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Speaker says use the best regimen ASAP in MM
NEW YORK—It’s important to use the best possible regimen as soon as possible when treating patients with multiple myeloma (MM), according to a speaker at Lymphoma & Myeloma 2016.
Antonio Palumbo, MD, of the University of Torino in Italy, explained that the urgency, from a biological point of view, is because myeloma accumulates genetic mutations that change the disease in a “dramatic way.”
“At diagnosis, you might have 5000 mutations, and, at first relapse, there are 12,000 mutations,” he said. “They are completely different tumors. So the first thing that we have to recognize is that, with time, myeloma is not the same. It’s becoming different tumors.”
Dr Palumbo noted that early intervention is important because genetic and epigenetic abnormalities increase as the disease progresses and becomes more resistant.
For example, if 100 patients receive first-line treatment, 40 of them will not reach the second line. Only 60 patients will receive second-line therapy, and only 35 patients will receive third-line treatment. By the fifth line, only 10 patients, or 10%, will receive it.
“If you have very good genomic stability, you can become sensitive to different treatments,” Dr Palumbo said. “But if you become a different disease, you will not be able to receive the next therapy. That’s why it’s so important . . . to use the best possible regimen as soon as possible.”
Best regimens
The triplet bortezomib-lenalidomide-dexamethasone is the “best possible regimen today,” Dr Palumbo said, “followed by continuous therapy.”
The 2-drug combination of lenalidomide and dexamethasone is probably more suitable for the elderly and the frail.
Alternative regimens include carfilzomib-cyclophosphamide-dexamethasone and ixazomib-lenalidomide-dexamethasone.
Continuous therapy
Continuous therapy has been “one of the major achievements” in the treatment of MM, Dr Palumbo said. Without continuous therapy, patients in complete response remain so for about 1 year when treated with conventional chemotherapy.
Investigators found that maintenance therapy significantly prolongs progression-free survival and overall survival (P=0.02). They recommend intensification with maintenance to optimize treatment efficacy and prolong survival.
Immunomodulatory drugs such as lenalidomide are the backbone of continuous therapy today.
However, ixazomib represents another option. Ixazomib maintenance has been shown to produce durable responses for a median of more than 2 years in previously untreated patients not undergoing autologous stem cell transplant.
Salvage therapy
Seven combinations are now available for salvage therapy, including those with proteasome inhibitors, monoclonal antibodies, pomalidomide, and histone deacetylase inhibitors.
Included in some of these combinations are the newer agents ixazomib, elotuzumab, and daratumumab, “which many might consider the new rituximab,” Dr Palumbo said.
Risk stratification
Dr Palumbo stressed the importance of risk stratification—both in clinical trials and in practice.
“[T]he moment you under-treat a patient, you transform a good-risk patient into a high-risk patient . . . ,” he said.
And if trials comparing treatments are not conducted within risk categories, researchers are comparing apples to oranges—good risk with high risk
The Revised International Staging System (R-ISS) for MM effectively stratifies newly diagnosed patients by combining the original ISS, chromosomal abnormalities, and serum lactate dehydrogenase levels to evaluate prognosis.
The R-ISS defines 3 new, distinct categories that researchers believe effectively define patients’ relative risk with respect to their survival.
Age and frailty
MM patients generally fall into 3 age categories: 25-64, 65-74, and 75-101.
The youngest group can receive autologous transplant, the fit patients ages 65 to 74 can receive full-dose chemotherapy, and the oldest, frailer patients should receive reduced-dose chemotherapy.
“It’s important to differentiate fit from frail,” Dr Palumbo said, “because we cannot give the same treatment schema to a 55-year-old versus 65 or 85. At 85, that schema would create a lot of toxicities.”
In frail patients, it’s always important to check which comorbidities are present using the Charlson comorbidity scale, Dr Palumbo said.
“Remember, when we put together age, chromosome abnormalities, and frailty, frailty is the most relevant prognostic factor when you add everything together,” he said.
“Two drugs versus 3 drugs doesn’t make much difference when you are starting to introduce treatment to these very frail patients with comorbidities.”
Minimal residual disease
Dr Palumbo indicated that a combination of MRI and PET-CT should be used for a more accurate indication of minimal residual disease.
“[W]e hope to have cure, [but] I don’t think, today, myeloma is a curable disease,” he said.
He clarified this by saying that patients who are in complete response and minimal residual disease-negative at 3 years do well, but, by 7 years, “something is happening.”
And at 10 years, progression-free survival has dropped off significantly, “telling us that cure is probably not yet there.” 
NEW YORK—It’s important to use the best possible regimen as soon as possible when treating patients with multiple myeloma (MM), according to a speaker at Lymphoma & Myeloma 2016.
Antonio Palumbo, MD, of the University of Torino in Italy, explained that the urgency, from a biological point of view, is because myeloma accumulates genetic mutations that change the disease in a “dramatic way.”
“At diagnosis, you might have 5000 mutations, and, at first relapse, there are 12,000 mutations,” he said. “They are completely different tumors. So the first thing that we have to recognize is that, with time, myeloma is not the same. It’s becoming different tumors.”
Dr Palumbo noted that early intervention is important because genetic and epigenetic abnormalities increase as the disease progresses and becomes more resistant.
For example, if 100 patients receive first-line treatment, 40 of them will not reach the second line. Only 60 patients will receive second-line therapy, and only 35 patients will receive third-line treatment. By the fifth line, only 10 patients, or 10%, will receive it.
“If you have very good genomic stability, you can become sensitive to different treatments,” Dr Palumbo said. “But if you become a different disease, you will not be able to receive the next therapy. That’s why it’s so important . . . to use the best possible regimen as soon as possible.”
Best regimens
The triplet bortezomib-lenalidomide-dexamethasone is the “best possible regimen today,” Dr Palumbo said, “followed by continuous therapy.”
The 2-drug combination of lenalidomide and dexamethasone is probably more suitable for the elderly and the frail.
Alternative regimens include carfilzomib-cyclophosphamide-dexamethasone and ixazomib-lenalidomide-dexamethasone.
Continuous therapy
Continuous therapy has been “one of the major achievements” in the treatment of MM, Dr Palumbo said. Without continuous therapy, patients in complete response remain so for about 1 year when treated with conventional chemotherapy.
Investigators found that maintenance therapy significantly prolongs progression-free survival and overall survival (P=0.02). They recommend intensification with maintenance to optimize treatment efficacy and prolong survival.
Immunomodulatory drugs such as lenalidomide are the backbone of continuous therapy today.
However, ixazomib represents another option. Ixazomib maintenance has been shown to produce durable responses for a median of more than 2 years in previously untreated patients not undergoing autologous stem cell transplant.
Salvage therapy
Seven combinations are now available for salvage therapy, including those with proteasome inhibitors, monoclonal antibodies, pomalidomide, and histone deacetylase inhibitors.
Included in some of these combinations are the newer agents ixazomib, elotuzumab, and daratumumab, “which many might consider the new rituximab,” Dr Palumbo said.
Risk stratification
Dr Palumbo stressed the importance of risk stratification—both in clinical trials and in practice.
“[T]he moment you under-treat a patient, you transform a good-risk patient into a high-risk patient . . . ,” he said.
And if trials comparing treatments are not conducted within risk categories, researchers are comparing apples to oranges—good risk with high risk
The Revised International Staging System (R-ISS) for MM effectively stratifies newly diagnosed patients by combining the original ISS, chromosomal abnormalities, and serum lactate dehydrogenase levels to evaluate prognosis.
The R-ISS defines 3 new, distinct categories that researchers believe effectively define patients’ relative risk with respect to their survival.
Age and frailty
MM patients generally fall into 3 age categories: 25-64, 65-74, and 75-101.
The youngest group can receive autologous transplant, the fit patients ages 65 to 74 can receive full-dose chemotherapy, and the oldest, frailer patients should receive reduced-dose chemotherapy.
“It’s important to differentiate fit from frail,” Dr Palumbo said, “because we cannot give the same treatment schema to a 55-year-old versus 65 or 85. At 85, that schema would create a lot of toxicities.”
In frail patients, it’s always important to check which comorbidities are present using the Charlson comorbidity scale, Dr Palumbo said.
“Remember, when we put together age, chromosome abnormalities, and frailty, frailty is the most relevant prognostic factor when you add everything together,” he said.
“Two drugs versus 3 drugs doesn’t make much difference when you are starting to introduce treatment to these very frail patients with comorbidities.”
Minimal residual disease
Dr Palumbo indicated that a combination of MRI and PET-CT should be used for a more accurate indication of minimal residual disease.
“[W]e hope to have cure, [but] I don’t think, today, myeloma is a curable disease,” he said.
He clarified this by saying that patients who are in complete response and minimal residual disease-negative at 3 years do well, but, by 7 years, “something is happening.”
And at 10 years, progression-free survival has dropped off significantly, “telling us that cure is probably not yet there.”
NEW YORK—It’s important to use the best possible regimen as soon as possible when treating patients with multiple myeloma (MM), according to a speaker at Lymphoma & Myeloma 2016.
Antonio Palumbo, MD, of the University of Torino in Italy, explained that the urgency, from a biological point of view, is because myeloma accumulates genetic mutations that change the disease in a “dramatic way.”
“At diagnosis, you might have 5000 mutations, and, at first relapse, there are 12,000 mutations,” he said. “They are completely different tumors. So the first thing that we have to recognize is that, with time, myeloma is not the same. It’s becoming different tumors.”
Dr Palumbo noted that early intervention is important because genetic and epigenetic abnormalities increase as the disease progresses and becomes more resistant.
For example, if 100 patients receive first-line treatment, 40 of them will not reach the second line. Only 60 patients will receive second-line therapy, and only 35 patients will receive third-line treatment. By the fifth line, only 10 patients, or 10%, will receive it.
“If you have very good genomic stability, you can become sensitive to different treatments,” Dr Palumbo said. “But if you become a different disease, you will not be able to receive the next therapy. That’s why it’s so important . . . to use the best possible regimen as soon as possible.”
Best regimens
The triplet bortezomib-lenalidomide-dexamethasone is the “best possible regimen today,” Dr Palumbo said, “followed by continuous therapy.”
The 2-drug combination of lenalidomide and dexamethasone is probably more suitable for the elderly and the frail.
Alternative regimens include carfilzomib-cyclophosphamide-dexamethasone and ixazomib-lenalidomide-dexamethasone.
Continuous therapy
Continuous therapy has been “one of the major achievements” in the treatment of MM, Dr Palumbo said. Without continuous therapy, patients in complete response remain so for about 1 year when treated with conventional chemotherapy.
Investigators found that maintenance therapy significantly prolongs progression-free survival and overall survival (P=0.02). They recommend intensification with maintenance to optimize treatment efficacy and prolong survival.
Immunomodulatory drugs such as lenalidomide are the backbone of continuous therapy today.
However, ixazomib represents another option. Ixazomib maintenance has been shown to produce durable responses for a median of more than 2 years in previously untreated patients not undergoing autologous stem cell transplant.
Salvage therapy
Seven combinations are now available for salvage therapy, including those with proteasome inhibitors, monoclonal antibodies, pomalidomide, and histone deacetylase inhibitors.
Included in some of these combinations are the newer agents ixazomib, elotuzumab, and daratumumab, “which many might consider the new rituximab,” Dr Palumbo said.
Risk stratification
Dr Palumbo stressed the importance of risk stratification—both in clinical trials and in practice.
“[T]he moment you under-treat a patient, you transform a good-risk patient into a high-risk patient . . . ,” he said.
And if trials comparing treatments are not conducted within risk categories, researchers are comparing apples to oranges—good risk with high risk
The Revised International Staging System (R-ISS) for MM effectively stratifies newly diagnosed patients by combining the original ISS, chromosomal abnormalities, and serum lactate dehydrogenase levels to evaluate prognosis.
The R-ISS defines 3 new, distinct categories that researchers believe effectively define patients’ relative risk with respect to their survival.
Age and frailty
MM patients generally fall into 3 age categories: 25-64, 65-74, and 75-101.
The youngest group can receive autologous transplant, the fit patients ages 65 to 74 can receive full-dose chemotherapy, and the oldest, frailer patients should receive reduced-dose chemotherapy.
“It’s important to differentiate fit from frail,” Dr Palumbo said, “because we cannot give the same treatment schema to a 55-year-old versus 65 or 85. At 85, that schema would create a lot of toxicities.”
In frail patients, it’s always important to check which comorbidities are present using the Charlson comorbidity scale, Dr Palumbo said.
“Remember, when we put together age, chromosome abnormalities, and frailty, frailty is the most relevant prognostic factor when you add everything together,” he said.
“Two drugs versus 3 drugs doesn’t make much difference when you are starting to introduce treatment to these very frail patients with comorbidities.”
Minimal residual disease
Dr Palumbo indicated that a combination of MRI and PET-CT should be used for a more accurate indication of minimal residual disease.
“[W]e hope to have cure, [but] I don’t think, today, myeloma is a curable disease,” he said.
He clarified this by saying that patients who are in complete response and minimal residual disease-negative at 3 years do well, but, by 7 years, “something is happening.”
And at 10 years, progression-free survival has dropped off significantly, “telling us that cure is probably not yet there.”
Combos produce ‘encouraging’ responses in MM
LEIPZIG, GERMANY—Combination therapies including the investigational drug MOR202 have produced “encouraging and long-lasting responses” in a phase 1/2 trial of patients with relapsed/refractory multiple myeloma (MM), according to researchers.
MOR202 is an antibody targeting CD38. In this trial, researchers are testing the drug in combination with dexamethasone (Dex), lenalidomide (Len) and Dex, or pomalidomide (Pom) and Dex.
Results thus far suggest the combinations are well-tolerated and can produce durable responses in heavily pretreated patients with relapsed/refractory MM.
The results were presented in a poster at the 2016 annual meeting of the German, Austrian and Swiss Societies for Hematology and Medical Oncology (abstract P235).
The study, which is ongoing, is sponsored by MorphoSys AG. The poster is available for download from the company’s website.
Treatment
This 3+3 dose-escalation study started with MOR202 monotherapy given at 0.01 mg/kg every 2 weeks, and the dose was escalated up to 16 mg/kg every 2 weeks and 8 mg/kg every week.
Once the dose-escalation phase was complete, researchers began testing MOR202 in combination with Dex, Pom and Dex, or Len and Dex.
Patients
As of September 05, 2016, 73 patients had been treated with MOR202, but the researchers only reported data on the 38 patients who received MOR202 as part of combination therapy.
Eighteen patients had received MOR202 plus Dex, 7 had received MOR202 plus Pom and Dex, and 13 had received MOR202 plus Len and Dex. The patients’ median age was 67, 64, and 64, respectively.
The median number of prior therapies was 3, 4, and 2, respectively. And the percentage of patients who were refractory to their last therapy was 78%, 100%, and 56%, respectively.
Safety
The researchers said the maximum-tolerated dose of MOR202, alone or in combination, has not yet been reached. However, the data suggest MOR202 can be safely administered as a 2-hour intravenous infusion at doses up to 16 mg/kg.
All 38 patients who received MOR202 in combination were evaluable for safety—18 in the Dex arm, 7 in the Pom/Dex arm, and 13 in the Len/Dex arm.
The most frequent grade 3 or higher adverse events were hematologic in nature. These included (in the Dex, Pom/Dex, and Len/Dex arms, respectively) leukopenia (11%, 57%, 31%), lymphopenia (39%, 29%, 54%), neutropenia (22%, 71%, 39%), thrombocytopenia (17%, 43%, 8%), and anemia (11%, 14%, 15%).
Infusion-related reactions occurred in 3 (8%) patients and were mainly limited to the first infusion. One patient developed a transient anti-MOR202 antibody response.
One patient discontinued treatment due to an adverse event that may have been caused by MOR202. However, researchers also said the event (decrease in platelet count) may have been caused by Dex.
There were no treatment-related deaths.
Efficacy
Efficacy data were available for 31 of the 38 patients. Fifteen patients responded, and 12 of these responses are ongoing for up to 56 weeks.
In all, there were 10 partial responses (PRs), 3 very good partial responses (VGPRs), and 2 complete responses (CRs).
There were 5 responses in the Dex arm—3 PRs and 2 VGPRs. There were 3 responses in the Pom/Dex arm—2 CRs and 1 PR. And there were 7 responses in the Len/Dex arm—6 PRs (3 unconfirmed) and 1 VGPR.
“We are very pleased that these results are consistent with earlier data from the ongoing trial and show further improved responses with more patients being evaluable for efficacy and safety assessment,” said Arndt Schottelius, MD, PhD, chief development officer of MorphoSys AG.
“In addition to the very short infusion time, we are particularly interested in the efficacy results in patients treated with MOR202 plus pomalidomide, who had a median of 4 prior therapies. The dose-escalation study is ongoing as planned, currently focusing on the highest dose cohorts of 16 mg/kg MOR202 in combination with pomalidomide and lenalidomide.”
LEIPZIG, GERMANY—Combination therapies including the investigational drug MOR202 have produced “encouraging and long-lasting responses” in a phase 1/2 trial of patients with relapsed/refractory multiple myeloma (MM), according to researchers.
MOR202 is an antibody targeting CD38. In this trial, researchers are testing the drug in combination with dexamethasone (Dex), lenalidomide (Len) and Dex, or pomalidomide (Pom) and Dex.
Results thus far suggest the combinations are well-tolerated and can produce durable responses in heavily pretreated patients with relapsed/refractory MM.
The results were presented in a poster at the 2016 annual meeting of the German, Austrian and Swiss Societies for Hematology and Medical Oncology (abstract P235).
The study, which is ongoing, is sponsored by MorphoSys AG. The poster is available for download from the company’s website.
Treatment
This 3+3 dose-escalation study started with MOR202 monotherapy given at 0.01 mg/kg every 2 weeks, and the dose was escalated up to 16 mg/kg every 2 weeks and 8 mg/kg every week.
Once the dose-escalation phase was complete, researchers began testing MOR202 in combination with Dex, Pom and Dex, or Len and Dex.
Patients
As of September 05, 2016, 73 patients had been treated with MOR202, but the researchers only reported data on the 38 patients who received MOR202 as part of combination therapy.
Eighteen patients had received MOR202 plus Dex, 7 had received MOR202 plus Pom and Dex, and 13 had received MOR202 plus Len and Dex. The patients’ median age was 67, 64, and 64, respectively.
The median number of prior therapies was 3, 4, and 2, respectively. And the percentage of patients who were refractory to their last therapy was 78%, 100%, and 56%, respectively.
Safety
The researchers said the maximum-tolerated dose of MOR202, alone or in combination, has not yet been reached. However, the data suggest MOR202 can be safely administered as a 2-hour intravenous infusion at doses up to 16 mg/kg.
All 38 patients who received MOR202 in combination were evaluable for safety—18 in the Dex arm, 7 in the Pom/Dex arm, and 13 in the Len/Dex arm.
The most frequent grade 3 or higher adverse events were hematologic in nature. These included (in the Dex, Pom/Dex, and Len/Dex arms, respectively) leukopenia (11%, 57%, 31%), lymphopenia (39%, 29%, 54%), neutropenia (22%, 71%, 39%), thrombocytopenia (17%, 43%, 8%), and anemia (11%, 14%, 15%).
Infusion-related reactions occurred in 3 (8%) patients and were mainly limited to the first infusion. One patient developed a transient anti-MOR202 antibody response.
One patient discontinued treatment due to an adverse event that may have been caused by MOR202. However, researchers also said the event (decrease in platelet count) may have been caused by Dex.
There were no treatment-related deaths.
Efficacy
Efficacy data were available for 31 of the 38 patients. Fifteen patients responded, and 12 of these responses are ongoing for up to 56 weeks.
In all, there were 10 partial responses (PRs), 3 very good partial responses (VGPRs), and 2 complete responses (CRs).
There were 5 responses in the Dex arm—3 PRs and 2 VGPRs. There were 3 responses in the Pom/Dex arm—2 CRs and 1 PR. And there were 7 responses in the Len/Dex arm—6 PRs (3 unconfirmed) and 1 VGPR.
“We are very pleased that these results are consistent with earlier data from the ongoing trial and show further improved responses with more patients being evaluable for efficacy and safety assessment,” said Arndt Schottelius, MD, PhD, chief development officer of MorphoSys AG.
“In addition to the very short infusion time, we are particularly interested in the efficacy results in patients treated with MOR202 plus pomalidomide, who had a median of 4 prior therapies. The dose-escalation study is ongoing as planned, currently focusing on the highest dose cohorts of 16 mg/kg MOR202 in combination with pomalidomide and lenalidomide.”
LEIPZIG, GERMANY—Combination therapies including the investigational drug MOR202 have produced “encouraging and long-lasting responses” in a phase 1/2 trial of patients with relapsed/refractory multiple myeloma (MM), according to researchers.
MOR202 is an antibody targeting CD38. In this trial, researchers are testing the drug in combination with dexamethasone (Dex), lenalidomide (Len) and Dex, or pomalidomide (Pom) and Dex.
Results thus far suggest the combinations are well-tolerated and can produce durable responses in heavily pretreated patients with relapsed/refractory MM.
The results were presented in a poster at the 2016 annual meeting of the German, Austrian and Swiss Societies for Hematology and Medical Oncology (abstract P235).
The study, which is ongoing, is sponsored by MorphoSys AG. The poster is available for download from the company’s website.
Treatment
This 3+3 dose-escalation study started with MOR202 monotherapy given at 0.01 mg/kg every 2 weeks, and the dose was escalated up to 16 mg/kg every 2 weeks and 8 mg/kg every week.
Once the dose-escalation phase was complete, researchers began testing MOR202 in combination with Dex, Pom and Dex, or Len and Dex.
Patients
As of September 05, 2016, 73 patients had been treated with MOR202, but the researchers only reported data on the 38 patients who received MOR202 as part of combination therapy.
Eighteen patients had received MOR202 plus Dex, 7 had received MOR202 plus Pom and Dex, and 13 had received MOR202 plus Len and Dex. The patients’ median age was 67, 64, and 64, respectively.
The median number of prior therapies was 3, 4, and 2, respectively. And the percentage of patients who were refractory to their last therapy was 78%, 100%, and 56%, respectively.
Safety
The researchers said the maximum-tolerated dose of MOR202, alone or in combination, has not yet been reached. However, the data suggest MOR202 can be safely administered as a 2-hour intravenous infusion at doses up to 16 mg/kg.
All 38 patients who received MOR202 in combination were evaluable for safety—18 in the Dex arm, 7 in the Pom/Dex arm, and 13 in the Len/Dex arm.
The most frequent grade 3 or higher adverse events were hematologic in nature. These included (in the Dex, Pom/Dex, and Len/Dex arms, respectively) leukopenia (11%, 57%, 31%), lymphopenia (39%, 29%, 54%), neutropenia (22%, 71%, 39%), thrombocytopenia (17%, 43%, 8%), and anemia (11%, 14%, 15%).
Infusion-related reactions occurred in 3 (8%) patients and were mainly limited to the first infusion. One patient developed a transient anti-MOR202 antibody response.
One patient discontinued treatment due to an adverse event that may have been caused by MOR202. However, researchers also said the event (decrease in platelet count) may have been caused by Dex.
There were no treatment-related deaths.
Efficacy
Efficacy data were available for 31 of the 38 patients. Fifteen patients responded, and 12 of these responses are ongoing for up to 56 weeks.
In all, there were 10 partial responses (PRs), 3 very good partial responses (VGPRs), and 2 complete responses (CRs).
There were 5 responses in the Dex arm—3 PRs and 2 VGPRs. There were 3 responses in the Pom/Dex arm—2 CRs and 1 PR. And there were 7 responses in the Len/Dex arm—6 PRs (3 unconfirmed) and 1 VGPR.
“We are very pleased that these results are consistent with earlier data from the ongoing trial and show further improved responses with more patients being evaluable for efficacy and safety assessment,” said Arndt Schottelius, MD, PhD, chief development officer of MorphoSys AG.
“In addition to the very short infusion time, we are particularly interested in the efficacy results in patients treated with MOR202 plus pomalidomide, who had a median of 4 prior therapies. The dose-escalation study is ongoing as planned, currently focusing on the highest dose cohorts of 16 mg/kg MOR202 in combination with pomalidomide and lenalidomide.”
FDA issues warning about radiation therapy devices
to receive radiation
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has warned healthcare providers to stop using radiation therapy devices manufactured and sold by Multidata Systems International Corporation.
The FDA said the company has distributed at least 2 devices in the US that were never reviewed by or registered with the FDA—(1) accessories to radiation therapy devices including the Real Time Dosimetry Waterphantom System and (2) the Dual Channel Electrometer.
Since 2003, Multidata has been under a decree that prohibits the company from designing, manufacturing, processing, and distributing medical devices, among other restrictions.
However, the FDA learned that Multidata manufactured and distributed medical devices in violation of the decree, including repairing and exchanging Waterphantom devices for newer design models.
As a result, on March 3, 2016, the FDA sent a letter to Multidata ordering the firm to stop designing, manufacturing, processing, packing, repacking, labeling, installing, holding for sale, and distributing any medical device. The company has permanently ceased operations and will be dissolving.
The FDA said it doesn’t know how many devices manufactured by Multidata are in use throughout the US or if any of these devices have caused adverse events since the decree was issued.
The agency has urged healthcare providers to stop using and dispose of any devices manufactured by Multidata.
Instead, providers should use accessories to radiation therapy devices and radiation treatment planning software that have been cleared by the FDA. Registered manufacturers of such products are listed under the IYE product code in the FDA’s Registration and Listing Database.
The FDA has also recommended that providers report any adverse events related to Multidata devices. Reports can be submitted through MedWatch, the FDA’s Safety Information and Adverse Event Reporting Program.
to receive radiation
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has warned healthcare providers to stop using radiation therapy devices manufactured and sold by Multidata Systems International Corporation.
The FDA said the company has distributed at least 2 devices in the US that were never reviewed by or registered with the FDA—(1) accessories to radiation therapy devices including the Real Time Dosimetry Waterphantom System and (2) the Dual Channel Electrometer.
Since 2003, Multidata has been under a decree that prohibits the company from designing, manufacturing, processing, and distributing medical devices, among other restrictions.
However, the FDA learned that Multidata manufactured and distributed medical devices in violation of the decree, including repairing and exchanging Waterphantom devices for newer design models.
As a result, on March 3, 2016, the FDA sent a letter to Multidata ordering the firm to stop designing, manufacturing, processing, packing, repacking, labeling, installing, holding for sale, and distributing any medical device. The company has permanently ceased operations and will be dissolving.
The FDA said it doesn’t know how many devices manufactured by Multidata are in use throughout the US or if any of these devices have caused adverse events since the decree was issued.
The agency has urged healthcare providers to stop using and dispose of any devices manufactured by Multidata.
Instead, providers should use accessories to radiation therapy devices and radiation treatment planning software that have been cleared by the FDA. Registered manufacturers of such products are listed under the IYE product code in the FDA’s Registration and Listing Database.
The FDA has also recommended that providers report any adverse events related to Multidata devices. Reports can be submitted through MedWatch, the FDA’s Safety Information and Adverse Event Reporting Program.
to receive radiation
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has warned healthcare providers to stop using radiation therapy devices manufactured and sold by Multidata Systems International Corporation.
The FDA said the company has distributed at least 2 devices in the US that were never reviewed by or registered with the FDA—(1) accessories to radiation therapy devices including the Real Time Dosimetry Waterphantom System and (2) the Dual Channel Electrometer.
Since 2003, Multidata has been under a decree that prohibits the company from designing, manufacturing, processing, and distributing medical devices, among other restrictions.
However, the FDA learned that Multidata manufactured and distributed medical devices in violation of the decree, including repairing and exchanging Waterphantom devices for newer design models.
As a result, on March 3, 2016, the FDA sent a letter to Multidata ordering the firm to stop designing, manufacturing, processing, packing, repacking, labeling, installing, holding for sale, and distributing any medical device. The company has permanently ceased operations and will be dissolving.
The FDA said it doesn’t know how many devices manufactured by Multidata are in use throughout the US or if any of these devices have caused adverse events since the decree was issued.
The agency has urged healthcare providers to stop using and dispose of any devices manufactured by Multidata.
Instead, providers should use accessories to radiation therapy devices and radiation treatment planning software that have been cleared by the FDA. Registered manufacturers of such products are listed under the IYE product code in the FDA’s Registration and Listing Database.
The FDA has also recommended that providers report any adverse events related to Multidata devices. Reports can be submitted through MedWatch, the FDA’s Safety Information and Adverse Event Reporting Program.
Burden of cancer varies by cancer type, race
Photo by Rhoda Baer
A new study suggests that leukemia and non-Hodgkin lymphoma (NHL) are among the top 10 cancers with the greatest burden (most years of healthy life lost) in the US.
The research also showed that the burden of different cancer types varied between patients belonging to different racial/ethnic groups.
For example, the contribution of leukemia to the overall cancer burden was twice as high in Hispanics as it was in non-Hispanic blacks. The same was true for NHL.
Joannie Lortet-Tieulent, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in the American Journal of Preventive Medicine.
The researchers calculated the burden of cancer in the US in 2011 for 24 cancer types. They calculated burden using disability-adjusted life years (DALYs), which combine cancer incidence, mortality, survival, and quality of life into a summary indicator.
The results suggested the burden of cancer in 2011 was over 9.8 million DALYs, which was equally shared between men and women—4.9 million DALYs for each sex.
DALYs lost to cancer were mostly related to premature death due to cancer (91%). The remaining 9% were related to impaired quality of life because of the disease or its treatment, or other disease-related issues.
Top 10 contributors
The researchers calculated the proportion of DALYs lost for each of the cancer types. And they found that lung cancer was the largest contributor to the loss of healthy years, accounting for 24% of the burden (2.4 million DALYs).
The second biggest contributor to the loss of healthy years was breast cancer (10%), followed by colorectal cancer (9%), pancreatic cancer (6%), prostate cancer (5%), leukemia (4%), liver cancer (4%), brain cancer (3%), NHL (3%), and ovarian cancer (3%).
The researchers also calculated the proportion of DALYs lost from the top 10 cancer types according to race/ethnicity.
They found the contribution of leukemia to the loss of healthy years was greatest for Hispanics (6%), followed by non-Hispanic Asians (5%), non-Hispanic whites (4%), and non-Hispanic blacks (3%).
The contribution of NHL to the loss of healthy years was greatest for Hispanics (4%), followed by non-Hispanic Asians/non-Hispanic whites (3% for both), and non-Hispanic blacks (2%).
DALYs by race/ethnicity
The researchers found that, overall, the cancer burden was highest in non-Hispanic blacks, followed by non-Hispanic whites, Hispanics, and non-Hispanic Asians. However, this pattern was not consistent across the different cancer types.
Age-standardized DALYs lost (per 100,000 individuals) were as follows:
All cancers combined
3588 for non-Hispanic blacks
2898 for non-Hispanic whites
1978 for Hispanics
1798 for non-Hispanic Asians.
Leukemia
115 for non-Hispanic blacks and non-Hispanic whites
98 for Hispanics
82 for non-Hispanic Asians.
NHL
93 for non-Hispanic whites
86 for non-Hispanic blacks
78 for Hispanics
60 for non-Hispanic Asians.
Hodgkin lymphoma
11 for non-Hispanic blacks
10 for non-Hispanic whites and Hispanics
3 for non-Hispanic Asians.
Myeloma
93 for non-Hispanic blacks
43 for non-Hispanic whites
42 for Hispanics
26 for non-Hispanic Asians.
The researchers noted that, despite these differences, the cancer burden in all races/ethnicities was driven by years of life lost. They said this highlights the need to prevent deaths by improving prevention, early detection, and treatment of cancers.
Photo by Rhoda Baer
A new study suggests that leukemia and non-Hodgkin lymphoma (NHL) are among the top 10 cancers with the greatest burden (most years of healthy life lost) in the US.
The research also showed that the burden of different cancer types varied between patients belonging to different racial/ethnic groups.
For example, the contribution of leukemia to the overall cancer burden was twice as high in Hispanics as it was in non-Hispanic blacks. The same was true for NHL.
Joannie Lortet-Tieulent, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in the American Journal of Preventive Medicine.
The researchers calculated the burden of cancer in the US in 2011 for 24 cancer types. They calculated burden using disability-adjusted life years (DALYs), which combine cancer incidence, mortality, survival, and quality of life into a summary indicator.
The results suggested the burden of cancer in 2011 was over 9.8 million DALYs, which was equally shared between men and women—4.9 million DALYs for each sex.
DALYs lost to cancer were mostly related to premature death due to cancer (91%). The remaining 9% were related to impaired quality of life because of the disease or its treatment, or other disease-related issues.
Top 10 contributors
The researchers calculated the proportion of DALYs lost for each of the cancer types. And they found that lung cancer was the largest contributor to the loss of healthy years, accounting for 24% of the burden (2.4 million DALYs).
The second biggest contributor to the loss of healthy years was breast cancer (10%), followed by colorectal cancer (9%), pancreatic cancer (6%), prostate cancer (5%), leukemia (4%), liver cancer (4%), brain cancer (3%), NHL (3%), and ovarian cancer (3%).
The researchers also calculated the proportion of DALYs lost from the top 10 cancer types according to race/ethnicity.
They found the contribution of leukemia to the loss of healthy years was greatest for Hispanics (6%), followed by non-Hispanic Asians (5%), non-Hispanic whites (4%), and non-Hispanic blacks (3%).
The contribution of NHL to the loss of healthy years was greatest for Hispanics (4%), followed by non-Hispanic Asians/non-Hispanic whites (3% for both), and non-Hispanic blacks (2%).
DALYs by race/ethnicity
The researchers found that, overall, the cancer burden was highest in non-Hispanic blacks, followed by non-Hispanic whites, Hispanics, and non-Hispanic Asians. However, this pattern was not consistent across the different cancer types.
Age-standardized DALYs lost (per 100,000 individuals) were as follows:
All cancers combined
3588 for non-Hispanic blacks
2898 for non-Hispanic whites
1978 for Hispanics
1798 for non-Hispanic Asians.
Leukemia
115 for non-Hispanic blacks and non-Hispanic whites
98 for Hispanics
82 for non-Hispanic Asians.
NHL
93 for non-Hispanic whites
86 for non-Hispanic blacks
78 for Hispanics
60 for non-Hispanic Asians.
Hodgkin lymphoma
11 for non-Hispanic blacks
10 for non-Hispanic whites and Hispanics
3 for non-Hispanic Asians.
Myeloma
93 for non-Hispanic blacks
43 for non-Hispanic whites
42 for Hispanics
26 for non-Hispanic Asians.
The researchers noted that, despite these differences, the cancer burden in all races/ethnicities was driven by years of life lost. They said this highlights the need to prevent deaths by improving prevention, early detection, and treatment of cancers.
Photo by Rhoda Baer
A new study suggests that leukemia and non-Hodgkin lymphoma (NHL) are among the top 10 cancers with the greatest burden (most years of healthy life lost) in the US.
The research also showed that the burden of different cancer types varied between patients belonging to different racial/ethnic groups.
For example, the contribution of leukemia to the overall cancer burden was twice as high in Hispanics as it was in non-Hispanic blacks. The same was true for NHL.
Joannie Lortet-Tieulent, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in the American Journal of Preventive Medicine.
The researchers calculated the burden of cancer in the US in 2011 for 24 cancer types. They calculated burden using disability-adjusted life years (DALYs), which combine cancer incidence, mortality, survival, and quality of life into a summary indicator.
The results suggested the burden of cancer in 2011 was over 9.8 million DALYs, which was equally shared between men and women—4.9 million DALYs for each sex.
DALYs lost to cancer were mostly related to premature death due to cancer (91%). The remaining 9% were related to impaired quality of life because of the disease or its treatment, or other disease-related issues.
Top 10 contributors
The researchers calculated the proportion of DALYs lost for each of the cancer types. And they found that lung cancer was the largest contributor to the loss of healthy years, accounting for 24% of the burden (2.4 million DALYs).
The second biggest contributor to the loss of healthy years was breast cancer (10%), followed by colorectal cancer (9%), pancreatic cancer (6%), prostate cancer (5%), leukemia (4%), liver cancer (4%), brain cancer (3%), NHL (3%), and ovarian cancer (3%).
The researchers also calculated the proportion of DALYs lost from the top 10 cancer types according to race/ethnicity.
They found the contribution of leukemia to the loss of healthy years was greatest for Hispanics (6%), followed by non-Hispanic Asians (5%), non-Hispanic whites (4%), and non-Hispanic blacks (3%).
The contribution of NHL to the loss of healthy years was greatest for Hispanics (4%), followed by non-Hispanic Asians/non-Hispanic whites (3% for both), and non-Hispanic blacks (2%).
DALYs by race/ethnicity
The researchers found that, overall, the cancer burden was highest in non-Hispanic blacks, followed by non-Hispanic whites, Hispanics, and non-Hispanic Asians. However, this pattern was not consistent across the different cancer types.
Age-standardized DALYs lost (per 100,000 individuals) were as follows:
All cancers combined
3588 for non-Hispanic blacks
2898 for non-Hispanic whites
1978 for Hispanics
1798 for non-Hispanic Asians.
Leukemia
115 for non-Hispanic blacks and non-Hispanic whites
98 for Hispanics
82 for non-Hispanic Asians.
NHL
93 for non-Hispanic whites
86 for non-Hispanic blacks
78 for Hispanics
60 for non-Hispanic Asians.
Hodgkin lymphoma
11 for non-Hispanic blacks
10 for non-Hispanic whites and Hispanics
3 for non-Hispanic Asians.
Myeloma
93 for non-Hispanic blacks
43 for non-Hispanic whites
42 for Hispanics
26 for non-Hispanic Asians.
The researchers noted that, despite these differences, the cancer burden in all races/ethnicities was driven by years of life lost. They said this highlights the need to prevent deaths by improving prevention, early detection, and treatment of cancers.
‘Achilles heels’ open doors to myeloma advances
NEW YORK – Three “Achilles heels” of multiple myeloma offer exciting promise for additional advances that will begin to see therapeutic payoffs within the next year, according to Kenneth C. Anderson, MD.
The three targets – excess protein production, immune suppression, and genomic abnormalities – can be addressed by focusing on protein degradation, restoring anti–multiple myeloma immunity, and targeting and overcoming genomic abnormalities, respectively, Dr. Anderson of Dana-Farber Cancer Institute in Boston said at Imedex: Lymphoma & Myeloma, an international congress on hematologic malignancies.
“So if you block those so-called DUBs, you block this same pathway upstream of the proteasome,” he said.
One DUB inhibitor (P5091) was shown in a preclinical trial to overcome bortezomib resistance in multiple myeloma, as was another novel, more user-friendly agent (b-AP15) that blocks USP14/UCHL5 and can be active with immunomodulatory drugs. A clinical trial of b-AP15 is ongoing, Dr. Anderson said.
In contrast to the conventional approach of inhibiting proteins and signaling pathways needed for the survival of the cancer cells, a new technology called “degronimids” turns on the cereblon gene and delivers protein-degrading machinery to targeted proteins. Cereblon, a protein-degrading enzyme that forms part of the ubiquitin E3 ligase complex, tags proteins in the cell for destruction, he noted.
As for immune suppression, he said, the selective plasma cell antigen BCMA (B-cell maturation antigen) is “probably a better target than either CD38 or SLAMF7,” and has already been targeted with an auristatin immunotoxin that induced strong anti–multiple myeloma effects.
“Excitingly, there is this concept of BCMA-BiTEs (B-cell maturation antigen–bispecific T-cell engagers) where we have one linkage of BCMA to the myeloma cell and CD3 attracting a local immune response,” he said.
Other promising new approaches with respect to immune suppression involve checkpoint inhibitors, histone deacetylase (HDAC) inhibitors, and chimeric antigen receptor (CAR) T-cells, he added.
Genomic abnormalities represent another potential vulnerability, and venetoclax (Venclexta) could prove to be the first precision medicine for multiple myeloma, he suggested.
In myeloma, “we are trying to treat the abnormality, but what about treating the genetic consequences of this abnormality,” he said, adding that clinical trials that target the consequences of genomic heterogeneity or instability are on the horizon.
Dr. Anderson reported serving as a consultant for, or receiving other financial support from Acetylon, Bristol-Myers Squibb, C4 Therapeutics, Celgene, Gilead, Millennium, and OncoPep.
NEW YORK – Three “Achilles heels” of multiple myeloma offer exciting promise for additional advances that will begin to see therapeutic payoffs within the next year, according to Kenneth C. Anderson, MD.
The three targets – excess protein production, immune suppression, and genomic abnormalities – can be addressed by focusing on protein degradation, restoring anti–multiple myeloma immunity, and targeting and overcoming genomic abnormalities, respectively, Dr. Anderson of Dana-Farber Cancer Institute in Boston said at Imedex: Lymphoma & Myeloma, an international congress on hematologic malignancies.
“So if you block those so-called DUBs, you block this same pathway upstream of the proteasome,” he said.
One DUB inhibitor (P5091) was shown in a preclinical trial to overcome bortezomib resistance in multiple myeloma, as was another novel, more user-friendly agent (b-AP15) that blocks USP14/UCHL5 and can be active with immunomodulatory drugs. A clinical trial of b-AP15 is ongoing, Dr. Anderson said.
In contrast to the conventional approach of inhibiting proteins and signaling pathways needed for the survival of the cancer cells, a new technology called “degronimids” turns on the cereblon gene and delivers protein-degrading machinery to targeted proteins. Cereblon, a protein-degrading enzyme that forms part of the ubiquitin E3 ligase complex, tags proteins in the cell for destruction, he noted.
As for immune suppression, he said, the selective plasma cell antigen BCMA (B-cell maturation antigen) is “probably a better target than either CD38 or SLAMF7,” and has already been targeted with an auristatin immunotoxin that induced strong anti–multiple myeloma effects.
“Excitingly, there is this concept of BCMA-BiTEs (B-cell maturation antigen–bispecific T-cell engagers) where we have one linkage of BCMA to the myeloma cell and CD3 attracting a local immune response,” he said.
Other promising new approaches with respect to immune suppression involve checkpoint inhibitors, histone deacetylase (HDAC) inhibitors, and chimeric antigen receptor (CAR) T-cells, he added.
Genomic abnormalities represent another potential vulnerability, and venetoclax (Venclexta) could prove to be the first precision medicine for multiple myeloma, he suggested.
In myeloma, “we are trying to treat the abnormality, but what about treating the genetic consequences of this abnormality,” he said, adding that clinical trials that target the consequences of genomic heterogeneity or instability are on the horizon.
Dr. Anderson reported serving as a consultant for, or receiving other financial support from Acetylon, Bristol-Myers Squibb, C4 Therapeutics, Celgene, Gilead, Millennium, and OncoPep.
NEW YORK – Three “Achilles heels” of multiple myeloma offer exciting promise for additional advances that will begin to see therapeutic payoffs within the next year, according to Kenneth C. Anderson, MD.
The three targets – excess protein production, immune suppression, and genomic abnormalities – can be addressed by focusing on protein degradation, restoring anti–multiple myeloma immunity, and targeting and overcoming genomic abnormalities, respectively, Dr. Anderson of Dana-Farber Cancer Institute in Boston said at Imedex: Lymphoma & Myeloma, an international congress on hematologic malignancies.
“So if you block those so-called DUBs, you block this same pathway upstream of the proteasome,” he said.
One DUB inhibitor (P5091) was shown in a preclinical trial to overcome bortezomib resistance in multiple myeloma, as was another novel, more user-friendly agent (b-AP15) that blocks USP14/UCHL5 and can be active with immunomodulatory drugs. A clinical trial of b-AP15 is ongoing, Dr. Anderson said.
In contrast to the conventional approach of inhibiting proteins and signaling pathways needed for the survival of the cancer cells, a new technology called “degronimids” turns on the cereblon gene and delivers protein-degrading machinery to targeted proteins. Cereblon, a protein-degrading enzyme that forms part of the ubiquitin E3 ligase complex, tags proteins in the cell for destruction, he noted.
As for immune suppression, he said, the selective plasma cell antigen BCMA (B-cell maturation antigen) is “probably a better target than either CD38 or SLAMF7,” and has already been targeted with an auristatin immunotoxin that induced strong anti–multiple myeloma effects.
“Excitingly, there is this concept of BCMA-BiTEs (B-cell maturation antigen–bispecific T-cell engagers) where we have one linkage of BCMA to the myeloma cell and CD3 attracting a local immune response,” he said.
Other promising new approaches with respect to immune suppression involve checkpoint inhibitors, histone deacetylase (HDAC) inhibitors, and chimeric antigen receptor (CAR) T-cells, he added.
Genomic abnormalities represent another potential vulnerability, and venetoclax (Venclexta) could prove to be the first precision medicine for multiple myeloma, he suggested.
In myeloma, “we are trying to treat the abnormality, but what about treating the genetic consequences of this abnormality,” he said, adding that clinical trials that target the consequences of genomic heterogeneity or instability are on the horizon.
Dr. Anderson reported serving as a consultant for, or receiving other financial support from Acetylon, Bristol-Myers Squibb, C4 Therapeutics, Celgene, Gilead, Millennium, and OncoPep.
EXPERT ANALYSIS FROM IMEDEX: LYMPHOMA & MYELOMA
Team explains how MM cells alter BM to thrive
New research helps explain how multiple myeloma (MM) cells manipulate the bone marrow (BM) environment to promote disease progression.
The researchers knew that mesenchymal stem cells (MSCs) are often altered in MM in a way that favors disease progression, but the mechanisms behind this phenomenon weren’t well understood.
So the team set out to determine how and when normal MSCs evolve into tumor-promoting MSCs.
Mahmoud Dabbah, of Meir Medical Center in Kfar Saba, Israel, and his colleagues conducted this research and reported the results in the Journal of Leukocyte Biology.
The researchers cultured the MM cell lines U266 and ARP1 with MSCs from healthy donors, looking for changes in the MSCs. The team observed changes in migration and protein translation initiation.
Specifically, they found that co-culturing MSCs with MM cell lines induced an elevation in translation initiation factors eIF4E and eIF4GI as well as their regulators and targets. But these changes were reversible.
MM-conditioned MSCs had significantly elevated levels of peIF4E, total eIF4E, peIF4GI, and total eIF4GI after 3 days of co-culture with both MM cell lines (all increased about 200%, P<0.05).
In fact, levels of peIF4GI and peIF4E were significantly elevated in the MSCs within 1.5 hours of co-culture (both increased more than 250%, P<0.05).
However, when the MSCs were removed from co-culture, the levels returned to baseline within 3 to 6 hours.
MM-conditioned MSCs also showed a significant increase in migration. When cultured for 16 hours, MSC migration increased more than 400% (P<0.05).
Accordingly, the MM-conditioned MSCs expressed lower levels of microRNAs with established roles in cell migration.
The MSCs showed decreased levels of MIR-125a-5p and MIR-199b-3p after 12 hours of co-culture (a decrease of 160% to 250%, P<0.05). And this effect was maintained as long as the co-culture continued.
The researchers said their findings suggest a dynamic interaction between MM cells and the BM niche that causes profound changes in non-malignant BM constituents. They hope that future studies will reveal clinically relevant means of blocking this crosstalk to improve MM therapy.
“Our research should help identify therapeutic targets that may be used to minimize the collateral damage,” Dabbah said. “The identification of the translation initiation phase as a dialogue platform affords a potential new therapeutic target to be explored.”
New research helps explain how multiple myeloma (MM) cells manipulate the bone marrow (BM) environment to promote disease progression.
The researchers knew that mesenchymal stem cells (MSCs) are often altered in MM in a way that favors disease progression, but the mechanisms behind this phenomenon weren’t well understood.
So the team set out to determine how and when normal MSCs evolve into tumor-promoting MSCs.
Mahmoud Dabbah, of Meir Medical Center in Kfar Saba, Israel, and his colleagues conducted this research and reported the results in the Journal of Leukocyte Biology.
The researchers cultured the MM cell lines U266 and ARP1 with MSCs from healthy donors, looking for changes in the MSCs. The team observed changes in migration and protein translation initiation.
Specifically, they found that co-culturing MSCs with MM cell lines induced an elevation in translation initiation factors eIF4E and eIF4GI as well as their regulators and targets. But these changes were reversible.
MM-conditioned MSCs had significantly elevated levels of peIF4E, total eIF4E, peIF4GI, and total eIF4GI after 3 days of co-culture with both MM cell lines (all increased about 200%, P<0.05).
In fact, levels of peIF4GI and peIF4E were significantly elevated in the MSCs within 1.5 hours of co-culture (both increased more than 250%, P<0.05).
However, when the MSCs were removed from co-culture, the levels returned to baseline within 3 to 6 hours.
MM-conditioned MSCs also showed a significant increase in migration. When cultured for 16 hours, MSC migration increased more than 400% (P<0.05).
Accordingly, the MM-conditioned MSCs expressed lower levels of microRNAs with established roles in cell migration.
The MSCs showed decreased levels of MIR-125a-5p and MIR-199b-3p after 12 hours of co-culture (a decrease of 160% to 250%, P<0.05). And this effect was maintained as long as the co-culture continued.
The researchers said their findings suggest a dynamic interaction between MM cells and the BM niche that causes profound changes in non-malignant BM constituents. They hope that future studies will reveal clinically relevant means of blocking this crosstalk to improve MM therapy.
“Our research should help identify therapeutic targets that may be used to minimize the collateral damage,” Dabbah said. “The identification of the translation initiation phase as a dialogue platform affords a potential new therapeutic target to be explored.”
New research helps explain how multiple myeloma (MM) cells manipulate the bone marrow (BM) environment to promote disease progression.
The researchers knew that mesenchymal stem cells (MSCs) are often altered in MM in a way that favors disease progression, but the mechanisms behind this phenomenon weren’t well understood.
So the team set out to determine how and when normal MSCs evolve into tumor-promoting MSCs.
Mahmoud Dabbah, of Meir Medical Center in Kfar Saba, Israel, and his colleagues conducted this research and reported the results in the Journal of Leukocyte Biology.
The researchers cultured the MM cell lines U266 and ARP1 with MSCs from healthy donors, looking for changes in the MSCs. The team observed changes in migration and protein translation initiation.
Specifically, they found that co-culturing MSCs with MM cell lines induced an elevation in translation initiation factors eIF4E and eIF4GI as well as their regulators and targets. But these changes were reversible.
MM-conditioned MSCs had significantly elevated levels of peIF4E, total eIF4E, peIF4GI, and total eIF4GI after 3 days of co-culture with both MM cell lines (all increased about 200%, P<0.05).
In fact, levels of peIF4GI and peIF4E were significantly elevated in the MSCs within 1.5 hours of co-culture (both increased more than 250%, P<0.05).
However, when the MSCs were removed from co-culture, the levels returned to baseline within 3 to 6 hours.
MM-conditioned MSCs also showed a significant increase in migration. When cultured for 16 hours, MSC migration increased more than 400% (P<0.05).
Accordingly, the MM-conditioned MSCs expressed lower levels of microRNAs with established roles in cell migration.
The MSCs showed decreased levels of MIR-125a-5p and MIR-199b-3p after 12 hours of co-culture (a decrease of 160% to 250%, P<0.05). And this effect was maintained as long as the co-culture continued.
The researchers said their findings suggest a dynamic interaction between MM cells and the BM niche that causes profound changes in non-malignant BM constituents. They hope that future studies will reveal clinically relevant means of blocking this crosstalk to improve MM therapy.
“Our research should help identify therapeutic targets that may be used to minimize the collateral damage,” Dabbah said. “The identification of the translation initiation phase as a dialogue platform affords a potential new therapeutic target to be explored.”
FDA grants priority review for MM drug
Photo courtesy of Janssen
The US Food and Drug Administration (FDA) has granted priority review for part of a supplemental biologics license application (sBLA) for daratumumab (Darzalex®).
The priority review pertains to the use of daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.
To grant an application priority review, the FDA must believe the drug would provide a significant improvement in the treatment, diagnosis, or prevention of a serious condition.
The priority review designation means the FDA’s goal is to take action on an application within 6 months, rather than the 10 months typically taken for a standard review.
The FDA has assigned a Prescription Drug User Fee Act target date of February 17, 2017, to make a decision on daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone.
Standard review
The FDA has also granted a standard review period for part of the sBLA.
The standard review pertains to the use of daratumumab in combination with pomalidomide and dexamethasone to treat patients with relapsed or refractory MM who have received at least 2 prior therapies, including a proteasome inhibitor and an immunomodulatory agent.
The Prescription Drug User Fee Act date for the combination of daratumumab with pomalidomide and dexamethasone is June 17, 2017.
Trial data
The sBLA submission included data from a pair of phase 3 studies:
- The CASTOR study, in which researchers compared the combination of daratumumab, bortezomib, and dexamethasone to bortezomib and dexamethasone in patients with relapsed or refractory MM
- The POLLUX study, in which researchers compared daratumumab in combination with lenalidomide and dexamethasone to lenalidomide and dexamethasone in patients with relapsed or refractory MM.
The sBLA submission also included data from a phase 1 study of daratumumab in combination with pomalidomide and dexamethasone in patients with relapsed or refractory MM.
About daratumumab
Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.
Daratumumab already has accelerated approval in the US as monotherapy for MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab to develop, manufacture, and commercialize daratumumab.
For more information on daratumumab, visit www.DARZALEX.com.
Photo courtesy of Janssen
The US Food and Drug Administration (FDA) has granted priority review for part of a supplemental biologics license application (sBLA) for daratumumab (Darzalex®).
The priority review pertains to the use of daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.
To grant an application priority review, the FDA must believe the drug would provide a significant improvement in the treatment, diagnosis, or prevention of a serious condition.
The priority review designation means the FDA’s goal is to take action on an application within 6 months, rather than the 10 months typically taken for a standard review.
The FDA has assigned a Prescription Drug User Fee Act target date of February 17, 2017, to make a decision on daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone.
Standard review
The FDA has also granted a standard review period for part of the sBLA.
The standard review pertains to the use of daratumumab in combination with pomalidomide and dexamethasone to treat patients with relapsed or refractory MM who have received at least 2 prior therapies, including a proteasome inhibitor and an immunomodulatory agent.
The Prescription Drug User Fee Act date for the combination of daratumumab with pomalidomide and dexamethasone is June 17, 2017.
Trial data
The sBLA submission included data from a pair of phase 3 studies:
- The CASTOR study, in which researchers compared the combination of daratumumab, bortezomib, and dexamethasone to bortezomib and dexamethasone in patients with relapsed or refractory MM
- The POLLUX study, in which researchers compared daratumumab in combination with lenalidomide and dexamethasone to lenalidomide and dexamethasone in patients with relapsed or refractory MM.
The sBLA submission also included data from a phase 1 study of daratumumab in combination with pomalidomide and dexamethasone in patients with relapsed or refractory MM.
About daratumumab
Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.
Daratumumab already has accelerated approval in the US as monotherapy for MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab to develop, manufacture, and commercialize daratumumab.
For more information on daratumumab, visit www.DARZALEX.com.
Photo courtesy of Janssen
The US Food and Drug Administration (FDA) has granted priority review for part of a supplemental biologics license application (sBLA) for daratumumab (Darzalex®).
The priority review pertains to the use of daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.
To grant an application priority review, the FDA must believe the drug would provide a significant improvement in the treatment, diagnosis, or prevention of a serious condition.
The priority review designation means the FDA’s goal is to take action on an application within 6 months, rather than the 10 months typically taken for a standard review.
The FDA has assigned a Prescription Drug User Fee Act target date of February 17, 2017, to make a decision on daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone.
Standard review
The FDA has also granted a standard review period for part of the sBLA.
The standard review pertains to the use of daratumumab in combination with pomalidomide and dexamethasone to treat patients with relapsed or refractory MM who have received at least 2 prior therapies, including a proteasome inhibitor and an immunomodulatory agent.
The Prescription Drug User Fee Act date for the combination of daratumumab with pomalidomide and dexamethasone is June 17, 2017.
Trial data
The sBLA submission included data from a pair of phase 3 studies:
- The CASTOR study, in which researchers compared the combination of daratumumab, bortezomib, and dexamethasone to bortezomib and dexamethasone in patients with relapsed or refractory MM
- The POLLUX study, in which researchers compared daratumumab in combination with lenalidomide and dexamethasone to lenalidomide and dexamethasone in patients with relapsed or refractory MM.
The sBLA submission also included data from a phase 1 study of daratumumab in combination with pomalidomide and dexamethasone in patients with relapsed or refractory MM.
About daratumumab
Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.
Daratumumab already has accelerated approval in the US as monotherapy for MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab to develop, manufacture, and commercialize daratumumab.
For more information on daratumumab, visit www.DARZALEX.com.
Supportive care isn’t palliative care, speaker says
Photo courtesy of NCI
NEW YORK—Two presentations at the NCCN 11th Annual Congress: Hematologic Malignancies addressed the importance of supportive care in the treatment of patients with T-cell lymphomas and multiple myeloma.
Erin Kopp, ACNP-BC, of City of Hope Comprehensive Cancer Center in Duarte, California, reminded the audience that supportive care is not palliative care.
Supportive care “complements critical care so that the patient doesn’t have to stop treatment,” she said.
Kopp focused primarily on cutaneous T-cell lymphoma (CTCL) in her presentation, with some recommendations for managing tumor lysis syndrome in patients undergoing therapy for peripheral T-cell lymphoma (PTCL).
And Kathleen Colson, RN, of the Dana-Farber Cancer Institute in Boston, Massachusetts, discussed supportive care for patients with multiple myeloma (MM).
T-cell lymphomas
Most T-cell lymphoma patients will require multiple treatment regimens over their lifetimes, Kopp said. And each type of therapy brings different treatment-related toxicities, which in turn require distinct supportive care measures to manage them.
Topical steroids, for example, may cause skin-thinning, stretch marks, skin irritation, and may be absorbed systemically when a high-potency formulation is used. So the lowest potency steroid that provides the maximum efficacy should be utilized. Practitioners should assess systemic effects if high-potency steroids are utilized.
Topical nitrogen mustard can darken the skin, which often occurs as the lesions resolve, Kopp said. She cautioned that patients experiencing hyperpigmentation often stop treatment without telling their physicians.
So Kopp recommends appropriate patient education to go along with the treatment. With nitrogen mustard, this includes applying a thin layer only to the affected areas and refrigerating the topical ointment to increase soothing.
Topical retinoids may cause redness, itching, warmth, swelling, burning, scaling or other irritation. They also increase the patients’ sensitivity to light. Kopp indicated that for the first week, topical retinoids should be applied once every other day and then titrated as tolerated.
Phototherapy with PUVA or narrowband-UVB may also cause itching, in addition to skin burn, nausea, and other side effects.
“Do not underestimate emollients,” Kopp said, for relief of pruritus. And skin baths with bleach significantly decrease infections that may result from treatment.
Systemic therapy with retinoids, interferon, cytotoxic agents, monoclonal antibodies, and HDAC inhibitors may also cause distinct reactions. For example, the retinoid bexarotene may cause primary hypothyroidism and major lipid abnormalities. Therefore, TSH, free T4, and triglycerides should be monitored every 8 weeks.
Cytotoxic agents such as pralatrexate and methotrexate significantly increase the risk for infection.
Monoclonal antibodies can reactivate previous viral infection, induce tumor lysis syndrome (TLS), and cause progressive multifocal leukoencephalopathy.
HDAC inhibitors such as vorinostat and romidepsin may cause QT prolongation and myelosuppression, among other side effects.
Practitioners need to assess symptoms and side effects thoroughly and often and provide options for supportive care management.
PTCL is an under recognized risk for TLS, Kopp said.
“It should be addressed aggressively,” she added, with monitoring and correction of electrolyte imbalance.
Patients should be rigorously hydrated, and allopurinol should be administered 2-3 days prior to treatment and adjusted based on the patient response and uric acid level.
Multiple myeloma
Colson described supportive care as “keeping all the pieces together.” MM itself can result in a broad spectrum of clinical manifestations, including renal compromise, neuropathy, infection, hypercalcemia, bone pain, lytic lesions, and anemia.
To preserve renal health, patients should drink plenty of water and avoid certain medications, such as IV contrast and nonsteroidal anti-inflammatory drugs.
Peripheral neuropathy can be a side effect of treatment or be caused by the disease itself. Bortezomib-related neuropathy can be reduced with weekly instead of twice weekly dosing and with subcutaneous administration.
Duration of higher doses of thalidomide treatment also impacts neuropathy. Carfilzomib and pomalidomide have a lower incidence of neuropathy.
Myeloma patients have a 15-fold increased risk of recurrent infection because white blood cell production is decreased and the normal immune role of plasma cells is lost.
Supportive therapy includes antibiotics and IVIG therapy. In addition, Colson said pneumonia and influenza vaccines should be considered, as well as prophylaxis for Pneumocystis carinii, herpes zoster, and fungal infections.
Hypercalcemia results from increased bone deterioration. Symptoms include loss of appetite, fatigue, vomiting, muscle weakness, confusion, constipation, increased thirst, and increased urine output. Supportive measures are adequate hydration, furosemide, bisphosphonates, and steroids.
Supportive therapy for bone pain includes bisphosphonates, radiation, pain medication, kyphoplasty, and vertebroplasty. Bisphosphonates, such as pamidronate and zoledronic acid, inhibit bone destruction and are recommended for all myeloma patients with bone disease. However, patients should be monitored for renal dysfunction and osteonecrosis of the jaw when taking bisphosphonates.
And Colson advises, “Hold bisphosphonate therapy if the patient needs a root canal or extraction.” Additionally, dental implants are not recommended for MM patients.
Anemia is another common presenting symptom of myeloma and may also be a result of decreased kidney function. Colson said the use of red blood cell supplements may be used with caution to ameliorate the symptom. Red blood cell transfusion may be considered and a reduction in the medication dose may be required.
MM is a hypercoagulable disease, and measures should be taken to avoid deep vein thrombosis (DVT) and pulmonary embolism (PE). Patients should wear anti-embolism stockings, exercise regularly, take low-dose aspirin, and move about frequently instead of sitting for long periods. Immunomodulatory medications may be adjusted to reduce the risk of a blot clot forming.
Infusion-related reactions are also a risk of therapy, and symptoms of a reaction need to be managed immediately and appropriately, with antihistamines, corticosteroids, interruption of the infusion, slowing of the infusion rate after symptom resolution, and permanent discontinuation in the case of grade 4 reactions.
The potential for longer survival exists, Colson said, due to appropriate supportive care measures.
Photo courtesy of NCI
NEW YORK—Two presentations at the NCCN 11th Annual Congress: Hematologic Malignancies addressed the importance of supportive care in the treatment of patients with T-cell lymphomas and multiple myeloma.
Erin Kopp, ACNP-BC, of City of Hope Comprehensive Cancer Center in Duarte, California, reminded the audience that supportive care is not palliative care.
Supportive care “complements critical care so that the patient doesn’t have to stop treatment,” she said.
Kopp focused primarily on cutaneous T-cell lymphoma (CTCL) in her presentation, with some recommendations for managing tumor lysis syndrome in patients undergoing therapy for peripheral T-cell lymphoma (PTCL).
And Kathleen Colson, RN, of the Dana-Farber Cancer Institute in Boston, Massachusetts, discussed supportive care for patients with multiple myeloma (MM).
T-cell lymphomas
Most T-cell lymphoma patients will require multiple treatment regimens over their lifetimes, Kopp said. And each type of therapy brings different treatment-related toxicities, which in turn require distinct supportive care measures to manage them.
Topical steroids, for example, may cause skin-thinning, stretch marks, skin irritation, and may be absorbed systemically when a high-potency formulation is used. So the lowest potency steroid that provides the maximum efficacy should be utilized. Practitioners should assess systemic effects if high-potency steroids are utilized.
Topical nitrogen mustard can darken the skin, which often occurs as the lesions resolve, Kopp said. She cautioned that patients experiencing hyperpigmentation often stop treatment without telling their physicians.
So Kopp recommends appropriate patient education to go along with the treatment. With nitrogen mustard, this includes applying a thin layer only to the affected areas and refrigerating the topical ointment to increase soothing.
Topical retinoids may cause redness, itching, warmth, swelling, burning, scaling or other irritation. They also increase the patients’ sensitivity to light. Kopp indicated that for the first week, topical retinoids should be applied once every other day and then titrated as tolerated.
Phototherapy with PUVA or narrowband-UVB may also cause itching, in addition to skin burn, nausea, and other side effects.
“Do not underestimate emollients,” Kopp said, for relief of pruritus. And skin baths with bleach significantly decrease infections that may result from treatment.
Systemic therapy with retinoids, interferon, cytotoxic agents, monoclonal antibodies, and HDAC inhibitors may also cause distinct reactions. For example, the retinoid bexarotene may cause primary hypothyroidism and major lipid abnormalities. Therefore, TSH, free T4, and triglycerides should be monitored every 8 weeks.
Cytotoxic agents such as pralatrexate and methotrexate significantly increase the risk for infection.
Monoclonal antibodies can reactivate previous viral infection, induce tumor lysis syndrome (TLS), and cause progressive multifocal leukoencephalopathy.
HDAC inhibitors such as vorinostat and romidepsin may cause QT prolongation and myelosuppression, among other side effects.
Practitioners need to assess symptoms and side effects thoroughly and often and provide options for supportive care management.
PTCL is an under recognized risk for TLS, Kopp said.
“It should be addressed aggressively,” she added, with monitoring and correction of electrolyte imbalance.
Patients should be rigorously hydrated, and allopurinol should be administered 2-3 days prior to treatment and adjusted based on the patient response and uric acid level.
Multiple myeloma
Colson described supportive care as “keeping all the pieces together.” MM itself can result in a broad spectrum of clinical manifestations, including renal compromise, neuropathy, infection, hypercalcemia, bone pain, lytic lesions, and anemia.
To preserve renal health, patients should drink plenty of water and avoid certain medications, such as IV contrast and nonsteroidal anti-inflammatory drugs.
Peripheral neuropathy can be a side effect of treatment or be caused by the disease itself. Bortezomib-related neuropathy can be reduced with weekly instead of twice weekly dosing and with subcutaneous administration.
Duration of higher doses of thalidomide treatment also impacts neuropathy. Carfilzomib and pomalidomide have a lower incidence of neuropathy.
Myeloma patients have a 15-fold increased risk of recurrent infection because white blood cell production is decreased and the normal immune role of plasma cells is lost.
Supportive therapy includes antibiotics and IVIG therapy. In addition, Colson said pneumonia and influenza vaccines should be considered, as well as prophylaxis for Pneumocystis carinii, herpes zoster, and fungal infections.
Hypercalcemia results from increased bone deterioration. Symptoms include loss of appetite, fatigue, vomiting, muscle weakness, confusion, constipation, increased thirst, and increased urine output. Supportive measures are adequate hydration, furosemide, bisphosphonates, and steroids.
Supportive therapy for bone pain includes bisphosphonates, radiation, pain medication, kyphoplasty, and vertebroplasty. Bisphosphonates, such as pamidronate and zoledronic acid, inhibit bone destruction and are recommended for all myeloma patients with bone disease. However, patients should be monitored for renal dysfunction and osteonecrosis of the jaw when taking bisphosphonates.
And Colson advises, “Hold bisphosphonate therapy if the patient needs a root canal or extraction.” Additionally, dental implants are not recommended for MM patients.
Anemia is another common presenting symptom of myeloma and may also be a result of decreased kidney function. Colson said the use of red blood cell supplements may be used with caution to ameliorate the symptom. Red blood cell transfusion may be considered and a reduction in the medication dose may be required.
MM is a hypercoagulable disease, and measures should be taken to avoid deep vein thrombosis (DVT) and pulmonary embolism (PE). Patients should wear anti-embolism stockings, exercise regularly, take low-dose aspirin, and move about frequently instead of sitting for long periods. Immunomodulatory medications may be adjusted to reduce the risk of a blot clot forming.
Infusion-related reactions are also a risk of therapy, and symptoms of a reaction need to be managed immediately and appropriately, with antihistamines, corticosteroids, interruption of the infusion, slowing of the infusion rate after symptom resolution, and permanent discontinuation in the case of grade 4 reactions.
The potential for longer survival exists, Colson said, due to appropriate supportive care measures.
Photo courtesy of NCI
NEW YORK—Two presentations at the NCCN 11th Annual Congress: Hematologic Malignancies addressed the importance of supportive care in the treatment of patients with T-cell lymphomas and multiple myeloma.
Erin Kopp, ACNP-BC, of City of Hope Comprehensive Cancer Center in Duarte, California, reminded the audience that supportive care is not palliative care.
Supportive care “complements critical care so that the patient doesn’t have to stop treatment,” she said.
Kopp focused primarily on cutaneous T-cell lymphoma (CTCL) in her presentation, with some recommendations for managing tumor lysis syndrome in patients undergoing therapy for peripheral T-cell lymphoma (PTCL).
And Kathleen Colson, RN, of the Dana-Farber Cancer Institute in Boston, Massachusetts, discussed supportive care for patients with multiple myeloma (MM).
T-cell lymphomas
Most T-cell lymphoma patients will require multiple treatment regimens over their lifetimes, Kopp said. And each type of therapy brings different treatment-related toxicities, which in turn require distinct supportive care measures to manage them.
Topical steroids, for example, may cause skin-thinning, stretch marks, skin irritation, and may be absorbed systemically when a high-potency formulation is used. So the lowest potency steroid that provides the maximum efficacy should be utilized. Practitioners should assess systemic effects if high-potency steroids are utilized.
Topical nitrogen mustard can darken the skin, which often occurs as the lesions resolve, Kopp said. She cautioned that patients experiencing hyperpigmentation often stop treatment without telling their physicians.
So Kopp recommends appropriate patient education to go along with the treatment. With nitrogen mustard, this includes applying a thin layer only to the affected areas and refrigerating the topical ointment to increase soothing.
Topical retinoids may cause redness, itching, warmth, swelling, burning, scaling or other irritation. They also increase the patients’ sensitivity to light. Kopp indicated that for the first week, topical retinoids should be applied once every other day and then titrated as tolerated.
Phototherapy with PUVA or narrowband-UVB may also cause itching, in addition to skin burn, nausea, and other side effects.
“Do not underestimate emollients,” Kopp said, for relief of pruritus. And skin baths with bleach significantly decrease infections that may result from treatment.
Systemic therapy with retinoids, interferon, cytotoxic agents, monoclonal antibodies, and HDAC inhibitors may also cause distinct reactions. For example, the retinoid bexarotene may cause primary hypothyroidism and major lipid abnormalities. Therefore, TSH, free T4, and triglycerides should be monitored every 8 weeks.
Cytotoxic agents such as pralatrexate and methotrexate significantly increase the risk for infection.
Monoclonal antibodies can reactivate previous viral infection, induce tumor lysis syndrome (TLS), and cause progressive multifocal leukoencephalopathy.
HDAC inhibitors such as vorinostat and romidepsin may cause QT prolongation and myelosuppression, among other side effects.
Practitioners need to assess symptoms and side effects thoroughly and often and provide options for supportive care management.
PTCL is an under recognized risk for TLS, Kopp said.
“It should be addressed aggressively,” she added, with monitoring and correction of electrolyte imbalance.
Patients should be rigorously hydrated, and allopurinol should be administered 2-3 days prior to treatment and adjusted based on the patient response and uric acid level.
Multiple myeloma
Colson described supportive care as “keeping all the pieces together.” MM itself can result in a broad spectrum of clinical manifestations, including renal compromise, neuropathy, infection, hypercalcemia, bone pain, lytic lesions, and anemia.
To preserve renal health, patients should drink plenty of water and avoid certain medications, such as IV contrast and nonsteroidal anti-inflammatory drugs.
Peripheral neuropathy can be a side effect of treatment or be caused by the disease itself. Bortezomib-related neuropathy can be reduced with weekly instead of twice weekly dosing and with subcutaneous administration.
Duration of higher doses of thalidomide treatment also impacts neuropathy. Carfilzomib and pomalidomide have a lower incidence of neuropathy.
Myeloma patients have a 15-fold increased risk of recurrent infection because white blood cell production is decreased and the normal immune role of plasma cells is lost.
Supportive therapy includes antibiotics and IVIG therapy. In addition, Colson said pneumonia and influenza vaccines should be considered, as well as prophylaxis for Pneumocystis carinii, herpes zoster, and fungal infections.
Hypercalcemia results from increased bone deterioration. Symptoms include loss of appetite, fatigue, vomiting, muscle weakness, confusion, constipation, increased thirst, and increased urine output. Supportive measures are adequate hydration, furosemide, bisphosphonates, and steroids.
Supportive therapy for bone pain includes bisphosphonates, radiation, pain medication, kyphoplasty, and vertebroplasty. Bisphosphonates, such as pamidronate and zoledronic acid, inhibit bone destruction and are recommended for all myeloma patients with bone disease. However, patients should be monitored for renal dysfunction and osteonecrosis of the jaw when taking bisphosphonates.
And Colson advises, “Hold bisphosphonate therapy if the patient needs a root canal or extraction.” Additionally, dental implants are not recommended for MM patients.
Anemia is another common presenting symptom of myeloma and may also be a result of decreased kidney function. Colson said the use of red blood cell supplements may be used with caution to ameliorate the symptom. Red blood cell transfusion may be considered and a reduction in the medication dose may be required.
MM is a hypercoagulable disease, and measures should be taken to avoid deep vein thrombosis (DVT) and pulmonary embolism (PE). Patients should wear anti-embolism stockings, exercise regularly, take low-dose aspirin, and move about frequently instead of sitting for long periods. Immunomodulatory medications may be adjusted to reduce the risk of a blot clot forming.
Infusion-related reactions are also a risk of therapy, and symptoms of a reaction need to be managed immediately and appropriately, with antihistamines, corticosteroids, interruption of the infusion, slowing of the infusion rate after symptom resolution, and permanent discontinuation in the case of grade 4 reactions.
The potential for longer survival exists, Colson said, due to appropriate supportive care measures.
Triplet improves PFS in relapsed/refractory MM
Results of the phase 3 POLLUX trial suggest that adding daratumumab to treatment with lenalidomide and dexamethasone can improve progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (MM).
Compared to patients who received only lenalidomide and dexamethasone, those who received daratumumab as well had a significantly higher response rate and longer PFS.
Treatment with daratumumab was also associated with infusion-related reactions and a higher incidence of neutropenia.
These results were published in NEJM. They were previously presented at the 21st Congress of the European Hematology Association. The POLLUX trial was funded by Janssen Research and Development.
POLLUX enrolled 569 patients who had relapsed or refractory MM. The patients were randomized to receive either daratumumab, lenalidomide, and dexamethasone (DRd, n=286) or lenalidomide and dexamethasone alone (Rd, n=283).
Patient characteristics were similar between the treatment arms. The median age was 65 in both arms (overall range, 34-89). About half of patients in each arm had ISS stage I disease, about half had an ECOG performance score of 1 or 2, and patients were, roughly, a median of 4 years from diagnosis.
In both arms, patients had a median of 1 prior lines of therapy (overall range, 1-11).
More than 60% of patients in both arms (63%-64%) had received a prior transplant; 86% had received a proteasome inhibitor; 55% had received an immunomodulatory agent; 44% had received a proteasome inhibitor and an immunomodulatory agent; and 41%-43% had received a proteasome inhibitor, an immunomodulatory agent, and an alkylating agent.
Discontinuation
At the clinical cutoff date on March 7, 2016, 23.3% (n=66) of patients in the DRd arm and 47.0% (n=132) of those in the Rd arm discontinued treatment.
The most common reasons for discontinuation were progression (14.1% in the DRd arm and 34.2% in the Rd arm) and adverse events (6.7% and 8.2%, respectively).
Response
The overall response rate among evaluable patients (281 in the DRd arm and 276 in the Rd arm) was 92.9% in DRd arm and 76.4% in the Rd arm (P<0.001).
The rates of complete response or better were 43.1% and 19.2%, respectively. And the rates of stringent complete response were 18.1% and 7.2%, respectively.
In the DRd arm, 22.4% of patients had results below the threshold for minimal residual disease (1 tumor cell per 105 white cells). The same was true for 4.6% of patients in the Rd arm (P<0.001).
PFS and OS
At a median follow-up of 13.5 months, there were 169 events of disease progression or death. The incidence was 18.5% (53/286) in the DRd arm and 41% (116/283) in the Rd arm. The hazard ratio was 0.37 (P<0.001).
At 12 months, the rate of PFS was 83.2% in the DRd arm and 60.1% in the Rd arm. The median PFS has not been reached in the DRd arm but was 18.4 months for patients in the Rd arm.
The improvement in PFS for the DRd arm was seen across all patient subgroups, regardless of age, ISS stage, prior treatment, etc.
In addition, there was an overall survival (OS) advantage with DRd. The 12-month OS was 92.1% in the DRd arm and 86.8% in the Rd arm.
The median OS was not reached in the DRd arm and was 20.3 months in the Rd arm. The hazard ratio was 0.64 (P=0.0534). The researchers said follow-up for long-term survival is ongoing.
Safety
The most common hematologic adverse events (in the DRd and Rd arms, respectively) were neutropenia (59.4% and 43.1%), anemia (31.1% and 34.9%), thrombocytopenia (26.9% and 27.4%), lymphopenia (6.0% and 5.3%), and febrile neutropenia (5.7% and 2.5%). Deep vein thrombosis occurred in 1.8% and 3.9% of patients, respectively.
The most common non-hematologic adverse events (in the DRd and Rd arms, respectively) were diarrhea (42.8% and 24.6%), fatigue (35.3% and 27.8%), upper respiratory tract infection (31.8% and 20.6%), constipation (29.3% and 25.3%), cough (29.0% and 12.5%), muscle spasms (25.8% and 18.5%), and pneumonia (14.1% and 13.2%).
Patients in the DRd arm had a higher rate of several grade 3/4 events, including neutropenia (51.9% and 37.0%), diarrhea (5.3% and 3.2%), fatigue (6.4% and 2.5%), nausea (1.4% and 0%), dyspnea (3.2% and 0.7%), and infection (28.3% and 22.8%).
Serious adverse events occurred in 48.8% of patients in the DRd arm and 42.0% in the Rd arm. Pneumonia was the most common serious event, occurring in 8.1% and 8.5% of patients, respectively.
Daratumumab-infusion-related reactions occurred in 47.7% of patients, were mostly grade 1/2, and occurred predominantly during the first infusion.
The researchers also noted that daratumumab interferes with laboratory-based blood compatibility tests because the drug binds to CD38 on red cells.
Daratumumab development
Data from the phase 3 CASTOR trial—in which researchers compared daratumumab, bortezomib, and dexamethasone to bortezomib and dexamethasone alone—were also recently published in NEJM.
“Following the publication of the phase 3 CASTOR data, we are pleased that the positive data from the phase 3 POLLUX study has now also been published in the New England Journal of Medicine,” said Jan van de Winkel, PhD, chief executive officer of Genmab.
“The data from this study formed the basis, along with data from the CASTOR study, of 2 regulatory submissions in August—the supplemental Biologics License Application submitted to the US Food and Drug Administration and the submission of the variation to the Marketing Authorization to the European Medicines Agency.”
Both submissions seek to expand the current indication for daratumumab so the drug can be used in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least 1 prior therapy.
Daratumumab currently has conditional approval from the European Commission as monotherapy for adults with relapsed and refractory MM who progressed on their last therapy and have received treatment with a proteasome inhibitor and an immunomodulatory agent.
Daratumumab has accelerated approval in the US as monotherapy for MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab to develop, manufacture, and commercialize daratumumab.
Results of the phase 3 POLLUX trial suggest that adding daratumumab to treatment with lenalidomide and dexamethasone can improve progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (MM).
Compared to patients who received only lenalidomide and dexamethasone, those who received daratumumab as well had a significantly higher response rate and longer PFS.
Treatment with daratumumab was also associated with infusion-related reactions and a higher incidence of neutropenia.
These results were published in NEJM. They were previously presented at the 21st Congress of the European Hematology Association. The POLLUX trial was funded by Janssen Research and Development.
POLLUX enrolled 569 patients who had relapsed or refractory MM. The patients were randomized to receive either daratumumab, lenalidomide, and dexamethasone (DRd, n=286) or lenalidomide and dexamethasone alone (Rd, n=283).
Patient characteristics were similar between the treatment arms. The median age was 65 in both arms (overall range, 34-89). About half of patients in each arm had ISS stage I disease, about half had an ECOG performance score of 1 or 2, and patients were, roughly, a median of 4 years from diagnosis.
In both arms, patients had a median of 1 prior lines of therapy (overall range, 1-11).
More than 60% of patients in both arms (63%-64%) had received a prior transplant; 86% had received a proteasome inhibitor; 55% had received an immunomodulatory agent; 44% had received a proteasome inhibitor and an immunomodulatory agent; and 41%-43% had received a proteasome inhibitor, an immunomodulatory agent, and an alkylating agent.
Discontinuation
At the clinical cutoff date on March 7, 2016, 23.3% (n=66) of patients in the DRd arm and 47.0% (n=132) of those in the Rd arm discontinued treatment.
The most common reasons for discontinuation were progression (14.1% in the DRd arm and 34.2% in the Rd arm) and adverse events (6.7% and 8.2%, respectively).
Response
The overall response rate among evaluable patients (281 in the DRd arm and 276 in the Rd arm) was 92.9% in DRd arm and 76.4% in the Rd arm (P<0.001).
The rates of complete response or better were 43.1% and 19.2%, respectively. And the rates of stringent complete response were 18.1% and 7.2%, respectively.
In the DRd arm, 22.4% of patients had results below the threshold for minimal residual disease (1 tumor cell per 105 white cells). The same was true for 4.6% of patients in the Rd arm (P<0.001).
PFS and OS
At a median follow-up of 13.5 months, there were 169 events of disease progression or death. The incidence was 18.5% (53/286) in the DRd arm and 41% (116/283) in the Rd arm. The hazard ratio was 0.37 (P<0.001).
At 12 months, the rate of PFS was 83.2% in the DRd arm and 60.1% in the Rd arm. The median PFS has not been reached in the DRd arm but was 18.4 months for patients in the Rd arm.
The improvement in PFS for the DRd arm was seen across all patient subgroups, regardless of age, ISS stage, prior treatment, etc.
In addition, there was an overall survival (OS) advantage with DRd. The 12-month OS was 92.1% in the DRd arm and 86.8% in the Rd arm.
The median OS was not reached in the DRd arm and was 20.3 months in the Rd arm. The hazard ratio was 0.64 (P=0.0534). The researchers said follow-up for long-term survival is ongoing.
Safety
The most common hematologic adverse events (in the DRd and Rd arms, respectively) were neutropenia (59.4% and 43.1%), anemia (31.1% and 34.9%), thrombocytopenia (26.9% and 27.4%), lymphopenia (6.0% and 5.3%), and febrile neutropenia (5.7% and 2.5%). Deep vein thrombosis occurred in 1.8% and 3.9% of patients, respectively.
The most common non-hematologic adverse events (in the DRd and Rd arms, respectively) were diarrhea (42.8% and 24.6%), fatigue (35.3% and 27.8%), upper respiratory tract infection (31.8% and 20.6%), constipation (29.3% and 25.3%), cough (29.0% and 12.5%), muscle spasms (25.8% and 18.5%), and pneumonia (14.1% and 13.2%).
Patients in the DRd arm had a higher rate of several grade 3/4 events, including neutropenia (51.9% and 37.0%), diarrhea (5.3% and 3.2%), fatigue (6.4% and 2.5%), nausea (1.4% and 0%), dyspnea (3.2% and 0.7%), and infection (28.3% and 22.8%).
Serious adverse events occurred in 48.8% of patients in the DRd arm and 42.0% in the Rd arm. Pneumonia was the most common serious event, occurring in 8.1% and 8.5% of patients, respectively.
Daratumumab-infusion-related reactions occurred in 47.7% of patients, were mostly grade 1/2, and occurred predominantly during the first infusion.
The researchers also noted that daratumumab interferes with laboratory-based blood compatibility tests because the drug binds to CD38 on red cells.
Daratumumab development
Data from the phase 3 CASTOR trial—in which researchers compared daratumumab, bortezomib, and dexamethasone to bortezomib and dexamethasone alone—were also recently published in NEJM.
“Following the publication of the phase 3 CASTOR data, we are pleased that the positive data from the phase 3 POLLUX study has now also been published in the New England Journal of Medicine,” said Jan van de Winkel, PhD, chief executive officer of Genmab.
“The data from this study formed the basis, along with data from the CASTOR study, of 2 regulatory submissions in August—the supplemental Biologics License Application submitted to the US Food and Drug Administration and the submission of the variation to the Marketing Authorization to the European Medicines Agency.”
Both submissions seek to expand the current indication for daratumumab so the drug can be used in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least 1 prior therapy.
Daratumumab currently has conditional approval from the European Commission as monotherapy for adults with relapsed and refractory MM who progressed on their last therapy and have received treatment with a proteasome inhibitor and an immunomodulatory agent.
Daratumumab has accelerated approval in the US as monotherapy for MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab to develop, manufacture, and commercialize daratumumab.
Results of the phase 3 POLLUX trial suggest that adding daratumumab to treatment with lenalidomide and dexamethasone can improve progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (MM).
Compared to patients who received only lenalidomide and dexamethasone, those who received daratumumab as well had a significantly higher response rate and longer PFS.
Treatment with daratumumab was also associated with infusion-related reactions and a higher incidence of neutropenia.
These results were published in NEJM. They were previously presented at the 21st Congress of the European Hematology Association. The POLLUX trial was funded by Janssen Research and Development.
POLLUX enrolled 569 patients who had relapsed or refractory MM. The patients were randomized to receive either daratumumab, lenalidomide, and dexamethasone (DRd, n=286) or lenalidomide and dexamethasone alone (Rd, n=283).
Patient characteristics were similar between the treatment arms. The median age was 65 in both arms (overall range, 34-89). About half of patients in each arm had ISS stage I disease, about half had an ECOG performance score of 1 or 2, and patients were, roughly, a median of 4 years from diagnosis.
In both arms, patients had a median of 1 prior lines of therapy (overall range, 1-11).
More than 60% of patients in both arms (63%-64%) had received a prior transplant; 86% had received a proteasome inhibitor; 55% had received an immunomodulatory agent; 44% had received a proteasome inhibitor and an immunomodulatory agent; and 41%-43% had received a proteasome inhibitor, an immunomodulatory agent, and an alkylating agent.
Discontinuation
At the clinical cutoff date on March 7, 2016, 23.3% (n=66) of patients in the DRd arm and 47.0% (n=132) of those in the Rd arm discontinued treatment.
The most common reasons for discontinuation were progression (14.1% in the DRd arm and 34.2% in the Rd arm) and adverse events (6.7% and 8.2%, respectively).
Response
The overall response rate among evaluable patients (281 in the DRd arm and 276 in the Rd arm) was 92.9% in DRd arm and 76.4% in the Rd arm (P<0.001).
The rates of complete response or better were 43.1% and 19.2%, respectively. And the rates of stringent complete response were 18.1% and 7.2%, respectively.
In the DRd arm, 22.4% of patients had results below the threshold for minimal residual disease (1 tumor cell per 105 white cells). The same was true for 4.6% of patients in the Rd arm (P<0.001).
PFS and OS
At a median follow-up of 13.5 months, there were 169 events of disease progression or death. The incidence was 18.5% (53/286) in the DRd arm and 41% (116/283) in the Rd arm. The hazard ratio was 0.37 (P<0.001).
At 12 months, the rate of PFS was 83.2% in the DRd arm and 60.1% in the Rd arm. The median PFS has not been reached in the DRd arm but was 18.4 months for patients in the Rd arm.
The improvement in PFS for the DRd arm was seen across all patient subgroups, regardless of age, ISS stage, prior treatment, etc.
In addition, there was an overall survival (OS) advantage with DRd. The 12-month OS was 92.1% in the DRd arm and 86.8% in the Rd arm.
The median OS was not reached in the DRd arm and was 20.3 months in the Rd arm. The hazard ratio was 0.64 (P=0.0534). The researchers said follow-up for long-term survival is ongoing.
Safety
The most common hematologic adverse events (in the DRd and Rd arms, respectively) were neutropenia (59.4% and 43.1%), anemia (31.1% and 34.9%), thrombocytopenia (26.9% and 27.4%), lymphopenia (6.0% and 5.3%), and febrile neutropenia (5.7% and 2.5%). Deep vein thrombosis occurred in 1.8% and 3.9% of patients, respectively.
The most common non-hematologic adverse events (in the DRd and Rd arms, respectively) were diarrhea (42.8% and 24.6%), fatigue (35.3% and 27.8%), upper respiratory tract infection (31.8% and 20.6%), constipation (29.3% and 25.3%), cough (29.0% and 12.5%), muscle spasms (25.8% and 18.5%), and pneumonia (14.1% and 13.2%).
Patients in the DRd arm had a higher rate of several grade 3/4 events, including neutropenia (51.9% and 37.0%), diarrhea (5.3% and 3.2%), fatigue (6.4% and 2.5%), nausea (1.4% and 0%), dyspnea (3.2% and 0.7%), and infection (28.3% and 22.8%).
Serious adverse events occurred in 48.8% of patients in the DRd arm and 42.0% in the Rd arm. Pneumonia was the most common serious event, occurring in 8.1% and 8.5% of patients, respectively.
Daratumumab-infusion-related reactions occurred in 47.7% of patients, were mostly grade 1/2, and occurred predominantly during the first infusion.
The researchers also noted that daratumumab interferes with laboratory-based blood compatibility tests because the drug binds to CD38 on red cells.
Daratumumab development
Data from the phase 3 CASTOR trial—in which researchers compared daratumumab, bortezomib, and dexamethasone to bortezomib and dexamethasone alone—were also recently published in NEJM.
“Following the publication of the phase 3 CASTOR data, we are pleased that the positive data from the phase 3 POLLUX study has now also been published in the New England Journal of Medicine,” said Jan van de Winkel, PhD, chief executive officer of Genmab.
“The data from this study formed the basis, along with data from the CASTOR study, of 2 regulatory submissions in August—the supplemental Biologics License Application submitted to the US Food and Drug Administration and the submission of the variation to the Marketing Authorization to the European Medicines Agency.”
Both submissions seek to expand the current indication for daratumumab so the drug can be used in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least 1 prior therapy.
Daratumumab currently has conditional approval from the European Commission as monotherapy for adults with relapsed and refractory MM who progressed on their last therapy and have received treatment with a proteasome inhibitor and an immunomodulatory agent.
Daratumumab has accelerated approval in the US as monotherapy for MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab to develop, manufacture, and commercialize daratumumab.
Study Points to Risk Factors for Lymphoma
Certain lifestyle, dietary, environmental, serologic, and genetic factors may raise the risk of non-Hodgkin lymphoma (NHL), according to researchers who reviewed 40 years of follow-up data from the Nurses’ Health Study (NHS).
Related: Exercise Lowers Risk of Some Cancers
The researchers, from Brigham and Women’s Hospital, Harvard, and Boston University, all in Massachusetts, aimed to highlight the NHS’s contributions to epidemiologic knowledge of endometrial, ovarian, pancreatic, and hematologic cancers. They focused on findings that identified novel risk factors or markers of early detection or helped clarify discrepant literature.
Because the researchers say severe immune compromise is the “strongest, best-established risk factor” for NHL, they studied factors that might lead to subclinical immune dysregulation, such as diet, body mass index (BMI), and supplement use. They found several risk factors and biomarkers for NHL and more than 35 distinct tumors in that category, including chronic lymphocytic leukemia. Trans fats and red meat, for instance, doubled the risk of NHL. The researchers also found a higher risk for women who reported long-term multivitamin use. However, they found no risk associated with diet or sugar-sweetened soda or aspartame or with dietary intake of vitamin D.
Related: IBD and the Risk of Oral Cancer
Greater adiposity during childhood and adolescence was significantly associated with NHL. The researchers also observed a 19% increased risk of all NHL per 5 kg/m2 increase in BMI in young adulthood. Interestingly, taller women also had a higher risk of NHL.
The researchers conducted one of the first prospective studies to evaluate a putative inverse association of NHL risk with exposure to ambient ultraviolet radiation. They found, “contrary to expectation,” a 10% to 20% increased risk of NHL among women with the highest (vs lowest) ultraviolet-B exposure at baseline and birth, 15 years, and 30 years.
In investigating biomarkers, the researchers noted a “suggestive increase” in chronic lymphocytic leukemia risk associated with an Epstein-Barr virus antibody profile indicative of poor host immune control of the virus.
Related: Sexual Orientation and Cancer Risk
The researchers have established several working groups to study cancers, such as NHL and multiple myeloma. They also are collecting archival tissue specimens for NHL, multiple myeloma, and Hodgkin lymphoma, for better evaluation of factors related to the unique molecular subsets of hematologic tumors.
Source:
Birmann BM, Barnard ME, Bertrand KA, et al. Am J Public Health. 2016;106(9):1608-1615.
doi: 10.2105/AJPH.2016.303337.
Certain lifestyle, dietary, environmental, serologic, and genetic factors may raise the risk of non-Hodgkin lymphoma (NHL), according to researchers who reviewed 40 years of follow-up data from the Nurses’ Health Study (NHS).
Related: Exercise Lowers Risk of Some Cancers
The researchers, from Brigham and Women’s Hospital, Harvard, and Boston University, all in Massachusetts, aimed to highlight the NHS’s contributions to epidemiologic knowledge of endometrial, ovarian, pancreatic, and hematologic cancers. They focused on findings that identified novel risk factors or markers of early detection or helped clarify discrepant literature.
Because the researchers say severe immune compromise is the “strongest, best-established risk factor” for NHL, they studied factors that might lead to subclinical immune dysregulation, such as diet, body mass index (BMI), and supplement use. They found several risk factors and biomarkers for NHL and more than 35 distinct tumors in that category, including chronic lymphocytic leukemia. Trans fats and red meat, for instance, doubled the risk of NHL. The researchers also found a higher risk for women who reported long-term multivitamin use. However, they found no risk associated with diet or sugar-sweetened soda or aspartame or with dietary intake of vitamin D.
Related: IBD and the Risk of Oral Cancer
Greater adiposity during childhood and adolescence was significantly associated with NHL. The researchers also observed a 19% increased risk of all NHL per 5 kg/m2 increase in BMI in young adulthood. Interestingly, taller women also had a higher risk of NHL.
The researchers conducted one of the first prospective studies to evaluate a putative inverse association of NHL risk with exposure to ambient ultraviolet radiation. They found, “contrary to expectation,” a 10% to 20% increased risk of NHL among women with the highest (vs lowest) ultraviolet-B exposure at baseline and birth, 15 years, and 30 years.
In investigating biomarkers, the researchers noted a “suggestive increase” in chronic lymphocytic leukemia risk associated with an Epstein-Barr virus antibody profile indicative of poor host immune control of the virus.
Related: Sexual Orientation and Cancer Risk
The researchers have established several working groups to study cancers, such as NHL and multiple myeloma. They also are collecting archival tissue specimens for NHL, multiple myeloma, and Hodgkin lymphoma, for better evaluation of factors related to the unique molecular subsets of hematologic tumors.
Source:
Birmann BM, Barnard ME, Bertrand KA, et al. Am J Public Health. 2016;106(9):1608-1615.
doi: 10.2105/AJPH.2016.303337.
Certain lifestyle, dietary, environmental, serologic, and genetic factors may raise the risk of non-Hodgkin lymphoma (NHL), according to researchers who reviewed 40 years of follow-up data from the Nurses’ Health Study (NHS).
Related: Exercise Lowers Risk of Some Cancers
The researchers, from Brigham and Women’s Hospital, Harvard, and Boston University, all in Massachusetts, aimed to highlight the NHS’s contributions to epidemiologic knowledge of endometrial, ovarian, pancreatic, and hematologic cancers. They focused on findings that identified novel risk factors or markers of early detection or helped clarify discrepant literature.
Because the researchers say severe immune compromise is the “strongest, best-established risk factor” for NHL, they studied factors that might lead to subclinical immune dysregulation, such as diet, body mass index (BMI), and supplement use. They found several risk factors and biomarkers for NHL and more than 35 distinct tumors in that category, including chronic lymphocytic leukemia. Trans fats and red meat, for instance, doubled the risk of NHL. The researchers also found a higher risk for women who reported long-term multivitamin use. However, they found no risk associated with diet or sugar-sweetened soda or aspartame or with dietary intake of vitamin D.
Related: IBD and the Risk of Oral Cancer
Greater adiposity during childhood and adolescence was significantly associated with NHL. The researchers also observed a 19% increased risk of all NHL per 5 kg/m2 increase in BMI in young adulthood. Interestingly, taller women also had a higher risk of NHL.
The researchers conducted one of the first prospective studies to evaluate a putative inverse association of NHL risk with exposure to ambient ultraviolet radiation. They found, “contrary to expectation,” a 10% to 20% increased risk of NHL among women with the highest (vs lowest) ultraviolet-B exposure at baseline and birth, 15 years, and 30 years.
In investigating biomarkers, the researchers noted a “suggestive increase” in chronic lymphocytic leukemia risk associated with an Epstein-Barr virus antibody profile indicative of poor host immune control of the virus.
Related: Sexual Orientation and Cancer Risk
The researchers have established several working groups to study cancers, such as NHL and multiple myeloma. They also are collecting archival tissue specimens for NHL, multiple myeloma, and Hodgkin lymphoma, for better evaluation of factors related to the unique molecular subsets of hematologic tumors.
Source:
Birmann BM, Barnard ME, Bertrand KA, et al. Am J Public Health. 2016;106(9):1608-1615.
doi: 10.2105/AJPH.2016.303337.