Multiple Myeloma

Doctor consults with a family

Credit: Rhoda Baer

A new analysis suggests family dysfunction is the greatest predictor of emotional and behavioral problems among children who have a parent with cancer.

Other variables, such as the child’s age, did not predict the risk as accurately.

And illness-related factors, such as the parent’s prognosis, did not appear to have an impact at all.

Birgit Möller, PhD, of the University Medical Center Hamburg-Eppendorf in Germany, and her colleagues reported these findings in Cancer.

The researchers evaluated 235 families in which at least 1 parent was diagnosed with cancer. This included 402 parents and 324 children aged 11 to 21 years. Parents and children completed questionnaires that assessed emotional and behavioral health.

Responses suggested that children of cancer patients have higher-than-average levels of emotional and behavioral symptoms.

The overall mean values for emotional and behavioral problems—from both the parents’ and children’s perspectives—were significantly higher in the study population than the average values from a representative non-cancer population.

General family functioning was the strongest predictor of children’s symptom status from both the parents’ and child’s perspectives.

The effects of the child’s age and gender on behavioral and emotional symptoms varied according to the subject asked. But none of the respondents reported an association between child adjustment and illness-related factors such as poor prognoses or recurrent illness.

Dr Möller noted that screening for child mental health problems, family dysfunction, and parental depression can be easily adopted into cancer care so that families in need of support can be identified.

“Additional training of oncologists, interdisciplinary approaches, and family-based mental health liaison services are recommended to meet the needs of minor

children and their families and to minimize negative long-term effects in children,” she said.

Dr Möller and her team have developed a preventive counseling program—called the Children of Somatically Ill Parents (COSIP) program—that focuses on family communication, involvement of family members, flexible problem solving, mutual support, and parenting issues.

Doctor consults with a family

Credit: Rhoda Baer

A new analysis suggests family dysfunction is the greatest predictor of emotional and behavioral problems among children who have a parent with cancer.

Other variables, such as the child’s age, did not predict the risk as accurately.

And illness-related factors, such as the parent’s prognosis, did not appear to have an impact at all.

Birgit Möller, PhD, of the University Medical Center Hamburg-Eppendorf in Germany, and her colleagues reported these findings in Cancer.

The researchers evaluated 235 families in which at least 1 parent was diagnosed with cancer. This included 402 parents and 324 children aged 11 to 21 years. Parents and children completed questionnaires that assessed emotional and behavioral health.

Responses suggested that children of cancer patients have higher-than-average levels of emotional and behavioral symptoms.

The overall mean values for emotional and behavioral problems—from both the parents’ and children’s perspectives—were significantly higher in the study population than the average values from a representative non-cancer population.

General family functioning was the strongest predictor of children’s symptom status from both the parents’ and child’s perspectives.

The effects of the child’s age and gender on behavioral and emotional symptoms varied according to the subject asked. But none of the respondents reported an association between child adjustment and illness-related factors such as poor prognoses or recurrent illness.

Dr Möller noted that screening for child mental health problems, family dysfunction, and parental depression can be easily adopted into cancer care so that families in need of support can be identified.

“Additional training of oncologists, interdisciplinary approaches, and family-based mental health liaison services are recommended to meet the needs of minor

children and their families and to minimize negative long-term effects in children,” she said.

Dr Möller and her team have developed a preventive counseling program—called the Children of Somatically Ill Parents (COSIP) program—that focuses on family communication, involvement of family members, flexible problem solving, mutual support, and parenting issues.

Doctor consults with a family

Credit: Rhoda Baer

A new analysis suggests family dysfunction is the greatest predictor of emotional and behavioral problems among children who have a parent with cancer.

Other variables, such as the child’s age, did not predict the risk as accurately.

And illness-related factors, such as the parent’s prognosis, did not appear to have an impact at all.

Birgit Möller, PhD, of the University Medical Center Hamburg-Eppendorf in Germany, and her colleagues reported these findings in Cancer.

The researchers evaluated 235 families in which at least 1 parent was diagnosed with cancer. This included 402 parents and 324 children aged 11 to 21 years. Parents and children completed questionnaires that assessed emotional and behavioral health.

Responses suggested that children of cancer patients have higher-than-average levels of emotional and behavioral symptoms.

The overall mean values for emotional and behavioral problems—from both the parents’ and children’s perspectives—were significantly higher in the study population than the average values from a representative non-cancer population.

General family functioning was the strongest predictor of children’s symptom status from both the parents’ and child’s perspectives.

The effects of the child’s age and gender on behavioral and emotional symptoms varied according to the subject asked. But none of the respondents reported an association between child adjustment and illness-related factors such as poor prognoses or recurrent illness.

Dr Möller noted that screening for child mental health problems, family dysfunction, and parental depression can be easily adopted into cancer care so that families in need of support can be identified.

“Additional training of oncologists, interdisciplinary approaches, and family-based mental health liaison services are recommended to meet the needs of minor

children and their families and to minimize negative long-term effects in children,” she said.

Dr Möller and her team have developed a preventive counseling program—called the Children of Somatically Ill Parents (COSIP) program—that focuses on family communication, involvement of family members, flexible problem solving, mutual support, and parenting issues.

Doctor consults with a cancer

patient and her father

Credit: Rhoda Baer

A new questionnaire can measure a cancer patient’s risk for financial stress, according to a paper published in Cancer.

Researchers developed the 11-item questionnaire, called the COmprehensive Score for financial Toxicity (COST), through conversations with more than 150 cancer patients.

The team used the term “financial toxicity” to describe the expense, anxiety, and loss of confidence confronting patients who face big, unpredictable costs of cancer treatment.

And the researchers said financial toxicity can be considered another side effect of cancer care.

“Few physicians discuss this increasingly significant side effect with their patients,” said study author Jonas de Souza, MD, of the University of Chicago Medicine in Illinois.

“Physicians aren’t trained to do this. It makes them, as well as patients, feel uncomfortable. [However,] we believe that a thoughtful, concise tool that could help predict a patient’s risk for financial toxicity might open the lines of communication. This gives us a way to launch that discussion.”

Development of the COST questionnaire began with a literature review and a series of extensive interviews. Dr de Souza and his colleagues spoke with 20 patients and 6 cancer professionals, as well as nurses and social workers, and this produced a list of 147 questions.

The researchers pared the list down to 58 questions. Then, they asked 35 patients to help them decide which of the remaining questions were the most important. And the patients narrowed the list down to 30.

“In the end, 155 patients led us, with some judicious editing, to a set of 11 statements,” Dr de Souza said. “This was sufficiently brief to prevent annoying those responding to the questions but thorough enough to get us the information we need.”

All 11 entries are short and easy to understand, according to the researchers. For example, item 2 states, “My out-of-pocket medical expenses are more than I thought they would be.” And item 7 states, “I am able to meet my monthly expenses.”

For each question, patients choose from 5 potential responses: “not at all”, “a little bit,” “somewhat,” “quite a bit,” or “very much.”

Learning how a patient responds may help caregivers determine who is likely to need education, financial counseling, or referral to a support network. The quiz may also predict who is likely to have problems and require interventions.

All patients who helped develop the study had been in treatment for at least 2 months and had received bills. Excluding the top 10% and the bottom 10%, patients in the study earned between $37,000 and $111,000. The median annual income for these patients was about $63,000.

The researchers expected that financial toxicity would correlate with income.

“But, in our small sample, that did not hold up,” Dr de Souza said. “People with less education seemed to have more financial distress, but variations in income did not make much difference. We need bigger studies to confirm that, but at least we now have a tool we can use to study this.”

The researchers are now conducting a larger study to validate these findings and correlate the newly developed scale with quality of life and anxiety in cancer patients.

“We need to assess outcomes that are important for patients,” Dr de Souza said. “[T]his is another important piece of information in the shared-decision-making process.”

Doctor consults with a cancer

patient and her father

Credit: Rhoda Baer

A new questionnaire can measure a cancer patient’s risk for financial stress, according to a paper published in Cancer.

Researchers developed the 11-item questionnaire, called the COmprehensive Score for financial Toxicity (COST), through conversations with more than 150 cancer patients.

The team used the term “financial toxicity” to describe the expense, anxiety, and loss of confidence confronting patients who face big, unpredictable costs of cancer treatment.

And the researchers said financial toxicity can be considered another side effect of cancer care.

“Few physicians discuss this increasingly significant side effect with their patients,” said study author Jonas de Souza, MD, of the University of Chicago Medicine in Illinois.

“Physicians aren’t trained to do this. It makes them, as well as patients, feel uncomfortable. [However,] we believe that a thoughtful, concise tool that could help predict a patient’s risk for financial toxicity might open the lines of communication. This gives us a way to launch that discussion.”

Development of the COST questionnaire began with a literature review and a series of extensive interviews. Dr de Souza and his colleagues spoke with 20 patients and 6 cancer professionals, as well as nurses and social workers, and this produced a list of 147 questions.

The researchers pared the list down to 58 questions. Then, they asked 35 patients to help them decide which of the remaining questions were the most important. And the patients narrowed the list down to 30.

“In the end, 155 patients led us, with some judicious editing, to a set of 11 statements,” Dr de Souza said. “This was sufficiently brief to prevent annoying those responding to the questions but thorough enough to get us the information we need.”

All 11 entries are short and easy to understand, according to the researchers. For example, item 2 states, “My out-of-pocket medical expenses are more than I thought they would be.” And item 7 states, “I am able to meet my monthly expenses.”

For each question, patients choose from 5 potential responses: “not at all”, “a little bit,” “somewhat,” “quite a bit,” or “very much.”

Learning how a patient responds may help caregivers determine who is likely to need education, financial counseling, or referral to a support network. The quiz may also predict who is likely to have problems and require interventions.

All patients who helped develop the study had been in treatment for at least 2 months and had received bills. Excluding the top 10% and the bottom 10%, patients in the study earned between $37,000 and $111,000. The median annual income for these patients was about $63,000.

The researchers expected that financial toxicity would correlate with income.

“But, in our small sample, that did not hold up,” Dr de Souza said. “People with less education seemed to have more financial distress, but variations in income did not make much difference. We need bigger studies to confirm that, but at least we now have a tool we can use to study this.”

The researchers are now conducting a larger study to validate these findings and correlate the newly developed scale with quality of life and anxiety in cancer patients.

“We need to assess outcomes that are important for patients,” Dr de Souza said. “[T]his is another important piece of information in the shared-decision-making process.”

Doctor consults with a cancer

patient and her father

Credit: Rhoda Baer

A new questionnaire can measure a cancer patient’s risk for financial stress, according to a paper published in Cancer.

Researchers developed the 11-item questionnaire, called the COmprehensive Score for financial Toxicity (COST), through conversations with more than 150 cancer patients.

The team used the term “financial toxicity” to describe the expense, anxiety, and loss of confidence confronting patients who face big, unpredictable costs of cancer treatment.

And the researchers said financial toxicity can be considered another side effect of cancer care.

“Few physicians discuss this increasingly significant side effect with their patients,” said study author Jonas de Souza, MD, of the University of Chicago Medicine in Illinois.

“Physicians aren’t trained to do this. It makes them, as well as patients, feel uncomfortable. [However,] we believe that a thoughtful, concise tool that could help predict a patient’s risk for financial toxicity might open the lines of communication. This gives us a way to launch that discussion.”

Development of the COST questionnaire began with a literature review and a series of extensive interviews. Dr de Souza and his colleagues spoke with 20 patients and 6 cancer professionals, as well as nurses and social workers, and this produced a list of 147 questions.

The researchers pared the list down to 58 questions. Then, they asked 35 patients to help them decide which of the remaining questions were the most important. And the patients narrowed the list down to 30.

“In the end, 155 patients led us, with some judicious editing, to a set of 11 statements,” Dr de Souza said. “This was sufficiently brief to prevent annoying those responding to the questions but thorough enough to get us the information we need.”

All 11 entries are short and easy to understand, according to the researchers. For example, item 2 states, “My out-of-pocket medical expenses are more than I thought they would be.” And item 7 states, “I am able to meet my monthly expenses.”

For each question, patients choose from 5 potential responses: “not at all”, “a little bit,” “somewhat,” “quite a bit,” or “very much.”

Learning how a patient responds may help caregivers determine who is likely to need education, financial counseling, or referral to a support network. The quiz may also predict who is likely to have problems and require interventions.

All patients who helped develop the study had been in treatment for at least 2 months and had received bills. Excluding the top 10% and the bottom 10%, patients in the study earned between $37,000 and $111,000. The median annual income for these patients was about $63,000.

The researchers expected that financial toxicity would correlate with income.

“But, in our small sample, that did not hold up,” Dr de Souza said. “People with less education seemed to have more financial distress, but variations in income did not make much difference. We need bigger studies to confirm that, but at least we now have a tool we can use to study this.”

The researchers are now conducting a larger study to validate these findings and correlate the newly developed scale with quality of life and anxiety in cancer patients.

“We need to assess outcomes that are important for patients,” Dr de Souza said. “[T]his is another important piece of information in the shared-decision-making process.”

CHICAGO—Investigators have found evidence to suggest that identifying central nervous system (CNS) involvement at diagnosis does not impact overall survival for patients with AIDS-related lymphoma (ARL).

The research showed that ARL patients with CNS involvement at diagnosis were nearly 3 times as likely as their peers to have CNS relapse during cancer treatment.

But there was no significant difference between the 2 groups with regard to survival.

This may be due to the low overall incidence of CNS relapse, the use of insufficient treatments, and/or inadequate methods for identifying patients with CNS involvement, according to the investigators.

Stefan K. Barta, MD, of the Fox Chase Cancer Center in Philadelphia, Pennsylvania, and his colleagues conducted this research and presented the results at the 2014 ASCO Annual Meeting (abstract 8570).

In 2013, Dr Barta led the assembly of a database containing medical data from more than 1500 patients newly diagnosed with ARL who participated in clinical trials in Europe and the US from 1990 through 2010.

In the new study, he and his colleagues used the database to identify 880 patients with ARL whose data included complete information on CNS involvement at diagnosis and CNS relapse.

The team set out to find associations between CNS relapse and patient characteristics, including age, sex, CD4 count, lymphoma subtype, treatment history with combination antiretroviral therapies (cART), rituximab use, and the type of initial chemotherapy.

All of the patients had received either intrathecal therapy for CNS involvement or intrathecal prophylaxis with single-agent or 3-agent regimens. Sixty-nine percent of patients (n=607) had received cART, and 31% (n=276) had received rituximab-containing induction chemoimmunotherapy.

CNS involvement was identified in 13% of patients at diagnosis, including 27% of patients with Burkitt lymphoma or Burkitt-like lymphoma and 6% of patients with diffuse large B-cell lymphoma.

There was no difference in the prevalence of baseline CNS involvement between patients treated before and after the introduction of cART (13% each).

In all, 5.3% of patients experienced CNS relapse at a median of 4.2 months after diagnosis (range, 0.3-19.3 months). This included 12% of patients diagnosed with CNS involvement at baseline and 4% of patients who were not.

The median overall survival after CNS relapse was 1.6 months (range, 0-86.4 months). There was no significant difference in overall survival between patients with CNS involvement at diagnosis and those without it. The hazard ratio was 0.85 (P=0.32).

Multivariate analysis showed the only baseline characteristic significantly associated with the frequency of CNS relapse was CNS involvement, with a hazard ratio of 2.9 (P=0.01). None of the treatments had a significant impact on CNS relapse.

Dr Barta said these results suggest that current treatments are insufficient, and the approaches used to identify CNS involvement may be missing many patients who are at risk of CNS relapse.

“A lot of patients who relapsed probably had undetected CNS involvement at diagnosis,” he said. “We want to figure out if there are better strategies to identify patients at risk.”

CHICAGO—Investigators have found evidence to suggest that identifying central nervous system (CNS) involvement at diagnosis does not impact overall survival for patients with AIDS-related lymphoma (ARL).

The research showed that ARL patients with CNS involvement at diagnosis were nearly 3 times as likely as their peers to have CNS relapse during cancer treatment.

But there was no significant difference between the 2 groups with regard to survival.

This may be due to the low overall incidence of CNS relapse, the use of insufficient treatments, and/or inadequate methods for identifying patients with CNS involvement, according to the investigators.

Stefan K. Barta, MD, of the Fox Chase Cancer Center in Philadelphia, Pennsylvania, and his colleagues conducted this research and presented the results at the 2014 ASCO Annual Meeting (abstract 8570).

In 2013, Dr Barta led the assembly of a database containing medical data from more than 1500 patients newly diagnosed with ARL who participated in clinical trials in Europe and the US from 1990 through 2010.

In the new study, he and his colleagues used the database to identify 880 patients with ARL whose data included complete information on CNS involvement at diagnosis and CNS relapse.

The team set out to find associations between CNS relapse and patient characteristics, including age, sex, CD4 count, lymphoma subtype, treatment history with combination antiretroviral therapies (cART), rituximab use, and the type of initial chemotherapy.

All of the patients had received either intrathecal therapy for CNS involvement or intrathecal prophylaxis with single-agent or 3-agent regimens. Sixty-nine percent of patients (n=607) had received cART, and 31% (n=276) had received rituximab-containing induction chemoimmunotherapy.

CNS involvement was identified in 13% of patients at diagnosis, including 27% of patients with Burkitt lymphoma or Burkitt-like lymphoma and 6% of patients with diffuse large B-cell lymphoma.

There was no difference in the prevalence of baseline CNS involvement between patients treated before and after the introduction of cART (13% each).

In all, 5.3% of patients experienced CNS relapse at a median of 4.2 months after diagnosis (range, 0.3-19.3 months). This included 12% of patients diagnosed with CNS involvement at baseline and 4% of patients who were not.

The median overall survival after CNS relapse was 1.6 months (range, 0-86.4 months). There was no significant difference in overall survival between patients with CNS involvement at diagnosis and those without it. The hazard ratio was 0.85 (P=0.32).

Multivariate analysis showed the only baseline characteristic significantly associated with the frequency of CNS relapse was CNS involvement, with a hazard ratio of 2.9 (P=0.01). None of the treatments had a significant impact on CNS relapse.

Dr Barta said these results suggest that current treatments are insufficient, and the approaches used to identify CNS involvement may be missing many patients who are at risk of CNS relapse.

“A lot of patients who relapsed probably had undetected CNS involvement at diagnosis,” he said. “We want to figure out if there are better strategies to identify patients at risk.”

CHICAGO—Investigators have found evidence to suggest that identifying central nervous system (CNS) involvement at diagnosis does not impact overall survival for patients with AIDS-related lymphoma (ARL).

The research showed that ARL patients with CNS involvement at diagnosis were nearly 3 times as likely as their peers to have CNS relapse during cancer treatment.

But there was no significant difference between the 2 groups with regard to survival.

This may be due to the low overall incidence of CNS relapse, the use of insufficient treatments, and/or inadequate methods for identifying patients with CNS involvement, according to the investigators.

Stefan K. Barta, MD, of the Fox Chase Cancer Center in Philadelphia, Pennsylvania, and his colleagues conducted this research and presented the results at the 2014 ASCO Annual Meeting (abstract 8570).

In 2013, Dr Barta led the assembly of a database containing medical data from more than 1500 patients newly diagnosed with ARL who participated in clinical trials in Europe and the US from 1990 through 2010.

In the new study, he and his colleagues used the database to identify 880 patients with ARL whose data included complete information on CNS involvement at diagnosis and CNS relapse.

The team set out to find associations between CNS relapse and patient characteristics, including age, sex, CD4 count, lymphoma subtype, treatment history with combination antiretroviral therapies (cART), rituximab use, and the type of initial chemotherapy.

All of the patients had received either intrathecal therapy for CNS involvement or intrathecal prophylaxis with single-agent or 3-agent regimens. Sixty-nine percent of patients (n=607) had received cART, and 31% (n=276) had received rituximab-containing induction chemoimmunotherapy.

CNS involvement was identified in 13% of patients at diagnosis, including 27% of patients with Burkitt lymphoma or Burkitt-like lymphoma and 6% of patients with diffuse large B-cell lymphoma.

There was no difference in the prevalence of baseline CNS involvement between patients treated before and after the introduction of cART (13% each).

In all, 5.3% of patients experienced CNS relapse at a median of 4.2 months after diagnosis (range, 0.3-19.3 months). This included 12% of patients diagnosed with CNS involvement at baseline and 4% of patients who were not.

The median overall survival after CNS relapse was 1.6 months (range, 0-86.4 months). There was no significant difference in overall survival between patients with CNS involvement at diagnosis and those without it. The hazard ratio was 0.85 (P=0.32).

Multivariate analysis showed the only baseline characteristic significantly associated with the frequency of CNS relapse was CNS involvement, with a hazard ratio of 2.9 (P=0.01). None of the treatments had a significant impact on CNS relapse.

Dr Barta said these results suggest that current treatments are insufficient, and the approaches used to identify CNS involvement may be missing many patients who are at risk of CNS relapse.

“A lot of patients who relapsed probably had undetected CNS involvement at diagnosis,” he said. “We want to figure out if there are better strategies to identify patients at risk.”

Info booth at ASCO 2014

©ASCO/Scott Morgan

CHICAGO—Substituting lenalidomide for thalidomide in the standard treatment of newly diagnosed multiple myeloma (MM) improves quality of life and

lowers toxicity without significant loss of response, results of a phase 3 study suggest.

Combination melphalan, prednisone, and thalidomide (MPT) is considered a standard treatment option for transplant ineligible, newly diagnosed MM.

Early phase 1/2 studies suggested substituting lenalidomide for thalidomide might result in similar efficacy and less toxicity.

“However, neither feature can be confidently predicted, since long-term follow-up of the melphalan, prednisone, and lenalidomide (MPR) regimen is lacking, and myelosuppression may prove limiting, compromising drug dose and efficacy,” said A. Keith Stewart, MD, from the Mayo Clinic in Scottsdale, Arizona.

So Dr Stewart and his colleagues conducted a randomized, multicenter, phase 3 trial comparing MPT to MPR in untreated, symptomatic, transplant-ineligible MM patients. Dr Stewart presented the results at the 2014 ASCO Annual Meeting as abstract 8511.

The study included 306 patients with a median age of 76 years. The primary objective was to evaluate the  difference in progression-free survival (PFS) between patients receiving MPT and those treated with MPR.

Patients received melphalan at 9 mg/m² and prednisone at 100 mg orally on days 1-4, with thalidomide at 100 mg daily. Or they received melphalan at 5 mg/m² and prednisone at 100 mg orally on days 1-4, with lenalidomide at 10 mg orally on days 1-21.

MPT or MPR therapy was continued for twelve 28-day cycles, followed by thalidomide at 100 mg or lenalidomide at 10 mg daily until relapse. Patients were required to have aspirin prophylaxis.

Secondary study objectives included overall survival, toxicities, response rates, depth of response, and quality of life change. Treatment arms were balanced for age, ISS stage, and other major prognostic factors.

The median follow-up was 40.7 months. The median time on therapy was 12 months overall and 23 months for the 46% of patients on maintenance therapy, with no differences by arm. Some 7% of patients remained on treatment through cycle 60.

The results showed similar response rates between the 2 arms. The partial response rate was 64% for the MPT group, compared with 60% for the MPR group, with no difference in very good partial response/complete response rates (18.8% vs 23%).

The median PFS was 21 months for patients receiving MPT and 18.7 months for those receiving MPR. The median overall survival was not significantly different between the arms—52.6% for the MPT arm and 47.7% for the MPR arm.

Toxicities of grade 3 or higher were significantly more likely in the MPT arm (73%) than in the MPR arm (58%), as was non-hematologic toxicity (59% and 40%, respectively).

The incidence of second primary malignancies was higher with MPT (3.47/100 person years) than with MPR (2.01/100 person years). And deep vein thrombosis or pulmonary embolism occurred in 8.8% of MPT patients and 6.7% MPR patients.

“The quality of life analysis favored MPR by induction end,” Dr Stewart said. “Response rates, PFS, and overall survival were similar between the 2 arms. However, there was significantly better quality of life at 12 months and lower toxicity with MPR.”

Dr Stewart noted, however, that in the US, “melphalan-based regimens are now seldom utilized due to availability of lenalidomide and bortezomib in newly diagnosed patients.”

Info booth at ASCO 2014

©ASCO/Scott Morgan

CHICAGO—Substituting lenalidomide for thalidomide in the standard treatment of newly diagnosed multiple myeloma (MM) improves quality of life and

lowers toxicity without significant loss of response, results of a phase 3 study suggest.

Combination melphalan, prednisone, and thalidomide (MPT) is considered a standard treatment option for transplant ineligible, newly diagnosed MM.

Early phase 1/2 studies suggested substituting lenalidomide for thalidomide might result in similar efficacy and less toxicity.

“However, neither feature can be confidently predicted, since long-term follow-up of the melphalan, prednisone, and lenalidomide (MPR) regimen is lacking, and myelosuppression may prove limiting, compromising drug dose and efficacy,” said A. Keith Stewart, MD, from the Mayo Clinic in Scottsdale, Arizona.

So Dr Stewart and his colleagues conducted a randomized, multicenter, phase 3 trial comparing MPT to MPR in untreated, symptomatic, transplant-ineligible MM patients. Dr Stewart presented the results at the 2014 ASCO Annual Meeting as abstract 8511.

The study included 306 patients with a median age of 76 years. The primary objective was to evaluate the  difference in progression-free survival (PFS) between patients receiving MPT and those treated with MPR.

Patients received melphalan at 9 mg/m² and prednisone at 100 mg orally on days 1-4, with thalidomide at 100 mg daily. Or they received melphalan at 5 mg/m² and prednisone at 100 mg orally on days 1-4, with lenalidomide at 10 mg orally on days 1-21.

MPT or MPR therapy was continued for twelve 28-day cycles, followed by thalidomide at 100 mg or lenalidomide at 10 mg daily until relapse. Patients were required to have aspirin prophylaxis.

Secondary study objectives included overall survival, toxicities, response rates, depth of response, and quality of life change. Treatment arms were balanced for age, ISS stage, and other major prognostic factors.

The median follow-up was 40.7 months. The median time on therapy was 12 months overall and 23 months for the 46% of patients on maintenance therapy, with no differences by arm. Some 7% of patients remained on treatment through cycle 60.

The results showed similar response rates between the 2 arms. The partial response rate was 64% for the MPT group, compared with 60% for the MPR group, with no difference in very good partial response/complete response rates (18.8% vs 23%).

The median PFS was 21 months for patients receiving MPT and 18.7 months for those receiving MPR. The median overall survival was not significantly different between the arms—52.6% for the MPT arm and 47.7% for the MPR arm.

Toxicities of grade 3 or higher were significantly more likely in the MPT arm (73%) than in the MPR arm (58%), as was non-hematologic toxicity (59% and 40%, respectively).

The incidence of second primary malignancies was higher with MPT (3.47/100 person years) than with MPR (2.01/100 person years). And deep vein thrombosis or pulmonary embolism occurred in 8.8% of MPT patients and 6.7% MPR patients.

“The quality of life analysis favored MPR by induction end,” Dr Stewart said. “Response rates, PFS, and overall survival were similar between the 2 arms. However, there was significantly better quality of life at 12 months and lower toxicity with MPR.”

Dr Stewart noted, however, that in the US, “melphalan-based regimens are now seldom utilized due to availability of lenalidomide and bortezomib in newly diagnosed patients.”

Info booth at ASCO 2014

©ASCO/Scott Morgan

CHICAGO—Substituting lenalidomide for thalidomide in the standard treatment of newly diagnosed multiple myeloma (MM) improves quality of life and

lowers toxicity without significant loss of response, results of a phase 3 study suggest.

Combination melphalan, prednisone, and thalidomide (MPT) is considered a standard treatment option for transplant ineligible, newly diagnosed MM.

Early phase 1/2 studies suggested substituting lenalidomide for thalidomide might result in similar efficacy and less toxicity.

“However, neither feature can be confidently predicted, since long-term follow-up of the melphalan, prednisone, and lenalidomide (MPR) regimen is lacking, and myelosuppression may prove limiting, compromising drug dose and efficacy,” said A. Keith Stewart, MD, from the Mayo Clinic in Scottsdale, Arizona.

So Dr Stewart and his colleagues conducted a randomized, multicenter, phase 3 trial comparing MPT to MPR in untreated, symptomatic, transplant-ineligible MM patients. Dr Stewart presented the results at the 2014 ASCO Annual Meeting as abstract 8511.

The study included 306 patients with a median age of 76 years. The primary objective was to evaluate the  difference in progression-free survival (PFS) between patients receiving MPT and those treated with MPR.

Patients received melphalan at 9 mg/m² and prednisone at 100 mg orally on days 1-4, with thalidomide at 100 mg daily. Or they received melphalan at 5 mg/m² and prednisone at 100 mg orally on days 1-4, with lenalidomide at 10 mg orally on days 1-21.

MPT or MPR therapy was continued for twelve 28-day cycles, followed by thalidomide at 100 mg or lenalidomide at 10 mg daily until relapse. Patients were required to have aspirin prophylaxis.

Secondary study objectives included overall survival, toxicities, response rates, depth of response, and quality of life change. Treatment arms were balanced for age, ISS stage, and other major prognostic factors.

The median follow-up was 40.7 months. The median time on therapy was 12 months overall and 23 months for the 46% of patients on maintenance therapy, with no differences by arm. Some 7% of patients remained on treatment through cycle 60.

The results showed similar response rates between the 2 arms. The partial response rate was 64% for the MPT group, compared with 60% for the MPR group, with no difference in very good partial response/complete response rates (18.8% vs 23%).

The median PFS was 21 months for patients receiving MPT and 18.7 months for those receiving MPR. The median overall survival was not significantly different between the arms—52.6% for the MPT arm and 47.7% for the MPR arm.

Toxicities of grade 3 or higher were significantly more likely in the MPT arm (73%) than in the MPR arm (58%), as was non-hematologic toxicity (59% and 40%, respectively).

The incidence of second primary malignancies was higher with MPT (3.47/100 person years) than with MPR (2.01/100 person years). And deep vein thrombosis or pulmonary embolism occurred in 8.8% of MPT patients and 6.7% MPR patients.

“The quality of life analysis favored MPR by induction end,” Dr Stewart said. “Response rates, PFS, and overall survival were similar between the 2 arms. However, there was significantly better quality of life at 12 months and lower toxicity with MPR.”

Dr Stewart noted, however, that in the US, “melphalan-based regimens are now seldom utilized due to availability of lenalidomide and bortezomib in newly diagnosed patients.”

Tumor cells producing p53

Credit: A.T. Tikhonenko

A novel sequencing technique has allowed researchers to identify direct targets of p53, providing new insight into this gene’s anticancer activity.

The research, published in eLife, revealed nearly 200 genes that were directly regulated by p53, and many of these had never been identified before.

The study’s authors said this work lays the foundation for investigations into which of these genes are necessary for p53’s cancer-killing effects and how cancer cells evade these genes.

The researchers noted that all cancers must deal with p53’s antitumor effects. Generally, there are 2 ways they do this: by mutating p53 directly or by producing the protein MDM2, which inhibits p53 function. With the current study, the team explored the second strategy.

“MDM2 inhibitors, which are through phase 1 human trials, effectively activate p53 but manage to kill only about 1 in 20 tumors,” said study author Joaquín Espinosa, PhD, of the University of Colorado in Boulder.

“The question is why. What else is happening in these cancer cells that allow them to evade p53?”

According to the researchers, the answer is in the downstream effects of p53. The gene sets in motion a cascade of events that lead to cancer cell destruction. But it has been unclear exactly which other genes are directly activated by p53.

To identify genetic targets of p53, Dr Espinosa and his colleagues used a technique called Global Run-On Sequencing (GRO-Seq). Unlike other methods, GRO-Seq measures new RNA being created, not overall RNA levels.

“Many teams around the world have been getting cancer cells, treating them with MDM2 inhibitors, and waiting hours and hours to see what genes turn on, and then, only imprecisely,” Dr Espinosa said. “GRO-Seq lets us do it in minutes, and the discoveries are massive.”

The technique generates a large quantity of data because it requires counting tens of thousands of RNA molecules before and after p53 activation. So this research required designing algorithms to sort through the data, as well as a computational biologist driving a supercomputer.

But the researchers were able to pinpoint new genes directly regulated by p53. And they believe this could aid the future development of cancer-fighting strategies.

Tumor cells producing p53

Credit: A.T. Tikhonenko

A novel sequencing technique has allowed researchers to identify direct targets of p53, providing new insight into this gene’s anticancer activity.

The research, published in eLife, revealed nearly 200 genes that were directly regulated by p53, and many of these had never been identified before.

The study’s authors said this work lays the foundation for investigations into which of these genes are necessary for p53’s cancer-killing effects and how cancer cells evade these genes.

The researchers noted that all cancers must deal with p53’s antitumor effects. Generally, there are 2 ways they do this: by mutating p53 directly or by producing the protein MDM2, which inhibits p53 function. With the current study, the team explored the second strategy.

“MDM2 inhibitors, which are through phase 1 human trials, effectively activate p53 but manage to kill only about 1 in 20 tumors,” said study author Joaquín Espinosa, PhD, of the University of Colorado in Boulder.

“The question is why. What else is happening in these cancer cells that allow them to evade p53?”

According to the researchers, the answer is in the downstream effects of p53. The gene sets in motion a cascade of events that lead to cancer cell destruction. But it has been unclear exactly which other genes are directly activated by p53.

To identify genetic targets of p53, Dr Espinosa and his colleagues used a technique called Global Run-On Sequencing (GRO-Seq). Unlike other methods, GRO-Seq measures new RNA being created, not overall RNA levels.

“Many teams around the world have been getting cancer cells, treating them with MDM2 inhibitors, and waiting hours and hours to see what genes turn on, and then, only imprecisely,” Dr Espinosa said. “GRO-Seq lets us do it in minutes, and the discoveries are massive.”

The technique generates a large quantity of data because it requires counting tens of thousands of RNA molecules before and after p53 activation. So this research required designing algorithms to sort through the data, as well as a computational biologist driving a supercomputer.

But the researchers were able to pinpoint new genes directly regulated by p53. And they believe this could aid the future development of cancer-fighting strategies.

Tumor cells producing p53

Credit: A.T. Tikhonenko

A novel sequencing technique has allowed researchers to identify direct targets of p53, providing new insight into this gene’s anticancer activity.

The research, published in eLife, revealed nearly 200 genes that were directly regulated by p53, and many of these had never been identified before.

The study’s authors said this work lays the foundation for investigations into which of these genes are necessary for p53’s cancer-killing effects and how cancer cells evade these genes.

The researchers noted that all cancers must deal with p53’s antitumor effects. Generally, there are 2 ways they do this: by mutating p53 directly or by producing the protein MDM2, which inhibits p53 function. With the current study, the team explored the second strategy.

“MDM2 inhibitors, which are through phase 1 human trials, effectively activate p53 but manage to kill only about 1 in 20 tumors,” said study author Joaquín Espinosa, PhD, of the University of Colorado in Boulder.

“The question is why. What else is happening in these cancer cells that allow them to evade p53?”

According to the researchers, the answer is in the downstream effects of p53. The gene sets in motion a cascade of events that lead to cancer cell destruction. But it has been unclear exactly which other genes are directly activated by p53.

To identify genetic targets of p53, Dr Espinosa and his colleagues used a technique called Global Run-On Sequencing (GRO-Seq). Unlike other methods, GRO-Seq measures new RNA being created, not overall RNA levels.

“Many teams around the world have been getting cancer cells, treating them with MDM2 inhibitors, and waiting hours and hours to see what genes turn on, and then, only imprecisely,” Dr Espinosa said. “GRO-Seq lets us do it in minutes, and the discoveries are massive.”

The technique generates a large quantity of data because it requires counting tens of thousands of RNA molecules before and after p53 activation. So this research required designing algorithms to sort through the data, as well as a computational biologist driving a supercomputer.

But the researchers were able to pinpoint new genes directly regulated by p53. And they believe this could aid the future development of cancer-fighting strategies.

Cancer patient receives therapy

Credit: Rhoda Baer

Results of a large study suggest certain malignanices are more concentrated in areas with high levels of poverty, while other cancer types arise more often in wealthy regions.

The research, conducted using data from nearly 3 million US cancer cases, also indicated that areas with higher poverty levels tended to have a lower cancer incidence but higher mortality rate than areas with lower poverty levels.

Researchers reported these findings in the journal Cancer.

Francis Boscoe, PhD, of the New York State Cancer Registry in Albany, and his colleagues conducted this research to evaluate the role of socioeconomics in cancer incidence and mortality.

So the team compared individuals living in areas with the highest poverty levels to those living in areas with the lowest poverty levels.

The researchers collected information on nearly 3 million cancer cases diagnosed between 2005 and 2009 in16 states, plus Los Angeles (an area covering 42% of the US population). Cases were divided into 1 of 4 groupings based on the poverty rate of the residential census tract at the time of diagnosis.

For all malignancies combined, there was a negligible association between cancer incidence and poverty. However, 32 of 39 cancer types showed a significant association with poverty.

Fourteen cancers were positively associated with poverty, and 18 were negatively associated. Myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma (NHL) were among the negatively associated malignancies.

The cancers most significantly associated with higher poverty levels were Kaposi sarcoma and cancers of the larynx, cervix, penis, and liver. The cancers most significantly associated with lower poverty levels were melanoma, thyroid cancer, other non-epithelial skin cancers, and testis cancer.

Overall, male malignancy rates were more sensitive to poverty level than female rates. And, in general, the race-specific cancer incidence rates differed, but the poverty gradients were similar.

For example, there was a roughly 20-fold difference in rates of melanoma between white and black individuals, but the relationship between poverty and incidence remained regardless of race.

This was not true for NHL, however. Among black individuals, the incidence of NHL increased as the poverty level increased. But among white individuals, the incidence of NHL decreased as the poverty level increased.

The researchers pointed out that—for all cancer sites, races, and sexes combined—the difference in risk between the greatest and lowest poverty category was less than 2%.

“At first glance, the effects seem to cancel one another out,” Dr Boscoe said. “But the cancers more associated with poverty have lower incidence and higher mortality, and those associated with wealth have higher incidence and lower mortality. When it comes to cancer, the poor are more likely to die of the disease, while the affluent are more likely to die with the disease.”

Dr Boscoe noted that recent gains in technology have made it much easier to link patient addresses with neighborhood characteristics, therefore making it possible to incorporate socioeconomic status into cancer surveillance.

“Our hope is that our paper will illustrate the value and necessity of doing this routinely in the future,” he concluded.

Cancer patient receives therapy

Credit: Rhoda Baer

Results of a large study suggest certain malignanices are more concentrated in areas with high levels of poverty, while other cancer types arise more often in wealthy regions.

The research, conducted using data from nearly 3 million US cancer cases, also indicated that areas with higher poverty levels tended to have a lower cancer incidence but higher mortality rate than areas with lower poverty levels.

Researchers reported these findings in the journal Cancer.

Francis Boscoe, PhD, of the New York State Cancer Registry in Albany, and his colleagues conducted this research to evaluate the role of socioeconomics in cancer incidence and mortality.

So the team compared individuals living in areas with the highest poverty levels to those living in areas with the lowest poverty levels.

The researchers collected information on nearly 3 million cancer cases diagnosed between 2005 and 2009 in16 states, plus Los Angeles (an area covering 42% of the US population). Cases were divided into 1 of 4 groupings based on the poverty rate of the residential census tract at the time of diagnosis.

For all malignancies combined, there was a negligible association between cancer incidence and poverty. However, 32 of 39 cancer types showed a significant association with poverty.

Fourteen cancers were positively associated with poverty, and 18 were negatively associated. Myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma (NHL) were among the negatively associated malignancies.

The cancers most significantly associated with higher poverty levels were Kaposi sarcoma and cancers of the larynx, cervix, penis, and liver. The cancers most significantly associated with lower poverty levels were melanoma, thyroid cancer, other non-epithelial skin cancers, and testis cancer.

Overall, male malignancy rates were more sensitive to poverty level than female rates. And, in general, the race-specific cancer incidence rates differed, but the poverty gradients were similar.

For example, there was a roughly 20-fold difference in rates of melanoma between white and black individuals, but the relationship between poverty and incidence remained regardless of race.

This was not true for NHL, however. Among black individuals, the incidence of NHL increased as the poverty level increased. But among white individuals, the incidence of NHL decreased as the poverty level increased.

The researchers pointed out that—for all cancer sites, races, and sexes combined—the difference in risk between the greatest and lowest poverty category was less than 2%.

“At first glance, the effects seem to cancel one another out,” Dr Boscoe said. “But the cancers more associated with poverty have lower incidence and higher mortality, and those associated with wealth have higher incidence and lower mortality. When it comes to cancer, the poor are more likely to die of the disease, while the affluent are more likely to die with the disease.”

Dr Boscoe noted that recent gains in technology have made it much easier to link patient addresses with neighborhood characteristics, therefore making it possible to incorporate socioeconomic status into cancer surveillance.

“Our hope is that our paper will illustrate the value and necessity of doing this routinely in the future,” he concluded.

Cancer patient receives therapy

Credit: Rhoda Baer

Results of a large study suggest certain malignanices are more concentrated in areas with high levels of poverty, while other cancer types arise more often in wealthy regions.

The research, conducted using data from nearly 3 million US cancer cases, also indicated that areas with higher poverty levels tended to have a lower cancer incidence but higher mortality rate than areas with lower poverty levels.

Researchers reported these findings in the journal Cancer.

Francis Boscoe, PhD, of the New York State Cancer Registry in Albany, and his colleagues conducted this research to evaluate the role of socioeconomics in cancer incidence and mortality.

So the team compared individuals living in areas with the highest poverty levels to those living in areas with the lowest poverty levels.

The researchers collected information on nearly 3 million cancer cases diagnosed between 2005 and 2009 in16 states, plus Los Angeles (an area covering 42% of the US population). Cases were divided into 1 of 4 groupings based on the poverty rate of the residential census tract at the time of diagnosis.

For all malignancies combined, there was a negligible association between cancer incidence and poverty. However, 32 of 39 cancer types showed a significant association with poverty.

Fourteen cancers were positively associated with poverty, and 18 were negatively associated. Myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma (NHL) were among the negatively associated malignancies.

The cancers most significantly associated with higher poverty levels were Kaposi sarcoma and cancers of the larynx, cervix, penis, and liver. The cancers most significantly associated with lower poverty levels were melanoma, thyroid cancer, other non-epithelial skin cancers, and testis cancer.

Overall, male malignancy rates were more sensitive to poverty level than female rates. And, in general, the race-specific cancer incidence rates differed, but the poverty gradients were similar.

For example, there was a roughly 20-fold difference in rates of melanoma between white and black individuals, but the relationship between poverty and incidence remained regardless of race.

This was not true for NHL, however. Among black individuals, the incidence of NHL increased as the poverty level increased. But among white individuals, the incidence of NHL decreased as the poverty level increased.

The researchers pointed out that—for all cancer sites, races, and sexes combined—the difference in risk between the greatest and lowest poverty category was less than 2%.

“At first glance, the effects seem to cancel one another out,” Dr Boscoe said. “But the cancers more associated with poverty have lower incidence and higher mortality, and those associated with wealth have higher incidence and lower mortality. When it comes to cancer, the poor are more likely to die of the disease, while the affluent are more likely to die with the disease.”

Dr Boscoe noted that recent gains in technology have made it much easier to link patient addresses with neighborhood characteristics, therefore making it possible to incorporate socioeconomic status into cancer surveillance.

“Our hope is that our paper will illustrate the value and necessity of doing this routinely in the future,” he concluded.

Cancer patient receives therapy

Credit: Rhoda Baer

A review of clinical trial data from 2012 suggests Hispanic patients are underrepresented in US cancer studies, and many trial publications fail to provide information on patients’ racial/ethnic backgrounds.

Researchers analyzed 159 reports of phase 2 and 3 trials and found that roughly 21% included information on the number of minority patients enrolled.

About 8% of the publications included data on the number of Hispanic patients enrolled.

And from this data, the investigators found the accrual rate for Hispanic patients was about 4%.

According to the researchers, this lack of information and low representation inhibits physicians’ ability to provide optimal treatment to Hispanic cancer patients and patients belonging to other minority groups.

“We have a major responsibility to ensure adequate representation,” said study author Ian M. Thompson Jr, MD, of The University of Texas Health Science Center at San Antonio.

“How else will we know how best to treat our patients, and how else are we going to reduce the health disparities in [the Hispanic] population?”

Dr Thompson and his colleagues have a particular interest in the Hispanic population because 58% of San Antonio residents are Hispanic, as are 68% of residents in South Texas as a whole.

So the investigators wanted to determine Hispanic accrual rates in randomized trials of cancer patients. The team evaluated data from phase 2 and 3 cancer trials published in 2012. They focused on studies that were considered likely to change the standard of care and were published in “high-impact” journals.

The researchers identified 159 trials—68 phase 2 studies and 91 phase 3 studies. They discovered that 33 of the trial publications—about 21%—disclosed data on minority accrual. And 13 publications—about 8%—included data on the accrual of Hispanic cancer patients.

Of the 4154 patients enrolled on those 13 trials, 162 were Hispanic, which translates to an overall accrual rate of 3.9%. The enrollment of Hispanic patients ranged from 1 patient (0.5%) in a phase 2 trial of lung cancer to 17 patients (26%) in a phase 2 study of acute lymphoblastic leukemia.

“Fundamentally, in the most recent published cancer clinical trials, either the number and proportion of Hispanics are not reported or are far below their actual representation in the national population,” Dr Thompson summarized.

“For institutions like ours that serve a ‘minority-majority’ population, it’s a major responsibility for us to ensure adequate representation so that we can tell our patients how they can best be treated and how we can reduce the disparities of this rapidly growing population.”

Dr Thompson and his colleagues described this research in the Journal of Clinical Oncology.

Cancer patient receives therapy

Credit: Rhoda Baer

A review of clinical trial data from 2012 suggests Hispanic patients are underrepresented in US cancer studies, and many trial publications fail to provide information on patients’ racial/ethnic backgrounds.

Researchers analyzed 159 reports of phase 2 and 3 trials and found that roughly 21% included information on the number of minority patients enrolled.

About 8% of the publications included data on the number of Hispanic patients enrolled.

And from this data, the investigators found the accrual rate for Hispanic patients was about 4%.

According to the researchers, this lack of information and low representation inhibits physicians’ ability to provide optimal treatment to Hispanic cancer patients and patients belonging to other minority groups.

“We have a major responsibility to ensure adequate representation,” said study author Ian M. Thompson Jr, MD, of The University of Texas Health Science Center at San Antonio.

“How else will we know how best to treat our patients, and how else are we going to reduce the health disparities in [the Hispanic] population?”

Dr Thompson and his colleagues have a particular interest in the Hispanic population because 58% of San Antonio residents are Hispanic, as are 68% of residents in South Texas as a whole.

So the investigators wanted to determine Hispanic accrual rates in randomized trials of cancer patients. The team evaluated data from phase 2 and 3 cancer trials published in 2012. They focused on studies that were considered likely to change the standard of care and were published in “high-impact” journals.

The researchers identified 159 trials—68 phase 2 studies and 91 phase 3 studies. They discovered that 33 of the trial publications—about 21%—disclosed data on minority accrual. And 13 publications—about 8%—included data on the accrual of Hispanic cancer patients.

Of the 4154 patients enrolled on those 13 trials, 162 were Hispanic, which translates to an overall accrual rate of 3.9%. The enrollment of Hispanic patients ranged from 1 patient (0.5%) in a phase 2 trial of lung cancer to 17 patients (26%) in a phase 2 study of acute lymphoblastic leukemia.

“Fundamentally, in the most recent published cancer clinical trials, either the number and proportion of Hispanics are not reported or are far below their actual representation in the national population,” Dr Thompson summarized.

“For institutions like ours that serve a ‘minority-majority’ population, it’s a major responsibility for us to ensure adequate representation so that we can tell our patients how they can best be treated and how we can reduce the disparities of this rapidly growing population.”

Dr Thompson and his colleagues described this research in the Journal of Clinical Oncology.

Cancer patient receives therapy

Credit: Rhoda Baer

A review of clinical trial data from 2012 suggests Hispanic patients are underrepresented in US cancer studies, and many trial publications fail to provide information on patients’ racial/ethnic backgrounds.

Researchers analyzed 159 reports of phase 2 and 3 trials and found that roughly 21% included information on the number of minority patients enrolled.

About 8% of the publications included data on the number of Hispanic patients enrolled.

And from this data, the investigators found the accrual rate for Hispanic patients was about 4%.

According to the researchers, this lack of information and low representation inhibits physicians’ ability to provide optimal treatment to Hispanic cancer patients and patients belonging to other minority groups.

“We have a major responsibility to ensure adequate representation,” said study author Ian M. Thompson Jr, MD, of The University of Texas Health Science Center at San Antonio.

“How else will we know how best to treat our patients, and how else are we going to reduce the health disparities in [the Hispanic] population?”

Dr Thompson and his colleagues have a particular interest in the Hispanic population because 58% of San Antonio residents are Hispanic, as are 68% of residents in South Texas as a whole.

So the investigators wanted to determine Hispanic accrual rates in randomized trials of cancer patients. The team evaluated data from phase 2 and 3 cancer trials published in 2012. They focused on studies that were considered likely to change the standard of care and were published in “high-impact” journals.

The researchers identified 159 trials—68 phase 2 studies and 91 phase 3 studies. They discovered that 33 of the trial publications—about 21%—disclosed data on minority accrual. And 13 publications—about 8%—included data on the accrual of Hispanic cancer patients.

Of the 4154 patients enrolled on those 13 trials, 162 were Hispanic, which translates to an overall accrual rate of 3.9%. The enrollment of Hispanic patients ranged from 1 patient (0.5%) in a phase 2 trial of lung cancer to 17 patients (26%) in a phase 2 study of acute lymphoblastic leukemia.

“Fundamentally, in the most recent published cancer clinical trials, either the number and proportion of Hispanics are not reported or are far below their actual representation in the national population,” Dr Thompson summarized.

“For institutions like ours that serve a ‘minority-majority’ population, it’s a major responsibility for us to ensure adequate representation so that we can tell our patients how they can best be treated and how we can reduce the disparities of this rapidly growing population.”

Dr Thompson and his colleagues described this research in the Journal of Clinical Oncology.

Monoclonal antibodies

Credit: Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for elotuzumab, a humanized monoclonal antibody

(mAb).

The designation is for elotuzumab used in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received 1 or more prior therapies.

The FDA’s decision is based on findings from a phase 2 trial in which MM patients received that treatment combination.

According to the FDA, breakthrough designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. For a treatment to receive this designation, there must be preliminary clinical evidence that demonstrates the drug may offer substantial improvement over currently available therapy on at least 1 clinically significant endpoint.

About elotuzumab

Elotuzumab is a humanized IgG1 mAb targeting signaling lymphocyte activation molecule (SLAMF7, also known as CS1), a glycoprotein expressed on myeloma and natural killer cells but not detectable in normal tissue.

Researchers are investigating whether, through both direct activation and engagement of natural killer cells, elotuzumab may selectively target and kill SLAMF7-expressing myeloma cells.

Elotuzumab is under investigation as a monotherapy in smoldering myeloma and in combination with other therapies in first-line and relapsed or refractory MM.

A clinical development program for the mAb is underway, including phase 3 trials in first-line MM (ELOQUENT-1) and relapsed or refractory MM (ELOQUENT-2). The agent is also under investigation in a randomized, phase 2 study of bortezomib and dexamethasone in patients with relapsed or refractory MM.

Elotuzumab is under development by AbbVie and Bristol-Myers Squibb.

Phase 2 trial results

The breakthrough therapy designation for elotuzumab is based on results of a randomized, phase 2 trial presented at the EHA 2013 Annual Congress (abstract 14). Study investigators tested 2 doses of the mAb in combination with lenalidomide and low-dose dexamethasone in patients with previously treated MM.

Patients were randomized 1:1 to receive elotuzumab at 10 mg/kg or 20 mg/kg (intravenous infusion on days 1, 8, 15, and 22 of a 28-day cycle in the first 2 cycles and then days 1 and 15 of subsequent cycles) in combination with oral lenalidomide at 25 mg/day on days 1 to 21 and oral dexamethasone at 40 mg/week. Patients were treated until their disease progressed or they developed unacceptable toxicity.

In the 10 mg/kg arm (n=36), which is the dose used in the ongoing phase 3 trials, the median progression-free survival was 33 months, after a median follow-up of 20.8 months. And the objective response rate was 92%.

In the 20 mg/kg arm (n=37), the median progression-free survival was 18 months, after a median follow-up of 17.1 months. And the objective response rate was 76%.

The safety data were consistent with previously reported results for elotuzumab from this trial. In patients receiving elotuzumab at 10 mg/kg or 20 mg/kg, most treatment-emergent adverse events occurred within 18 months of starting therapy.

The most common grade 3/4 adverse events for the 10 mg/kg and 20 mg/kg arms, respectively, were lymphopenia (26% and 9%), neutropenia (21% and 22%), thrombocytopenia (21% and 17%), anemia (13% and 12%), leukopenia (8% and 7%), hyperglycemia (5% and 12%), pneumonia (8% and 5%), diarrhea (10% and 5%), fatigue (8% and 9%), and hypokalemia (8% and 5%).

Two deaths occurred on study. One patient died of pneumonia, multiple organ failure, and sepsis. The other died of disease progression.

Monoclonal antibodies

Credit: Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for elotuzumab, a humanized monoclonal antibody

(mAb).

The designation is for elotuzumab used in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received 1 or more prior therapies.

The FDA’s decision is based on findings from a phase 2 trial in which MM patients received that treatment combination.

According to the FDA, breakthrough designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. For a treatment to receive this designation, there must be preliminary clinical evidence that demonstrates the drug may offer substantial improvement over currently available therapy on at least 1 clinically significant endpoint.

About elotuzumab

Elotuzumab is a humanized IgG1 mAb targeting signaling lymphocyte activation molecule (SLAMF7, also known as CS1), a glycoprotein expressed on myeloma and natural killer cells but not detectable in normal tissue.

Researchers are investigating whether, through both direct activation and engagement of natural killer cells, elotuzumab may selectively target and kill SLAMF7-expressing myeloma cells.

Elotuzumab is under investigation as a monotherapy in smoldering myeloma and in combination with other therapies in first-line and relapsed or refractory MM.

A clinical development program for the mAb is underway, including phase 3 trials in first-line MM (ELOQUENT-1) and relapsed or refractory MM (ELOQUENT-2). The agent is also under investigation in a randomized, phase 2 study of bortezomib and dexamethasone in patients with relapsed or refractory MM.

Elotuzumab is under development by AbbVie and Bristol-Myers Squibb.

Phase 2 trial results

The breakthrough therapy designation for elotuzumab is based on results of a randomized, phase 2 trial presented at the EHA 2013 Annual Congress (abstract 14). Study investigators tested 2 doses of the mAb in combination with lenalidomide and low-dose dexamethasone in patients with previously treated MM.

Patients were randomized 1:1 to receive elotuzumab at 10 mg/kg or 20 mg/kg (intravenous infusion on days 1, 8, 15, and 22 of a 28-day cycle in the first 2 cycles and then days 1 and 15 of subsequent cycles) in combination with oral lenalidomide at 25 mg/day on days 1 to 21 and oral dexamethasone at 40 mg/week. Patients were treated until their disease progressed or they developed unacceptable toxicity.

In the 10 mg/kg arm (n=36), which is the dose used in the ongoing phase 3 trials, the median progression-free survival was 33 months, after a median follow-up of 20.8 months. And the objective response rate was 92%.

In the 20 mg/kg arm (n=37), the median progression-free survival was 18 months, after a median follow-up of 17.1 months. And the objective response rate was 76%.

The safety data were consistent with previously reported results for elotuzumab from this trial. In patients receiving elotuzumab at 10 mg/kg or 20 mg/kg, most treatment-emergent adverse events occurred within 18 months of starting therapy.

The most common grade 3/4 adverse events for the 10 mg/kg and 20 mg/kg arms, respectively, were lymphopenia (26% and 9%), neutropenia (21% and 22%), thrombocytopenia (21% and 17%), anemia (13% and 12%), leukopenia (8% and 7%), hyperglycemia (5% and 12%), pneumonia (8% and 5%), diarrhea (10% and 5%), fatigue (8% and 9%), and hypokalemia (8% and 5%).

Two deaths occurred on study. One patient died of pneumonia, multiple organ failure, and sepsis. The other died of disease progression.

Monoclonal antibodies

Credit: Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for elotuzumab, a humanized monoclonal antibody

(mAb).

The designation is for elotuzumab used in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received 1 or more prior therapies.

The FDA’s decision is based on findings from a phase 2 trial in which MM patients received that treatment combination.

According to the FDA, breakthrough designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. For a treatment to receive this designation, there must be preliminary clinical evidence that demonstrates the drug may offer substantial improvement over currently available therapy on at least 1 clinically significant endpoint.

About elotuzumab

Elotuzumab is a humanized IgG1 mAb targeting signaling lymphocyte activation molecule (SLAMF7, also known as CS1), a glycoprotein expressed on myeloma and natural killer cells but not detectable in normal tissue.

Researchers are investigating whether, through both direct activation and engagement of natural killer cells, elotuzumab may selectively target and kill SLAMF7-expressing myeloma cells.

Elotuzumab is under investigation as a monotherapy in smoldering myeloma and in combination with other therapies in first-line and relapsed or refractory MM.

A clinical development program for the mAb is underway, including phase 3 trials in first-line MM (ELOQUENT-1) and relapsed or refractory MM (ELOQUENT-2). The agent is also under investigation in a randomized, phase 2 study of bortezomib and dexamethasone in patients with relapsed or refractory MM.

Elotuzumab is under development by AbbVie and Bristol-Myers Squibb.

Phase 2 trial results

The breakthrough therapy designation for elotuzumab is based on results of a randomized, phase 2 trial presented at the EHA 2013 Annual Congress (abstract 14). Study investigators tested 2 doses of the mAb in combination with lenalidomide and low-dose dexamethasone in patients with previously treated MM.

Patients were randomized 1:1 to receive elotuzumab at 10 mg/kg or 20 mg/kg (intravenous infusion on days 1, 8, 15, and 22 of a 28-day cycle in the first 2 cycles and then days 1 and 15 of subsequent cycles) in combination with oral lenalidomide at 25 mg/day on days 1 to 21 and oral dexamethasone at 40 mg/week. Patients were treated until their disease progressed or they developed unacceptable toxicity.

In the 10 mg/kg arm (n=36), which is the dose used in the ongoing phase 3 trials, the median progression-free survival was 33 months, after a median follow-up of 20.8 months. And the objective response rate was 92%.

In the 20 mg/kg arm (n=37), the median progression-free survival was 18 months, after a median follow-up of 17.1 months. And the objective response rate was 76%.

The safety data were consistent with previously reported results for elotuzumab from this trial. In patients receiving elotuzumab at 10 mg/kg or 20 mg/kg, most treatment-emergent adverse events occurred within 18 months of starting therapy.

The most common grade 3/4 adverse events for the 10 mg/kg and 20 mg/kg arms, respectively, were lymphopenia (26% and 9%), neutropenia (21% and 22%), thrombocytopenia (21% and 17%), anemia (13% and 12%), leukopenia (8% and 7%), hyperglycemia (5% and 12%), pneumonia (8% and 5%), diarrhea (10% and 5%), fatigue (8% and 9%), and hypokalemia (8% and 5%).

Two deaths occurred on study. One patient died of pneumonia, multiple organ failure, and sepsis. The other died of disease progression.

Lab-on-a-chip device

Institute of Photonic Sciences

Scientists say they’ve developed a lab-on-a-chip device capable of detecting protein markers for cancer.

The device can detect very low concentrations of protein markers in the blood, enabling cancer diagnosis in its earliest stages, the team says.

Romain Quidant, PhD, of The Institute of Photonic Sciences in Barcelona, Spain, and his colleagues described the device in Nano Letters.

The lab on a chip hosts 32 sensing sites distributed across a network of 8 fluidic microchannels that enables it to conduct multiple analyses.

Gold nanoparticles lie on the surface of the chip and are chemically programed with an antibody receptor in such a way that they are capable of specifically attracting the protein markers circulating in blood.

When a drop of blood is injected into the chip, it circulates through the microchannels, and, if cancer markers are present in the blood, they will stick to the nanoparticles located on the microchannels as they pass by, setting off changes in what is known as the plasmonic resonance.

The device monitors these changes, the magnitude of which is directly related to the concentration/number of markers in the patient’s blood. In this way, it provides a direct assessment of the patient’s risk of developing cancer.

“The most fascinating finding is that we are capable of detecting extremely low concentrations of this protein in a matter of minutes, making this device an ultra-high-sensitivity, state-of-the-art, powerful instrument that will benefit early detection and treatment monitoring of cancer,” Dr Quidant said.

Lab-on-a-chip device

Institute of Photonic Sciences

Scientists say they’ve developed a lab-on-a-chip device capable of detecting protein markers for cancer.

The device can detect very low concentrations of protein markers in the blood, enabling cancer diagnosis in its earliest stages, the team says.

Romain Quidant, PhD, of The Institute of Photonic Sciences in Barcelona, Spain, and his colleagues described the device in Nano Letters.

The lab on a chip hosts 32 sensing sites distributed across a network of 8 fluidic microchannels that enables it to conduct multiple analyses.

Gold nanoparticles lie on the surface of the chip and are chemically programed with an antibody receptor in such a way that they are capable of specifically attracting the protein markers circulating in blood.

When a drop of blood is injected into the chip, it circulates through the microchannels, and, if cancer markers are present in the blood, they will stick to the nanoparticles located on the microchannels as they pass by, setting off changes in what is known as the plasmonic resonance.

The device monitors these changes, the magnitude of which is directly related to the concentration/number of markers in the patient’s blood. In this way, it provides a direct assessment of the patient’s risk of developing cancer.

“The most fascinating finding is that we are capable of detecting extremely low concentrations of this protein in a matter of minutes, making this device an ultra-high-sensitivity, state-of-the-art, powerful instrument that will benefit early detection and treatment monitoring of cancer,” Dr Quidant said.

Lab-on-a-chip device

Institute of Photonic Sciences

Scientists say they’ve developed a lab-on-a-chip device capable of detecting protein markers for cancer.

The device can detect very low concentrations of protein markers in the blood, enabling cancer diagnosis in its earliest stages, the team says.

Romain Quidant, PhD, of The Institute of Photonic Sciences in Barcelona, Spain, and his colleagues described the device in Nano Letters.

The lab on a chip hosts 32 sensing sites distributed across a network of 8 fluidic microchannels that enables it to conduct multiple analyses.

Gold nanoparticles lie on the surface of the chip and are chemically programed with an antibody receptor in such a way that they are capable of specifically attracting the protein markers circulating in blood.

When a drop of blood is injected into the chip, it circulates through the microchannels, and, if cancer markers are present in the blood, they will stick to the nanoparticles located on the microchannels as they pass by, setting off changes in what is known as the plasmonic resonance.

The device monitors these changes, the magnitude of which is directly related to the concentration/number of markers in the patient’s blood. In this way, it provides a direct assessment of the patient’s risk of developing cancer.

“The most fascinating finding is that we are capable of detecting extremely low concentrations of this protein in a matter of minutes, making this device an ultra-high-sensitivity, state-of-the-art, powerful instrument that will benefit early detection and treatment monitoring of cancer,” Dr Quidant said.

Tumor cells producing p53

Credit: A.T. Tikhonenko

A new study reveals how the protein p53 attaches to its regulatory molecule, BCL-xL.

Understanding how these molecular puzzle pieces fit together could help scientists design drugs that would unleash p53 to battle a range of cancers, according to study author Richard Kriwacki, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee.

He and his colleagues described this research in Nature Structural & Molecular Biology.

In guarding the cell against genetic damage, the p53 machinery functions both in the nucleus of the cell and in the cytosol. When this machinery detects irreparable damage to the cell, p53 is unleashed to trigger apoptosis.

In about half of all cancers, this machinery is rendered inoperable by mutation, enabling cancer cells to proliferate despite their genetic malfunctions. The protein BCL-xL is a central inhibitor of the p53 machinery, binding both p53 and BH3 proteins, which also drive apoptosis.

“The molecular details of how BCL-xl performs this dual inhibitory function were not understood,” Dr Kriwacki said. “Having those details has enabled us to determine exactly how BCL-xL can restrain or inhibit apoptosis through interactions with BH3-domain-containing proteins, as well as p53.”

He and his colleagues used a structural analysis technique called NMR spectroscopy to map the 3-D structure of p53 binding to BCL-xL.

Their experiments revealed how the DNA-binding domain of the p53 protein serves double duty in the machinery. It enables p53 to attach to DNA in the cell’s nucleus, helping the cell repair genetic damage. The same domain also acts as an attachment point for BCL-xL in the cytosol.

“The structural details that we report are novel,” Dr Kriwacki said. “And they provide the key insights for really dissecting the dual roles of BCL-xL in inhibiting apoptosis . . ., inhibiting the BH3-containing proteins on the one side and p53 on the other. Also, through these studies, we solidified the mechanistic understanding for how p53 functions in the cytosol, which complements its pro-apoptotic role in the nucleus.”

Dr Kriwacki added that these findings could help scientists design better anticancer agents. In many cancers, p53 is prevented from triggering apoptosis by its attachment to BCL-xL.

Drugs are currently being tested that bind to BCL-xL to free BH3 proteins to trigger apoptosis. However, Dr Kriwacki said new drugs could be developed that also block BCL-xL from binding p53.

“Our hypothesis is that many cancers have normal p53, but it is being tied up by BCL-xL,” he said. “If it could be released, it could play its role in triggering apoptosis. A drug that could block both of BCL-xL’s anti-apoptotic functions could potentially more profoundly induce apoptosis in cancer cells.”

Tumor cells producing p53

Credit: A.T. Tikhonenko

A new study reveals how the protein p53 attaches to its regulatory molecule, BCL-xL.

Understanding how these molecular puzzle pieces fit together could help scientists design drugs that would unleash p53 to battle a range of cancers, according to study author Richard Kriwacki, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee.

He and his colleagues described this research in Nature Structural & Molecular Biology.

In guarding the cell against genetic damage, the p53 machinery functions both in the nucleus of the cell and in the cytosol. When this machinery detects irreparable damage to the cell, p53 is unleashed to trigger apoptosis.

In about half of all cancers, this machinery is rendered inoperable by mutation, enabling cancer cells to proliferate despite their genetic malfunctions. The protein BCL-xL is a central inhibitor of the p53 machinery, binding both p53 and BH3 proteins, which also drive apoptosis.

“The molecular details of how BCL-xl performs this dual inhibitory function were not understood,” Dr Kriwacki said. “Having those details has enabled us to determine exactly how BCL-xL can restrain or inhibit apoptosis through interactions with BH3-domain-containing proteins, as well as p53.”

He and his colleagues used a structural analysis technique called NMR spectroscopy to map the 3-D structure of p53 binding to BCL-xL.

Their experiments revealed how the DNA-binding domain of the p53 protein serves double duty in the machinery. It enables p53 to attach to DNA in the cell’s nucleus, helping the cell repair genetic damage. The same domain also acts as an attachment point for BCL-xL in the cytosol.

“The structural details that we report are novel,” Dr Kriwacki said. “And they provide the key insights for really dissecting the dual roles of BCL-xL in inhibiting apoptosis . . ., inhibiting the BH3-containing proteins on the one side and p53 on the other. Also, through these studies, we solidified the mechanistic understanding for how p53 functions in the cytosol, which complements its pro-apoptotic role in the nucleus.”

Dr Kriwacki added that these findings could help scientists design better anticancer agents. In many cancers, p53 is prevented from triggering apoptosis by its attachment to BCL-xL.

Drugs are currently being tested that bind to BCL-xL to free BH3 proteins to trigger apoptosis. However, Dr Kriwacki said new drugs could be developed that also block BCL-xL from binding p53.

“Our hypothesis is that many cancers have normal p53, but it is being tied up by BCL-xL,” he said. “If it could be released, it could play its role in triggering apoptosis. A drug that could block both of BCL-xL’s anti-apoptotic functions could potentially more profoundly induce apoptosis in cancer cells.”

Tumor cells producing p53

Credit: A.T. Tikhonenko

A new study reveals how the protein p53 attaches to its regulatory molecule, BCL-xL.

Understanding how these molecular puzzle pieces fit together could help scientists design drugs that would unleash p53 to battle a range of cancers, according to study author Richard Kriwacki, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee.

He and his colleagues described this research in Nature Structural & Molecular Biology.

In guarding the cell against genetic damage, the p53 machinery functions both in the nucleus of the cell and in the cytosol. When this machinery detects irreparable damage to the cell, p53 is unleashed to trigger apoptosis.

In about half of all cancers, this machinery is rendered inoperable by mutation, enabling cancer cells to proliferate despite their genetic malfunctions. The protein BCL-xL is a central inhibitor of the p53 machinery, binding both p53 and BH3 proteins, which also drive apoptosis.

“The molecular details of how BCL-xl performs this dual inhibitory function were not understood,” Dr Kriwacki said. “Having those details has enabled us to determine exactly how BCL-xL can restrain or inhibit apoptosis through interactions with BH3-domain-containing proteins, as well as p53.”

He and his colleagues used a structural analysis technique called NMR spectroscopy to map the 3-D structure of p53 binding to BCL-xL.

Their experiments revealed how the DNA-binding domain of the p53 protein serves double duty in the machinery. It enables p53 to attach to DNA in the cell’s nucleus, helping the cell repair genetic damage. The same domain also acts as an attachment point for BCL-xL in the cytosol.

“The structural details that we report are novel,” Dr Kriwacki said. “And they provide the key insights for really dissecting the dual roles of BCL-xL in inhibiting apoptosis . . ., inhibiting the BH3-containing proteins on the one side and p53 on the other. Also, through these studies, we solidified the mechanistic understanding for how p53 functions in the cytosol, which complements its pro-apoptotic role in the nucleus.”

Dr Kriwacki added that these findings could help scientists design better anticancer agents. In many cancers, p53 is prevented from triggering apoptosis by its attachment to BCL-xL.

Drugs are currently being tested that bind to BCL-xL to free BH3 proteins to trigger apoptosis. However, Dr Kriwacki said new drugs could be developed that also block BCL-xL from binding p53.

“Our hypothesis is that many cancers have normal p53, but it is being tied up by BCL-xL,” he said. “If it could be released, it could play its role in triggering apoptosis. A drug that could block both of BCL-xL’s anti-apoptotic functions could potentially more profoundly induce apoptosis in cancer cells.”