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Immunotherapy with two novel drugs shows activity in colorectal cancer

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Newswise — BOSTON –A combination of two next-generation immunotherapy drugs has shown promising clinical activity in treating patients with refractory metastatic colorectal cancer, a disease which has not previously responded well to immunotherapies, according to a Dana-Farber Cancer Institute researcher.

The results of an expanded phase 1 trial of the two drugs, botensilimab and balstilimab, are to be presented at the ASCO Gastrointestinal Cancers Symposium Jan. 19-21 in San Francisco. The study is led by Benjamin L. Schlechter, MD, a senior physician in the Gastrointestinal Cancer Treatment Center at Dana-Farber.

The trial included 70 patients with metastatic colorectal cancer who had been previously treated with several lines of drugs, including immunotherapies. These patients all had tumors termed microsatellite stable, or MSS, meaning that their genes for repairing certain types of DNA damage were intact. MSS colorectal tumors account for the vast majority of colorectal cancers, and the first generation of immunotherapy drugs have had little effect on them. While immunotherapy has succeeded in microsatellite unstable (MSI) colorectal cancers, only about 3-5% advanced colorectal cancers are MSI and there are no approved immunotherapies for the far more common MSS colorectal cancers.

The two-drug combination being tested in the expanded phase 1a/1b trial of patients with metastatic MSS colorectal cancers were novel, next-generation antibodies. Botensilimab is an antibody directed against the T-cell receptor cytotoxic T-lymphocyte-associated antigen 4, or CTLA-4, which is an immune checkpoint that regulates T-cell activation. Balstilimab is a novel monoclonal antibody designed to block PD-1 – another immune checkpoint protein – from interacting with PD-L1 and PD-L2. By inhibiting this interaction, balstilimab is aimed at freeing the immune system to attack cancers.

The patients in the trial were followed for a median of 7 months after receiving the drug combination. During that period, 23% of the patients had a reduction in the size of their tumors, and the median duration of response was not reached. The disease control rate – the percentage of patients with metastatic cancer who had a complete or partial response and stable disease – was 76%. The 12-month overall survival was 63%. The main population of patients who benefited from the combination were those who did not have active metastatic cancer in their liver.

Treatment-related adverse events occurred in 91% of patients, including grade 3 in 40% and grade 4 in 3%. Twelve percent of patients discontinued both drugs because of adverse events.

The researchers concluded that “in patients with heavily pretreated metastatic MSS colorectal cancer, botensilimab plus balstilimab continues to demonstrate promising clinical activity with durable response, and was well tolerated, with no new immune-mediated safety signals.”

“Harnessing the power of immune therapy in refractory colorectal cancer has been a key goal of multiple clinical trials in advanced colorectal cancer, but in MSS colorectal cancer efforts have been universally disappointing,” said Schlechter. “These data are a meaningful and important advance in the care of this very sick population.” 

Based on these findings, a randomized phase 2 trial in patients with MSS colorectal cancer is currently enrolling.

Funding for this research comes from Agenus, Inc.

About Dana-Farber Cancer Institute 

Dana-Farber Cancer Institute is one of the world’s leading centers of cancer research and treatment. Dana-Farber’s mission is to reduce the burden of cancer through scientific inquiry, clinical care, education, community engagement, and advocacy. Dana-Farber is a federally designated Comprehensive Cancer Center and a teaching affiliate of Harvard Medical School.

We provide the latest treatments in cancer for adults through Dana-Farber Brigham Cancer Center and for children through Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Dana-Farber is the only hospital nationwide with a top 5 U.S. News & World Report Best Cancer Hospital ranking in both adult and pediatric care.

Source: Dana-Farber Cancer Institute 

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health and wellness

Breathe Better with Asthma, Wherever You Are

Identify and avoid asthma triggers to breathe easier and manage your symptoms.

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Manage asthma triggers for easier breathing.

(Family Features) If you have asthma, you know that symptoms can come on quickly, then worsen.

The things that make them do that are called triggers. An important part of managing asthma is knowing your triggers at home, work, school or while you’re outdoors.

A health care provider can help you figure that out, then you can take steps to avoid those triggers and breathe easier.

At Home
Because asthma is usually due to allergies, triggers are often allergens, or things that cause allergic reactions. Allergens such as pet dander, dust mites, pests and smoke can make asthma symptoms worse in some people, and for others, even trigger an asthma attack.  

The National Heart, Lung, and Blood Institute (NHLBI) suggests that it may be helpful to combine a few different strategies to help reduce exposure to triggers.

People sensitive to dust can clean with a high-efficiency particulate air (HEPA) filtration vacuum and use mattress and pillow covers that prevent exposure to dust mites. If you’re sensitive to pests like cockroaches and rodents, consider integrated pest management, which involves removing and controlling pests through methods such as traps or poison. Avoiding tobacco smoke, including secondhand smoke, can be especially helpful for some people with asthma.

At School
Asthma is one of the leading reasons children miss school. At school, kids may be exposed to dust mites, pests and mold, which may be asthma triggers for some children.

Because children spend lots of time at school, it can be helpful for teachers, school nurses or coaches to know what to do if your child’s symptoms flare up. Team up with a health care provider to develop an asthma action plan and share it with trusted adults at your child’s school.

At Work
The workplace can have hundreds of potential triggers, like chlorine-based cleaning products, bleaches, hair dyes and metal dust. Repeated exposures in the workplace can also lead to new triggers. Report new or worsening symptoms that occur at work to your health care provider and your workplace supervisor.

Outdoors
Everyday weather like cold, dry air can set off breathing problems. Air pollution can affect asthma, too.

It may be helpful to avoid some of the worst pollution by adjusting when and where you exercise. Try to avoid exercising near busy roads or industrial areas. Visit airnow.gov to check your local air quality so you can plan to avoid outdoor activities when pollution is highest.

Managing your triggers is just one part of keeping your asthma under control. Work with a health care provider to develop an asthma treatment plan that includes taking medicines as prescribed and keeping track of your symptoms and where you are when they occur. That way, you can know what’s making your asthma worse or better.

To learn more about asthma, visit NHLBI’s Learn More Breathe Better® program at nhlbi.nih.gov/BreatheBetter.

Photo courtesy of Shutterstock


SOURCE:
National Heart, Lung, and Blood Institute

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Child Health

4 Things Parents and Youth Athletes Should Know About Concussions

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(Family Features) Despite the attention drawn to the topic of concussions over the past decade, it can be difficult to find readily available answers about what parents and young athletes should do after sustaining a concussion.

The Katsuyama family started 2023 without a single concussion, even with quite a few hockey and lacrosse seasons under its belt. That changed when Rylan, 11, received two concussions within five months from sports. One week after Rylan’s second concussion, his brother, Brandon, 13, was illegally checked from behind in a hockey game and sustained his first concussion. After clearing protocol in four weeks, he suffered a second concussion six weeks later.

Both boys endured months of headaches, missed school, dizziness, nausea and the added difficulty of navigating a significant injury peers and adults couldn’t see.

Their father, Brad Katsuyama, co-founder of IEX – a disruptive stock exchange featured in the best-selling book by Michael Lewis, “Flash Boys: A Wall Street Revolt” – sought out expert opinions to guide his family’s decisions and shares some acquired knowledge to help parents and athletes.

1.      Brain injuries should be diagnosed by a concussion specialist.
There is no X-ray, MRI or CT scan that can show the extent of most concussion-related injuries, which makes diagnosing them subjective. Symptoms can also appear days after a hit. For example, Brandon was cleared by the emergency room after his first concussion, but two days later failed every test administered by a doctor specializing in concussions.

2.     Rushing back to play is one of the worst mistakes you can make.
Experts consistently reinforced that coming back from a concussion too soon can significantly increase long-term brain injury risks. There is likely no tournament, playoff game or tryout worth this risk. An example of how to return smartly is Patrice Bergeron of the National Hockey League’s Boston Bruins, who sat out an entire year to properly heal from a concussion.

“Patrice had four more concussions over his career, and each one was less severe than the last,” renowned concussion specialist Dr. Robert Cantu said. “That wouldn’t have happened without recovery from the first one.”

3.       Parents and kids need to be honest about symptoms.
The culture in youth sports praises toughness. Getting your “bell rung” and continuing to play can be viewed as a badge of honor. However, this same mentality can cause athletes to lie to parents, trainers and coaches to get back in the game, which can greatly increase long-term risks. Conversely, the same adults can unduly influence a potentially vulnerable player back on to the field of play. Proper diagnosis requires both adults and athletes to be level-headed and honest in their assessment of concussions.

4.    Every person and every concussion is different.
One person’s history and experience with concussions seldom carries any relevance to the concussions experienced by another. For example, Katsuyama played varsity football, hockey and rugby for four years in high school and football in college.

“For the longest time, my definition of a ‘real’ concussion was blacking out, vomiting or pupils dilating,” Katsuyama said. “My sons had none of those symptoms after their hits, but it turns out the severity of their injuries were far greater than anything I had experienced.”

The Katsuyamas turned to the Concussion Legacy Foundation and the Cantu Concussion Center, in addition to their local concussion specialist, to advise their path forward, which has led them to racquet sports and golf in the near-term and long-term playing no more than one contact sport in a school year. Learn more at concussionfoundation.org.

Photo courtesy of Shutterstock


SOURCE:
Brad Katsuyama

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health and wellness

A Genetic Connection to Kidney Disease

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How APOL1-mediated kidney disease can impact you, your kidneys and your family

(Family Features) A genetic condition that can cause kidney failure, APOL1-mediated kidney disease (AMKD) represents a group of kidney diseases associated with mutations (changes or variants) in the apolipoprotein L1 (APOL1) genes.

Typically, the APOL1 genes – of which every person has two, one from each parent – create proteins that play a role in immunity. However, some people are born with mutations in one or both genes, and having mutations in both can increase the risk of developing kidney disease and even kidney failure.

In honor of National AMKD Awareness Day on April 30, consider this information from the experts at the American Kidney Fund to better understand the disease and become APOL1 aware.

Understanding Risk Factors
Research shows Black people with kidney disease are more likely to develop kidney failure than any other racial or ethnic group. The reasons for these health disparities include social determinants of health, a higher burden of diabetes and high blood pressure in the Black community, barriers to health care access and genetics.

The APOL1 gene mutations evolved over the past 3,000-10,000 years in people who lived in western and central Africa and are associated with increased protection from a parasite carried by the tse tse fly that causes African sleeping sickness. While protecting from one disease, the mutation – if inherited in both APOL1 genes – is more likely to lead to kidney disease in those of certain African descent, including people who identify as Black, African American, Afro-Caribbean or Latina or Latino.

In fact, an estimated 13% of Black Americans have two APOL1 gene mutations, according to the American Kidney Fund. While not everyone who has two APOL1 mutations will get kidney disease, there is a 1 in 5 chance they will go on to develop AMKD.

Identifying Symptoms
If you have kidney damage, symptoms may not occur until your kidneys are close to failing. As kidney damage worsens, one or more of these symptoms may occur:

  • Protein in urine
  • Swelling in legs or weight gain
  • Feeling weak or tired
  • High blood pressure

Should these symptoms occur and you have a family history of kidney disease, talk to a doctor about getting tested for kidney disease, as testing is the only way to determine kidney function. AMKD can cause damage to parts of the kidney that filter blood or, in some cases, cause cells in the kidneys to die, which can lead to damage and scarring that may eventually lead to kidney failure.

Getting a Diagnosis
The only way to know if you have APOL1 gene mutations is to do genetic testing via a blood or saliva sample. Genetic testing may be considered if you have kidney disease and don’t know the cause or if you’re considering donating a kidney. Testing may also be considered if a family member is a carrier for the mutation. If you have questions about genetic testing, discuss your options with a doctor or ask for a referral to a genetic counselor.

Taking Steps to Prevent Kidney Disease
There are currently no treatments available for AMKD. However, there are steps you can take to protect your kidneys and promote general health. Work with your doctor to create a plan to prevent or delay the progression of kidney disease, which may include:

  • Doctor visits to check how your kidneys are working through urine and blood tests
  • Checking for and managing diabetes and high blood pressure
  • A healthy eating plan, which may involve limiting things like sodium (salt)
  • Taking prescription medications as directed
  • Being active at least 30 minutes each day of the week
  • Quitting smoking or using tobacco

If you have the APOL1 gene mutations, you may be able to take part in clinical trials. Trials could provide an opportunity for researchers to develop and test safe treatments for AMKD. Also speak with family members about having genetic testing done if you have the mutation as they may also have it.

Learn more and find additional resources at kidneyfund.org/APOL1aware.

Photo courtesy of Shutterstock


SOURCE:
American Kidney Fund

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