Non-Hodgkin Lymphoma

Photo by Bill Branson

Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*

Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.

Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).

The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).

For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.

To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.

Results

The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).

The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).

Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.

Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).

Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.

Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.

The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.

The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.

This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).

*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.

Photo by Bill Branson

Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*

Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.

Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).

The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).

For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.

To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.

Results

The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).

The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).

Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.

Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).

Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.

Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.

The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.

The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.

This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).

*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.

Photo by Bill Branson

Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*

Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.

Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).

The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).

For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.

To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.

Results

The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).

The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).

Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.

Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).

Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.

Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.

The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.

The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.

This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).

*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).

The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.

This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.

The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.

The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.

Phase 2 trial

The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.

According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.

The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).

Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.

This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).

The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.

This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.

The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.

The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.

Phase 2 trial

The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.

According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.

The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).

Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.

This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).

The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.

This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.

The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.

The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.

Phase 2 trial

The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.

According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.

The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).

Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.

This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.

Photo by Bill Branson

Survey results suggest childhood cancer survivors (CCSs) in the US are more likely than individuals without a history of cancer to experience “job lock,” or staying at a job to keep work-related health insurance.

CCSs are also more likely than individuals without a history of cancer to report problems paying medical bills and being denied health insurance.

Anne Kirchhoff, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City, and her colleagues reported these findings in JAMA Oncology.

The researchers analyzed 394 CCSs from pediatric oncology institutions across the US, along with 128 of their siblings who had no history of cancer. All study participants worked 35 hours or more per week.

The most common cancer diagnosis among CCSs was leukemia (35.4%), followed by Hodgkin lymphoma (14.9%). Most patients had undergone chemotherapy (77.2%), radiotherapy (63.9%), and surgery (81.1%).

Overall, sociodemographic and clinical characteristics were similar between CCSs and siblings. However, CCSs were more likely than siblings to have severe, disabling, or life-threatening chronic conditions—33.9% and 17.7%, respectively (P<0.001).

Most CCSs (88.0%) and siblings (88.5%) had employer-sponsored health insurance. Three percent of siblings and 5.3% of CCSs had individual insurance; 1.9% and 2.3%, respectively, had public insurance; and 6.7% and 4.4%, respectively, were uninsured.

Results

CCSs were more likely than siblings to report:

• Job lock—23.2% and 16.9%, respectively (P=0.16)
• Problems paying medical bills—20.1% and 12.9%, respectively (P=0.09)
• Denial of health insurance—13.4% and 1.8%, respectively (P<0.001).

In a multivariable analysis, insurance denial remained significantly more common among CCSs than siblings (relative risk [RR]=7.38).

In another multivariable analysis, 38% of CCSs with a previous insurance denial reported job lock, compared with 20% of those who never experienced insurance denial (RR=1.60). And 44% of CCSs who reported problems paying their medical bills also reported job lock, compared to 16% of those who had no problems paying medical bills (RR=2.43).

The researchers also found that female CCSs (RR=1.70) and CCSs with severe, disabling, or life-threatening chronic conditions (RR=1.72) were more likely to report job lock.

“This information gives us a feel for high-risk groups of survivors who may need more information about insurance,” Dr Kirchhoff said. “Many people experience a gap in education and literacy around insurance, and it’s important for people to understand their options—even those who are employed and consistently had access to insurance through work. We want to know what their concerns are so we can help patients and survivors. Getting healthcare should not be a worry for cancer survivors.”

“Survivors have been through a lot when they were younger and understand the importance of making sure they can get healthcare when they need it. I think a lot of them also saw what their parents and families went through in terms of the financial stress and burden of dealing with a health crisis. So they’re just primed to understand the importance of health insurance.”

Dr Kirchhoff noted that this study was conducted as the Affordable Care Act was rolling out. Therefore, she would like to do a follow-up study to see if the insurance exchanges and Medicaid expansion lessened job-related insurance worries.

Photo by Bill Branson

Survey results suggest childhood cancer survivors (CCSs) in the US are more likely than individuals without a history of cancer to experience “job lock,” or staying at a job to keep work-related health insurance.

CCSs are also more likely than individuals without a history of cancer to report problems paying medical bills and being denied health insurance.

Anne Kirchhoff, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City, and her colleagues reported these findings in JAMA Oncology.

The researchers analyzed 394 CCSs from pediatric oncology institutions across the US, along with 128 of their siblings who had no history of cancer. All study participants worked 35 hours or more per week.

The most common cancer diagnosis among CCSs was leukemia (35.4%), followed by Hodgkin lymphoma (14.9%). Most patients had undergone chemotherapy (77.2%), radiotherapy (63.9%), and surgery (81.1%).

Overall, sociodemographic and clinical characteristics were similar between CCSs and siblings. However, CCSs were more likely than siblings to have severe, disabling, or life-threatening chronic conditions—33.9% and 17.7%, respectively (P<0.001).

Most CCSs (88.0%) and siblings (88.5%) had employer-sponsored health insurance. Three percent of siblings and 5.3% of CCSs had individual insurance; 1.9% and 2.3%, respectively, had public insurance; and 6.7% and 4.4%, respectively, were uninsured.

Results

CCSs were more likely than siblings to report:

• Job lock—23.2% and 16.9%, respectively (P=0.16)
• Problems paying medical bills—20.1% and 12.9%, respectively (P=0.09)
• Denial of health insurance—13.4% and 1.8%, respectively (P<0.001).

In a multivariable analysis, insurance denial remained significantly more common among CCSs than siblings (relative risk [RR]=7.38).

In another multivariable analysis, 38% of CCSs with a previous insurance denial reported job lock, compared with 20% of those who never experienced insurance denial (RR=1.60). And 44% of CCSs who reported problems paying their medical bills also reported job lock, compared to 16% of those who had no problems paying medical bills (RR=2.43).

The researchers also found that female CCSs (RR=1.70) and CCSs with severe, disabling, or life-threatening chronic conditions (RR=1.72) were more likely to report job lock.

“This information gives us a feel for high-risk groups of survivors who may need more information about insurance,” Dr Kirchhoff said. “Many people experience a gap in education and literacy around insurance, and it’s important for people to understand their options—even those who are employed and consistently had access to insurance through work. We want to know what their concerns are so we can help patients and survivors. Getting healthcare should not be a worry for cancer survivors.”

“Survivors have been through a lot when they were younger and understand the importance of making sure they can get healthcare when they need it. I think a lot of them also saw what their parents and families went through in terms of the financial stress and burden of dealing with a health crisis. So they’re just primed to understand the importance of health insurance.”

Dr Kirchhoff noted that this study was conducted as the Affordable Care Act was rolling out. Therefore, she would like to do a follow-up study to see if the insurance exchanges and Medicaid expansion lessened job-related insurance worries.

Photo by Bill Branson

Survey results suggest childhood cancer survivors (CCSs) in the US are more likely than individuals without a history of cancer to experience “job lock,” or staying at a job to keep work-related health insurance.

CCSs are also more likely than individuals without a history of cancer to report problems paying medical bills and being denied health insurance.

Anne Kirchhoff, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City, and her colleagues reported these findings in JAMA Oncology.

The researchers analyzed 394 CCSs from pediatric oncology institutions across the US, along with 128 of their siblings who had no history of cancer. All study participants worked 35 hours or more per week.

The most common cancer diagnosis among CCSs was leukemia (35.4%), followed by Hodgkin lymphoma (14.9%). Most patients had undergone chemotherapy (77.2%), radiotherapy (63.9%), and surgery (81.1%).

Overall, sociodemographic and clinical characteristics were similar between CCSs and siblings. However, CCSs were more likely than siblings to have severe, disabling, or life-threatening chronic conditions—33.9% and 17.7%, respectively (P<0.001).

Most CCSs (88.0%) and siblings (88.5%) had employer-sponsored health insurance. Three percent of siblings and 5.3% of CCSs had individual insurance; 1.9% and 2.3%, respectively, had public insurance; and 6.7% and 4.4%, respectively, were uninsured.

Results

CCSs were more likely than siblings to report:

• Job lock—23.2% and 16.9%, respectively (P=0.16)
• Problems paying medical bills—20.1% and 12.9%, respectively (P=0.09)
• Denial of health insurance—13.4% and 1.8%, respectively (P<0.001).

In a multivariable analysis, insurance denial remained significantly more common among CCSs than siblings (relative risk [RR]=7.38).

In another multivariable analysis, 38% of CCSs with a previous insurance denial reported job lock, compared with 20% of those who never experienced insurance denial (RR=1.60). And 44% of CCSs who reported problems paying their medical bills also reported job lock, compared to 16% of those who had no problems paying medical bills (RR=2.43).

The researchers also found that female CCSs (RR=1.70) and CCSs with severe, disabling, or life-threatening chronic conditions (RR=1.72) were more likely to report job lock.

“This information gives us a feel for high-risk groups of survivors who may need more information about insurance,” Dr Kirchhoff said. “Many people experience a gap in education and literacy around insurance, and it’s important for people to understand their options—even those who are employed and consistently had access to insurance through work. We want to know what their concerns are so we can help patients and survivors. Getting healthcare should not be a worry for cancer survivors.”

“Survivors have been through a lot when they were younger and understand the importance of making sure they can get healthcare when they need it. I think a lot of them also saw what their parents and families went through in terms of the financial stress and burden of dealing with a health crisis. So they’re just primed to understand the importance of health insurance.”

Dr Kirchhoff noted that this study was conducted as the Affordable Care Act was rolling out. Therefore, she would like to do a follow-up study to see if the insurance exchanges and Medicaid expansion lessened job-related insurance worries.

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to MOR208, an Fc-enhanced monoclonal antibody directed against CD19.

The designation is for MOR208 to be used in combination with lenalidomide to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for high-dose chemotherapy and autologous stem cell transplant.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The breakthrough designation for MOR208 is based on preliminary data from the ongoing phase 2 L-MIND study (NCT02399085).

In this trial, researchers are evaluating MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are ineligible for high-dose chemotherapy and autologous stem cell transplant.

Preliminary data from this trial were presented at ASCO 2017.* Of the 44 patients enrolled at the data cut-off, 34 were evaluable for efficacy.

The objective response rate was 56% (19/34), and the complete response rate was 32% (11/34). Sixteen of the 19 responders were still on study at the data cut-off point.

The most frequent adverse events of grade 3 or higher were neutropenia (32%), thrombocytopenia (9%), and leukopenia (9%). As of the data cut-off, 27% of patients required a reduction of the lenalidomide dose due to side effects.

“We expect to report further data from our ongoing phase 2 L-MIND trial with MOR208 plus lenalidomide at this year’s American Society of Hematology conference in December,” said Malte Peters, chief development officer of MorphoSys AG, the company developing MOR208.

“In addition, we are currently evaluating MOR208 in combination with bendamustine in our phase 3 B-MIND trial.”

The B-MIND study is designed to compare MOR208 plus bendamustine to rituximab plus bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy and autologous stem cell transplant.

*Data in the abstract differ from the data presented at the meeting.

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to MOR208, an Fc-enhanced monoclonal antibody directed against CD19.

The designation is for MOR208 to be used in combination with lenalidomide to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for high-dose chemotherapy and autologous stem cell transplant.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The breakthrough designation for MOR208 is based on preliminary data from the ongoing phase 2 L-MIND study (NCT02399085).

In this trial, researchers are evaluating MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are ineligible for high-dose chemotherapy and autologous stem cell transplant.

Preliminary data from this trial were presented at ASCO 2017.* Of the 44 patients enrolled at the data cut-off, 34 were evaluable for efficacy.

The objective response rate was 56% (19/34), and the complete response rate was 32% (11/34). Sixteen of the 19 responders were still on study at the data cut-off point.

The most frequent adverse events of grade 3 or higher were neutropenia (32%), thrombocytopenia (9%), and leukopenia (9%). As of the data cut-off, 27% of patients required a reduction of the lenalidomide dose due to side effects.

“We expect to report further data from our ongoing phase 2 L-MIND trial with MOR208 plus lenalidomide at this year’s American Society of Hematology conference in December,” said Malte Peters, chief development officer of MorphoSys AG, the company developing MOR208.

“In addition, we are currently evaluating MOR208 in combination with bendamustine in our phase 3 B-MIND trial.”

The B-MIND study is designed to compare MOR208 plus bendamustine to rituximab plus bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy and autologous stem cell transplant.

*Data in the abstract differ from the data presented at the meeting.

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to MOR208, an Fc-enhanced monoclonal antibody directed against CD19.

The designation is for MOR208 to be used in combination with lenalidomide to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for high-dose chemotherapy and autologous stem cell transplant.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The breakthrough designation for MOR208 is based on preliminary data from the ongoing phase 2 L-MIND study (NCT02399085).

In this trial, researchers are evaluating MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are ineligible for high-dose chemotherapy and autologous stem cell transplant.

Preliminary data from this trial were presented at ASCO 2017.* Of the 44 patients enrolled at the data cut-off, 34 were evaluable for efficacy.

The objective response rate was 56% (19/34), and the complete response rate was 32% (11/34). Sixteen of the 19 responders were still on study at the data cut-off point.

The most frequent adverse events of grade 3 or higher were neutropenia (32%), thrombocytopenia (9%), and leukopenia (9%). As of the data cut-off, 27% of patients required a reduction of the lenalidomide dose due to side effects.

“We expect to report further data from our ongoing phase 2 L-MIND trial with MOR208 plus lenalidomide at this year’s American Society of Hematology conference in December,” said Malte Peters, chief development officer of MorphoSys AG, the company developing MOR208.

“In addition, we are currently evaluating MOR208 in combination with bendamustine in our phase 3 B-MIND trial.”

The B-MIND study is designed to compare MOR208 plus bendamustine to rituximab plus bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy and autologous stem cell transplant.

*Data in the abstract differ from the data presented at the meeting.

follicular lymphoma

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has recommended orphan designation for G100 for the treatment of follicular lymphoma (FL).

G100 contains the synthetic small molecule toll-like receptor-4 agonist glucopyranosyl lipid A.

G100 works by activating innate and adaptive immunity in the tumor microenvironment to generate an immune response against the tumor’s pre-existing antigens.

Clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The induction of local and systemic immune responses has been shown in preclinical studies to result in local and abscopal tumor control.

Immune Design, the company developing G100, is currently evaluating G100 plus local radiation, with or without pembrolizumab, in a phase 1/2 trial of FL patients.

Results from this trial were presented at the 2017 ASCO Annual Meeting (abstract 7537). Nine patients who received G100 (3 patients each at the 5, 10, or 20 μg dose) with radiation (but not pembrolizumab) were evaluable for safety and efficacy.

The overall response rate was 44%, and all of these were partial responses (n=4). Thirty-three percent of patients had stable disease (n=3).

Among the responders, tumor regression ranged from 58% to 89%, which included up to 56% shrinkage of abscopal sites. Tumor biopsies showed increased inflammatory responses and T-cell infiltrates in abscopal tumors.

An additional 13 patients treated at the 10 μg dose were evaluable for safety.  There were no dose-limiting toxicities, serious adverse events (AEs), or grade 3/4 AEs observed.

Common AEs included injection site disorders, abdominal pain/discomfort, nausea, pruritus, and decrease in lymphocytes.

Immune Design said that, if this trial produces a sufficiently robust clinical benefit for patients, the company may pursue FL as the first indication for regulatory approval of G100.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission. 

follicular lymphoma

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has recommended orphan designation for G100 for the treatment of follicular lymphoma (FL).

G100 contains the synthetic small molecule toll-like receptor-4 agonist glucopyranosyl lipid A.

G100 works by activating innate and adaptive immunity in the tumor microenvironment to generate an immune response against the tumor’s pre-existing antigens.

Clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The induction of local and systemic immune responses has been shown in preclinical studies to result in local and abscopal tumor control.

Immune Design, the company developing G100, is currently evaluating G100 plus local radiation, with or without pembrolizumab, in a phase 1/2 trial of FL patients.

Results from this trial were presented at the 2017 ASCO Annual Meeting (abstract 7537). Nine patients who received G100 (3 patients each at the 5, 10, or 20 μg dose) with radiation (but not pembrolizumab) were evaluable for safety and efficacy.

The overall response rate was 44%, and all of these were partial responses (n=4). Thirty-three percent of patients had stable disease (n=3).

Among the responders, tumor regression ranged from 58% to 89%, which included up to 56% shrinkage of abscopal sites. Tumor biopsies showed increased inflammatory responses and T-cell infiltrates in abscopal tumors.

An additional 13 patients treated at the 10 μg dose were evaluable for safety.  There were no dose-limiting toxicities, serious adverse events (AEs), or grade 3/4 AEs observed.

Common AEs included injection site disorders, abdominal pain/discomfort, nausea, pruritus, and decrease in lymphocytes.

Immune Design said that, if this trial produces a sufficiently robust clinical benefit for patients, the company may pursue FL as the first indication for regulatory approval of G100.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission. 

follicular lymphoma

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has recommended orphan designation for G100 for the treatment of follicular lymphoma (FL).

G100 contains the synthetic small molecule toll-like receptor-4 agonist glucopyranosyl lipid A.

G100 works by activating innate and adaptive immunity in the tumor microenvironment to generate an immune response against the tumor’s pre-existing antigens.

Clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The induction of local and systemic immune responses has been shown in preclinical studies to result in local and abscopal tumor control.

Immune Design, the company developing G100, is currently evaluating G100 plus local radiation, with or without pembrolizumab, in a phase 1/2 trial of FL patients.

Results from this trial were presented at the 2017 ASCO Annual Meeting (abstract 7537). Nine patients who received G100 (3 patients each at the 5, 10, or 20 μg dose) with radiation (but not pembrolizumab) were evaluable for safety and efficacy.

The overall response rate was 44%, and all of these were partial responses (n=4). Thirty-three percent of patients had stable disease (n=3).

Among the responders, tumor regression ranged from 58% to 89%, which included up to 56% shrinkage of abscopal sites. Tumor biopsies showed increased inflammatory responses and T-cell infiltrates in abscopal tumors.

An additional 13 patients treated at the 10 μg dose were evaluable for safety.  There were no dose-limiting toxicities, serious adverse events (AEs), or grade 3/4 AEs observed.

Common AEs included injection site disorders, abdominal pain/discomfort, nausea, pruritus, and decrease in lymphocytes.

Immune Design said that, if this trial produces a sufficiently robust clinical benefit for patients, the company may pursue FL as the first indication for regulatory approval of G100.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission. 

Micrograph showing DLBCL

A new assay may help improve the diagnosis and treatment of diffuse large B-cell lymphoma (DLBCL), according to researchers.

The gene expression signature assay can be used to classify subtypes of DLBCL and may enhance disease management by helping to match tumors with the appropriate targeted therapy.

Researchers described the assay in the Journal of Molecular Diagnostics.

The assay is a novel gene expression profiling DLBCL classifier based on reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA).

It can simultaneously evaluate the expression of 21 markers, allowing differentiation of the 3 subtypes of DLBCL—germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal B-cell lymphoma (PMBL)—as well as other individualized disease characteristics, such as Epstein-Barr infection status.

Researchers used the RT-MLPA assay to test 150 samples from DLBCL patients. Forty-two percent of the samples were the ABC subtype, 37% the GCB subtype, and 10% molecular PMBL. Eleven percent of the samples could not be classified.

Overall, the RT-MLPA assay correctly assigned 85.0% of the cases into the expected subtypes, compared to 78.8% of samples assigned via immunohistochemistry.

The RT-MLPA assay was also able to detect the MYD88 L265P mutation, one of the most common genetic abnormalities found in ABC DLBCLs. This information can influence treatment, since the presence of the mutation is thought to be predictive of ibrutinib sensitivity.

The researchers said RT-MLPA is a robust, efficient, rapid, and cost-effective alternative to current methods used in the clinic to establish the cell-of-origin classification of DLBCLs.

RT-MLPA requires only common laboratory equipment and can be applied to formalin-fixed, paraffin-embedded samples. Other types of diagnostic methods may not provide the level of detail needed and may also be limited by poor reproducibility and lack of adaptability to routine use in standard laboratories.

“Because we have provided the classification algorithms, other laboratories will be able to verify our results and adjust the procedures to suit their environment,” said study author Philippe Ruminy, PhD, of the Henri Becquerel Cancer Treatment Center, INSERM U1245 in Rouen, France.

“It is our hope that the assay we have developed, which addresses an important recommendation of the recent WHO classifications, will contribute to better management of these tumors and improved patient outcomes.”

Micrograph showing DLBCL

A new assay may help improve the diagnosis and treatment of diffuse large B-cell lymphoma (DLBCL), according to researchers.

The gene expression signature assay can be used to classify subtypes of DLBCL and may enhance disease management by helping to match tumors with the appropriate targeted therapy.

Researchers described the assay in the Journal of Molecular Diagnostics.

The assay is a novel gene expression profiling DLBCL classifier based on reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA).

It can simultaneously evaluate the expression of 21 markers, allowing differentiation of the 3 subtypes of DLBCL—germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal B-cell lymphoma (PMBL)—as well as other individualized disease characteristics, such as Epstein-Barr infection status.

Researchers used the RT-MLPA assay to test 150 samples from DLBCL patients. Forty-two percent of the samples were the ABC subtype, 37% the GCB subtype, and 10% molecular PMBL. Eleven percent of the samples could not be classified.

Overall, the RT-MLPA assay correctly assigned 85.0% of the cases into the expected subtypes, compared to 78.8% of samples assigned via immunohistochemistry.

The RT-MLPA assay was also able to detect the MYD88 L265P mutation, one of the most common genetic abnormalities found in ABC DLBCLs. This information can influence treatment, since the presence of the mutation is thought to be predictive of ibrutinib sensitivity.

The researchers said RT-MLPA is a robust, efficient, rapid, and cost-effective alternative to current methods used in the clinic to establish the cell-of-origin classification of DLBCLs.

RT-MLPA requires only common laboratory equipment and can be applied to formalin-fixed, paraffin-embedded samples. Other types of diagnostic methods may not provide the level of detail needed and may also be limited by poor reproducibility and lack of adaptability to routine use in standard laboratories.

“Because we have provided the classification algorithms, other laboratories will be able to verify our results and adjust the procedures to suit their environment,” said study author Philippe Ruminy, PhD, of the Henri Becquerel Cancer Treatment Center, INSERM U1245 in Rouen, France.

“It is our hope that the assay we have developed, which addresses an important recommendation of the recent WHO classifications, will contribute to better management of these tumors and improved patient outcomes.”

Micrograph showing DLBCL

A new assay may help improve the diagnosis and treatment of diffuse large B-cell lymphoma (DLBCL), according to researchers.

The gene expression signature assay can be used to classify subtypes of DLBCL and may enhance disease management by helping to match tumors with the appropriate targeted therapy.

Researchers described the assay in the Journal of Molecular Diagnostics.

The assay is a novel gene expression profiling DLBCL classifier based on reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA).

It can simultaneously evaluate the expression of 21 markers, allowing differentiation of the 3 subtypes of DLBCL—germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal B-cell lymphoma (PMBL)—as well as other individualized disease characteristics, such as Epstein-Barr infection status.

Researchers used the RT-MLPA assay to test 150 samples from DLBCL patients. Forty-two percent of the samples were the ABC subtype, 37% the GCB subtype, and 10% molecular PMBL. Eleven percent of the samples could not be classified.

Overall, the RT-MLPA assay correctly assigned 85.0% of the cases into the expected subtypes, compared to 78.8% of samples assigned via immunohistochemistry.

The RT-MLPA assay was also able to detect the MYD88 L265P mutation, one of the most common genetic abnormalities found in ABC DLBCLs. This information can influence treatment, since the presence of the mutation is thought to be predictive of ibrutinib sensitivity.

The researchers said RT-MLPA is a robust, efficient, rapid, and cost-effective alternative to current methods used in the clinic to establish the cell-of-origin classification of DLBCLs.

RT-MLPA requires only common laboratory equipment and can be applied to formalin-fixed, paraffin-embedded samples. Other types of diagnostic methods may not provide the level of detail needed and may also be limited by poor reproducibility and lack of adaptability to routine use in standard laboratories.

“Because we have provided the classification algorithms, other laboratories will be able to verify our results and adjust the procedures to suit their environment,” said study author Philippe Ruminy, PhD, of the Henri Becquerel Cancer Treatment Center, INSERM U1245 in Rouen, France.

“It is our hope that the assay we have developed, which addresses an important recommendation of the recent WHO classifications, will contribute to better management of these tumors and improved patient outcomes.”

Photo courtesy of FDA

Results of a systematic review suggest a need for more research and long-term follow-up of patients with breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

Although data suggest BIA-ALCL is likely associated with textured implants and may result from chronic inflammation, neither of these theories has been confirmed.

Furthermore, researchers have yet to establish optimal prognostic and treatment guidelines for BIA-ALCL.

Dino Ravnic, DO, of Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania, and his colleagues highlighted these areas of need in an article published in JAMA Surgery.

The team conducted a literature review to learn more about the development, risk factors, diagnosis, and treatment of BIA-ALCL. They reviewed data from 115 articles and 95 patients.

The researchers noted that the incidence of BIA-ALCL is unknown. The Association of Breast Surgery estimates an incidence of 1 in 300,000 breast implants, while the Australian Therapeutic Goods Administration estimates BIA-ALCL could affect between 1 in 1000 and 1 in 10,000 women with breast implants.

“We’re seeing that this cancer is likely very underreported, and, as more information on this type of cancer comes to light, the number of cases is likely to increase in the coming years,” Dr Ravnic said.

He and his colleagues noted that almost all documented cases of BIA-ALCL have been associated with textured implants. These implants rose in popularity in the 1990s, and the first case of BIA-ALCL was documented in 1997.

The researchers said that because they could find no incidents of BIA-ALCL prior to the introduction of textured implants, this suggests a causal relationship, but more research is needed to confirm this theory.

“We’re still exploring the exact causes, but according to current knowledge, this cancer only really started to appear after textured implants came on the market in the 1990s,” Dr Ravnic said.

“All manufacturers of textured implants have had cases linked to this type of lymphoma, and we haven’t seen cases linked to smooth implants. But, in many of these cases, the implant was removed without testing the surrounding fluid and tissue for lymphoma cells, so it’s difficult to definitively correlate the two.”

The researchers also said the evidence suggests BIA-ALCL may occur as a result of inflammation surrounding the breast implant, and tissue that grows into pores in the textured implant may prolong inflammation.

Chronic inflammation may lead to malignant transformation of T cells that are anaplastic lymphoma kinase-negative and CD30-positive.

The data also suggest BIA-ALCL tends to develop slowly. The mean time to BIA-ALCL presentation in the 95 patients analyzed was about 10 years after the patients received their implants.

The researchers said treatment of BIA-ALCL must include removal of the implant and surrounding capsule. However, patients with advanced disease—including a tumor mass (stage II), lymph node involvement (stage II/III), or distant disease (stage IV)—may require chemotherapy, radiotherapy, or both. Brentuximab vedotin has also been used.

Overall, the patients included in this review appeared to have a good prognosis, with only 5 patients experiencing disease recurrence and dying of BIA-ALCL.

However, the researchers noted that it was difficult to calculate the mean overall survival and disease-free survival of these patients due to a lack of data and inadequate follow-up.

Photo courtesy of FDA

Results of a systematic review suggest a need for more research and long-term follow-up of patients with breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

Although data suggest BIA-ALCL is likely associated with textured implants and may result from chronic inflammation, neither of these theories has been confirmed.

Furthermore, researchers have yet to establish optimal prognostic and treatment guidelines for BIA-ALCL.

Dino Ravnic, DO, of Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania, and his colleagues highlighted these areas of need in an article published in JAMA Surgery.

The team conducted a literature review to learn more about the development, risk factors, diagnosis, and treatment of BIA-ALCL. They reviewed data from 115 articles and 95 patients.

The researchers noted that the incidence of BIA-ALCL is unknown. The Association of Breast Surgery estimates an incidence of 1 in 300,000 breast implants, while the Australian Therapeutic Goods Administration estimates BIA-ALCL could affect between 1 in 1000 and 1 in 10,000 women with breast implants.

“We’re seeing that this cancer is likely very underreported, and, as more information on this type of cancer comes to light, the number of cases is likely to increase in the coming years,” Dr Ravnic said.

He and his colleagues noted that almost all documented cases of BIA-ALCL have been associated with textured implants. These implants rose in popularity in the 1990s, and the first case of BIA-ALCL was documented in 1997.

The researchers said that because they could find no incidents of BIA-ALCL prior to the introduction of textured implants, this suggests a causal relationship, but more research is needed to confirm this theory.

“We’re still exploring the exact causes, but according to current knowledge, this cancer only really started to appear after textured implants came on the market in the 1990s,” Dr Ravnic said.

“All manufacturers of textured implants have had cases linked to this type of lymphoma, and we haven’t seen cases linked to smooth implants. But, in many of these cases, the implant was removed without testing the surrounding fluid and tissue for lymphoma cells, so it’s difficult to definitively correlate the two.”

The researchers also said the evidence suggests BIA-ALCL may occur as a result of inflammation surrounding the breast implant, and tissue that grows into pores in the textured implant may prolong inflammation.

Chronic inflammation may lead to malignant transformation of T cells that are anaplastic lymphoma kinase-negative and CD30-positive.

The data also suggest BIA-ALCL tends to develop slowly. The mean time to BIA-ALCL presentation in the 95 patients analyzed was about 10 years after the patients received their implants.

The researchers said treatment of BIA-ALCL must include removal of the implant and surrounding capsule. However, patients with advanced disease—including a tumor mass (stage II), lymph node involvement (stage II/III), or distant disease (stage IV)—may require chemotherapy, radiotherapy, or both. Brentuximab vedotin has also been used.

Overall, the patients included in this review appeared to have a good prognosis, with only 5 patients experiencing disease recurrence and dying of BIA-ALCL.

However, the researchers noted that it was difficult to calculate the mean overall survival and disease-free survival of these patients due to a lack of data and inadequate follow-up.

Photo courtesy of FDA

Results of a systematic review suggest a need for more research and long-term follow-up of patients with breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

Although data suggest BIA-ALCL is likely associated with textured implants and may result from chronic inflammation, neither of these theories has been confirmed.

Furthermore, researchers have yet to establish optimal prognostic and treatment guidelines for BIA-ALCL.

Dino Ravnic, DO, of Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania, and his colleagues highlighted these areas of need in an article published in JAMA Surgery.

The team conducted a literature review to learn more about the development, risk factors, diagnosis, and treatment of BIA-ALCL. They reviewed data from 115 articles and 95 patients.

The researchers noted that the incidence of BIA-ALCL is unknown. The Association of Breast Surgery estimates an incidence of 1 in 300,000 breast implants, while the Australian Therapeutic Goods Administration estimates BIA-ALCL could affect between 1 in 1000 and 1 in 10,000 women with breast implants.

“We’re seeing that this cancer is likely very underreported, and, as more information on this type of cancer comes to light, the number of cases is likely to increase in the coming years,” Dr Ravnic said.

He and his colleagues noted that almost all documented cases of BIA-ALCL have been associated with textured implants. These implants rose in popularity in the 1990s, and the first case of BIA-ALCL was documented in 1997.

The researchers said that because they could find no incidents of BIA-ALCL prior to the introduction of textured implants, this suggests a causal relationship, but more research is needed to confirm this theory.

“We’re still exploring the exact causes, but according to current knowledge, this cancer only really started to appear after textured implants came on the market in the 1990s,” Dr Ravnic said.

“All manufacturers of textured implants have had cases linked to this type of lymphoma, and we haven’t seen cases linked to smooth implants. But, in many of these cases, the implant was removed without testing the surrounding fluid and tissue for lymphoma cells, so it’s difficult to definitively correlate the two.”

The researchers also said the evidence suggests BIA-ALCL may occur as a result of inflammation surrounding the breast implant, and tissue that grows into pores in the textured implant may prolong inflammation.

Chronic inflammation may lead to malignant transformation of T cells that are anaplastic lymphoma kinase-negative and CD30-positive.

The data also suggest BIA-ALCL tends to develop slowly. The mean time to BIA-ALCL presentation in the 95 patients analyzed was about 10 years after the patients received their implants.

The researchers said treatment of BIA-ALCL must include removal of the implant and surrounding capsule. However, patients with advanced disease—including a tumor mass (stage II), lymph node involvement (stage II/III), or distant disease (stage IV)—may require chemotherapy, radiotherapy, or both. Brentuximab vedotin has also been used.

Overall, the patients included in this review appeared to have a good prognosis, with only 5 patients experiencing disease recurrence and dying of BIA-ALCL.

However, the researchers noted that it was difficult to calculate the mean overall survival and disease-free survival of these patients due to a lack of data and inadequate follow-up.

Diffuse large B-cell lymphoma

The US Food and Drug Administration (FDA) has approved axicabtagene ciloleucel (Yescarta™, formerly KTE-C19) for use in adults with relapsed or refractory large B-cell lymphoma who have received 2 or more lines of systemic therapy.

Axicabtagene ciloleucel is the first chimeric antigen receptor (CAR) T-cell therapy approved to treat lymphomas.

The approval encompasses diffuse large B-cell lymphoma not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and transformed follicular lymphoma.

Axicabtagene ciloleucel is not approved to treat primary central nervous system lymphoma.

The FDA’s approval of axicabtagene ciloleucel was based on results from the phase 2 ZUMA-1 trial. Updated results from this trial were presented at the AACR Annual Meeting 2017.

Risks

Axicabtagene ciloleucel has a Boxed Warning in its product label noting that the therapy can cause cytokine release syndrome (CRS) and neurologic toxicities. Full prescribing information for axicabtagene ciloleucel is available at https://www.yescarta.com/.

Because of the risk of CRS and neurologic toxicities, axicabtagene ciloleucel was approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use. The FDA is requiring that hospitals and clinics that dispense axicabtagene ciloleucel be specially certified.

As part of that certification, staff who prescribe, dispense, or administer axicabtagene ciloleucel are required to be trained to recognize and manage CRS and nervous system toxicities. In addition, patients must be informed of the potential serious side effects associated with axicabtagene ciloleucel and of the importance of promptly returning to the treatment site if side effects develop.

Additional information about the REMS program can be found at https://www.yescartarems.com/.

To further evaluate the long-term safety of axicabtagene ciloleucel, the FDA is requiring the manufacturer—Kite, a Gilead company—to conduct a post-marketing observational study of patients treated with axicabtagene ciloleucel.

Access and cost

The list price of axicabtagene ciloleucel is $373,000.

The product will be manufactured in Kite’s commercial manufacturing facility in El Segundo, California.

In 2017, Kite established a multi-disciplinary field team focused on providing education and logistics training for medical centers. Now, this team has provided final site certification to 16 centers, enabling them to make axicabtagene ciloleucel available to appropriate patients.

Kite is working to train staff at more than 30 additional centers, with an eventual target of 70 to 90 centers across the US. The latest information on authorized centers is available at https://www.yescarta.com/authorized-treatment-centers/.

Diffuse large B-cell lymphoma

The US Food and Drug Administration (FDA) has approved axicabtagene ciloleucel (Yescarta™, formerly KTE-C19) for use in adults with relapsed or refractory large B-cell lymphoma who have received 2 or more lines of systemic therapy.

Axicabtagene ciloleucel is the first chimeric antigen receptor (CAR) T-cell therapy approved to treat lymphomas.

The approval encompasses diffuse large B-cell lymphoma not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and transformed follicular lymphoma.

Axicabtagene ciloleucel is not approved to treat primary central nervous system lymphoma.

The FDA’s approval of axicabtagene ciloleucel was based on results from the phase 2 ZUMA-1 trial. Updated results from this trial were presented at the AACR Annual Meeting 2017.

Risks

Axicabtagene ciloleucel has a Boxed Warning in its product label noting that the therapy can cause cytokine release syndrome (CRS) and neurologic toxicities. Full prescribing information for axicabtagene ciloleucel is available at https://www.yescarta.com/.

Because of the risk of CRS and neurologic toxicities, axicabtagene ciloleucel was approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use. The FDA is requiring that hospitals and clinics that dispense axicabtagene ciloleucel be specially certified.

As part of that certification, staff who prescribe, dispense, or administer axicabtagene ciloleucel are required to be trained to recognize and manage CRS and nervous system toxicities. In addition, patients must be informed of the potential serious side effects associated with axicabtagene ciloleucel and of the importance of promptly returning to the treatment site if side effects develop.

Additional information about the REMS program can be found at https://www.yescartarems.com/.

To further evaluate the long-term safety of axicabtagene ciloleucel, the FDA is requiring the manufacturer—Kite, a Gilead company—to conduct a post-marketing observational study of patients treated with axicabtagene ciloleucel.

Access and cost

The list price of axicabtagene ciloleucel is $373,000.

The product will be manufactured in Kite’s commercial manufacturing facility in El Segundo, California.

In 2017, Kite established a multi-disciplinary field team focused on providing education and logistics training for medical centers. Now, this team has provided final site certification to 16 centers, enabling them to make axicabtagene ciloleucel available to appropriate patients.

Kite is working to train staff at more than 30 additional centers, with an eventual target of 70 to 90 centers across the US. The latest information on authorized centers is available at https://www.yescarta.com/authorized-treatment-centers/.

Diffuse large B-cell lymphoma

The US Food and Drug Administration (FDA) has approved axicabtagene ciloleucel (Yescarta™, formerly KTE-C19) for use in adults with relapsed or refractory large B-cell lymphoma who have received 2 or more lines of systemic therapy.

Axicabtagene ciloleucel is the first chimeric antigen receptor (CAR) T-cell therapy approved to treat lymphomas.

The approval encompasses diffuse large B-cell lymphoma not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and transformed follicular lymphoma.

Axicabtagene ciloleucel is not approved to treat primary central nervous system lymphoma.

The FDA’s approval of axicabtagene ciloleucel was based on results from the phase 2 ZUMA-1 trial. Updated results from this trial were presented at the AACR Annual Meeting 2017.

Risks

Axicabtagene ciloleucel has a Boxed Warning in its product label noting that the therapy can cause cytokine release syndrome (CRS) and neurologic toxicities. Full prescribing information for axicabtagene ciloleucel is available at https://www.yescarta.com/.

Because of the risk of CRS and neurologic toxicities, axicabtagene ciloleucel was approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use. The FDA is requiring that hospitals and clinics that dispense axicabtagene ciloleucel be specially certified.

As part of that certification, staff who prescribe, dispense, or administer axicabtagene ciloleucel are required to be trained to recognize and manage CRS and nervous system toxicities. In addition, patients must be informed of the potential serious side effects associated with axicabtagene ciloleucel and of the importance of promptly returning to the treatment site if side effects develop.

Additional information about the REMS program can be found at https://www.yescartarems.com/.

To further evaluate the long-term safety of axicabtagene ciloleucel, the FDA is requiring the manufacturer—Kite, a Gilead company—to conduct a post-marketing observational study of patients treated with axicabtagene ciloleucel.

Access and cost

The list price of axicabtagene ciloleucel is $373,000.

The product will be manufactured in Kite’s commercial manufacturing facility in El Segundo, California.

In 2017, Kite established a multi-disciplinary field team focused on providing education and logistics training for medical centers. Now, this team has provided final site certification to 16 centers, enabling them to make axicabtagene ciloleucel available to appropriate patients.

Kite is working to train staff at more than 30 additional centers, with an eventual target of 70 to 90 centers across the US. The latest information on authorized centers is available at https://www.yescarta.com/authorized-treatment-centers/.

mycosis fungoides

LONDON—Results of a phase 2 trial suggest the topical histone deacetylase (HDAC) inhibitor remetinostat can elicit responses in patients with early stage mycosis fungoides (MF).

At the highest dose level tested, remetinostat gel reduced the severity of skin lesions in 40% of patients and reduced the severity of pruritus in 80% of patients.

In addition, the HDAC inhibitor was considered well tolerated and did not produce systemic adverse effects.

These results were presented at the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force meeting, which took place October 13-15.

The study was sponsored by Medivir AB, which purchased remetinostat from TetraLogic Pharmaceuticals last year.

The trial of remetinostat enrolled 60 patients with stage IA-IIA MF across 5 clinical sites in the US. Patients were randomized to receive remetinostat gel 0.5% twice daily, remetinostat gel 1% once daily, or remetinostat gel 1% twice daily for up to 12 months.

The study’s primary endpoint was the proportion of patients with a confirmed response to therapy, assessed using the Composite Assessment of Index Lesion Severity.

The researchers observed a dose response, with patients in the 1% twice-daily arm having the highest proportion of confirmed responses.

Based on an intent-to-treat analysis, confirmed response rates were as follows:

The researchers also assessed the effect of remetinostat gel on the severity of pruritus. This was assessed monthly for the duration of the study using the visual analogue scale.

Among patients with clinically significant pruritus at baseline, those who received remetinostat gel 1% twice daily were most likely to have a clinically significant reduction in pruritus. This was defined as at least a 30 mm reduction in the visual analogue scale score sustained for more than 4 weeks.

The proportion of patients who had confirmed, clinically significant reductions in pruritus from baseline was 80% in the 1% twice-daily arm, 50% in the 0.5% twice-daily arm, and 37.5% in the 1% once-daily arm.

The researchers said remetinostat was generally well tolerated, with adverse events evenly distributed across the treatment arms. The most common adverse events were skin-related and mostly grade 1-2.

There were no signs of systemic adverse effects related to remetinostat, including those associated with systemic HDAC inhibitors.

Most patients remained on study for the maximum possible duration, and the median treatment time was 350 days.

Based on the outcomes of this study, Medivir expects to meet with regulatory authorities to discuss the design of a pivotal clinical program for remetinostat in MF.

mycosis fungoides

LONDON—Results of a phase 2 trial suggest the topical histone deacetylase (HDAC) inhibitor remetinostat can elicit responses in patients with early stage mycosis fungoides (MF).

At the highest dose level tested, remetinostat gel reduced the severity of skin lesions in 40% of patients and reduced the severity of pruritus in 80% of patients.

In addition, the HDAC inhibitor was considered well tolerated and did not produce systemic adverse effects.

These results were presented at the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force meeting, which took place October 13-15.

The study was sponsored by Medivir AB, which purchased remetinostat from TetraLogic Pharmaceuticals last year.

The trial of remetinostat enrolled 60 patients with stage IA-IIA MF across 5 clinical sites in the US. Patients were randomized to receive remetinostat gel 0.5% twice daily, remetinostat gel 1% once daily, or remetinostat gel 1% twice daily for up to 12 months.

The study’s primary endpoint was the proportion of patients with a confirmed response to therapy, assessed using the Composite Assessment of Index Lesion Severity.

The researchers observed a dose response, with patients in the 1% twice-daily arm having the highest proportion of confirmed responses.

Based on an intent-to-treat analysis, confirmed response rates were as follows:

The researchers also assessed the effect of remetinostat gel on the severity of pruritus. This was assessed monthly for the duration of the study using the visual analogue scale.

Among patients with clinically significant pruritus at baseline, those who received remetinostat gel 1% twice daily were most likely to have a clinically significant reduction in pruritus. This was defined as at least a 30 mm reduction in the visual analogue scale score sustained for more than 4 weeks.

The proportion of patients who had confirmed, clinically significant reductions in pruritus from baseline was 80% in the 1% twice-daily arm, 50% in the 0.5% twice-daily arm, and 37.5% in the 1% once-daily arm.

The researchers said remetinostat was generally well tolerated, with adverse events evenly distributed across the treatment arms. The most common adverse events were skin-related and mostly grade 1-2.

There were no signs of systemic adverse effects related to remetinostat, including those associated with systemic HDAC inhibitors.

Most patients remained on study for the maximum possible duration, and the median treatment time was 350 days.

Based on the outcomes of this study, Medivir expects to meet with regulatory authorities to discuss the design of a pivotal clinical program for remetinostat in MF.

mycosis fungoides

LONDON—Results of a phase 2 trial suggest the topical histone deacetylase (HDAC) inhibitor remetinostat can elicit responses in patients with early stage mycosis fungoides (MF).

At the highest dose level tested, remetinostat gel reduced the severity of skin lesions in 40% of patients and reduced the severity of pruritus in 80% of patients.

In addition, the HDAC inhibitor was considered well tolerated and did not produce systemic adverse effects.

These results were presented at the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force meeting, which took place October 13-15.

The study was sponsored by Medivir AB, which purchased remetinostat from TetraLogic Pharmaceuticals last year.

The trial of remetinostat enrolled 60 patients with stage IA-IIA MF across 5 clinical sites in the US. Patients were randomized to receive remetinostat gel 0.5% twice daily, remetinostat gel 1% once daily, or remetinostat gel 1% twice daily for up to 12 months.

The study’s primary endpoint was the proportion of patients with a confirmed response to therapy, assessed using the Composite Assessment of Index Lesion Severity.

The researchers observed a dose response, with patients in the 1% twice-daily arm having the highest proportion of confirmed responses.

Based on an intent-to-treat analysis, confirmed response rates were as follows:

The researchers also assessed the effect of remetinostat gel on the severity of pruritus. This was assessed monthly for the duration of the study using the visual analogue scale.

Among patients with clinically significant pruritus at baseline, those who received remetinostat gel 1% twice daily were most likely to have a clinically significant reduction in pruritus. This was defined as at least a 30 mm reduction in the visual analogue scale score sustained for more than 4 weeks.

The proportion of patients who had confirmed, clinically significant reductions in pruritus from baseline was 80% in the 1% twice-daily arm, 50% in the 0.5% twice-daily arm, and 37.5% in the 1% once-daily arm.

The researchers said remetinostat was generally well tolerated, with adverse events evenly distributed across the treatment arms. The most common adverse events were skin-related and mostly grade 1-2.

There were no signs of systemic adverse effects related to remetinostat, including those associated with systemic HDAC inhibitors.

Most patients remained on study for the maximum possible duration, and the median treatment time was 350 days.

Based on the outcomes of this study, Medivir expects to meet with regulatory authorities to discuss the design of a pivotal clinical program for remetinostat in MF.

Photo by Rhoda Baer

Countries with the lowest opportunities for natural selection have higher cancer rates than countries with the highest opportunities for natural selection, according to a study published in Evolutionary Applications.

Researchers said this is because modern medicine is enabling people to survive cancers, and their genetic backgrounds are passing from one generation to the next.

The team said the rate of some cancers has doubled and even quadrupled over the past 100 to 150 years, and human evolution has moved away from “survival of the fittest.”

“Modern medicine has enabled the human species to live much longer than would otherwise be expected in the natural world,” said study author Maciej Henneberg, PhD, DSc, of the University of Adelaide in South Australia.

“Besides the obvious benefits that modern medicine gives, it also brings with it an unexpected side-effect—allowing genetic material to be passed from one generation to the next that predisposes people to have poor health, such as type 1 diabetes or cancer.”

“Because of the quality of our healthcare in western society, we have almost removed natural selection as the ‘janitor of the gene pool.’ Unfortunately, the accumulation of genetic mutations over time and across multiple generations is like a delayed death sentence.”

Country comparison

The researchers studied global cancer data from the World Health Organization as well as other health and socioeconomic data from the United Nations and the World Bank of 173 countries. The team compared the top 10 countries with the highest opportunities for natural selection to the 10 countries with the lowest opportunities for natural selection.

“We looked at countries that offered the greatest opportunity to survive cancer compared with those that didn’t,” said study author Wenpeng You, a PhD student at the University of Adelaide. “This does not only take into account factors such as socioeconomic status, urbanization, and quality of medical services but also low mortality and fertility rates, which are the 2 distinguishing features in the ‘better’ world.”

“Countries with low mortality rates may allow more people with cancer genetic background to reproduce and pass cancer genes/mutations to the next generation. Meanwhile, low fertility rates in these countries may not be able to have diverse biological variations to provide the opportunity for selecting a naturally fit population—for example, people without or with less cancer genetic background. Low mortality rate and low fertility rate in the ‘better’ world may have formed a self-reinforcing cycle which has accumulated cancer genetic background at a greater rate than previously thought.”

Based on the researchers’ analysis, the 20 countries are:

Cancer incidence

The researchers found the rates of most cancers were higher in the 10 countries with the lowest opportunities for natural selection. The incidence of all cancers was 2.326 times higher in the low-opportunity countries than the high-opportunity ones.

The increased incidences of hematologic malignancies were as follows:

• Non-Hodgkin lymphoma—2.019 times higher in the low-opportunity countries
• Hodgkin lymphoma—3.314 times higher in the low-opportunity countries
• Leukemia—3.574 times higher in the low-opportunity countries
• Multiple myeloma—4.257 times higher in the low-opportunity countries .

Dr Henneberg said that, having removed natural selection as the “janitor of the gene pool,” our modern society is faced with a controversial issue.

“It may be that the only way humankind can be rid of cancer once and for all is through genetic engineering—to repair our genes and take cancer out of the equation,” he said.

Photo by Rhoda Baer

Countries with the lowest opportunities for natural selection have higher cancer rates than countries with the highest opportunities for natural selection, according to a study published in Evolutionary Applications.

Researchers said this is because modern medicine is enabling people to survive cancers, and their genetic backgrounds are passing from one generation to the next.

The team said the rate of some cancers has doubled and even quadrupled over the past 100 to 150 years, and human evolution has moved away from “survival of the fittest.”

“Modern medicine has enabled the human species to live much longer than would otherwise be expected in the natural world,” said study author Maciej Henneberg, PhD, DSc, of the University of Adelaide in South Australia.

“Besides the obvious benefits that modern medicine gives, it also brings with it an unexpected side-effect—allowing genetic material to be passed from one generation to the next that predisposes people to have poor health, such as type 1 diabetes or cancer.”

“Because of the quality of our healthcare in western society, we have almost removed natural selection as the ‘janitor of the gene pool.’ Unfortunately, the accumulation of genetic mutations over time and across multiple generations is like a delayed death sentence.”

Country comparison

The researchers studied global cancer data from the World Health Organization as well as other health and socioeconomic data from the United Nations and the World Bank of 173 countries. The team compared the top 10 countries with the highest opportunities for natural selection to the 10 countries with the lowest opportunities for natural selection.

“We looked at countries that offered the greatest opportunity to survive cancer compared with those that didn’t,” said study author Wenpeng You, a PhD student at the University of Adelaide. “This does not only take into account factors such as socioeconomic status, urbanization, and quality of medical services but also low mortality and fertility rates, which are the 2 distinguishing features in the ‘better’ world.”

“Countries with low mortality rates may allow more people with cancer genetic background to reproduce and pass cancer genes/mutations to the next generation. Meanwhile, low fertility rates in these countries may not be able to have diverse biological variations to provide the opportunity for selecting a naturally fit population—for example, people without or with less cancer genetic background. Low mortality rate and low fertility rate in the ‘better’ world may have formed a self-reinforcing cycle which has accumulated cancer genetic background at a greater rate than previously thought.”

Based on the researchers’ analysis, the 20 countries are:

Cancer incidence

The researchers found the rates of most cancers were higher in the 10 countries with the lowest opportunities for natural selection. The incidence of all cancers was 2.326 times higher in the low-opportunity countries than the high-opportunity ones.

The increased incidences of hematologic malignancies were as follows:

• Non-Hodgkin lymphoma—2.019 times higher in the low-opportunity countries
• Hodgkin lymphoma—3.314 times higher in the low-opportunity countries
• Leukemia—3.574 times higher in the low-opportunity countries
• Multiple myeloma—4.257 times higher in the low-opportunity countries .

Dr Henneberg said that, having removed natural selection as the “janitor of the gene pool,” our modern society is faced with a controversial issue.

“It may be that the only way humankind can be rid of cancer once and for all is through genetic engineering—to repair our genes and take cancer out of the equation,” he said.

Photo by Rhoda Baer

Countries with the lowest opportunities for natural selection have higher cancer rates than countries with the highest opportunities for natural selection, according to a study published in Evolutionary Applications.

Researchers said this is because modern medicine is enabling people to survive cancers, and their genetic backgrounds are passing from one generation to the next.

The team said the rate of some cancers has doubled and even quadrupled over the past 100 to 150 years, and human evolution has moved away from “survival of the fittest.”

“Modern medicine has enabled the human species to live much longer than would otherwise be expected in the natural world,” said study author Maciej Henneberg, PhD, DSc, of the University of Adelaide in South Australia.

“Besides the obvious benefits that modern medicine gives, it also brings with it an unexpected side-effect—allowing genetic material to be passed from one generation to the next that predisposes people to have poor health, such as type 1 diabetes or cancer.”

“Because of the quality of our healthcare in western society, we have almost removed natural selection as the ‘janitor of the gene pool.’ Unfortunately, the accumulation of genetic mutations over time and across multiple generations is like a delayed death sentence.”

Country comparison

The researchers studied global cancer data from the World Health Organization as well as other health and socioeconomic data from the United Nations and the World Bank of 173 countries. The team compared the top 10 countries with the highest opportunities for natural selection to the 10 countries with the lowest opportunities for natural selection.

“We looked at countries that offered the greatest opportunity to survive cancer compared with those that didn’t,” said study author Wenpeng You, a PhD student at the University of Adelaide. “This does not only take into account factors such as socioeconomic status, urbanization, and quality of medical services but also low mortality and fertility rates, which are the 2 distinguishing features in the ‘better’ world.”

“Countries with low mortality rates may allow more people with cancer genetic background to reproduce and pass cancer genes/mutations to the next generation. Meanwhile, low fertility rates in these countries may not be able to have diverse biological variations to provide the opportunity for selecting a naturally fit population—for example, people without or with less cancer genetic background. Low mortality rate and low fertility rate in the ‘better’ world may have formed a self-reinforcing cycle which has accumulated cancer genetic background at a greater rate than previously thought.”

Based on the researchers’ analysis, the 20 countries are:

Cancer incidence

The researchers found the rates of most cancers were higher in the 10 countries with the lowest opportunities for natural selection. The incidence of all cancers was 2.326 times higher in the low-opportunity countries than the high-opportunity ones.

The increased incidences of hematologic malignancies were as follows:

• Non-Hodgkin lymphoma—2.019 times higher in the low-opportunity countries
• Hodgkin lymphoma—3.314 times higher in the low-opportunity countries
• Leukemia—3.574 times higher in the low-opportunity countries
• Multiple myeloma—4.257 times higher in the low-opportunity countries .

Dr Henneberg said that, having removed natural selection as the “janitor of the gene pool,” our modern society is faced with a controversial issue.

“It may be that the only way humankind can be rid of cancer once and for all is through genetic engineering—to repair our genes and take cancer out of the equation,” he said.