developed acute kidney failure.

Of the 21 patients evaluable for response, 4 had an objective response following CPI-613 treatment, and 2 had prolonged stable disease.

One patient with MDS achieved a complete response that has been maintained for more than 3 years. A patient with acute myeloid leukemia achieved a morphologically leukemia-free state, went on to transplant, and is still alive and leukemia-free.

A patient with Burkitt lymphoma achieved a partial response after 3 cycles of therapy that was maintained for 17 cycles. She discontinued CPI-613 to have her residual disease resected, and has not received any treatment since. She is now disease-free more than 12 months later.

A patient with cutaneous T-cell lymphoma achieved a partial response that has been sustained for more than 2 years. At her request, she started to receive continuous therapy (no 1-week rest period), and she remains on treatment without significant toxicities and no evidence of marrow suppression.

The 2 patients with prolonged stable disease had MDS. Their disease was stable for 8 and 12 cycles, respectively. Two patients with multiple myeloma also initially had stable disease, but they progressed after 2 and 4 cycles, respectively.

Two patients died from disease progression while on study.

The researchers said these results suggest that agents targeting mitochondrial metabolism can be safe and active in hematologic malignancies. A phase 2 trial of CPI-613 is now underway.

Support for the phase 1 trial was provided by National Cancer Institute grants P30CA012197 and 1K08CA169809, the Doug Coley Foundation for Leukemia Research, the Frances P. Tutwiler Fund, The MacKay Foundation for Cancer Research, and Cornerstone Pharmaceuticals, which manufactured and provided CPI-613.

A drug that targets mitochondrial function is largely safe and can be active in heavily pretreated patients with hematologic malignancies, a phase 1 trial indicates.

The drug, CPI-613, prompted responses in only 4 of 21 evaluable patients. However, 2 of those responses lasted more than 2 years.

CPI-613 was generally well-tolerated and did not induce bone marrow suppression. Four patients experienced renal failure, but it was reversed in 3 of them.

These results appear in Clinical Cancer Research.

“This drug is selectively taken up by cancer cells and then shuts down the production of energy in the mitochondria,” said study author Timothy Pardee, MD, PhD, of the Comprehensive Cancer Center of Wake Forest University in Winston-Salem, North Carolina.

“This is the first drug to inhibit mitochondria in this way, and, if it proves effective in further clinical trials, it will open up a whole new approach to fighting cancer.”

Dr Pardee and his colleagues evaluated CPI-613 in 26 patients with relapsed or refractory hematologic malignancies—11 with acute myeloid leukemia, 6 with non-Hodgkin lymphoma, 4 with multiple myeloma, 4 with myelodysplastic syndrome (MDS), and 1 with Hodgkin lymphoma.

The median patient age was 65 years (range, 19-81), and the median number of prior therapies was 3 (range, 1-9).

Treatment dosing and toxicity

Patients received CPI-613 as a 2-hour infusion on days 1 and 4 for 3 weeks every 28 days.

When the infusion time was shortened to 1 hour, renal failure occurred in 2 patients. At 3780 mg/m², there were 2 dose-limiting toxicities. There were no such toxicities at a dose of 2940 mg/m² over 2 hours, so this was considered the maximum-tolerated dose.

The following grade 2 or higher toxicities were probably or definitely related to treatment: nausea (1 grade 2), vomiting (1 grade 3), diarrhea (3 grade 2), proteinuria (1 grade 2), renal failure (4 grade 3), hypotension (1 grade 2), hypocalcemia (1 grade 2), hypoalbuminemia (1 grade 2), and hyperkalemia (1 grade 3).

Renal failure was resolved in 3 of the 4 patients. The remaining patient chose hospice care.

Response data

Five patients discontinued treatment—1 refused therapy, 1 acquired an infection, and 3 developed acute kidney failure.

Of the 21 patients evaluable for response, 4 had an objective response following CPI-613 treatment, and 2 had prolonged stable disease.

One patient with MDS achieved a complete response that has been maintained for more than 3 years. A patient with acute myeloid leukemia achieved a morphologically leukemia-free state, went on to transplant, and is still alive and leukemia-free.

A patient with Burkitt lymphoma achieved a partial response after 3 cycles of therapy that was maintained for 17 cycles. She discontinued CPI-613 to have her residual disease resected, and has not received any treatment since. She is now disease-free more than 12 months later.

A patient with cutaneous T-cell lymphoma achieved a partial response that has been sustained for more than 2 years. At her request, she started to receive continuous therapy (no 1-week rest period), and she remains on treatment without significant toxicities and no evidence of marrow suppression.

The 2 patients with prolonged stable disease had MDS. Their disease was stable for 8 and 12 cycles, respectively. Two patients with multiple myeloma also initially had stable disease, but they progressed after 2 and 4 cycles, respectively.

Two patients died from disease progression while on study.

The researchers said these results suggest that agents targeting mitochondrial metabolism can be safe and active in hematologic malignancies. A phase 2 trial of CPI-613 is now underway.

Support for the phase 1 trial was provided by National Cancer Institute grants P30CA012197 and 1K08CA169809, the Doug Coley Foundation for Leukemia Research, the Frances P. Tutwiler Fund, The MacKay Foundation for Cancer Research, and Cornerstone Pharmaceuticals, which manufactured and provided CPI-613.

A drug that targets mitochondrial function is largely safe and can be active in heavily pretreated patients with hematologic malignancies, a phase 1 trial indicates.

The drug, CPI-613, prompted responses in only 4 of 21 evaluable patients. However, 2 of those responses lasted more than 2 years.

CPI-613 was generally well-tolerated and did not induce bone marrow suppression. Four patients experienced renal failure, but it was reversed in 3 of them.

These results appear in Clinical Cancer Research.

“This drug is selectively taken up by cancer cells and then shuts down the production of energy in the mitochondria,” said study author Timothy Pardee, MD, PhD, of the Comprehensive Cancer Center of Wake Forest University in Winston-Salem, North Carolina.

“This is the first drug to inhibit mitochondria in this way, and, if it proves effective in further clinical trials, it will open up a whole new approach to fighting cancer.”

Dr Pardee and his colleagues evaluated CPI-613 in 26 patients with relapsed or refractory hematologic malignancies—11 with acute myeloid leukemia, 6 with non-Hodgkin lymphoma, 4 with multiple myeloma, 4 with myelodysplastic syndrome (MDS), and 1 with Hodgkin lymphoma.

The median patient age was 65 years (range, 19-81), and the median number of prior therapies was 3 (range, 1-9).

Treatment dosing and toxicity

Patients received CPI-613 as a 2-hour infusion on days 1 and 4 for 3 weeks every 28 days.

When the infusion time was shortened to 1 hour, renal failure occurred in 2 patients. At 3780 mg/m², there were 2 dose-limiting toxicities. There were no such toxicities at a dose of 2940 mg/m² over 2 hours, so this was considered the maximum-tolerated dose.

The following grade 2 or higher toxicities were probably or definitely related to treatment: nausea (1 grade 2), vomiting (1 grade 3), diarrhea (3 grade 2), proteinuria (1 grade 2), renal failure (4 grade 3), hypotension (1 grade 2), hypocalcemia (1 grade 2), hypoalbuminemia (1 grade 2), and hyperkalemia (1 grade 3).

Renal failure was resolved in 3 of the 4 patients. The remaining patient chose hospice care.

Response data

Five patients discontinued treatment—1 refused therapy, 1 acquired an infection, and 3 developed acute kidney failure.

Of the 21 patients evaluable for response, 4 had an objective response following CPI-613 treatment, and 2 had prolonged stable disease.

One patient with MDS achieved a complete response that has been maintained for more than 3 years. A patient with acute myeloid leukemia achieved a morphologically leukemia-free state, went on to transplant, and is still alive and leukemia-free.

A patient with Burkitt lymphoma achieved a partial response after 3 cycles of therapy that was maintained for 17 cycles. She discontinued CPI-613 to have her residual disease resected, and has not received any treatment since. She is now disease-free more than 12 months later.

A patient with cutaneous T-cell lymphoma achieved a partial response that has been sustained for more than 2 years. At her request, she started to receive continuous therapy (no 1-week rest period), and she remains on treatment without significant toxicities and no evidence of marrow suppression.

The 2 patients with prolonged stable disease had MDS. Their disease was stable for 8 and 12 cycles, respectively. Two patients with multiple myeloma also initially had stable disease, but they progressed after 2 and 4 cycles, respectively.

Two patients died from disease progression while on study.

The researchers said these results suggest that agents targeting mitochondrial metabolism can be safe and active in hematologic malignancies. A phase 2 trial of CPI-613 is now underway.

Support for the phase 1 trial was provided by National Cancer Institute grants P30CA012197 and 1K08CA169809, the Doug Coley Foundation for Leukemia Research, the Frances P. Tutwiler Fund, The MacKay Foundation for Cancer Research, and Cornerstone Pharmaceuticals, which manufactured and provided CPI-613.

Prescription medications

Credit: CDC

In the phase 3 FIRST trial, a regimen of continuous lenalidomide and low-dose dexamethasone conferred the greatest progression-free survival (PFS) benefit among patients with newly diagnosed multiple myeloma (MM).

Patients who received this regimen had a significantly longer median PFS than patients who received a fixed course of lenalidomide plus low-dose dexamethasone or a combination of melphalan, prednisone, and thalidomide.

Results of this study appear in The New England Journal of Medicine. The research was previously presented at the 2013 ASH Annual Meeting. The study was supported by Intergroupe Francophone du Myélome and Celgene Corporation, the makers of lenalidomide.

Thierry Facon, MD, of Hôpital Claude Huriez in Lille, France, and his colleagues enrolled 1623 patients on this study. They were newly diagnosed with MM and not eligible for stem cell transplant.

Patients were randomized to receive lenalidomide and dexamethasone (Rd) in 28-day cycles until disease progression (n=535), to 18 cycles of lenalidomide and dexamethasone (Rd18) for 72 weeks (n=541), or to melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

Response rates were significantly better with continuous Rd (75%) and with Rd18 (73%) than with MPT (62%, P<0.001 for both comparisons). Complete response rates were 15%, 14%, and 9%, respectively.

The median duration of response was 35.0 months with continuous Rd compared with 22.3 months for MPT (hazard ratio [HR]=0.63, P<0.001) and 22.1 months for Rd18 (HR=0.60, P<0.001).

The median time to disease progression was 32.5 months for patients receiving continuous Rd compared with 23.9 months (HR=0.68, P<0.001) for MPT and 21.9 months for Rd18 (HR=0.62, P<0.001).

The median PFS was 25.5 months with continuous Rd, 20.7 months with Rd18, and 21.2 months with MPT. This resulted in a 28% reduction in the risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (HR=0.72, P<0.001) and a 30% reduction compared with Rd18 (HR=0.70, P<0.001).

The pre-planned interim analysis of overall survival demonstrated a 22% reduction in the risk of death for continuous Rd vs MPT (HR=0.78, P=0.02), but the difference did not cross the pre-specified superiority boundary (P<0.0096).

At the time of the analysis (May 24, 2013), 23% of patients in the continuous Rd arm were still on therapy.

Grade 3/4 adverse events that occurred in at least 8% of patients in the continuous Rd arm, Rd18 arm, or MPT arm included neutropenia (28%, 26%, 45%, respectively), anemia (18%, 16%, 19%), thrombocytopenia (8%, 8%,11%), febrile neutropenia (1%, 3%, 3%), leukopenia (5%, 6%, 10%), infection (29%, 22%, 17%), pneumonia (8%, 8%, 6%), deep vein thrombosis and/or pulmonary embolism (8%, 6%, 5%), asthenia (8%, 6%, 6%), fatigue (7%, 9%, 6%), and peripheral sensory neuropathy (1%, <1%, 9%).

Grade 3/4 cardiac disorders occurred in 12% of patients in the continuous Rd arm, 7% in the Rd18 arm, and 9% in the MPT arm.

The incidence of invasive second primary malignancies was 3% in patients taking continuous Rd, 6% in patients taking Rd18, and 5% in those taking MPT. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.

Prescription medications

Credit: CDC

In the phase 3 FIRST trial, a regimen of continuous lenalidomide and low-dose dexamethasone conferred the greatest progression-free survival (PFS) benefit among patients with newly diagnosed multiple myeloma (MM).

Patients who received this regimen had a significantly longer median PFS than patients who received a fixed course of lenalidomide plus low-dose dexamethasone or a combination of melphalan, prednisone, and thalidomide.

Results of this study appear in The New England Journal of Medicine. The research was previously presented at the 2013 ASH Annual Meeting. The study was supported by Intergroupe Francophone du Myélome and Celgene Corporation, the makers of lenalidomide.

Thierry Facon, MD, of Hôpital Claude Huriez in Lille, France, and his colleagues enrolled 1623 patients on this study. They were newly diagnosed with MM and not eligible for stem cell transplant.

Patients were randomized to receive lenalidomide and dexamethasone (Rd) in 28-day cycles until disease progression (n=535), to 18 cycles of lenalidomide and dexamethasone (Rd18) for 72 weeks (n=541), or to melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

Response rates were significantly better with continuous Rd (75%) and with Rd18 (73%) than with MPT (62%, P<0.001 for both comparisons). Complete response rates were 15%, 14%, and 9%, respectively.

The median duration of response was 35.0 months with continuous Rd compared with 22.3 months for MPT (hazard ratio [HR]=0.63, P<0.001) and 22.1 months for Rd18 (HR=0.60, P<0.001).

The median time to disease progression was 32.5 months for patients receiving continuous Rd compared with 23.9 months (HR=0.68, P<0.001) for MPT and 21.9 months for Rd18 (HR=0.62, P<0.001).

The median PFS was 25.5 months with continuous Rd, 20.7 months with Rd18, and 21.2 months with MPT. This resulted in a 28% reduction in the risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (HR=0.72, P<0.001) and a 30% reduction compared with Rd18 (HR=0.70, P<0.001).

The pre-planned interim analysis of overall survival demonstrated a 22% reduction in the risk of death for continuous Rd vs MPT (HR=0.78, P=0.02), but the difference did not cross the pre-specified superiority boundary (P<0.0096).

At the time of the analysis (May 24, 2013), 23% of patients in the continuous Rd arm were still on therapy.

Grade 3/4 adverse events that occurred in at least 8% of patients in the continuous Rd arm, Rd18 arm, or MPT arm included neutropenia (28%, 26%, 45%, respectively), anemia (18%, 16%, 19%), thrombocytopenia (8%, 8%,11%), febrile neutropenia (1%, 3%, 3%), leukopenia (5%, 6%, 10%), infection (29%, 22%, 17%), pneumonia (8%, 8%, 6%), deep vein thrombosis and/or pulmonary embolism (8%, 6%, 5%), asthenia (8%, 6%, 6%), fatigue (7%, 9%, 6%), and peripheral sensory neuropathy (1%, <1%, 9%).

Grade 3/4 cardiac disorders occurred in 12% of patients in the continuous Rd arm, 7% in the Rd18 arm, and 9% in the MPT arm.

The incidence of invasive second primary malignancies was 3% in patients taking continuous Rd, 6% in patients taking Rd18, and 5% in those taking MPT. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.

Prescription medications

Credit: CDC

In the phase 3 FIRST trial, a regimen of continuous lenalidomide and low-dose dexamethasone conferred the greatest progression-free survival (PFS) benefit among patients with newly diagnosed multiple myeloma (MM).

Patients who received this regimen had a significantly longer median PFS than patients who received a fixed course of lenalidomide plus low-dose dexamethasone or a combination of melphalan, prednisone, and thalidomide.

Results of this study appear in The New England Journal of Medicine. The research was previously presented at the 2013 ASH Annual Meeting. The study was supported by Intergroupe Francophone du Myélome and Celgene Corporation, the makers of lenalidomide.

Thierry Facon, MD, of Hôpital Claude Huriez in Lille, France, and his colleagues enrolled 1623 patients on this study. They were newly diagnosed with MM and not eligible for stem cell transplant.

Patients were randomized to receive lenalidomide and dexamethasone (Rd) in 28-day cycles until disease progression (n=535), to 18 cycles of lenalidomide and dexamethasone (Rd18) for 72 weeks (n=541), or to melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

Response rates were significantly better with continuous Rd (75%) and with Rd18 (73%) than with MPT (62%, P<0.001 for both comparisons). Complete response rates were 15%, 14%, and 9%, respectively.

The median duration of response was 35.0 months with continuous Rd compared with 22.3 months for MPT (hazard ratio [HR]=0.63, P<0.001) and 22.1 months for Rd18 (HR=0.60, P<0.001).

The median time to disease progression was 32.5 months for patients receiving continuous Rd compared with 23.9 months (HR=0.68, P<0.001) for MPT and 21.9 months for Rd18 (HR=0.62, P<0.001).

The median PFS was 25.5 months with continuous Rd, 20.7 months with Rd18, and 21.2 months with MPT. This resulted in a 28% reduction in the risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (HR=0.72, P<0.001) and a 30% reduction compared with Rd18 (HR=0.70, P<0.001).

The pre-planned interim analysis of overall survival demonstrated a 22% reduction in the risk of death for continuous Rd vs MPT (HR=0.78, P=0.02), but the difference did not cross the pre-specified superiority boundary (P<0.0096).

At the time of the analysis (May 24, 2013), 23% of patients in the continuous Rd arm were still on therapy.

Grade 3/4 adverse events that occurred in at least 8% of patients in the continuous Rd arm, Rd18 arm, or MPT arm included neutropenia (28%, 26%, 45%, respectively), anemia (18%, 16%, 19%), thrombocytopenia (8%, 8%,11%), febrile neutropenia (1%, 3%, 3%), leukopenia (5%, 6%, 10%), infection (29%, 22%, 17%), pneumonia (8%, 8%, 6%), deep vein thrombosis and/or pulmonary embolism (8%, 6%, 5%), asthenia (8%, 6%, 6%), fatigue (7%, 9%, 6%), and peripheral sensory neuropathy (1%, <1%, 9%).

Grade 3/4 cardiac disorders occurred in 12% of patients in the continuous Rd arm, 7% in the Rd18 arm, and 9% in the MPT arm.

The incidence of invasive second primary malignancies was 3% in patients taking continuous Rd, 6% in patients taking Rd18, and 5% in those taking MPT. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.

Purpose: Multiple myeloma and solid tumor metastases can cause bone disease leading to skeletal-related events (SREs) such as bone pain, fractures, and spinal cord compression. Intravenous bisphosphonate therapy—which is indicated in such cases—can lead to osteonecrosis of the jaw and hypocalcemia further putting patients at risk for SREs. These risks can be avoided by dental evaluation before bisphosphonate therapy and calcium and vitamin D supplementation throughout treatment. Our study of veterans treated with bisphosphonates for bone metastases or multiple myeloma aimed to (1) assess screening dental evaluation prior to treatment; and (2) measure effectiveness of calcium and vitamin D supplementation.

Methods: We performed a retrospective chart review at the James J. Peters VAMC of 117 veterans with multiple myeloma or bone metastases who received intravenous bisphosphonate therapy between January 2008 and November 2013. Those receiving bisphosphonates for other morbidities such as osteoporosis or hypercalcemia were excluded. Those getting dental clearance before intravenous bisphosphonate therapy and supplementation of vitamin D and calcium were assessed. Charts were further reviewed to gather outcomes data on incidence of osteonecrosis of the jaw and SREs such as bone pain, pathologic and traumatic fractures, orthopedic surgery, spine or nerve root compression. These data were analyzed using descriptive statistics to calculate frequencies, mean/median, and proportions. Odds ratios were calculated to assess differences in SRE outcomes for those who received supplementation as compared to those who did not get supplementation with calcium and vitamin D.

Results: Of the 117 patients included in the study, 97% were males aged from 58 to 92 years. Of these, 55 (47%) had prostate cancer, 21 (17%) had multiple myeloma, and 16 (14%) had lung cancer. All patients receiving bisphosphonates for bone metastases had undergone a dental evaluation prior to starting therapy; none were reported to have osteonecrosis of the jaw. However, only 78% had vitamin D levels checked before therapy; 69% of these were vitamin D deficient and received vitamin D supplementation. Overall, rates of calcium and vitamin D supplementation were very low (34% and 41%, respectively). Fifty-four percent of the patients reported an SRE; 49% with bone pain, 13% with pathological fractures, 7% with traumatic fractures, and 8% with nerve root compression. Vitamin D supplementation significantly reduced the odds of an SRE for our patients (OR 0.37, 95% CI = 0.19- 0.74, P < .05).

Conclusions: Onset of SREs can be reduced or delayed with bisphosphonates; however, patients need prior screening for osteonecrosis of the jaw and optimized calcium and vitamin D levels. Our study showed that although screening for osteonecrosis of the jaw was at optimum levels, supplementation with calcium and vitamin D was lacking in patients on bisphosphonates. In our study, vitamin D supplementation reduced the risk of an SRE by 63%. Hence, adequate prevention with vitamin D supplementation can improve bone health among veterans with multiple myeloma or bone metastases. Data-based policies and practices need to be incorporated to provide care to ensure adequate bone health.

Purpose: Multiple myeloma and solid tumor metastases can cause bone disease leading to skeletal-related events (SREs) such as bone pain, fractures, and spinal cord compression. Intravenous bisphosphonate therapy—which is indicated in such cases—can lead to osteonecrosis of the jaw and hypocalcemia further putting patients at risk for SREs. These risks can be avoided by dental evaluation before bisphosphonate therapy and calcium and vitamin D supplementation throughout treatment. Our study of veterans treated with bisphosphonates for bone metastases or multiple myeloma aimed to (1) assess screening dental evaluation prior to treatment; and (2) measure effectiveness of calcium and vitamin D supplementation.

Methods: We performed a retrospective chart review at the James J. Peters VAMC of 117 veterans with multiple myeloma or bone metastases who received intravenous bisphosphonate therapy between January 2008 and November 2013. Those receiving bisphosphonates for other morbidities such as osteoporosis or hypercalcemia were excluded. Those getting dental clearance before intravenous bisphosphonate therapy and supplementation of vitamin D and calcium were assessed. Charts were further reviewed to gather outcomes data on incidence of osteonecrosis of the jaw and SREs such as bone pain, pathologic and traumatic fractures, orthopedic surgery, spine or nerve root compression. These data were analyzed using descriptive statistics to calculate frequencies, mean/median, and proportions. Odds ratios were calculated to assess differences in SRE outcomes for those who received supplementation as compared to those who did not get supplementation with calcium and vitamin D.

Results: Of the 117 patients included in the study, 97% were males aged from 58 to 92 years. Of these, 55 (47%) had prostate cancer, 21 (17%) had multiple myeloma, and 16 (14%) had lung cancer. All patients receiving bisphosphonates for bone metastases had undergone a dental evaluation prior to starting therapy; none were reported to have osteonecrosis of the jaw. However, only 78% had vitamin D levels checked before therapy; 69% of these were vitamin D deficient and received vitamin D supplementation. Overall, rates of calcium and vitamin D supplementation were very low (34% and 41%, respectively). Fifty-four percent of the patients reported an SRE; 49% with bone pain, 13% with pathological fractures, 7% with traumatic fractures, and 8% with nerve root compression. Vitamin D supplementation significantly reduced the odds of an SRE for our patients (OR 0.37, 95% CI = 0.19- 0.74, P < .05).

Conclusions: Onset of SREs can be reduced or delayed with bisphosphonates; however, patients need prior screening for osteonecrosis of the jaw and optimized calcium and vitamin D levels. Our study showed that although screening for osteonecrosis of the jaw was at optimum levels, supplementation with calcium and vitamin D was lacking in patients on bisphosphonates. In our study, vitamin D supplementation reduced the risk of an SRE by 63%. Hence, adequate prevention with vitamin D supplementation can improve bone health among veterans with multiple myeloma or bone metastases. Data-based policies and practices need to be incorporated to provide care to ensure adequate bone health.

Purpose: Multiple myeloma and solid tumor metastases can cause bone disease leading to skeletal-related events (SREs) such as bone pain, fractures, and spinal cord compression. Intravenous bisphosphonate therapy—which is indicated in such cases—can lead to osteonecrosis of the jaw and hypocalcemia further putting patients at risk for SREs. These risks can be avoided by dental evaluation before bisphosphonate therapy and calcium and vitamin D supplementation throughout treatment. Our study of veterans treated with bisphosphonates for bone metastases or multiple myeloma aimed to (1) assess screening dental evaluation prior to treatment; and (2) measure effectiveness of calcium and vitamin D supplementation.

Methods: We performed a retrospective chart review at the James J. Peters VAMC of 117 veterans with multiple myeloma or bone metastases who received intravenous bisphosphonate therapy between January 2008 and November 2013. Those receiving bisphosphonates for other morbidities such as osteoporosis or hypercalcemia were excluded. Those getting dental clearance before intravenous bisphosphonate therapy and supplementation of vitamin D and calcium were assessed. Charts were further reviewed to gather outcomes data on incidence of osteonecrosis of the jaw and SREs such as bone pain, pathologic and traumatic fractures, orthopedic surgery, spine or nerve root compression. These data were analyzed using descriptive statistics to calculate frequencies, mean/median, and proportions. Odds ratios were calculated to assess differences in SRE outcomes for those who received supplementation as compared to those who did not get supplementation with calcium and vitamin D.

Results: Of the 117 patients included in the study, 97% were males aged from 58 to 92 years. Of these, 55 (47%) had prostate cancer, 21 (17%) had multiple myeloma, and 16 (14%) had lung cancer. All patients receiving bisphosphonates for bone metastases had undergone a dental evaluation prior to starting therapy; none were reported to have osteonecrosis of the jaw. However, only 78% had vitamin D levels checked before therapy; 69% of these were vitamin D deficient and received vitamin D supplementation. Overall, rates of calcium and vitamin D supplementation were very low (34% and 41%, respectively). Fifty-four percent of the patients reported an SRE; 49% with bone pain, 13% with pathological fractures, 7% with traumatic fractures, and 8% with nerve root compression. Vitamin D supplementation significantly reduced the odds of an SRE for our patients (OR 0.37, 95% CI = 0.19- 0.74, P < .05).

Conclusions: Onset of SREs can be reduced or delayed with bisphosphonates; however, patients need prior screening for osteonecrosis of the jaw and optimized calcium and vitamin D levels. Our study showed that although screening for osteonecrosis of the jaw was at optimum levels, supplementation with calcium and vitamin D was lacking in patients on bisphosphonates. In our study, vitamin D supplementation reduced the risk of an SRE by 63%. Hence, adequate prevention with vitamin D supplementation can improve bone health among veterans with multiple myeloma or bone metastases. Data-based policies and practices need to be incorporated to provide care to ensure adequate bone health.

Malignant plasma cells

Murine studies have revealed signaling molecules that appear to play crucial roles in plasma cell development and survival.

Investigators found the adaptor protein DOK3 promotes the differentiation of plasma cells, and the protein-tyrosine phosphatase SHP1 enables plasma cell migration.

The team said these discoveries advance our understanding of plasma cells and may help us improve treatment for multiple myeloma and autoimmune disorders.

In PNAS, Kong-Peng Lam, PhD, of the Bioprocessing Technology Institute in Singapore, and his colleagues reported their discovery that DOK3 plays an important role in the formation of plasma cells.

The team found that calcium signaling inhibits the expression of PDL1 and PDL2, membrane proteins that are essential for plasma cell formation.

But DOK3 can promote the production of plasma cells by reducing the effects of calcium signaling on these proteins. And conversely, the absence of DOK3 results in defective plasma cell formation.

In Nature Communications, Dr Lam and his colleagues reported their discovery that SHP1 signaling is important for the long-term survival of plasma cells.

The researchers found that, in the absence of SHP1, plasma cells fail to migrate from the spleen to the bone marrow. This can impair the body’s immune response and increase susceptibility to infections and diseases.

However, Dr Lam and his colleagues were able to rectify the defective immune response caused by SHP1 deletion with antibody injections, a result that might aid the development of therapeutics for autoimmune disorders.

On the other hand, targeting SHP1 might be a strategy to treat multiple myeloma, in which the accumulation of cancerous plasma cells in the bone marrow is undesirable.

“These findings allow better understanding of plasma cells and their role in the immune system,” Dr Lam said. “The identification of these targets not only paves the way for development of therapeutics for those with autoimmune diseases and multiple myeloma but also impacts the development of immunological agents for combating infections.”

Malignant plasma cells

Murine studies have revealed signaling molecules that appear to play crucial roles in plasma cell development and survival.

Investigators found the adaptor protein DOK3 promotes the differentiation of plasma cells, and the protein-tyrosine phosphatase SHP1 enables plasma cell migration.

The team said these discoveries advance our understanding of plasma cells and may help us improve treatment for multiple myeloma and autoimmune disorders.

In PNAS, Kong-Peng Lam, PhD, of the Bioprocessing Technology Institute in Singapore, and his colleagues reported their discovery that DOK3 plays an important role in the formation of plasma cells.

The team found that calcium signaling inhibits the expression of PDL1 and PDL2, membrane proteins that are essential for plasma cell formation.

But DOK3 can promote the production of plasma cells by reducing the effects of calcium signaling on these proteins. And conversely, the absence of DOK3 results in defective plasma cell formation.

In Nature Communications, Dr Lam and his colleagues reported their discovery that SHP1 signaling is important for the long-term survival of plasma cells.

The researchers found that, in the absence of SHP1, plasma cells fail to migrate from the spleen to the bone marrow. This can impair the body’s immune response and increase susceptibility to infections and diseases.

However, Dr Lam and his colleagues were able to rectify the defective immune response caused by SHP1 deletion with antibody injections, a result that might aid the development of therapeutics for autoimmune disorders.

On the other hand, targeting SHP1 might be a strategy to treat multiple myeloma, in which the accumulation of cancerous plasma cells in the bone marrow is undesirable.

“These findings allow better understanding of plasma cells and their role in the immune system,” Dr Lam said. “The identification of these targets not only paves the way for development of therapeutics for those with autoimmune diseases and multiple myeloma but also impacts the development of immunological agents for combating infections.”

Malignant plasma cells

Murine studies have revealed signaling molecules that appear to play crucial roles in plasma cell development and survival.

Investigators found the adaptor protein DOK3 promotes the differentiation of plasma cells, and the protein-tyrosine phosphatase SHP1 enables plasma cell migration.

The team said these discoveries advance our understanding of plasma cells and may help us improve treatment for multiple myeloma and autoimmune disorders.

In PNAS, Kong-Peng Lam, PhD, of the Bioprocessing Technology Institute in Singapore, and his colleagues reported their discovery that DOK3 plays an important role in the formation of plasma cells.

The team found that calcium signaling inhibits the expression of PDL1 and PDL2, membrane proteins that are essential for plasma cell formation.

But DOK3 can promote the production of plasma cells by reducing the effects of calcium signaling on these proteins. And conversely, the absence of DOK3 results in defective plasma cell formation.

In Nature Communications, Dr Lam and his colleagues reported their discovery that SHP1 signaling is important for the long-term survival of plasma cells.

The researchers found that, in the absence of SHP1, plasma cells fail to migrate from the spleen to the bone marrow. This can impair the body’s immune response and increase susceptibility to infections and diseases.

However, Dr Lam and his colleagues were able to rectify the defective immune response caused by SHP1 deletion with antibody injections, a result that might aid the development of therapeutics for autoimmune disorders.

On the other hand, targeting SHP1 might be a strategy to treat multiple myeloma, in which the accumulation of cancerous plasma cells in the bone marrow is undesirable.

“These findings allow better understanding of plasma cells and their role in the immune system,” Dr Lam said. “The identification of these targets not only paves the way for development of therapeutics for those with autoimmune diseases and multiple myeloma but also impacts the development of immunological agents for combating infections.”

Cells undergoing autophagy

Credit: Sarah Pfau

Researchers have devised a strategy that leverages autophagy to work against multiple myeloma (MM).

Their method involves targeting the p62 protein, which plays a role in disposing of unwanted cellular proteins during autophagy.

The team used anticancer agents to induce autophagy in MM cells and found that simultaneously blocking p62 expression, either pharmacologically or with shRNA, could prompt apoptosis in the cells, both in vitro and in vivo.

Steven Grant, MD, of Virginia Commonwealth University’s Massey Cancer Center, and his colleagues described this work in Molecular and Cellular Biology.

“Therapies that are designed to block the early stages of autophagy do not offer the possibility of exploiting its potentially lethal effects,” Dr Grant said. “Our strategy turns autophagy from a protective process into a toxic one, and these results suggest it could increase the effectiveness of a variety of cancer therapies that induce autophagy.”

The researchers conducted several experiments in MM cell lines and mouse models of the disease. They used an anticancer agent—obatoclax or bortezomib—to induce autophagy and a cyclin-dependent kinase (CDK) inhibitor—flavopiridol or dinaciclib—or shRNA to target p62.

And they discovered that blocking p62 disrupted autophagy and killed far more MM cells than administering anticancer agents alone.

Critical to the success of this strategy is Bik, a protein that plays a significant role in governing cell death and survival. With anticancer treatment, Bik accumulates in MM cells until it triggers apoptosis.

Normally, the MM cells would initiate autophagy to survive, and p62 would rid the cells of Bik by loading the proteins into autophagosomes for disposal.

However, the researchers found that blocking p62 production results in an inefficient form of autophagy, and the accumulation of Bik eventually causes the MM cells to undergo apoptosis.

This research builds upon more than a decade of work by Dr Grant’s lab, in which the team investigated novel treatment strategies and combination therapies that selectively kill MM cells and other blood cancer cells.

“We are now working to identify additional CDK inhibitors that can be used to disrupt autophagy,” Dr Grant said. “The ultimate goal will be to translate these findings into a clinical trial to test the therapy in patients with various blood cancers.”

The technology in his study has been made available for licensing through the Virginia Commonwealth University Office of Research.

Cells undergoing autophagy

Credit: Sarah Pfau

Researchers have devised a strategy that leverages autophagy to work against multiple myeloma (MM).

Their method involves targeting the p62 protein, which plays a role in disposing of unwanted cellular proteins during autophagy.

The team used anticancer agents to induce autophagy in MM cells and found that simultaneously blocking p62 expression, either pharmacologically or with shRNA, could prompt apoptosis in the cells, both in vitro and in vivo.

Steven Grant, MD, of Virginia Commonwealth University’s Massey Cancer Center, and his colleagues described this work in Molecular and Cellular Biology.

“Therapies that are designed to block the early stages of autophagy do not offer the possibility of exploiting its potentially lethal effects,” Dr Grant said. “Our strategy turns autophagy from a protective process into a toxic one, and these results suggest it could increase the effectiveness of a variety of cancer therapies that induce autophagy.”

The researchers conducted several experiments in MM cell lines and mouse models of the disease. They used an anticancer agent—obatoclax or bortezomib—to induce autophagy and a cyclin-dependent kinase (CDK) inhibitor—flavopiridol or dinaciclib—or shRNA to target p62.

And they discovered that blocking p62 disrupted autophagy and killed far more MM cells than administering anticancer agents alone.

Critical to the success of this strategy is Bik, a protein that plays a significant role in governing cell death and survival. With anticancer treatment, Bik accumulates in MM cells until it triggers apoptosis.

Normally, the MM cells would initiate autophagy to survive, and p62 would rid the cells of Bik by loading the proteins into autophagosomes for disposal.

However, the researchers found that blocking p62 production results in an inefficient form of autophagy, and the accumulation of Bik eventually causes the MM cells to undergo apoptosis.

This research builds upon more than a decade of work by Dr Grant’s lab, in which the team investigated novel treatment strategies and combination therapies that selectively kill MM cells and other blood cancer cells.

“We are now working to identify additional CDK inhibitors that can be used to disrupt autophagy,” Dr Grant said. “The ultimate goal will be to translate these findings into a clinical trial to test the therapy in patients with various blood cancers.”

The technology in his study has been made available for licensing through the Virginia Commonwealth University Office of Research.

Cells undergoing autophagy

Credit: Sarah Pfau

Researchers have devised a strategy that leverages autophagy to work against multiple myeloma (MM).

Their method involves targeting the p62 protein, which plays a role in disposing of unwanted cellular proteins during autophagy.

The team used anticancer agents to induce autophagy in MM cells and found that simultaneously blocking p62 expression, either pharmacologically or with shRNA, could prompt apoptosis in the cells, both in vitro and in vivo.

Steven Grant, MD, of Virginia Commonwealth University’s Massey Cancer Center, and his colleagues described this work in Molecular and Cellular Biology.

“Therapies that are designed to block the early stages of autophagy do not offer the possibility of exploiting its potentially lethal effects,” Dr Grant said. “Our strategy turns autophagy from a protective process into a toxic one, and these results suggest it could increase the effectiveness of a variety of cancer therapies that induce autophagy.”

The researchers conducted several experiments in MM cell lines and mouse models of the disease. They used an anticancer agent—obatoclax or bortezomib—to induce autophagy and a cyclin-dependent kinase (CDK) inhibitor—flavopiridol or dinaciclib—or shRNA to target p62.

And they discovered that blocking p62 disrupted autophagy and killed far more MM cells than administering anticancer agents alone.

Critical to the success of this strategy is Bik, a protein that plays a significant role in governing cell death and survival. With anticancer treatment, Bik accumulates in MM cells until it triggers apoptosis.

Normally, the MM cells would initiate autophagy to survive, and p62 would rid the cells of Bik by loading the proteins into autophagosomes for disposal.

However, the researchers found that blocking p62 production results in an inefficient form of autophagy, and the accumulation of Bik eventually causes the MM cells to undergo apoptosis.

This research builds upon more than a decade of work by Dr Grant’s lab, in which the team investigated novel treatment strategies and combination therapies that selectively kill MM cells and other blood cancer cells.

“We are now working to identify additional CDK inhibitors that can be used to disrupt autophagy,” Dr Grant said. “The ultimate goal will be to translate these findings into a clinical trial to test the therapy in patients with various blood cancers.”

The technology in his study has been made available for licensing through the Virginia Commonwealth University Office of Research.

Doctor consults with patient

Credit: NIH

Results of a large study suggest major depression is common—but largely untreated—among cancer patients in Scotland.

And 2 additional studies of Scottish patients showed that a program specifically designed for individuals with cancer can treat depression and improve quality of life more effectively than current methods of care.

These studies appear in The Lancet, The Lancet Oncology, and The Lancet Psychiatry.

In The Lancet Psychiatry, researchers recounted their analysis of data from 21,151 patients treated at cancer clinics in Scotland. The team found that major depression was substantially more common in cancer patients than in the general population.

Major depression was most common in patients with lung cancer (13%) and lowest in those with genitourinary cancer (6%). Moreover, nearly three-quarters (73%) of depressed cancer patients were not receiving treatment.

To address the problem of inadequate treatment, researchers initiated the SMaRT Oncology-2 trial. They reported the results in The Lancet.

The team evaluated a new treatment program called “Depression Care for People with Cancer” (DCPC). DCPC is delivered by specially trained cancer nurses and psychiatrists, working in collaboration with the patient’s cancer team and general practitioner, and is given as part of cancer care. It is a systematic treatment program that includes both antidepressants and psychological therapy.

The trial included 500 adults with major depression and a cancer with a good prognosis (predicted survival of more than 12 months).

Patients were randomized to receive either DCPC or “usual care,” which was provided by a patient’s general practitioner and might have included prescribing antidepressants or referring the patient to mental health services for assessment or psychological treatment.

Results showed that DCPC was more effective than usual care in reducing depression. At 6 months, 62% of patients who received DCPC responded to treatment (experiencing at least a 50% reduction in the severity of their depression), compared with 17% of those who received the usual care (P<0.0001). This benefit was sustained at 12 months.

In addition, DCPC improved anxiety, pain, fatigue, functioning, and overall quality of life (all P<0.05). The researchers also noted that the cost of providing DCPC was modest (£613 per patient).

“The huge benefit that DCPC delivers for patients with cancer and depression shows what we can achieve for patients if we take as much care with the treatment of their depression as we do with the treatment of their cancer,” said study author Michael Sharpe, MD, of the University of Oxford in the UK.

To see if patients with a poor-prognosis cancer could also benefit from DCPC, researchers initiated the SMaRT Oncology-3 trial. They reported the results in The Lancet Oncology.

The team tested a version of DCPC adapted for cancer patients with a poor prognosis. The trial included 142 patients with lung cancer and major depression.

Patients who received the modified version of DCPC had a significantly greater improvement in depression than those who received the usual care during 32 weeks of follow-up (P=0.0003). DCPC also improved patients’ anxiety (P=0.046), functioning (P=0.0019), and quality of life (P=0.018).

“Patients with lung cancer often have a poor prognosis,” said study author Jane Walker, MBChB, PhD, of the University of Oxford and Sobell House Hospice in Oxford, UK.

“If they also have major depression, that can blight the time they have left to live. This trial shows that we can effectively treat depression in patients with poor-prognosis cancers, like lung cancer, and really improve patients’ lives.”

Doctor consults with patient

Credit: NIH

Results of a large study suggest major depression is common—but largely untreated—among cancer patients in Scotland.

And 2 additional studies of Scottish patients showed that a program specifically designed for individuals with cancer can treat depression and improve quality of life more effectively than current methods of care.

These studies appear in The Lancet, The Lancet Oncology, and The Lancet Psychiatry.

In The Lancet Psychiatry, researchers recounted their analysis of data from 21,151 patients treated at cancer clinics in Scotland. The team found that major depression was substantially more common in cancer patients than in the general population.

Major depression was most common in patients with lung cancer (13%) and lowest in those with genitourinary cancer (6%). Moreover, nearly three-quarters (73%) of depressed cancer patients were not receiving treatment.

To address the problem of inadequate treatment, researchers initiated the SMaRT Oncology-2 trial. They reported the results in The Lancet.

The team evaluated a new treatment program called “Depression Care for People with Cancer” (DCPC). DCPC is delivered by specially trained cancer nurses and psychiatrists, working in collaboration with the patient’s cancer team and general practitioner, and is given as part of cancer care. It is a systematic treatment program that includes both antidepressants and psychological therapy.

The trial included 500 adults with major depression and a cancer with a good prognosis (predicted survival of more than 12 months).

Patients were randomized to receive either DCPC or “usual care,” which was provided by a patient’s general practitioner and might have included prescribing antidepressants or referring the patient to mental health services for assessment or psychological treatment.

Results showed that DCPC was more effective than usual care in reducing depression. At 6 months, 62% of patients who received DCPC responded to treatment (experiencing at least a 50% reduction in the severity of their depression), compared with 17% of those who received the usual care (P<0.0001). This benefit was sustained at 12 months.

In addition, DCPC improved anxiety, pain, fatigue, functioning, and overall quality of life (all P<0.05). The researchers also noted that the cost of providing DCPC was modest (£613 per patient).

“The huge benefit that DCPC delivers for patients with cancer and depression shows what we can achieve for patients if we take as much care with the treatment of their depression as we do with the treatment of their cancer,” said study author Michael Sharpe, MD, of the University of Oxford in the UK.

To see if patients with a poor-prognosis cancer could also benefit from DCPC, researchers initiated the SMaRT Oncology-3 trial. They reported the results in The Lancet Oncology.

The team tested a version of DCPC adapted for cancer patients with a poor prognosis. The trial included 142 patients with lung cancer and major depression.

Patients who received the modified version of DCPC had a significantly greater improvement in depression than those who received the usual care during 32 weeks of follow-up (P=0.0003). DCPC also improved patients’ anxiety (P=0.046), functioning (P=0.0019), and quality of life (P=0.018).

“Patients with lung cancer often have a poor prognosis,” said study author Jane Walker, MBChB, PhD, of the University of Oxford and Sobell House Hospice in Oxford, UK.

“If they also have major depression, that can blight the time they have left to live. This trial shows that we can effectively treat depression in patients with poor-prognosis cancers, like lung cancer, and really improve patients’ lives.”

Doctor consults with patient

Credit: NIH

Results of a large study suggest major depression is common—but largely untreated—among cancer patients in Scotland.

And 2 additional studies of Scottish patients showed that a program specifically designed for individuals with cancer can treat depression and improve quality of life more effectively than current methods of care.

These studies appear in The Lancet, The Lancet Oncology, and The Lancet Psychiatry.

In The Lancet Psychiatry, researchers recounted their analysis of data from 21,151 patients treated at cancer clinics in Scotland. The team found that major depression was substantially more common in cancer patients than in the general population.

Major depression was most common in patients with lung cancer (13%) and lowest in those with genitourinary cancer (6%). Moreover, nearly three-quarters (73%) of depressed cancer patients were not receiving treatment.

To address the problem of inadequate treatment, researchers initiated the SMaRT Oncology-2 trial. They reported the results in The Lancet.

The team evaluated a new treatment program called “Depression Care for People with Cancer” (DCPC). DCPC is delivered by specially trained cancer nurses and psychiatrists, working in collaboration with the patient’s cancer team and general practitioner, and is given as part of cancer care. It is a systematic treatment program that includes both antidepressants and psychological therapy.

The trial included 500 adults with major depression and a cancer with a good prognosis (predicted survival of more than 12 months).

Patients were randomized to receive either DCPC or “usual care,” which was provided by a patient’s general practitioner and might have included prescribing antidepressants or referring the patient to mental health services for assessment or psychological treatment.

Results showed that DCPC was more effective than usual care in reducing depression. At 6 months, 62% of patients who received DCPC responded to treatment (experiencing at least a 50% reduction in the severity of their depression), compared with 17% of those who received the usual care (P<0.0001). This benefit was sustained at 12 months.

In addition, DCPC improved anxiety, pain, fatigue, functioning, and overall quality of life (all P<0.05). The researchers also noted that the cost of providing DCPC was modest (£613 per patient).

“The huge benefit that DCPC delivers for patients with cancer and depression shows what we can achieve for patients if we take as much care with the treatment of their depression as we do with the treatment of their cancer,” said study author Michael Sharpe, MD, of the University of Oxford in the UK.

To see if patients with a poor-prognosis cancer could also benefit from DCPC, researchers initiated the SMaRT Oncology-3 trial. They reported the results in The Lancet Oncology.

The team tested a version of DCPC adapted for cancer patients with a poor prognosis. The trial included 142 patients with lung cancer and major depression.

Patients who received the modified version of DCPC had a significantly greater improvement in depression than those who received the usual care during 32 weeks of follow-up (P=0.0003). DCPC also improved patients’ anxiety (P=0.046), functioning (P=0.0019), and quality of life (P=0.018).

“Patients with lung cancer often have a poor prognosis,” said study author Jane Walker, MBChB, PhD, of the University of Oxford and Sobell House Hospice in Oxford, UK.

“If they also have major depression, that can blight the time they have left to live. This trial shows that we can effectively treat depression in patients with poor-prognosis cancers, like lung cancer, and really improve patients’ lives.”

Drug release in a cancer cell

Credit: PNAS

A new type of nanoparticle (NP) could aid the diagnosis and treatment of cancers, according to research published in Nature Communications.

Built on an easy-to-make polymer, these particles can be used as contrast agents to light up tumors for MRI and PET scans or to deliver chemotherapy and other treatments to cancer cells.

Furthermore, in vivo experiments showed the particles are biocompatible and elicit minimal side effects.

“These are amazingly useful particles,” said study author Yuanpei Li, PhD, of the UC Davis Comprehensive Cancer Center in Sacramento, California.

“As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors, apply light to make the nanoparticles release singlet oxygen (photodynamic therapy), or use a laser to heat them (photothermal therapy)—all proven ways to destroy tumors.”

These NPs are built on a porphyrin/cholic acid polymer. Porphyrins are common organic compounds, and cholic acid is produced by the liver.

To further stabilize the particles, the researchers added the amino acid cysteine (creating CNPs), which prevents them from prematurely releasing their therapeutic payload when exposed to blood proteins and other barriers.

Therapeutic applications

The researchers tested the CNPs, both in vitro and in vivo, for a wide range of tasks. On the therapeutic side, the particles effectively transported anticancer drugs, such as doxorubicin.

CNPs carrying doxorubicin provided excellent cancer control in animals, with minimal side effects.

Even when kept in the blood for many hours, CNPs only released small amounts of the drug. However, when exposed to light or agents such as glutathione, they readily released their payloads.

The researchers showed that, when exposed to a single wavelength of light, the CNPs could generate heat or produce singlet oxygen to destroy tumor cells.

Imaging applications

CNPs offer a number of advantages to enhance imaging, according to the researchers. The particles readily chelate imaging agents and can remain in the body for long periods.

In animal studies, CNPs largely accumulated in tumors, rather than in normal tissue. So they dramatically enhanced tumor contrast for MRI and may also be promising for PET-MRI scans, the researchers said.

“These particles can combine imaging and therapeutics,” Dr Li noted. “We could potentially use them to simultaneously deliver treatment and monitor treatment efficacy.”

The researchers are now conducting additional preclinical studies with the CNPs. If all goes well, they will proceed to human trials. In the meantime, the team is excited about these capabilities.

“This is the first nanoparticle to perform so many different jobs,” Dr Li said. “From delivering chemo, photodynamic, and photothermal therapies, to enhancing diagnostic imaging, it’s the complete package.”

Drug release in a cancer cell

Credit: PNAS

A new type of nanoparticle (NP) could aid the diagnosis and treatment of cancers, according to research published in Nature Communications.

Built on an easy-to-make polymer, these particles can be used as contrast agents to light up tumors for MRI and PET scans or to deliver chemotherapy and other treatments to cancer cells.

Furthermore, in vivo experiments showed the particles are biocompatible and elicit minimal side effects.

“These are amazingly useful particles,” said study author Yuanpei Li, PhD, of the UC Davis Comprehensive Cancer Center in Sacramento, California.

“As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors, apply light to make the nanoparticles release singlet oxygen (photodynamic therapy), or use a laser to heat them (photothermal therapy)—all proven ways to destroy tumors.”

These NPs are built on a porphyrin/cholic acid polymer. Porphyrins are common organic compounds, and cholic acid is produced by the liver.

To further stabilize the particles, the researchers added the amino acid cysteine (creating CNPs), which prevents them from prematurely releasing their therapeutic payload when exposed to blood proteins and other barriers.

Therapeutic applications

The researchers tested the CNPs, both in vitro and in vivo, for a wide range of tasks. On the therapeutic side, the particles effectively transported anticancer drugs, such as doxorubicin.

CNPs carrying doxorubicin provided excellent cancer control in animals, with minimal side effects.

Even when kept in the blood for many hours, CNPs only released small amounts of the drug. However, when exposed to light or agents such as glutathione, they readily released their payloads.

The researchers showed that, when exposed to a single wavelength of light, the CNPs could generate heat or produce singlet oxygen to destroy tumor cells.

Imaging applications

CNPs offer a number of advantages to enhance imaging, according to the researchers. The particles readily chelate imaging agents and can remain in the body for long periods.

In animal studies, CNPs largely accumulated in tumors, rather than in normal tissue. So they dramatically enhanced tumor contrast for MRI and may also be promising for PET-MRI scans, the researchers said.

“These particles can combine imaging and therapeutics,” Dr Li noted. “We could potentially use them to simultaneously deliver treatment and monitor treatment efficacy.”

The researchers are now conducting additional preclinical studies with the CNPs. If all goes well, they will proceed to human trials. In the meantime, the team is excited about these capabilities.

“This is the first nanoparticle to perform so many different jobs,” Dr Li said. “From delivering chemo, photodynamic, and photothermal therapies, to enhancing diagnostic imaging, it’s the complete package.”

Drug release in a cancer cell

Credit: PNAS

A new type of nanoparticle (NP) could aid the diagnosis and treatment of cancers, according to research published in Nature Communications.

Built on an easy-to-make polymer, these particles can be used as contrast agents to light up tumors for MRI and PET scans or to deliver chemotherapy and other treatments to cancer cells.

Furthermore, in vivo experiments showed the particles are biocompatible and elicit minimal side effects.

“These are amazingly useful particles,” said study author Yuanpei Li, PhD, of the UC Davis Comprehensive Cancer Center in Sacramento, California.

“As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors, apply light to make the nanoparticles release singlet oxygen (photodynamic therapy), or use a laser to heat them (photothermal therapy)—all proven ways to destroy tumors.”

These NPs are built on a porphyrin/cholic acid polymer. Porphyrins are common organic compounds, and cholic acid is produced by the liver.

To further stabilize the particles, the researchers added the amino acid cysteine (creating CNPs), which prevents them from prematurely releasing their therapeutic payload when exposed to blood proteins and other barriers.

Therapeutic applications

The researchers tested the CNPs, both in vitro and in vivo, for a wide range of tasks. On the therapeutic side, the particles effectively transported anticancer drugs, such as doxorubicin.

CNPs carrying doxorubicin provided excellent cancer control in animals, with minimal side effects.

Even when kept in the blood for many hours, CNPs only released small amounts of the drug. However, when exposed to light or agents such as glutathione, they readily released their payloads.

The researchers showed that, when exposed to a single wavelength of light, the CNPs could generate heat or produce singlet oxygen to destroy tumor cells.

Imaging applications

CNPs offer a number of advantages to enhance imaging, according to the researchers. The particles readily chelate imaging agents and can remain in the body for long periods.

In animal studies, CNPs largely accumulated in tumors, rather than in normal tissue. So they dramatically enhanced tumor contrast for MRI and may also be promising for PET-MRI scans, the researchers said.

“These particles can combine imaging and therapeutics,” Dr Li noted. “We could potentially use them to simultaneously deliver treatment and monitor treatment efficacy.”

The researchers are now conducting additional preclinical studies with the CNPs. If all goes well, they will proceed to human trials. In the meantime, the team is excited about these capabilities.

“This is the first nanoparticle to perform so many different jobs,” Dr Li said. “From delivering chemo, photodynamic, and photothermal therapies, to enhancing diagnostic imaging, it’s the complete package.”

The proteasome inhibitor carfilzomib (Kyprolis) did not meet its primary endpoint in the phase 3 FOCUS trial, according to the drug’s developers.

Single-agent carfilzomib did not improve overall survival compared to an active control regimen of corticosteroids plus optional cyclophosphamide in patients with relapsed and refractory multiple myeloma (MM).

This result raises questions about carfilzomib’s chances for regulatory approval around the world.

However, the companies developing the drug, Amgen and its subsidiary Onyx Pharmaceuticals, Inc., said results of the phase 3 ASPIRE trial should be sufficient to support carfilzomib’s approval.

At present, carfilzomib has accelerated approval from the US Food and Drug Administration for the treatment of MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of completing their last therapy.

That approval was based on response rates observed with carfilzomib. For the drug to gain full approval, it must demonstrate a clinical benefit.

The FOCUS trial

For the FOCUS trial, researchers enrolled 315 patients with relapsed and advanced refractory MM.

Patients were randomized to receive carfilzomib or an active control regimen consisting of low-dose dexamethasone, or equivalent corticosteroids, plus optional cyclophosphamide.

Nearly all patients in the control arm received cyclophosphamide. Patients were heavily pretreated and had received a median of 5 treatment regimens prior to study entry.

The trial’s primary endpoint was overall survival, and there was no significant difference between the 2 treatment arms. The hazard ratio was 0.975.

Treatment discontinuation due to adverse events and on-study deaths were comparable between the treatment arms. The rate of cardiac events in the carfilzomib arm was consistent with the current US label.

However, there was an increase in the incidence of renal adverse events of all grades observed in the carfilzomib arm compared to the active control arm and the label.

Full prescribing information for carfilzomib is available at www.kyprolis.com.

Amgen and Onyx said detailed results from the FOCUS trial will be submitted for presentation at an upcoming scientific meeting.

The proteasome inhibitor carfilzomib (Kyprolis) did not meet its primary endpoint in the phase 3 FOCUS trial, according to the drug’s developers.

Single-agent carfilzomib did not improve overall survival compared to an active control regimen of corticosteroids plus optional cyclophosphamide in patients with relapsed and refractory multiple myeloma (MM).

This result raises questions about carfilzomib’s chances for regulatory approval around the world.

However, the companies developing the drug, Amgen and its subsidiary Onyx Pharmaceuticals, Inc., said results of the phase 3 ASPIRE trial should be sufficient to support carfilzomib’s approval.

At present, carfilzomib has accelerated approval from the US Food and Drug Administration for the treatment of MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of completing their last therapy.

That approval was based on response rates observed with carfilzomib. For the drug to gain full approval, it must demonstrate a clinical benefit.

The FOCUS trial

For the FOCUS trial, researchers enrolled 315 patients with relapsed and advanced refractory MM.

Patients were randomized to receive carfilzomib or an active control regimen consisting of low-dose dexamethasone, or equivalent corticosteroids, plus optional cyclophosphamide.

Nearly all patients in the control arm received cyclophosphamide. Patients were heavily pretreated and had received a median of 5 treatment regimens prior to study entry.

The trial’s primary endpoint was overall survival, and there was no significant difference between the 2 treatment arms. The hazard ratio was 0.975.

Treatment discontinuation due to adverse events and on-study deaths were comparable between the treatment arms. The rate of cardiac events in the carfilzomib arm was consistent with the current US label.

However, there was an increase in the incidence of renal adverse events of all grades observed in the carfilzomib arm compared to the active control arm and the label.

Full prescribing information for carfilzomib is available at www.kyprolis.com.

Amgen and Onyx said detailed results from the FOCUS trial will be submitted for presentation at an upcoming scientific meeting.

The proteasome inhibitor carfilzomib (Kyprolis) did not meet its primary endpoint in the phase 3 FOCUS trial, according to the drug’s developers.

Single-agent carfilzomib did not improve overall survival compared to an active control regimen of corticosteroids plus optional cyclophosphamide in patients with relapsed and refractory multiple myeloma (MM).

This result raises questions about carfilzomib’s chances for regulatory approval around the world.

However, the companies developing the drug, Amgen and its subsidiary Onyx Pharmaceuticals, Inc., said results of the phase 3 ASPIRE trial should be sufficient to support carfilzomib’s approval.

At present, carfilzomib has accelerated approval from the US Food and Drug Administration for the treatment of MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of completing their last therapy.

That approval was based on response rates observed with carfilzomib. For the drug to gain full approval, it must demonstrate a clinical benefit.

The FOCUS trial

For the FOCUS trial, researchers enrolled 315 patients with relapsed and advanced refractory MM.

Patients were randomized to receive carfilzomib or an active control regimen consisting of low-dose dexamethasone, or equivalent corticosteroids, plus optional cyclophosphamide.

Nearly all patients in the control arm received cyclophosphamide. Patients were heavily pretreated and had received a median of 5 treatment regimens prior to study entry.

The trial’s primary endpoint was overall survival, and there was no significant difference between the 2 treatment arms. The hazard ratio was 0.975.

Treatment discontinuation due to adverse events and on-study deaths were comparable between the treatment arms. The rate of cardiac events in the carfilzomib arm was consistent with the current US label.

However, there was an increase in the incidence of renal adverse events of all grades observed in the carfilzomib arm compared to the active control arm and the label.

Full prescribing information for carfilzomib is available at www.kyprolis.com.

Amgen and Onyx said detailed results from the FOCUS trial will be submitted for presentation at an upcoming scientific meeting.

Blood samples

Credit: Graham Colm

Scientists have found that a technique used in Earth science research may be able to help physicians predict the course of multiple myeloma (MM).

The team showed they could use calcium isotope analysis to predict whether MM patients are at risk for developing bone lesions.

The group believes this technique could be used to chart the progression or recurrence of MM and help tailor therapies to better protect patients’ bones.

“At present, there is no good way to track changes in bone balance, except retrospectively using X-ray methods,” said Ariel Anbar, PhD, of Arizona State University in Tempe. “By the time the X-rays show something, the damage has been done.”

“Right now, pain is usually the first indication that cancer is affecting the bones,” added Rafael Fonseca, MD, of the Mayo Clinic in Scottsdale, Arizona. “If we could detect it earlier by an analysis of urine or blood in high-risk patients, it could significantly improve their care.”

To explore this possibility, Drs Fonseca, Anbar, and their colleagues performed calcium isotope analysis using blood samples from MM patients. The team recounted their results in a letter to Leukemia.

As the name suggests, calcium isotope analysis measures calcium isotopes that are naturally present in blood. The technique makes use of a fact well known to Earth scientists but not normally used in biomedicine: different isotopes of a chemical element can react at slightly different rates.

An earlier study testing this technique in healthy subjects showed that when bones form, the lighter isotopes of calcium enter bone a little faster than the heavier isotopes. That difference, called isotope fractionation, is the key to the method.

In healthy, active humans, bone is forming at about the same rate as it resorbs. But if bone loss is occurring, the isotopic composition of blood becomes enriched in the lighter isotopes as bones resorb more quickly than they are formed.

The effect on calcium isotopes is very small, typically less than a 0.02% change in the isotope ratio. But even effects that small can be measured using precise mass spectrometry methods.

Using these methods, the researchers tested peripheral blood samples from 71 adult patients—55 with MM, 9 with smoldering MM, and 7 with monoclonal gammopathy of undetermined significance.

The researchers found an association between how active a patient’s disease was and the change in the isotope ratios. In fact, the isotope ratios predicted disease activity better than, and independent from, standard clinical variables.

Blood samples from patients with active disease had significantly lower mean calcium isotope compositions than samples from patients with non-active disease (mean δ^44/42Ca=-0.8 vs -0.67, P=0.025), regardless of diagnosis.

For MM patients specifically, those with active disease had a significantly lower mean δ^44/42Ca than patients with non-active disease (-0.79 vs -0.63, P=0.016), which was consistent with resorption of bone containing lighter ⁴²Ca.

Dr Anbar noted that, although calcium isotope analysis has worked in this small set of patients, additional research is needed to verify these initial findings and improve the efficiency of analysis.

“If the method proves to be robust after more careful validation, it could provide earlier detection of bone involvement than presently possible,” he said, “and also provide the possibility to monitor the effectiveness of drugs to combat bone loss.”

Blood samples

Credit: Graham Colm

Scientists have found that a technique used in Earth science research may be able to help physicians predict the course of multiple myeloma (MM).

The team showed they could use calcium isotope analysis to predict whether MM patients are at risk for developing bone lesions.

The group believes this technique could be used to chart the progression or recurrence of MM and help tailor therapies to better protect patients’ bones.

“At present, there is no good way to track changes in bone balance, except retrospectively using X-ray methods,” said Ariel Anbar, PhD, of Arizona State University in Tempe. “By the time the X-rays show something, the damage has been done.”

“Right now, pain is usually the first indication that cancer is affecting the bones,” added Rafael Fonseca, MD, of the Mayo Clinic in Scottsdale, Arizona. “If we could detect it earlier by an analysis of urine or blood in high-risk patients, it could significantly improve their care.”

To explore this possibility, Drs Fonseca, Anbar, and their colleagues performed calcium isotope analysis using blood samples from MM patients. The team recounted their results in a letter to Leukemia.

As the name suggests, calcium isotope analysis measures calcium isotopes that are naturally present in blood. The technique makes use of a fact well known to Earth scientists but not normally used in biomedicine: different isotopes of a chemical element can react at slightly different rates.

An earlier study testing this technique in healthy subjects showed that when bones form, the lighter isotopes of calcium enter bone a little faster than the heavier isotopes. That difference, called isotope fractionation, is the key to the method.

In healthy, active humans, bone is forming at about the same rate as it resorbs. But if bone loss is occurring, the isotopic composition of blood becomes enriched in the lighter isotopes as bones resorb more quickly than they are formed.

The effect on calcium isotopes is very small, typically less than a 0.02% change in the isotope ratio. But even effects that small can be measured using precise mass spectrometry methods.

Using these methods, the researchers tested peripheral blood samples from 71 adult patients—55 with MM, 9 with smoldering MM, and 7 with monoclonal gammopathy of undetermined significance.

The researchers found an association between how active a patient’s disease was and the change in the isotope ratios. In fact, the isotope ratios predicted disease activity better than, and independent from, standard clinical variables.

Blood samples from patients with active disease had significantly lower mean calcium isotope compositions than samples from patients with non-active disease (mean δ^44/42Ca=-0.8 vs -0.67, P=0.025), regardless of diagnosis.

For MM patients specifically, those with active disease had a significantly lower mean δ^44/42Ca than patients with non-active disease (-0.79 vs -0.63, P=0.016), which was consistent with resorption of bone containing lighter ⁴²Ca.

Dr Anbar noted that, although calcium isotope analysis has worked in this small set of patients, additional research is needed to verify these initial findings and improve the efficiency of analysis.

“If the method proves to be robust after more careful validation, it could provide earlier detection of bone involvement than presently possible,” he said, “and also provide the possibility to monitor the effectiveness of drugs to combat bone loss.”

Blood samples

Credit: Graham Colm

Scientists have found that a technique used in Earth science research may be able to help physicians predict the course of multiple myeloma (MM).

The team showed they could use calcium isotope analysis to predict whether MM patients are at risk for developing bone lesions.

The group believes this technique could be used to chart the progression or recurrence of MM and help tailor therapies to better protect patients’ bones.

“At present, there is no good way to track changes in bone balance, except retrospectively using X-ray methods,” said Ariel Anbar, PhD, of Arizona State University in Tempe. “By the time the X-rays show something, the damage has been done.”

“Right now, pain is usually the first indication that cancer is affecting the bones,” added Rafael Fonseca, MD, of the Mayo Clinic in Scottsdale, Arizona. “If we could detect it earlier by an analysis of urine or blood in high-risk patients, it could significantly improve their care.”

To explore this possibility, Drs Fonseca, Anbar, and their colleagues performed calcium isotope analysis using blood samples from MM patients. The team recounted their results in a letter to Leukemia.

As the name suggests, calcium isotope analysis measures calcium isotopes that are naturally present in blood. The technique makes use of a fact well known to Earth scientists but not normally used in biomedicine: different isotopes of a chemical element can react at slightly different rates.

An earlier study testing this technique in healthy subjects showed that when bones form, the lighter isotopes of calcium enter bone a little faster than the heavier isotopes. That difference, called isotope fractionation, is the key to the method.

In healthy, active humans, bone is forming at about the same rate as it resorbs. But if bone loss is occurring, the isotopic composition of blood becomes enriched in the lighter isotopes as bones resorb more quickly than they are formed.

The effect on calcium isotopes is very small, typically less than a 0.02% change in the isotope ratio. But even effects that small can be measured using precise mass spectrometry methods.

Using these methods, the researchers tested peripheral blood samples from 71 adult patients—55 with MM, 9 with smoldering MM, and 7 with monoclonal gammopathy of undetermined significance.

The researchers found an association between how active a patient’s disease was and the change in the isotope ratios. In fact, the isotope ratios predicted disease activity better than, and independent from, standard clinical variables.

Blood samples from patients with active disease had significantly lower mean calcium isotope compositions than samples from patients with non-active disease (mean δ^44/42Ca=-0.8 vs -0.67, P=0.025), regardless of diagnosis.

For MM patients specifically, those with active disease had a significantly lower mean δ^44/42Ca than patients with non-active disease (-0.79 vs -0.63, P=0.016), which was consistent with resorption of bone containing lighter ⁴²Ca.

Dr Anbar noted that, although calcium isotope analysis has worked in this small set of patients, additional research is needed to verify these initial findings and improve the efficiency of analysis.

“If the method proves to be robust after more careful validation, it could provide earlier detection of bone involvement than presently possible,” he said, “and also provide the possibility to monitor the effectiveness of drugs to combat bone loss.”