CLL

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

TOPLINE:

Secondary cancers were flagged in 4.3% of all adverse event reports among patients who received CAR T therapy, with T-cell malignancies comprising only 0.15% of the total reports and 3.54% of all second primary malignancies, according to an analysis of adverse event reports submitted to the US Food and Drug Administration (FDA).

METHODOLOGY:

• In November 2023, the FDA announced its investigation into whether chimeric antigen receptor (CAR) T-cell immunotherapies can cause secondary blood cancers, specifically T-cell malignancies. At the time, the agency said: “Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T-cell malignancy with serious outcomes.”
• In January 2024, the FDA issued boxed warnings on the six approved CART cell therapies, citing the possibility of second primary malignancies, including CAR-positive lymphomas, in patients who had received a CAR T agent.
• To evaluate the extent of these secondary cancers, researchers analyzed the FDA Adverse Event Reporting System database for CAR T-cell reports citing second primary malignancies.

TAKEAWAY:

• Overall, the authors identified 12,394 unique adverse events associated with CAR T therapy; of these, 536 adverse events (4.3%) were second primary malignancies.
• Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) accounted for most of the second primary malignancies reports — 51.7% (277 of 536 patients) for axi-cel and 33% (177 of 536 patients) for tis-cel.
• The researchers identified 19 cases of T-cell malignancies, representing only 0.15% of all unique adverse events and 3.54% of all second primary malignancies (19 of 536 patients); 17 of these cases were T-cell non-Hodgkin lymphomas, and two were T-cell large granular lymphocytic leukemia.
• Among the reported 536 second primary malignancies, the most frequent cancers were leukemias (333 reports, or 62%), followed by skin neoplasms (54 reports, or 10.1%), hematopoietic neoplasms excluding leukemias and lymphomas (26 reports, 4.85%), nervous system tumors (21 reports, 3.92%), and respiratory neoplasms (20 reports, 3.73%).

IN PRACTICE:

“We will continue to monitor the data released by the FDA to learn more about CAR T-associated risks. However, it’s crucial to stress that the benefits of CAR T-cell therapies still outweigh the risks for the approved indications,” Magdi Elsallab, MD, the study’s co-lead author, said in a news release.

SOURCE:

This work, led by Dr. Elsallab from Harvard Medical School in Boston, was published online on March 14 in Blood.

LIMITATIONS:

The limitations of the analysis include the presence of duplicate report submissions, incomplete data, difficulty establishing causal relationships, and the potential for both underreporting and overreporting based on the severity of adverse events. Furthermore, without the total number of prescribed products, it was difficult to determine the adverse event frequency.

DISCLOSURES:

The study funding source was not disclosed. Some of the authors reported financial ties with various organizations outside this work, including Bristol Myers Squibb, Janssen Biotech, Johnson & Johnson, Kite Pharma, and Novartis.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Secondary cancers were flagged in 4.3% of all adverse event reports among patients who received CAR T therapy, with T-cell malignancies comprising only 0.15% of the total reports and 3.54% of all second primary malignancies, according to an analysis of adverse event reports submitted to the US Food and Drug Administration (FDA).

METHODOLOGY:

• In November 2023, the FDA announced its investigation into whether chimeric antigen receptor (CAR) T-cell immunotherapies can cause secondary blood cancers, specifically T-cell malignancies. At the time, the agency said: “Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T-cell malignancy with serious outcomes.”
• In January 2024, the FDA issued boxed warnings on the six approved CART cell therapies, citing the possibility of second primary malignancies, including CAR-positive lymphomas, in patients who had received a CAR T agent.
• To evaluate the extent of these secondary cancers, researchers analyzed the FDA Adverse Event Reporting System database for CAR T-cell reports citing second primary malignancies.

TAKEAWAY:

• Overall, the authors identified 12,394 unique adverse events associated with CAR T therapy; of these, 536 adverse events (4.3%) were second primary malignancies.
• Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) accounted for most of the second primary malignancies reports — 51.7% (277 of 536 patients) for axi-cel and 33% (177 of 536 patients) for tis-cel.
• The researchers identified 19 cases of T-cell malignancies, representing only 0.15% of all unique adverse events and 3.54% of all second primary malignancies (19 of 536 patients); 17 of these cases were T-cell non-Hodgkin lymphomas, and two were T-cell large granular lymphocytic leukemia.
• Among the reported 536 second primary malignancies, the most frequent cancers were leukemias (333 reports, or 62%), followed by skin neoplasms (54 reports, or 10.1%), hematopoietic neoplasms excluding leukemias and lymphomas (26 reports, 4.85%), nervous system tumors (21 reports, 3.92%), and respiratory neoplasms (20 reports, 3.73%).

IN PRACTICE:

“We will continue to monitor the data released by the FDA to learn more about CAR T-associated risks. However, it’s crucial to stress that the benefits of CAR T-cell therapies still outweigh the risks for the approved indications,” Magdi Elsallab, MD, the study’s co-lead author, said in a news release.

SOURCE:

This work, led by Dr. Elsallab from Harvard Medical School in Boston, was published online on March 14 in Blood.

LIMITATIONS:

The limitations of the analysis include the presence of duplicate report submissions, incomplete data, difficulty establishing causal relationships, and the potential for both underreporting and overreporting based on the severity of adverse events. Furthermore, without the total number of prescribed products, it was difficult to determine the adverse event frequency.

DISCLOSURES:

The study funding source was not disclosed. Some of the authors reported financial ties with various organizations outside this work, including Bristol Myers Squibb, Janssen Biotech, Johnson & Johnson, Kite Pharma, and Novartis.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Secondary cancers were flagged in 4.3% of all adverse event reports among patients who received CAR T therapy, with T-cell malignancies comprising only 0.15% of the total reports and 3.54% of all second primary malignancies, according to an analysis of adverse event reports submitted to the US Food and Drug Administration (FDA).

METHODOLOGY:

• In November 2023, the FDA announced its investigation into whether chimeric antigen receptor (CAR) T-cell immunotherapies can cause secondary blood cancers, specifically T-cell malignancies. At the time, the agency said: “Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T-cell malignancy with serious outcomes.”
• In January 2024, the FDA issued boxed warnings on the six approved CART cell therapies, citing the possibility of second primary malignancies, including CAR-positive lymphomas, in patients who had received a CAR T agent.
• To evaluate the extent of these secondary cancers, researchers analyzed the FDA Adverse Event Reporting System database for CAR T-cell reports citing second primary malignancies.

TAKEAWAY:

• Overall, the authors identified 12,394 unique adverse events associated with CAR T therapy; of these, 536 adverse events (4.3%) were second primary malignancies.
• Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) accounted for most of the second primary malignancies reports — 51.7% (277 of 536 patients) for axi-cel and 33% (177 of 536 patients) for tis-cel.
• The researchers identified 19 cases of T-cell malignancies, representing only 0.15% of all unique adverse events and 3.54% of all second primary malignancies (19 of 536 patients); 17 of these cases were T-cell non-Hodgkin lymphomas, and two were T-cell large granular lymphocytic leukemia.
• Among the reported 536 second primary malignancies, the most frequent cancers were leukemias (333 reports, or 62%), followed by skin neoplasms (54 reports, or 10.1%), hematopoietic neoplasms excluding leukemias and lymphomas (26 reports, 4.85%), nervous system tumors (21 reports, 3.92%), and respiratory neoplasms (20 reports, 3.73%).

IN PRACTICE:

“We will continue to monitor the data released by the FDA to learn more about CAR T-associated risks. However, it’s crucial to stress that the benefits of CAR T-cell therapies still outweigh the risks for the approved indications,” Magdi Elsallab, MD, the study’s co-lead author, said in a news release.

SOURCE:

This work, led by Dr. Elsallab from Harvard Medical School in Boston, was published online on March 14 in Blood.

LIMITATIONS:

The limitations of the analysis include the presence of duplicate report submissions, incomplete data, difficulty establishing causal relationships, and the potential for both underreporting and overreporting based on the severity of adverse events. Furthermore, without the total number of prescribed products, it was difficult to determine the adverse event frequency.

DISCLOSURES:

The study funding source was not disclosed. Some of the authors reported financial ties with various organizations outside this work, including Bristol Myers Squibb, Janssen Biotech, Johnson & Johnson, Kite Pharma, and Novartis.
 

A version of this article appeared on Medscape.com.

How should we define success in cancer policy — what should the endpoint be?

It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?

One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.

I’ll go a step further: It is not even a surrogate marker for success. The number of newly approved drugs is a meaningless metric. Here’s why.

Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.

Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.

However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.

When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.

This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.

In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.

Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.

Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.

When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.

5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.

Our profit-over-patients policy has landed us in a terrible paradox.

Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.

This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.

We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.

Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.

Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.

A version of this article appeared on Medscape.com.

How should we define success in cancer policy — what should the endpoint be?

It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?

One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.

I’ll go a step further: It is not even a surrogate marker for success. The number of newly approved drugs is a meaningless metric. Here’s why.

Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.

Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.

However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.

When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.

This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.

In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.

Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.

Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.

When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.

5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.

Our profit-over-patients policy has landed us in a terrible paradox.

Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.

This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.

We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.

Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.

Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.

A version of this article appeared on Medscape.com.

How should we define success in cancer policy — what should the endpoint be?

It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?

One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.

I’ll go a step further: It is not even a surrogate marker for success. The number of newly approved drugs is a meaningless metric. Here’s why.

Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.

Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.

However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.

When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.

This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.

In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.

Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.

Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.

When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.

5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.

Our profit-over-patients policy has landed us in a terrible paradox.

Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.

This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.

We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.

Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.

Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.

A version of this article appeared on Medscape.com.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

The US Food and Drug Administration (FDA) has granted accelerated approval for lisocabtagene maraleucel (liso-cel) for the treatment of certain adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Specifically, the CD19-directed chimeric antigen receptor (CAR) T-cell product (Breyanzi) from Juno Therapeutics, a Bristol-Myers Squib company, is approved for adults with CLL or SLL who have received at least two prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. It is the first CAR T-cell therapy approved in this setting.

“CLL and SLL are currently considered incurable diseases with few treatment options in the relapsed setting that can confer complete responses,” lead trial investigator Tanya Siddiqi, MD, of City of Hope in Duarte, California, said in the press release. 

The FDA’s approval of liso-cel in this setting “is a remarkable breakthrough, shifting the treatment paradigm from continuous therapy with sequential regimens to overcome drug resistance, to a one-time personalized T-cell based approach that has the potential to offer patients complete and lasting remission,” Dr. Siddiqi added.

Liso-cel was first approved in 2021 for relapsed or refractory large B-cell lymphoma, as reported at the time by this news organization.

Approval for the new CLL and SLL indication followed Priority Review and was based on findings from the pivotal TRANSCEND CLL 004 study, in which 20% of patients with CLL or SLL achieved a complete response after a one-time liso-cel infusion, according to a Bristol-Myers Squibb press release.

The 89 participants in the open-label, phase 1/2 study received a single dose of liso-cel containing 90-110 x 106CAR-positive viable T cells. The overall response rate was 45%, and median duration of response was 35.3 months. Among the 20% of patients achieving a complete response, the median duration of that response was not reached at the time of data cutoff.

Liso-cel had a tolerable safety profile. Cytokine release syndrome and neurologic events were mostly low grade. Cytokine release syndrome of any grade occurred in 83% of patients; 9% were grade 3, and none were grade 4 or 5.

Neurologic events of any grade occurred in 46% of patients, with grade 3 events occurring in 20% of patients; one grade 4 event and no grade 5 events occurred.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval for lisocabtagene maraleucel (liso-cel) for the treatment of certain adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Specifically, the CD19-directed chimeric antigen receptor (CAR) T-cell product (Breyanzi) from Juno Therapeutics, a Bristol-Myers Squib company, is approved for adults with CLL or SLL who have received at least two prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. It is the first CAR T-cell therapy approved in this setting.

“CLL and SLL are currently considered incurable diseases with few treatment options in the relapsed setting that can confer complete responses,” lead trial investigator Tanya Siddiqi, MD, of City of Hope in Duarte, California, said in the press release. 

The FDA’s approval of liso-cel in this setting “is a remarkable breakthrough, shifting the treatment paradigm from continuous therapy with sequential regimens to overcome drug resistance, to a one-time personalized T-cell based approach that has the potential to offer patients complete and lasting remission,” Dr. Siddiqi added.

Liso-cel was first approved in 2021 for relapsed or refractory large B-cell lymphoma, as reported at the time by this news organization.

Approval for the new CLL and SLL indication followed Priority Review and was based on findings from the pivotal TRANSCEND CLL 004 study, in which 20% of patients with CLL or SLL achieved a complete response after a one-time liso-cel infusion, according to a Bristol-Myers Squibb press release.

The 89 participants in the open-label, phase 1/2 study received a single dose of liso-cel containing 90-110 x 106CAR-positive viable T cells. The overall response rate was 45%, and median duration of response was 35.3 months. Among the 20% of patients achieving a complete response, the median duration of that response was not reached at the time of data cutoff.

Liso-cel had a tolerable safety profile. Cytokine release syndrome and neurologic events were mostly low grade. Cytokine release syndrome of any grade occurred in 83% of patients; 9% were grade 3, and none were grade 4 or 5.

Neurologic events of any grade occurred in 46% of patients, with grade 3 events occurring in 20% of patients; one grade 4 event and no grade 5 events occurred.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval for lisocabtagene maraleucel (liso-cel) for the treatment of certain adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Specifically, the CD19-directed chimeric antigen receptor (CAR) T-cell product (Breyanzi) from Juno Therapeutics, a Bristol-Myers Squib company, is approved for adults with CLL or SLL who have received at least two prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. It is the first CAR T-cell therapy approved in this setting.

“CLL and SLL are currently considered incurable diseases with few treatment options in the relapsed setting that can confer complete responses,” lead trial investigator Tanya Siddiqi, MD, of City of Hope in Duarte, California, said in the press release. 

The FDA’s approval of liso-cel in this setting “is a remarkable breakthrough, shifting the treatment paradigm from continuous therapy with sequential regimens to overcome drug resistance, to a one-time personalized T-cell based approach that has the potential to offer patients complete and lasting remission,” Dr. Siddiqi added.

Liso-cel was first approved in 2021 for relapsed or refractory large B-cell lymphoma, as reported at the time by this news organization.

Approval for the new CLL and SLL indication followed Priority Review and was based on findings from the pivotal TRANSCEND CLL 004 study, in which 20% of patients with CLL or SLL achieved a complete response after a one-time liso-cel infusion, according to a Bristol-Myers Squibb press release.

The 89 participants in the open-label, phase 1/2 study received a single dose of liso-cel containing 90-110 x 106CAR-positive viable T cells. The overall response rate was 45%, and median duration of response was 35.3 months. Among the 20% of patients achieving a complete response, the median duration of that response was not reached at the time of data cutoff.

Liso-cel had a tolerable safety profile. Cytokine release syndrome and neurologic events were mostly low grade. Cytokine release syndrome of any grade occurred in 83% of patients; 9% were grade 3, and none were grade 4 or 5.

Neurologic events of any grade occurred in 46% of patients, with grade 3 events occurring in 20% of patients; one grade 4 event and no grade 5 events occurred.
 

A version of this article appeared on Medscape.com.

TOPLINE:

When considering a job offer at an academic radiation oncology practice, the prospective employee should focus on three key factors — compensation, daily duties, and location — and accept an offer if the practice is “great” in at least two of those areas and “good” in the third, experts say in a recent editorial.

METHODOLOGY:

• Many physicians choose to go into academic medicine because they want to stay involved in research and education while still treating patients.
• However, graduating radiation oncology residents often lack or have limited guidance on what to look for in a prospective job and how to assess their contract.
• This recent editorial provides guidance to radiation oncologists seeking academic positions. The authors advise prospective employees to evaluate three main factors — compensation, daily duties, and location — as well as provide tips for identifying red flags in each category.

TAKEAWAY:

• Compensation: Prospective faculty should assess both direct compensation, that is, salary, and indirect compensation, which typically includes retirement contributions and other perks. For direct compensation, what is the base salary? Is extra work compensated? How does the salary offer measure up to salary data reported by national agencies? Also: Don’t overlook uncompensated duties, such as time in tumor boards or in meetings, which may be time-consuming, and make sure compensation terms are clearly delineated in a contract and equitable among physicians in a specific rank.
• Daily duties: When it comes to daily life on the job, a prospective employee should consider many factors, including the cancer center’s excitement to hire you, the reputation of the faculty and leaders at the organization, employee turnover rates, diversity among faculty, and the time line of career advancement.
• Location: The location of the job encompasses the geography — such as distance from home to work, the number of practices covered, cost of living, and the area itself — as well as the atmosphere for conducting research and publishing.
• Finally, carefully review the job contract. All the key aspects of the job, including compensation and benefits, should be clearly stated in the contract to “improve communication of expectations.”

IN PRACTICE:

“A prospective faculty member can ask 100 questions, but they can’t make 100 demands; consideration of the three domains can help to focus negotiation efforts where the efforts are needed,” the authors noted.

SOURCE:

This editorial, led by Nicholas G. Zaorsky from the Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve School of Medicine, Cleveland, Ohio, was published online in Practical Radiation Oncology

DISCLOSURES:

The lead author declared being supported by the American Cancer Society and National Institutes of Health. He also reported having ties with many other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

When considering a job offer at an academic radiation oncology practice, the prospective employee should focus on three key factors — compensation, daily duties, and location — and accept an offer if the practice is “great” in at least two of those areas and “good” in the third, experts say in a recent editorial.

METHODOLOGY:

• Many physicians choose to go into academic medicine because they want to stay involved in research and education while still treating patients.
• However, graduating radiation oncology residents often lack or have limited guidance on what to look for in a prospective job and how to assess their contract.
• This recent editorial provides guidance to radiation oncologists seeking academic positions. The authors advise prospective employees to evaluate three main factors — compensation, daily duties, and location — as well as provide tips for identifying red flags in each category.

TAKEAWAY:

• Compensation: Prospective faculty should assess both direct compensation, that is, salary, and indirect compensation, which typically includes retirement contributions and other perks. For direct compensation, what is the base salary? Is extra work compensated? How does the salary offer measure up to salary data reported by national agencies? Also: Don’t overlook uncompensated duties, such as time in tumor boards or in meetings, which may be time-consuming, and make sure compensation terms are clearly delineated in a contract and equitable among physicians in a specific rank.
• Daily duties: When it comes to daily life on the job, a prospective employee should consider many factors, including the cancer center’s excitement to hire you, the reputation of the faculty and leaders at the organization, employee turnover rates, diversity among faculty, and the time line of career advancement.
• Location: The location of the job encompasses the geography — such as distance from home to work, the number of practices covered, cost of living, and the area itself — as well as the atmosphere for conducting research and publishing.
• Finally, carefully review the job contract. All the key aspects of the job, including compensation and benefits, should be clearly stated in the contract to “improve communication of expectations.”

IN PRACTICE:

“A prospective faculty member can ask 100 questions, but they can’t make 100 demands; consideration of the three domains can help to focus negotiation efforts where the efforts are needed,” the authors noted.

SOURCE:

This editorial, led by Nicholas G. Zaorsky from the Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve School of Medicine, Cleveland, Ohio, was published online in Practical Radiation Oncology

DISCLOSURES:

The lead author declared being supported by the American Cancer Society and National Institutes of Health. He also reported having ties with many other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

When considering a job offer at an academic radiation oncology practice, the prospective employee should focus on three key factors — compensation, daily duties, and location — and accept an offer if the practice is “great” in at least two of those areas and “good” in the third, experts say in a recent editorial.

METHODOLOGY:

• Many physicians choose to go into academic medicine because they want to stay involved in research and education while still treating patients.
• However, graduating radiation oncology residents often lack or have limited guidance on what to look for in a prospective job and how to assess their contract.
• This recent editorial provides guidance to radiation oncologists seeking academic positions. The authors advise prospective employees to evaluate three main factors — compensation, daily duties, and location — as well as provide tips for identifying red flags in each category.

TAKEAWAY:

• Compensation: Prospective faculty should assess both direct compensation, that is, salary, and indirect compensation, which typically includes retirement contributions and other perks. For direct compensation, what is the base salary? Is extra work compensated? How does the salary offer measure up to salary data reported by national agencies? Also: Don’t overlook uncompensated duties, such as time in tumor boards or in meetings, which may be time-consuming, and make sure compensation terms are clearly delineated in a contract and equitable among physicians in a specific rank.
• Daily duties: When it comes to daily life on the job, a prospective employee should consider many factors, including the cancer center’s excitement to hire you, the reputation of the faculty and leaders at the organization, employee turnover rates, diversity among faculty, and the time line of career advancement.
• Location: The location of the job encompasses the geography — such as distance from home to work, the number of practices covered, cost of living, and the area itself — as well as the atmosphere for conducting research and publishing.
• Finally, carefully review the job contract. All the key aspects of the job, including compensation and benefits, should be clearly stated in the contract to “improve communication of expectations.”

IN PRACTICE:

“A prospective faculty member can ask 100 questions, but they can’t make 100 demands; consideration of the three domains can help to focus negotiation efforts where the efforts are needed,” the authors noted.

SOURCE:

This editorial, led by Nicholas G. Zaorsky from the Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve School of Medicine, Cleveland, Ohio, was published online in Practical Radiation Oncology

DISCLOSURES:

The lead author declared being supported by the American Cancer Society and National Institutes of Health. He also reported having ties with many other sources.

A version of this article appeared on Medscape.com.

While the increased risk of cancer in patients with metabolic syndrome is well established by research, the authors of a new study delve deeper by examining metabolic syndrome trajectories.

The new research finds that adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer.

The conditions that make up metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, and colleagues.

However, a single assessment of metabolic syndrome at one point in time is inadequate to show an association with cancer risk over time, they said. In the current study, the researchers used models to examine the association between trajectory patterns of metabolic syndrome over time and the risk of overall and specific cancer types. They also examined the impact of chronic inflammation concurrent with metabolic syndrome.
 

What We Know About Metabolic Syndrome and Cancer Risk

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2020 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

In addition, a 2022 study by some of the current study researchers of the same Chinese cohort focused on the role of inflammation in combination with metabolic syndrome on colorectal cancer specifically, and found an increased risk for cancer when both metabolic syndrome and inflammation were present.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.

“There is emerging evidence that even normal weight individuals who are metabolically unhealthy may be at an elevated cancer risk, and we need better metrics to define the underlying metabolic dysfunction in obesity,” Sheetal Hardikar, MBBS, PhD, MPH, an investigator at the Huntsman Cancer Institute, University of Utah, said in an interview.

Dr. Hardikar, who serves as assistant professor in the department of population health sciences at the University of Utah, was not involved in the current study. She and her colleagues published a research paper on data from the National Health and Nutrition Examination Survey in 2023 that showed an increased risk of obesity-related cancer.
 

What New Study Adds to Related Research

Previous studies have consistently reported an approximately 30% increased risk of cancer with metabolic syndrome, Dr. Hardikar said. “What is unique about this study is the examination of metabolic syndrome trajectories over four years, and not just the presence of metabolic syndrome at one point in time,” she said.

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years; the mean body mass index ranged from approximately 22 kg/m² in the low-stable group to approximately 28 kg/m² in the elevated-increasing group.

The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.

Using the International Diabetes Federation criteria was another limitation, because it prevented the assessment of cancer risk in normal weight individuals with metabolic dysfunction, Dr. Hardikar noted.
 

Does Metabolic Syndrome Cause Cancer?

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, noted in a statement on the study.

More research is needed to assess the impact of these interventions on cancer risk. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he continued.

“Current evidence based on this study and many other reports strongly suggests an increased risk for cancer associated with metabolic syndrome,” Dr. Hardikar said in an interview. The data serve as a reminder to clinicians to look beyond BMI as the only measure of obesity, and to consider metabolic factors together to identify individuals at increased risk for cancer, she said.

“We must continue to educate patients about obesity and all the chronic conditions it may lead to, but we cannot ignore this emerging phenotype of being of normal weight but metabolically unhealthy,” Dr. Hardikar emphasized.
 

What Additional Research is Needed?

Looking ahead, “we need well-designed interventions to test causality for metabolic syndrome and cancer risk, though the evidence from the observational studies is very strong,” Dr. Hardikar said.

In addition, a consensus is needed to better define metabolic dysfunction,and to explore cancer risk in normal weight but metabolically unhealthy individuals, she said.

The study was supported by the National Key Research and Development Program of China. The researchers and Dr. Hardikar had no financial conflicts to disclose.

While the increased risk of cancer in patients with metabolic syndrome is well established by research, the authors of a new study delve deeper by examining metabolic syndrome trajectories.

The new research finds that adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer.

The conditions that make up metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, and colleagues.

However, a single assessment of metabolic syndrome at one point in time is inadequate to show an association with cancer risk over time, they said. In the current study, the researchers used models to examine the association between trajectory patterns of metabolic syndrome over time and the risk of overall and specific cancer types. They also examined the impact of chronic inflammation concurrent with metabolic syndrome.
 

What We Know About Metabolic Syndrome and Cancer Risk

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2020 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

In addition, a 2022 study by some of the current study researchers of the same Chinese cohort focused on the role of inflammation in combination with metabolic syndrome on colorectal cancer specifically, and found an increased risk for cancer when both metabolic syndrome and inflammation were present.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.

“There is emerging evidence that even normal weight individuals who are metabolically unhealthy may be at an elevated cancer risk, and we need better metrics to define the underlying metabolic dysfunction in obesity,” Sheetal Hardikar, MBBS, PhD, MPH, an investigator at the Huntsman Cancer Institute, University of Utah, said in an interview.

Dr. Hardikar, who serves as assistant professor in the department of population health sciences at the University of Utah, was not involved in the current study. She and her colleagues published a research paper on data from the National Health and Nutrition Examination Survey in 2023 that showed an increased risk of obesity-related cancer.
 

What New Study Adds to Related Research

Previous studies have consistently reported an approximately 30% increased risk of cancer with metabolic syndrome, Dr. Hardikar said. “What is unique about this study is the examination of metabolic syndrome trajectories over four years, and not just the presence of metabolic syndrome at one point in time,” she said.

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years; the mean body mass index ranged from approximately 22 kg/m² in the low-stable group to approximately 28 kg/m² in the elevated-increasing group.

The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.

Using the International Diabetes Federation criteria was another limitation, because it prevented the assessment of cancer risk in normal weight individuals with metabolic dysfunction, Dr. Hardikar noted.
 

Does Metabolic Syndrome Cause Cancer?

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, noted in a statement on the study.

More research is needed to assess the impact of these interventions on cancer risk. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he continued.

“Current evidence based on this study and many other reports strongly suggests an increased risk for cancer associated with metabolic syndrome,” Dr. Hardikar said in an interview. The data serve as a reminder to clinicians to look beyond BMI as the only measure of obesity, and to consider metabolic factors together to identify individuals at increased risk for cancer, she said.

“We must continue to educate patients about obesity and all the chronic conditions it may lead to, but we cannot ignore this emerging phenotype of being of normal weight but metabolically unhealthy,” Dr. Hardikar emphasized.
 

What Additional Research is Needed?

Looking ahead, “we need well-designed interventions to test causality for metabolic syndrome and cancer risk, though the evidence from the observational studies is very strong,” Dr. Hardikar said.

In addition, a consensus is needed to better define metabolic dysfunction,and to explore cancer risk in normal weight but metabolically unhealthy individuals, she said.

The study was supported by the National Key Research and Development Program of China. The researchers and Dr. Hardikar had no financial conflicts to disclose.

While the increased risk of cancer in patients with metabolic syndrome is well established by research, the authors of a new study delve deeper by examining metabolic syndrome trajectories.

The new research finds that adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer.

The conditions that make up metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, and colleagues.

However, a single assessment of metabolic syndrome at one point in time is inadequate to show an association with cancer risk over time, they said. In the current study, the researchers used models to examine the association between trajectory patterns of metabolic syndrome over time and the risk of overall and specific cancer types. They also examined the impact of chronic inflammation concurrent with metabolic syndrome.
 

What We Know About Metabolic Syndrome and Cancer Risk

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2020 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

In addition, a 2022 study by some of the current study researchers of the same Chinese cohort focused on the role of inflammation in combination with metabolic syndrome on colorectal cancer specifically, and found an increased risk for cancer when both metabolic syndrome and inflammation were present.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.

“There is emerging evidence that even normal weight individuals who are metabolically unhealthy may be at an elevated cancer risk, and we need better metrics to define the underlying metabolic dysfunction in obesity,” Sheetal Hardikar, MBBS, PhD, MPH, an investigator at the Huntsman Cancer Institute, University of Utah, said in an interview.

Dr. Hardikar, who serves as assistant professor in the department of population health sciences at the University of Utah, was not involved in the current study. She and her colleagues published a research paper on data from the National Health and Nutrition Examination Survey in 2023 that showed an increased risk of obesity-related cancer.
 

What New Study Adds to Related Research

Previous studies have consistently reported an approximately 30% increased risk of cancer with metabolic syndrome, Dr. Hardikar said. “What is unique about this study is the examination of metabolic syndrome trajectories over four years, and not just the presence of metabolic syndrome at one point in time,” she said.

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years; the mean body mass index ranged from approximately 22 kg/m² in the low-stable group to approximately 28 kg/m² in the elevated-increasing group.

The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.

Using the International Diabetes Federation criteria was another limitation, because it prevented the assessment of cancer risk in normal weight individuals with metabolic dysfunction, Dr. Hardikar noted.
 

Does Metabolic Syndrome Cause Cancer?

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, noted in a statement on the study.

More research is needed to assess the impact of these interventions on cancer risk. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he continued.

“Current evidence based on this study and many other reports strongly suggests an increased risk for cancer associated with metabolic syndrome,” Dr. Hardikar said in an interview. The data serve as a reminder to clinicians to look beyond BMI as the only measure of obesity, and to consider metabolic factors together to identify individuals at increased risk for cancer, she said.

“We must continue to educate patients about obesity and all the chronic conditions it may lead to, but we cannot ignore this emerging phenotype of being of normal weight but metabolically unhealthy,” Dr. Hardikar emphasized.
 

What Additional Research is Needed?

Looking ahead, “we need well-designed interventions to test causality for metabolic syndrome and cancer risk, though the evidence from the observational studies is very strong,” Dr. Hardikar said.

In addition, a consensus is needed to better define metabolic dysfunction,and to explore cancer risk in normal weight but metabolically unhealthy individuals, she said.

The study was supported by the National Key Research and Development Program of China. The researchers and Dr. Hardikar had no financial conflicts to disclose.

The American Society for Radiation Oncology (ASTRO) recently sent a letter to the Centers for Medicare and Medicaid Services (CMS) opposing the extension of virtual supervision for radiation oncology services.

Although serious errors during virtual supervision are rare, ASTRO said radiation treatments (RT) should be done with a radiation oncologist on site to ensure high-quality care. But some radiation oncologists do not agree with the proposal to move back to direct in-person supervision only. 
 

Changes to Direct Supervision

Most radiation oncology treatments are delivered in an outpatient setting under a physician’s direction and control. 

During the COVID-19 pandemic when social distancing mandates were in place, CMS temporarily changed the definition of “direct supervision” to include telehealth, specifying that a physician must be immediately available to assist and direct a procedure virtually using real-time audio and video. In other words, a physician did not need to be physically present in the room when the treatment was being performed. 

CMS has extended this rule until the end of 2024 and is considering making it a permanent change. In the Calendar Year (CY) 2024 Medicare Physician Fee Schedule (PFS) Final Rule, CMS asked for comments on whether to extend the rule. 

“We received input from interested parties on potential patient safety or quality concerns when direct supervision occurs virtually, which we will consider for future rulemaking,” a CMS spokesperson told this news organization. “CMS is currently considering the best approach that will protect patient access and safety as well as quality of care and program integrity concerns following CY 2024.”

CMS also noted its concerns that an abrupt transition back to requiring a physician’s physical presence could interrupt care from practitioners who have established new patterns of practice with telehealth. 
 

What Are ASTRO’s Concerns?

Late last month, ASTRO sent CMS a letter, asking the agency to change the rules back to direct in-person supervision for all radiation services, citing that virtual supervision jeopardizes patient safety and quality of care. 

Jeff Michalski, MD, MBA, chair of the ASTRO Board of Directors, said in an interview that radiation oncologists should be physically present to supervise the treatments.

“ASTRO is concerned that blanket policies of general or virtual supervision could lead to patients not having direct, in-person access to their doctors’ care,” he said. “While serious errors are rare, real-world experiences of radiation oncologists across practice settings demonstrate how an in-person radiation oncology physician is best suited to ensure high-quality care.”
 

What Do Radiation Oncologists Think?

According to ASTRO, most radiation oncologists would agree that in-person supervision is best for patients. 

But that might not be the case. 

Radiation oncologists took to X (formerly Twitter) to voice their opinions about ASTRO’s letter. 

Jason Beckta, MD, PhD, of Rutland Regional’s Foley Cancer Center, Vermont, said “the February 26th ASTRO letter reads like an Onion article.” 

“I’m struggling to understand the Luddite-level myopia around this topic,” he said in another tweet. “Virtual direct/outpatient general supervision has done nothing but boost my productivity and in particular, face-to-face patient contact.”

Join Y. Luh, MD, with the Providence Medical Network in Eureka, California, said he understands the challenges faced by clinicians working in more isolated rural settings. “For them, it’s either having virtual supervision or closing the center,” Dr. Luh said.

“Virtual care is definitely at my clinic and is not only an option but is critical to my patients who are 2+ snowy, mountainous hours away,” Dr. Luh wrote. “But I’m still in the clinic directly supervising treatments.”

Sidney Roberts, MD, with the CHI St. Luke’s Health-Memorial, Texas, tweeted that supervision does require some face-to-face care but contended that “babysitting trained therapists for every routine treatment is a farce.”

Another issue Dr. Luh brought up is reimbursement for virtual supervision, noting that “the elephant in the room is whether that level of service should be reimbursed at the same rate. Reimbursement has not changed — but will it stay that way?”

ASTRO has acknowledged that radiation oncologists will have varying opinions and says it is working to balance these challenges.

CMS has not reached a decision on whether the change will be implemented permanently. The organization will assess concern, patient safety, and quality of care at the end of the year.

A version of this article first appeared on Medscape.com

The American Society for Radiation Oncology (ASTRO) recently sent a letter to the Centers for Medicare and Medicaid Services (CMS) opposing the extension of virtual supervision for radiation oncology services.

Although serious errors during virtual supervision are rare, ASTRO said radiation treatments (RT) should be done with a radiation oncologist on site to ensure high-quality care. But some radiation oncologists do not agree with the proposal to move back to direct in-person supervision only. 
 

Changes to Direct Supervision

Most radiation oncology treatments are delivered in an outpatient setting under a physician’s direction and control. 

During the COVID-19 pandemic when social distancing mandates were in place, CMS temporarily changed the definition of “direct supervision” to include telehealth, specifying that a physician must be immediately available to assist and direct a procedure virtually using real-time audio and video. In other words, a physician did not need to be physically present in the room when the treatment was being performed. 

CMS has extended this rule until the end of 2024 and is considering making it a permanent change. In the Calendar Year (CY) 2024 Medicare Physician Fee Schedule (PFS) Final Rule, CMS asked for comments on whether to extend the rule. 

“We received input from interested parties on potential patient safety or quality concerns when direct supervision occurs virtually, which we will consider for future rulemaking,” a CMS spokesperson told this news organization. “CMS is currently considering the best approach that will protect patient access and safety as well as quality of care and program integrity concerns following CY 2024.”

CMS also noted its concerns that an abrupt transition back to requiring a physician’s physical presence could interrupt care from practitioners who have established new patterns of practice with telehealth. 
 

What Are ASTRO’s Concerns?

Late last month, ASTRO sent CMS a letter, asking the agency to change the rules back to direct in-person supervision for all radiation services, citing that virtual supervision jeopardizes patient safety and quality of care. 

Jeff Michalski, MD, MBA, chair of the ASTRO Board of Directors, said in an interview that radiation oncologists should be physically present to supervise the treatments.

“ASTRO is concerned that blanket policies of general or virtual supervision could lead to patients not having direct, in-person access to their doctors’ care,” he said. “While serious errors are rare, real-world experiences of radiation oncologists across practice settings demonstrate how an in-person radiation oncology physician is best suited to ensure high-quality care.”
 

What Do Radiation Oncologists Think?

According to ASTRO, most radiation oncologists would agree that in-person supervision is best for patients. 

But that might not be the case. 

Radiation oncologists took to X (formerly Twitter) to voice their opinions about ASTRO’s letter. 

Jason Beckta, MD, PhD, of Rutland Regional’s Foley Cancer Center, Vermont, said “the February 26th ASTRO letter reads like an Onion article.” 

“I’m struggling to understand the Luddite-level myopia around this topic,” he said in another tweet. “Virtual direct/outpatient general supervision has done nothing but boost my productivity and in particular, face-to-face patient contact.”

Join Y. Luh, MD, with the Providence Medical Network in Eureka, California, said he understands the challenges faced by clinicians working in more isolated rural settings. “For them, it’s either having virtual supervision or closing the center,” Dr. Luh said.

“Virtual care is definitely at my clinic and is not only an option but is critical to my patients who are 2+ snowy, mountainous hours away,” Dr. Luh wrote. “But I’m still in the clinic directly supervising treatments.”

Sidney Roberts, MD, with the CHI St. Luke’s Health-Memorial, Texas, tweeted that supervision does require some face-to-face care but contended that “babysitting trained therapists for every routine treatment is a farce.”

Another issue Dr. Luh brought up is reimbursement for virtual supervision, noting that “the elephant in the room is whether that level of service should be reimbursed at the same rate. Reimbursement has not changed — but will it stay that way?”

ASTRO has acknowledged that radiation oncologists will have varying opinions and says it is working to balance these challenges.

CMS has not reached a decision on whether the change will be implemented permanently. The organization will assess concern, patient safety, and quality of care at the end of the year.

A version of this article first appeared on Medscape.com

The American Society for Radiation Oncology (ASTRO) recently sent a letter to the Centers for Medicare and Medicaid Services (CMS) opposing the extension of virtual supervision for radiation oncology services.

Although serious errors during virtual supervision are rare, ASTRO said radiation treatments (RT) should be done with a radiation oncologist on site to ensure high-quality care. But some radiation oncologists do not agree with the proposal to move back to direct in-person supervision only. 
 

Changes to Direct Supervision

Most radiation oncology treatments are delivered in an outpatient setting under a physician’s direction and control. 

During the COVID-19 pandemic when social distancing mandates were in place, CMS temporarily changed the definition of “direct supervision” to include telehealth, specifying that a physician must be immediately available to assist and direct a procedure virtually using real-time audio and video. In other words, a physician did not need to be physically present in the room when the treatment was being performed. 

CMS has extended this rule until the end of 2024 and is considering making it a permanent change. In the Calendar Year (CY) 2024 Medicare Physician Fee Schedule (PFS) Final Rule, CMS asked for comments on whether to extend the rule. 

“We received input from interested parties on potential patient safety or quality concerns when direct supervision occurs virtually, which we will consider for future rulemaking,” a CMS spokesperson told this news organization. “CMS is currently considering the best approach that will protect patient access and safety as well as quality of care and program integrity concerns following CY 2024.”

CMS also noted its concerns that an abrupt transition back to requiring a physician’s physical presence could interrupt care from practitioners who have established new patterns of practice with telehealth. 
 

What Are ASTRO’s Concerns?

Late last month, ASTRO sent CMS a letter, asking the agency to change the rules back to direct in-person supervision for all radiation services, citing that virtual supervision jeopardizes patient safety and quality of care. 

Jeff Michalski, MD, MBA, chair of the ASTRO Board of Directors, said in an interview that radiation oncologists should be physically present to supervise the treatments.

“ASTRO is concerned that blanket policies of general or virtual supervision could lead to patients not having direct, in-person access to their doctors’ care,” he said. “While serious errors are rare, real-world experiences of radiation oncologists across practice settings demonstrate how an in-person radiation oncology physician is best suited to ensure high-quality care.”
 

What Do Radiation Oncologists Think?

According to ASTRO, most radiation oncologists would agree that in-person supervision is best for patients. 

But that might not be the case. 

Radiation oncologists took to X (formerly Twitter) to voice their opinions about ASTRO’s letter. 

Jason Beckta, MD, PhD, of Rutland Regional’s Foley Cancer Center, Vermont, said “the February 26th ASTRO letter reads like an Onion article.” 

“I’m struggling to understand the Luddite-level myopia around this topic,” he said in another tweet. “Virtual direct/outpatient general supervision has done nothing but boost my productivity and in particular, face-to-face patient contact.”

Join Y. Luh, MD, with the Providence Medical Network in Eureka, California, said he understands the challenges faced by clinicians working in more isolated rural settings. “For them, it’s either having virtual supervision or closing the center,” Dr. Luh said.

“Virtual care is definitely at my clinic and is not only an option but is critical to my patients who are 2+ snowy, mountainous hours away,” Dr. Luh wrote. “But I’m still in the clinic directly supervising treatments.”

Sidney Roberts, MD, with the CHI St. Luke’s Health-Memorial, Texas, tweeted that supervision does require some face-to-face care but contended that “babysitting trained therapists for every routine treatment is a farce.”

Another issue Dr. Luh brought up is reimbursement for virtual supervision, noting that “the elephant in the room is whether that level of service should be reimbursed at the same rate. Reimbursement has not changed — but will it stay that way?”

ASTRO has acknowledged that radiation oncologists will have varying opinions and says it is working to balance these challenges.

CMS has not reached a decision on whether the change will be implemented permanently. The organization will assess concern, patient safety, and quality of care at the end of the year.

A version of this article first appeared on Medscape.com

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

Several clinical trials in leukemia and lymphoma have started enrolling recently. Maybe one of your patients could benefit from taking part?

Hematological malignancy scheduled for a human leukocyte antigen–mismatched unrelated donor transplant. Adult patients in this situation who are younger than 66 years may be eligible for a randomized, open-label, phase 2 study run by the Center for International Blood and Bone Marrow Transplant Research.

The purpose of the study is to test whether cyclophosphamide, which is given to prevent a dreaded complication of stem cell transplantation called graft-versus-host disease, can be safely reduced without increasing infection or reducing protection. All participants will receive cyclophosphamide on days 3 and 4 post transplant. One group will receive a reduced dose of cyclophosphamide (25 mg/kg per dose), and the other will be given a usual dose (37.5 mg/kg).

Sites in Michigan, Missouri, Oregon, Virginia, and Washington started recruiting for 190 participants in December 2023. Study centers in Florida, Massachusetts, New York, and Wisconsin are also planned. Infection-free survival is the primary endpoint, and overall survival is a secondary measure. Quality of life (QoL) is not recorded. More details at clinicaltrials.gov.

Untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Adults who are newly diagnosed with this type of cancer and have active disease may wish to consider a randomized, open-label, phase 3 trial testing an experimental Bruton tyrosine kinase (BTK) inhibitor, nemtabrutinib (from Merck Sharp & Dohme), against standard-of-care BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence).

BTK inhibitors target B-cell proliferation in B-cell cancers such as CLL/SLL and allow for chemotherapy-free treatment of some hematological malignancies. In this study, until disease progression, unacceptable toxicity, or another reason for discontinuation occurs, participants will take daily oral nemtabrutinib, ibrutinib, or acalabrutinib.

The study opened in December 2023 in Pennsylvania, Washington, Taiwan, Israel, and the United Kingdom seeking 1200 participants. The primary outcomes are objective response rate and progression-free survival. Overall survival is a secondary outcome, and QoL is not measured. More details at clinicaltrials.gov.

Relapsed or refractory leukemia with a KMT2A-gene rearrangement (KMT2A-r). Children aged 1 month to younger than 6 years with this diagnosis may be able to join an open-label, nonrandomized, Children’s Oncology Group phase 2 study to determine the most tolerable and/or effective dose of an experimental oral drug called revumenib when added to chemotherapy.

KMT2A-gene alterations are associated with a poor prognosis in leukemia. These alterations cause blood cells to dedifferentiate and start proliferating uncontrollably as leukemia cells. The expression of the damaged KMT2A gene relies on a protein called menin. Revumenib, from Syndax Pharmaceuticals, blocks menin and prevents expression of KMT2A.

Children in the study will receive two different regimens of revumenib in combination with chemotherapy for up to a year, or until disease progression or unacceptable toxicity, and will then be followed for up to 5 years. Trial centers in 12 US states opened their doors in January 2024 looking for 78 participants. Toxicities and minimal residual disease are the primary outcomes; overall survival is a secondary outcome, and QoL is not assessed. More details at clinicaltrials.gov.

Previously untreated follicular lymphoma or diffuse large B-cell lymphoma. Adults with one of these types of lymphoma may be eligible for one of three open-label, randomized, phase 3 trials testing odronextamab (from Regeneron). This bispecific antibody is designed to ‘lock together’ CD20 on cancer cells with CD3-expressing cancer-killing T cells. It has shown anti-lymphoma activity in heavily pretreated patients.

Late in 2023, three phase 3 trials turned the spotlight on treatment-naive patients and started recruiting 2115 participants to assess odronextamab in this setting. The trial OLYMPIA-1 will compare odronextamab with standard-of-care rituximab (Rituxan) plus chemotherapy in follicular lymphoma. OLYMPIA-2 will test the drug in combination with chemotherapy, also in follicular lymphoma. OLYMPIA-3 will evaluate odronextamab plus chemotherapy against rituximab and chemotherapy in people with large B-cell lymphoma.

All study drugs, including odronextamab, will be administered by intravenous infusion, and participants will be followed for up to 5 years. Research centers across eight US states and Australia, Czechia, France, Italy, Poland, Spain, Turkey, and Thailand are currently accepting participants for the three trials. The primary outcomes are various measures of toxicity and complete response at 30 months in the follicular lymphoma studies and toxicity and progression-free survival in large B-cell lymphoma. All three trials are measuring overall survival and QoL as secondary endpoints.

Previously untreated stage II, III, or IV follicular lymphoma. Adults with this type of cancer may be eligible to participate in a randomized, open-label, phase 3 study testing whether an experimental therapy called epcoritamab (from AbbVie) improves disease response and is tolerable when added to standard therapy. For up to 120 weeks, one group of participants will receive a combination of intravenous rituximab and oral lenalidomide (Revlimid), while a second group will also receive subcutaneous injections of epcoritamab. Some participants may be offered investigators’ choice of chemotherapy as well.

Sites across Iowa, Maryland, Missouri, Ohio, Washington, and Montana started welcoming their 900 participants in February 2024. The primary outcome is complete response at 30 months. Overall survival and QoL are secondary outcomes. More details at clinicaltrials.gov.

Relapsed or refractory mantle cell lymphoma. Adults facing one of these clinical scenarios can join an Academic and Community Cancer Research United open label, phase 2 trial examining the effectiveness of combining tafasitamab (Monjuvi), lenalidomide, and venetoclax (Venclexta) for such patients.

Frontline therapy does not cure mantle cell lymphoma, and continued relapses are common. In this situation, treatments can include acalabrutinib, ibrutinib, stem cell transplantation, venetoclax, lenalidomide, and rituximab.

In this study, participants will take venetoclax and lenalidomide daily and receive intravenous tafasitamab every 2 weeks after an initial ramp-up period as per clinic standards. Participants will be followed for 5 years after entering the trial. The Mayo Clinic in Rochester, Minnesota, began recruiting the planned 100 trial participants in January 2024. The primary outcome is objective response rate; overall survival is a secondary outcome, and QoL will not be tracked. More details at clinicaltrials.gov.

All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

Several clinical trials in leukemia and lymphoma have started enrolling recently. Maybe one of your patients could benefit from taking part?

Hematological malignancy scheduled for a human leukocyte antigen–mismatched unrelated donor transplant. Adult patients in this situation who are younger than 66 years may be eligible for a randomized, open-label, phase 2 study run by the Center for International Blood and Bone Marrow Transplant Research.

The purpose of the study is to test whether cyclophosphamide, which is given to prevent a dreaded complication of stem cell transplantation called graft-versus-host disease, can be safely reduced without increasing infection or reducing protection. All participants will receive cyclophosphamide on days 3 and 4 post transplant. One group will receive a reduced dose of cyclophosphamide (25 mg/kg per dose), and the other will be given a usual dose (37.5 mg/kg).

Sites in Michigan, Missouri, Oregon, Virginia, and Washington started recruiting for 190 participants in December 2023. Study centers in Florida, Massachusetts, New York, and Wisconsin are also planned. Infection-free survival is the primary endpoint, and overall survival is a secondary measure. Quality of life (QoL) is not recorded. More details at clinicaltrials.gov.

Untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Adults who are newly diagnosed with this type of cancer and have active disease may wish to consider a randomized, open-label, phase 3 trial testing an experimental Bruton tyrosine kinase (BTK) inhibitor, nemtabrutinib (from Merck Sharp & Dohme), against standard-of-care BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence).

BTK inhibitors target B-cell proliferation in B-cell cancers such as CLL/SLL and allow for chemotherapy-free treatment of some hematological malignancies. In this study, until disease progression, unacceptable toxicity, or another reason for discontinuation occurs, participants will take daily oral nemtabrutinib, ibrutinib, or acalabrutinib.

The study opened in December 2023 in Pennsylvania, Washington, Taiwan, Israel, and the United Kingdom seeking 1200 participants. The primary outcomes are objective response rate and progression-free survival. Overall survival is a secondary outcome, and QoL is not measured. More details at clinicaltrials.gov.

Relapsed or refractory leukemia with a KMT2A-gene rearrangement (KMT2A-r). Children aged 1 month to younger than 6 years with this diagnosis may be able to join an open-label, nonrandomized, Children’s Oncology Group phase 2 study to determine the most tolerable and/or effective dose of an experimental oral drug called revumenib when added to chemotherapy.

KMT2A-gene alterations are associated with a poor prognosis in leukemia. These alterations cause blood cells to dedifferentiate and start proliferating uncontrollably as leukemia cells. The expression of the damaged KMT2A gene relies on a protein called menin. Revumenib, from Syndax Pharmaceuticals, blocks menin and prevents expression of KMT2A.

Children in the study will receive two different regimens of revumenib in combination with chemotherapy for up to a year, or until disease progression or unacceptable toxicity, and will then be followed for up to 5 years. Trial centers in 12 US states opened their doors in January 2024 looking for 78 participants. Toxicities and minimal residual disease are the primary outcomes; overall survival is a secondary outcome, and QoL is not assessed. More details at clinicaltrials.gov.

Previously untreated follicular lymphoma or diffuse large B-cell lymphoma. Adults with one of these types of lymphoma may be eligible for one of three open-label, randomized, phase 3 trials testing odronextamab (from Regeneron). This bispecific antibody is designed to ‘lock together’ CD20 on cancer cells with CD3-expressing cancer-killing T cells. It has shown anti-lymphoma activity in heavily pretreated patients.

Late in 2023, three phase 3 trials turned the spotlight on treatment-naive patients and started recruiting 2115 participants to assess odronextamab in this setting. The trial OLYMPIA-1 will compare odronextamab with standard-of-care rituximab (Rituxan) plus chemotherapy in follicular lymphoma. OLYMPIA-2 will test the drug in combination with chemotherapy, also in follicular lymphoma. OLYMPIA-3 will evaluate odronextamab plus chemotherapy against rituximab and chemotherapy in people with large B-cell lymphoma.

All study drugs, including odronextamab, will be administered by intravenous infusion, and participants will be followed for up to 5 years. Research centers across eight US states and Australia, Czechia, France, Italy, Poland, Spain, Turkey, and Thailand are currently accepting participants for the three trials. The primary outcomes are various measures of toxicity and complete response at 30 months in the follicular lymphoma studies and toxicity and progression-free survival in large B-cell lymphoma. All three trials are measuring overall survival and QoL as secondary endpoints.

Previously untreated stage II, III, or IV follicular lymphoma. Adults with this type of cancer may be eligible to participate in a randomized, open-label, phase 3 study testing whether an experimental therapy called epcoritamab (from AbbVie) improves disease response and is tolerable when added to standard therapy. For up to 120 weeks, one group of participants will receive a combination of intravenous rituximab and oral lenalidomide (Revlimid), while a second group will also receive subcutaneous injections of epcoritamab. Some participants may be offered investigators’ choice of chemotherapy as well.

Sites across Iowa, Maryland, Missouri, Ohio, Washington, and Montana started welcoming their 900 participants in February 2024. The primary outcome is complete response at 30 months. Overall survival and QoL are secondary outcomes. More details at clinicaltrials.gov.

Relapsed or refractory mantle cell lymphoma. Adults facing one of these clinical scenarios can join an Academic and Community Cancer Research United open label, phase 2 trial examining the effectiveness of combining tafasitamab (Monjuvi), lenalidomide, and venetoclax (Venclexta) for such patients.

Frontline therapy does not cure mantle cell lymphoma, and continued relapses are common. In this situation, treatments can include acalabrutinib, ibrutinib, stem cell transplantation, venetoclax, lenalidomide, and rituximab.

In this study, participants will take venetoclax and lenalidomide daily and receive intravenous tafasitamab every 2 weeks after an initial ramp-up period as per clinic standards. Participants will be followed for 5 years after entering the trial. The Mayo Clinic in Rochester, Minnesota, began recruiting the planned 100 trial participants in January 2024. The primary outcome is objective response rate; overall survival is a secondary outcome, and QoL will not be tracked. More details at clinicaltrials.gov.

All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

Several clinical trials in leukemia and lymphoma have started enrolling recently. Maybe one of your patients could benefit from taking part?

Hematological malignancy scheduled for a human leukocyte antigen–mismatched unrelated donor transplant. Adult patients in this situation who are younger than 66 years may be eligible for a randomized, open-label, phase 2 study run by the Center for International Blood and Bone Marrow Transplant Research.

The purpose of the study is to test whether cyclophosphamide, which is given to prevent a dreaded complication of stem cell transplantation called graft-versus-host disease, can be safely reduced without increasing infection or reducing protection. All participants will receive cyclophosphamide on days 3 and 4 post transplant. One group will receive a reduced dose of cyclophosphamide (25 mg/kg per dose), and the other will be given a usual dose (37.5 mg/kg).

Sites in Michigan, Missouri, Oregon, Virginia, and Washington started recruiting for 190 participants in December 2023. Study centers in Florida, Massachusetts, New York, and Wisconsin are also planned. Infection-free survival is the primary endpoint, and overall survival is a secondary measure. Quality of life (QoL) is not recorded. More details at clinicaltrials.gov.

Untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Adults who are newly diagnosed with this type of cancer and have active disease may wish to consider a randomized, open-label, phase 3 trial testing an experimental Bruton tyrosine kinase (BTK) inhibitor, nemtabrutinib (from Merck Sharp & Dohme), against standard-of-care BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence).

BTK inhibitors target B-cell proliferation in B-cell cancers such as CLL/SLL and allow for chemotherapy-free treatment of some hematological malignancies. In this study, until disease progression, unacceptable toxicity, or another reason for discontinuation occurs, participants will take daily oral nemtabrutinib, ibrutinib, or acalabrutinib.

The study opened in December 2023 in Pennsylvania, Washington, Taiwan, Israel, and the United Kingdom seeking 1200 participants. The primary outcomes are objective response rate and progression-free survival. Overall survival is a secondary outcome, and QoL is not measured. More details at clinicaltrials.gov.

Relapsed or refractory leukemia with a KMT2A-gene rearrangement (KMT2A-r). Children aged 1 month to younger than 6 years with this diagnosis may be able to join an open-label, nonrandomized, Children’s Oncology Group phase 2 study to determine the most tolerable and/or effective dose of an experimental oral drug called revumenib when added to chemotherapy.

KMT2A-gene alterations are associated with a poor prognosis in leukemia. These alterations cause blood cells to dedifferentiate and start proliferating uncontrollably as leukemia cells. The expression of the damaged KMT2A gene relies on a protein called menin. Revumenib, from Syndax Pharmaceuticals, blocks menin and prevents expression of KMT2A.

Children in the study will receive two different regimens of revumenib in combination with chemotherapy for up to a year, or until disease progression or unacceptable toxicity, and will then be followed for up to 5 years. Trial centers in 12 US states opened their doors in January 2024 looking for 78 participants. Toxicities and minimal residual disease are the primary outcomes; overall survival is a secondary outcome, and QoL is not assessed. More details at clinicaltrials.gov.

Previously untreated follicular lymphoma or diffuse large B-cell lymphoma. Adults with one of these types of lymphoma may be eligible for one of three open-label, randomized, phase 3 trials testing odronextamab (from Regeneron). This bispecific antibody is designed to ‘lock together’ CD20 on cancer cells with CD3-expressing cancer-killing T cells. It has shown anti-lymphoma activity in heavily pretreated patients.

Late in 2023, three phase 3 trials turned the spotlight on treatment-naive patients and started recruiting 2115 participants to assess odronextamab in this setting. The trial OLYMPIA-1 will compare odronextamab with standard-of-care rituximab (Rituxan) plus chemotherapy in follicular lymphoma. OLYMPIA-2 will test the drug in combination with chemotherapy, also in follicular lymphoma. OLYMPIA-3 will evaluate odronextamab plus chemotherapy against rituximab and chemotherapy in people with large B-cell lymphoma.

All study drugs, including odronextamab, will be administered by intravenous infusion, and participants will be followed for up to 5 years. Research centers across eight US states and Australia, Czechia, France, Italy, Poland, Spain, Turkey, and Thailand are currently accepting participants for the three trials. The primary outcomes are various measures of toxicity and complete response at 30 months in the follicular lymphoma studies and toxicity and progression-free survival in large B-cell lymphoma. All three trials are measuring overall survival and QoL as secondary endpoints.

Previously untreated stage II, III, or IV follicular lymphoma. Adults with this type of cancer may be eligible to participate in a randomized, open-label, phase 3 study testing whether an experimental therapy called epcoritamab (from AbbVie) improves disease response and is tolerable when added to standard therapy. For up to 120 weeks, one group of participants will receive a combination of intravenous rituximab and oral lenalidomide (Revlimid), while a second group will also receive subcutaneous injections of epcoritamab. Some participants may be offered investigators’ choice of chemotherapy as well.

Sites across Iowa, Maryland, Missouri, Ohio, Washington, and Montana started welcoming their 900 participants in February 2024. The primary outcome is complete response at 30 months. Overall survival and QoL are secondary outcomes. More details at clinicaltrials.gov.

Relapsed or refractory mantle cell lymphoma. Adults facing one of these clinical scenarios can join an Academic and Community Cancer Research United open label, phase 2 trial examining the effectiveness of combining tafasitamab (Monjuvi), lenalidomide, and venetoclax (Venclexta) for such patients.

Frontline therapy does not cure mantle cell lymphoma, and continued relapses are common. In this situation, treatments can include acalabrutinib, ibrutinib, stem cell transplantation, venetoclax, lenalidomide, and rituximab.

In this study, participants will take venetoclax and lenalidomide daily and receive intravenous tafasitamab every 2 weeks after an initial ramp-up period as per clinic standards. Participants will be followed for 5 years after entering the trial. The Mayo Clinic in Rochester, Minnesota, began recruiting the planned 100 trial participants in January 2024. The primary outcome is objective response rate; overall survival is a secondary outcome, and QoL will not be tracked. More details at clinicaltrials.gov.

All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .