Libtayo™

Libtayo™ (cemiplimab) was only approved as an immunotherapy for lung cancer in March 2021.  It had previously been marketed in the skin cancer setting, used for squamous cell and basal cell skin cancer.  Of course the vast majority of skin cancers do not require systemic treatment with chemotherapy or immunotherapy. Unfortunately some patients do develop progressive disease, or may have skin cancers in difficult locations to operate, such as around the eye.  Also some patients do not respond to topical treatment or radiation commonly used in recurrent skin cancer.  Here in Southern California we have warm sunshine most of the year, but that also leads to excess skin cancer cases, and occasionally these can become problematic to treat.

Many times dermatologists are not aware of treatment options such as systemic intravenous immunotherapy.

Both Libtayo™ and Keytruda™ are approved in the setting of recurrent or inoperable squamous cell skin cancer. Only libtayo™ is approved in basal cell cancer in the recurrent or unresectable setting.

There are several immunotherapy checkpoint inhibitors for lung cancer.  Libtayo™ is approved as a single agent for first line (“up front”) treatment for non-small cell lung cancer (NSCLC) that is metastatic or unresectable and that does not carry a “driver mutation” like ALK, EGFR, or ROS1.  Doctors also must check for PD-L1 expression of greater than 50% before offering treatment with libtayo™.

Keytruda™ has a firm advantage in the marketplace since it’s been approved for lung cancer since April 2019.  It’s also approved as a single agent for high-expressors of PD-L1 but also approved as a combination with chemotherapy for all non-squamous cell NSCLC, and also approved in many other types of cancer such as renal cell, melanoma, colorectal cancer, and several others.

Another immunotherapy combination, Opdivo™ and Yervoy™ are also approved in the setting of lung cancer, and this duo also makes an appearance in melanoma as well as renal cell carcinoma, liver cancer, and several other tumor types.  Opdivo™ is another checkpoint immunotherapy, but Yervoy™ is a CTLA-4 inhibitor

This is a crowded marketplace and perhaps libtayo™’s unique skin cancer story will help differentiate it from a crowded field of other similar treatments.

All of the checkpoint inhibitors carry warnings of adverse effects in the 10% range, so 90% of patients may not have major side effects.  This is probably less chance of toxicity compared to conventional chemotherapy and its usual side effects of hair loss, nausea, and weakness. The checkpoint inhibitor effects are thought of as the “itis” type of problems, such as hepatitis (liver inflammation), pneumonitis (lung inflammation), or dermatitis (rashes), among other possible organ systems.  Thankfully, these effects are fairly rare. Doctors need to watch patients closely while on these medications and periodically check lab testing.

New drug category shows promise, perils of treating anemia in chronic kidney disease

Doctors learned about a new treatment for anemia in clinical trials this week from the prestigious New England Journal of Medicine.  The medications are known as HIF prolyl hydroxylase inhibitors, and the one profiled this week is called vadadustat.  These medications are oral, and encourage the kidney to produce more of its own erythropoeitin, or EPO.  Right now, doctors are able to prescribe erythropoeitin treatments to treat anemia due to chronic kidney disease, including medications like Procrit® and Aranesp®.

These medications, called ESAs or erythopoeisis stimulating agents, work well for the treatment of anemia but have the drawback of only staying active in the human body for about a week before they “wear off,” so patients need to return weekly for ongoing injections.  Also, the ESAs are so far only injectable (a shot). These medications work by stimulating the bone marrow to produce more red cells.  The kidneys usually produce enough of this substance naturally, but when kidney function is reduced, erythropoetin levels can drop and this can lead to anemia.

The new class of agents, in this case vadudastat, was found to be no worse than the comparison medication, Aranesp®, in terms of effectiveness.  The problem is that they were a little more harmful in terms of cardiac toxicity.

The drawbacks of the ESAs is that they can lead to increased heart attacks and strokes, at least at higher doses.  Doctors have found that if the hemoglobin target is between 11.0 and 12.0, the ESAs are safe and do not lead to excessive risk.

The FDA has not approved a HIF prolyl hydroxylase inhibitor yet, though one is approved in Japan, China and Chile.  I suspect that the FDA may have some reservations about approving vadudastat or other members of the category, until researchers can show that these medications are at least as safe as our existing treatments.

What is IVIg

Some doctors will recommend treatment with “IVIg” or intravenous gamma globulin, for several different possible reasons.  IVIg is a collection of antibodies pooled from donors and then subjected to a detergent to make sure the solution is sterile and safe to administer.  The treatment is usually infused in a vein (that’s the “IV” part) or it can be infused under the skin.  The antibodies are also known as immunoglobulins, so that’s the “Ig” part.

The main indication or reason for giving IVIg is hypogammaglobulinemia.  Hypogammaglobulinemia or hypogamma, is a condition of low antibody production.  Some patients have hypogamma as a result of blood disorders like myeloma or CLL, while others may have hypogammaglobulinemia for no specific reason.  Doctors test for hypogammaglobulinemia using a test called IgG.  If the IgG level is low and the patient is prone to chronic or recurrent infections, especially dangerous infections like pneumonia, doctors may recommend treatment with IVIg.  These treatments may help prevent infections in people otherwise prone to them.

There are many other indications or reasons doctors may want to use IVIg.  The autoimmune diseases such as Kawasaki syndrome, CIDP or myasthenia gravis may be treated with IVIg.  The hematological disorders of ITP and hemolytic anemia are also treated sometimes with IVIg.  There are also a number of “off label” uses for IVIg that doctors may recommend for specific patients in particular situations.

If you need IVIg, you want to know you can trust your infusion center.  Ideally infusion centers use nurses trained and experienced in in-office infusions, use the best IVIg products, and have a doctor on site in case there are infusion reactions.  Rarely, patients can have allergic type reactions to their IVIg infusion and sometimes may experience headache or neck stiffness after an infusion.  These side effects usually pass within a day or so after an infusion.

Regatta Health doctors and nurses are experienced in giving IVIg infusions for many different indications.  We use tested and regulated products like Gammagard®, Hizentra®, Octagam®, Gamunex®, and Privigen®, among others. We value our relationship with Amerisource Bergen, our medication distributor for 8 years, and one of the largest distributors in the US. Check with your treating physician to see if a referral to our infusion center makes sense for you.

What is immunotherapy?

Immunotherapy to Treat Cancer

Immunotherapy is a type of cancer treatment that helps your immune system fight cancer. The immune system helps your body fight infections and other diseases. It is made up of white blood cells and organs and tissues of the lymph system.

Immunotherapy is a type of biological therapy. Biological therapy is a type of treatment that uses substances made from living organisms to treat cancer.

As part of its normal function, the immune system detects and destroys abnormal cells and most likely prevents or curbs the growth of many cancers. For instance, immune cells are sometimes found in and around tumors. These cells, called tumor-infiltrating lymphocytes or TILs, are a sign that the immune system is responding to the tumor. People whose tumors contain TILs often do better than people whose tumors don’t contain them.

Even though the immune system can prevent or slow cancer growth, cancer cells have ways to avoid destruction by the immune system. For example, cancer cells may:

  • Have genetic changes that make them less visible to the immune system.
  • Have proteins on their surface that turn off immune cells.
  • Change the normal cells around the tumor so they interfere with how the immune system responds to the cancer cells.

Immunotherapy helps the immune system to better act against cancer.

What are the types of immunotherapy?

Several types of immunotherapy are used to treat cancer. These include:

  • Immune checkpoint inhibitors, which are drugs that block immune checkpoints. These checkpoints are a normal part of the immune system and keep immune responses from being too strong. By blocking them, these drugs allow immune cells to respond more strongly to cancer. Learn more about immune checkpoint inhibitors.
  • T-cell transfer therapy, which is a treatment that boosts the natural ability of your T cells to fight cancer. In this treatment, immune cells are taken from your tumor. Those that are most active against your cancer are selected or changed in the lab to better attack your cancer cells, grown in large batches, and put back into your body through a needle in a vein. T-cell transfer therapy may also be called adoptive cell therapy, adoptive immunotherapy, or immune cell therapy.Learn more about T-cell transfer therapy.
  • Monoclonal antibodies, which are immune system proteins created in the lab that are designed to bind to specific targets on cancer cells. Some monoclonal antibodies mark cancer cells so that they will be better seen and destroyed by the immune system. Such monoclonal antibodies are a type of immunotherapy. Monoclonal antibodies may also be called therapeutic antibodies.Learn more about monoclonal antibodies.
  • Treatment vaccines, which work against cancer by boosting your immune system’s response to cancer cells. Treatment vaccines are different from the ones that help prevent disease.
  • Immune system modulators, which enhance the body’s immune response against cancer. Some of these agents affect specific parts of the immune system, whereas others affect the immune system in a more general way.
Which cancers are treated with immunotherapy?

Immunotherapy drugs have been approved to treat many types of cancer. However, immunotherapy is not yet as widely used as surgery, chemotherapy, or radiation therapy. To learn about whether immunotherapy may be used to treat your cancer, see the PDQ® adult cancer treatment summaries and childhood cancer treatment summaries.

What are the side effects of immunotherapy?

Immunotherapy can cause side effects, many of which happen when the immune system that has been revved-up to act against the cancer also acts against healthy cells and tissues in your body.

Learn more about immunotherapy side effects.

How is immunotherapy given?

Different forms of immunotherapy may be given in different ways. These include:

  • Intravenous (IV)
    The immunotherapy goes directly into a vein.
  • Oral
    The immunotherapy comes in pills or capsules that you swallow.
  • Topical
    The immunotherapy comes in a cream that you rub onto your skin. This type of immunotherapy can be used for very early skin cancer.
  • Intravesical
    The immunotherapy goes directly into the bladder.
Where do you go for immunotherapy?

You may receive immunotherapy in a doctor’s office, clinic, or outpatient unit in a hospital. Outpatient means you do not spend the night in the hospital.

How often do you receive immunotherapy?

How often and how long you receive immunotherapy depends on:

  • Your type of cancer and how advanced it is
  • The type of immunotherapy you get
  • How your body reacts to treatment

You may have treatment every day, week, or month. Some types of immunotherapy given in cycles. A cycle is a period of treatment followed by a period of rest. The rest period gives your body a chance to recover, respond to the immunotherapy, and build new healthy cells.

How can you tell if immunotherapy is working?

You will see your doctor often. He or she will give you physical exams and ask you how you feel. You will have medical tests, such as blood tests and different types of scans. These tests will measure the size of your tumor and look for changes in your blood work.

(cancer.gov content accessed 4/20/21)

What is targeted therapy?

What is targeted therapy?

Targeted therapy is the foundation of precision medicine. It is a type of cancer treatment that targets proteins that control how cancer cells grow, divide, and spread. As researchers learn more about the DNA changes and proteins that drive cancer, they are better able to design promising treatments that target these proteins.

What are the types of targeted therapy?

Most targeted therapies are either small-molecule drugs or monoclonal antibodies.

Small-molecule drugs are small enough to enter cells easily, so they are used for targets that are inside cells.

Monoclonal antibodies, also known as therapeutic antibodies, are proteins produced in the lab. These proteins are designed to attach to specific targets found on cancer cells. Some monoclonal antibodies mark cancer cells so that they will be better seen and destroyed by the immune system. Other monoclonal antibodies directly stop cancer cells from growing or cause them to self-destruct. Still others carry toxins to cancer cells.

Who is treated with targeted therapy?

Different types of cancer are treated differently. Some cancers are mostly treated with targeted therapy, while others are treated with mostly conventional chemotherapy.   In many cases, your tumor will need to be tested to see if it contains targets for which we have drugs.  Your doctor would like to tailor your cancer treatment to your particular kind of cancer and your particular targets, to get the best possible outcome for you and your family.  This is called individualized treatment, and it’s one of our guiding principles of practice here at Regatta Health.

To have your tumor tested for targets, you may need to have a biopsy. A biopsy is a procedure in which your doctor removes a piece of the tumor for testing. There are some risks to having a biopsy. These risks vary depending on the size of the tumor and where it is located. Your doctor will explain the risks of having a biopsy for your type of tumor.

Testing for targets for targeted therapy usually involves sending a biopsy sample to a lab.  Patients often ask if they have to go somewhere or have additional procedures to do targeted therapy testing, but often doctors are able to test the biopsy already taken to establish the cancer diagnosis.  This type of testing occurs “behind the scenes” often in labs that are in different parts of the country from the patient.  Examples of targeted therapy testing labs include Neogenomics, Quest Laboratories,

How does targeted therapy work against cancer?

Most types of targeted therapy help treat cancer by interfering with specific proteins that help tumors grow and spread throughout the body. They treat cancer in many ways. They can:

  • Help the immune system destroy cancer cells. One reason that cancer cells thrive is because they can hide from your immune system. Certain targeted therapies can mark cancer cells so it is easier for the immune system to find and destroy them. Other targeted therapies help boost your immune system to work better against cancer.
  • Stop cancer cells from growing. Healthy cells in your body usually divide to make new cells only when they receive strong signals to do so. These signals bind to proteins on the cell surface, telling the cells to divide. This process helps new cells form only as your body needs them. But, some cancer cells have changes in the proteins on their surface that tell them to divide whether or not signals are present. Some targeted therapies interfere with these proteins, preventing them from telling the cells to divide. This process helps slow cancer’s uncontrolled growth.
  • Stop signals that help form blood vessels. Tumors need to form new blood vessels to grow beyond a certain size. In a process called angiogenesis, these new blood vessels form in response to signals from the tumor. Some targeted therapies called angiogenesis inhibitors are designed to interfere with these signals to prevent a blood supply from forming. Without a blood supply, tumors stay small. Or, if a tumor already has a blood supply, these treatments can cause blood vessels to die, which causes the tumor to shrink. Learn more about Angiogenesis Inhibitors.
  • Deliver cell-killing substances to cancer cells. Some monoclonal antibodies are combined with toxins, chemotherapy drugs, and radiation. Once these monoclonal antibodies attach to targets on the surface of cancer cells, the cells take up the cell-killing substances, causing them to die. Cells that don’t have the target will not be harmed.
  • Cause cancer cell death. Healthy cells die in an orderly manner when they become damaged or are no longer needed. But, cancer cells have ways of avoiding this dying process. Some targeted therapies can cause cancer cells to go through this process of cell death.
  • Starve cancer of the hormones it needs to grow. Some breast and prostate cancers require certain hormones to grow. Hormone therapies are a type of targeted therapy that can work in two ways. Some hormone therapies prevent your body from making specific hormones. Others prevent the hormones from acting on your cells, including cancer cells.
Are there drawbacks to targeted therapy?

Targeted therapy does have some drawbacks. These include:

  • Cancer cells can become resistant to targeted therapy. For this reason, they may work best when used with other types of targeted therapy or with other cancer treatments, such as chemotherapy and radiation.
  • Drugs for some targets are hard to develop. Reasons include the target’s structure, the target’s function in the cell, or both.
What are the side effects of targeted therapy?

Targeted therapy can cause side effects. The side effects you may have depend on the type of targeted therapy you receive and how your body reacts to the therapy.

The most common side effects of targeted therapy include diarrhea and liver problems. Other side effects might include problems with blood clotting and wound healing, high blood pressure, fatigue, mouth sores, nail changes, the loss of hair color, and skin problems. Skin problems might include rash or dry skin. Very rarely, a hole might form through the wall of the esophagus, stomach, small intestine, large bowel, rectum, or gallbladder.

There are medicines for many of these side effects. These medicines may prevent the side effects from happening or treat them once they occur.

Most side effects of targeted therapy go away after treatment ends.

Learn more about side effects caused by cancer treatment and ways to manage them.

What are other risks of targeted therapy?

Since your tumor may be tested to find targets for treatment, there may be risks to the privacy of your personal information. The privacy of all information found from these tests is protected by law. But, there is a slight risk that genetic or other information from your health records may be obtained by people outside of the medical team.

What can I expect when having targeted therapy?

How is targeted therapy given?

Small-molecule drugs are pills or capsules that you can swallow.

Monoclonal antibodies are usually given through a needle in a blood vein.

Where do I go for targeted therapy?

Where you go for treatment depends on which drugs you are getting and how they are given. You may take targeted therapy at home. Or, you may receive targeted therapy in your doctor’s office.

How often will I receive targeted therapy?

How often and how long you receive targeted therapy depends on:

  • Your type of cancer and how advanced it is
  • The type of targeted therapy
  • How your body reacts to treatment

You may have treatment every day, every week, or every month. Some targeted therapies are given in cycles. A cycle is a period of treatment followed by a period of rest. The rest period gives your body a chance to recover and build new healthy cells.

How will targeted therapy affect me?

Targeted therapy affects people in different ways. How you feel depends on how healthy you are before treatment, your type of cancer, how advanced it is, the kind of targeted therapy you are getting, and the dose. Doctors and nurses cannot know for certain how you will feel during treatment.

How will I know whether targeted therapy is working?

While you are receiving targeted therapy, you will see your doctor often. He or she will give you physical exams and ask you how you feel. You will have medical tests, such as blood tests, x-rays, and different types of scans. These regular visits and tests will help the doctor know whether the treatment is working.

(Excerpted from https://cancer.gov 4/19/21)

Anemia treatments including procrit, retacrit and aranesp

Many adults experience symptoms of anemia including fatigue, daytime sleepiness, and lack of energy. Anemia is a condition of low blood hemoglobin.  Normal levels of hemoglobin are between 12.5 and 17.0.

Anemia can be a sign of more serious underlying problems.  The possible causes of anemia are broad and include blood loss, bleeding, iron deficiency, vitamin B12 and folate deficiencies, renal disease, hereditary anemias like thalassemia, hemolytic anemia, and cancer or blood disorders like leukemia.  Another blood disorder, known as MDS or myelodysplastic syndrome, accounts for some anemias as well but thankfully it’s rare.

Anemia should first be checked out by a physician and many patients are referred to hematologists to get a full workup for their anemia.  Often, simple causes are discovered like iron deficiency or renal disease.  Other times, more extensive workup will need to be done to discover the cause of anemia including scans or other procedures.

Many times, the aging process causes a reduced kidney function.  Scientists estimate that humans lose about 1 cc per minute of glomerlular filtration rate (GFR) per year of life.  The GFR is the rate at which the kidneys can filter blood to produce urine.

In addition to producing urine, the kidneys also produce a hormone known as EPO or erythropoeitin.  This hormone then goes to the bone marrow and stimulates the production of red cells.

With reduced kidney function can come reduced levels of EPO. Hematologists can replace reduced EPO levels with medication called ESAs or erythropoiesis stimulating agents.  Erythropoiesis is the process by which the body produces red cells.

These agents, including procrit® and aranesp® and also the newly-approved retacrit®, can help treat anemia due to reduced renal function.

Patients may have more than one cause for anemia so before starting on these medications, they should have a full workup to rule out other causes for anemia.

Many patients find that they have improved energy levels while taking medication like procrit®.  Symptoms like fatigue and lack of energy may respond within a week or so to treatment with ESAs.

Medicare guidelines indicate that patients may only start treatment with ESAs in the setting of renal disease for a hemoglobin less than 10.0 and may only continue treatment when their hemoglobin is less than 12.0.

Side effects of ESAs include thickening of the blood and even strokes if the treatment is targeted to hemoglobins above 12.5.  Ideally treatments with ESAs would target a hemoglobin between 11 and 12.  Blood pressure can also rise with ESA treatment and this should be tracked by your treating doctor.

Hemoglobin is the protein in the red cell that gives it the red color.  It is a pigmented molecule that carries oxygen.  Doctors can directly measure hemoglobin in the blood by using a laser and  a detector to determine the red color of the blood in the lab.

You may also hear about hematocrit and that could be low in the setting of anemia as well. Hematocrit is the percent of blood that is red cells (as opposed to water, called plasma).  Usually hematocrit and hemoglobin are related to each other by a factor of 3:1.

Your doctors at Regatta Health are able to instantly check the hemoglobin when you visit the office using FDA-approved technology. If your hemoglobin is low, they may suggest a workup to determine the reasons why, and they may suggest treatment with medication like procrit.  Treatment with procrit or other ESAs is usually covered by insurance if treatment guidelines are followed.

Bleeding disorder diagnosis and treatment

Bleeding disorders can be confusing to patients  and families and can be tricky to diagnose and treat. At Regatta Health, we have the expertise and experience to diagnose and treat multiple types of bleeding disorders.  Bleeding disorders, where the blood is too thin, can lead to significant bleeding either during or after an invasive procedure, or at any time.

Across all patients, von Willebrand’s Disease (vWD) is the most common diagnosed bleeding disorder. It can manifest with bleeding symptoms like nosebleeds, bleeding around the time of surgery, gum bleeding with tooth extraction, or heavy menstrual periods.  Lab testing can show a prolonged PTT clotting time.  Specialized testing can reveal a vWD diagnosis.  Treatments may include a nasal inhaler called ddAVP, or replacement with clotting factors like Humate-P® or Vonvendi®.

Occasionally we do also find clotting factor deficiencies, known as hemophilia.  Factor VIII (8) deficiency is the most common and actual cases are only seen in males.  There are many other hemophilias besides Factor VIII hemophilia (Hemophilia A) but thankfully these are rare.  Current guidelines include prophylactic treatment to prevent bleeding problems.

Many patients are referred for a prolonged PTT (partial thromboplastin) or PT (prothrombin time) on lab testing prior to a procedure.  Many surgeons and other doctors routinely order these clotting times to “clear” a patient for surgery. Usually abnormal clotting results do not reflect a real problem with blood clotting, but they usually require a workup in the office to rule out any kind of underlying blood disease and to assess the risk of surgery or other procedures.

Antibodies like antiphospholipid antibodies can also cause prolonged clotting times.  This is known as “Hughes’ Syndrome” and can cause thickening of the blood.

The key to evaluating a suspected bleeding disorder is a careful history from the patient and then evaluation of the prior lab tests and planning a set of lab tests to work up the potential problem.  Ideally this evaluation happens well before any planned procedure to reduce any delay to a procedure if it becomes more urgent.  Sometimes we have to do testing while the patient is planning to have a procedure soon, so we try to proceed with due caution while trying to get the answer ASAP.

As board-certified hematologists, Dr. Benjamin and Dr. Melkonian are able to evaluate your potential bleeding disorder and recommend the right testing program to make an accurate and rapid diagnosis. They have treated many patients with hemophilia, von Willebrand’s Disease, and other bleeding disorders. Making a rapid diagnosis could improve the safety of procedures you might be planning, or reduce the risk of bleeding during your daily routine.