CAR T Cells as “Living Drugs”

“Incredibly exciting” is how experts are describing the new development with chimeric antigen receptor (CAR) T cells, as the first of these novel therapies approaches the market.

“Living Drugs”

The treatment product is made individually for each patient. After blood is taken from the patient, it undergoes a process that involves extracting immune system T cells, subjecting the cells to CAR cell engineering, and then infusing the engineered T cells back into the patient. The engineering changes the T cell in two ways. First, it adds a receptor that targets the CD19 antigen that is found on most leukemia cells. When the cells are returned to the patient’s body, they home in on this antigen, latch on, and destroy the leukemia cell. Second, the process inserts a viral vector mechanism into the cells that, once the cells have latched onto the leukemia cell, triggers these T cells to expand and proliferate, so that they seek out and destroy all the remaining leukemia cells.

Because they grow and expand in the body and then lie dormant, CAR T cells have been described as “living drugs.” It is not clear whether CAR T cells will also last a lifetime or whether will they gradually disappear over decades. It is also not clear how long immunosurveillance may be needed, he said. While policing the blood, these cells wipe out any leukemia B cells that may reappear, but there can be a downside. In some patients, this has also led to depletion of healthy B cells, a condition known as known as B cell aplasia. “This is not a major problem, at least not so far,” commented one expert, because this deficiency can be corrected by giving immunoglobulin supplements, in some cases long-term.

The worst of the side effects occur within a week or two of infusion, when the cells are expanding and attacking the leukemia. Some of the side effects can be very severe, even life-threatening. The two most concerning side effects are cytokine release syndrome, which was severe in about half of the patients in the pivotal trial, and neurologic toxicity, which developed in nearly half of the patients (44%). Because there can be severe side effects, patient care needs to be overseen by clinicians with experience in this field, and suitable facilities are required. Patients may need to be treated in the intensive care unit, for example, and some patients may need to undergo intubation.

Having industry involvement has streamlined a complicated production process and has shortened the manufacturing time. Whereas patients at the beginning of the clinical trial needed to wait 44 days between giving blood and undergoing CAR T-cell infusion, the process now takes only 22 days from “vein to vein,” the drug company Novartis reports. For the future, there is hope that it may be possible to make “off the shelf” products that would require no waiting time. There is also work underway to incorporate a “genetic switch” into the CAR T cell, which would make it possible to “turn off” the therapy by taking another drug. This could be useful when side effects become very severe, he suggested.

There is a tremendous amount of work ongoing involving other blood cancers, all of which appear suitable to this approach. There is also hope that the therapy could be made to work against solid tumors. This first product that is heading to market is just the tip of the iceberg. I’m Dr. Michael Hunter. Medscape did a great job reporting it, and I thought I’d share this news with you.

Reference: http://www.medscape.com/viewarticle/882968#vp_3

 

New app for Android: My Breast Cancer by Dr. Michael Hunter

 

Remarkable Breakthrough for Metastatic Breast Cancer?

What You Need to Know: Got HER2 positive cancer that is metastatic? Final results from the CLEOPATRA study show that the combination of two targeted agents (with chemotherapy) significantly improves survival, compared to Herceptin (trastazumab) alone. This may be the biggest breakthrough ever for metastatic breast cancer, but only applies to those whose tumors overexpress HER2.

Background: HER2/neu (human epidermal growth factor receptor 2), also called ErbB2, is a protein that appears on the surface of some breast cancer cells. This protein is an important part of the pathway for cell growth and survival.

  • HER2/neu-positive (HER2+) breast cancers have a lot of HER2/neu protein.
  • HER2/neu-negative (HER2-) breast cancers have little or no HER2/neu protein.
  • About 15 to 20 percent of all breast cancers are HER2+ (you also may hear the term “HER2 over-expression”). HER2 status helps guide treatment.
  • HER2+ breast cancers can benefit from anti-HER2/neu drugs, such as the drug trastuzumab (Herceptin), which directly target the HER2/neu receptor. Trastuzumab and other anti-HER2/neu targeted therapies are not used for HER2- cancers.

– See more at: http://ww5.komen.org/BreastCancer/TumorCharacteristics.html#sthash.VebNtup0.dpuf

What We Just Learned: Final results from the CLEOPATRA study show that the combination of 2 targeted agents, trastuzumab (Herceptin, Roche/Genentech) and pertuzumab (Perjeta, Roche/Genentech), significantly prolonged survival in HER2-positive metastatic breast cancer, compared with trastuzumab alone. The targeted agents were added to chemotherapy with docetaxel.

Patients with metastatic breast cancer treated with the combination of Herceptin and Perjeta plus chemotherapy lived 15.7 months longer than those who received trastuzumab and chemotherapy (median overall survival, 56.5 vs. 40.8 months; hazard ratio [HR], 0.68; P = .0002).

“I think these results are phenomenal,” said Dr. Swain, who spoke during a press briefing here at the European Society for Medical Oncology (ESMO) Congress 2014. “We all believe that the 56.5-month median overall survival is unprecedented in this indication and confirms that the pertuzumab plus trastuzumab regimen is a first-line therapy for patients with HER2-positive metastatic breast cancer.”

She noted that the median survival with trastuzumab is already very good, at 40.8 months. “That already changed things for patients with HER2-positive breast cancer, but adding pertuzumab has increased that by 15.7 months,” Dr. Swain continued.    “I’ve never seen that in any other trial of metastatic breast cancer,” she said, noting that she has worked in the field for 30 years.

These final results add another 20 months of follow-up to the last presentation of the data, Dr. Swain said. The new results include an updated progression-free survival analysis, which was 18.7 months, an improvement of 6.3 months, compared with a median of 12.4 months with trastuzumab and chemotherapy alone. “This is also very good,” she said. “For those who are looking at different end points in this blinded study, progression-free survival was a good surrogate end point for overall survival.”

“We should consider this combination as the standard of care for our patients,” coauthor Javier Cortés, MD, director of the breast cancer program at Vall d’Hebron Institute of Oncology in Barcelona, Spain, said in a statement. “I can see no reason to justify the use of trastuzumab without pertuzumab.”

“What is more surprising is that the improvement in median overall survival exceeds the improvement in progression-free survival, maybe because of the different mechanisms of action that monoclonal antibodies have,” he explained.

My Take: This study is a peek into the future for most cancers: Cancer cells are driven by a particular pathway (in this case in the HER2 overexpression track), and we are at the very beginning of learning to target them. Kudos to Dennis Slayman, MD for kicking open the HER2 door. We need more such breakthroughs by stubborn courageous big thinkers. Want to hear the thrilling story of the development of the breakthrough drug Herceptin (trastazumab)? Head to amazon.com (http://www.amazon.com/Her-2-Making-Herceptin-Revolutionary-Treatment/dp/0812991842), or better yet, order from your local bookseller. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

References:

Combating Chemobrain: Keeping Your Memory Sharp

I recently ran across this helpful article in Chemotherapy Advisor, and want to share it with you. 

Background: Many people going through cancer treatment notice changes in their memory and thinking abilities. Coping with symptoms of chemobrain involves finding ways to help you remember things better, and doing activities that keep your memory sharp.

Here are some tips for combating chemobrain:

  • Make lists. Carry a pad with you and write down the things you need to do. For example, keep lists of things to buy, errands to run, phone calls to return, and even the times you need to take your medicines. Cross items off as you finish them.
  • Use a portable planner or personal organizer. These can help you stay on top of day-to-day tasks and keep track of appointments and special days like birthdays and anniversaries. Paper and electronic versions are available.
  • Get a wall calendar. For some people, this works better than a portable planner because you can hang it up in a place that is easy for you to see every day. Put it on your refrigerator or even on your bathroom mirror so you’ll be sure to look at it several times a day.
  • Keep a notebook. For many people, a simple, ruled notebook works just as well as a planner. Use one to record everything you need to remember, such as:
    • to-do lists
    • the dates, times and addresses for appointments
    • your medication schedule
    • important telephone numbers
    • the names of people you meet and a brief description of who they are.
    • You can also use your “memory notebook” as a journal to track chemobrain symptoms or other side effects, or to write down questions to ask your doctor at your next appointment.
  • Leave a message on your voicemail to remind yourself of something important. When you listen to the message later, write down the information so you don’t forget it.
  • Organize your environment. Keep things in familiar places so you’ll remember where you put them.
  • Avoid distractions. Work, read, and do your thinking in an uncluttered, peaceful environment. This can help you stay focused for longer periods of time.
  • Have conversations in quiet places. This minimizes distractions and lets you concentrate better on what the other person is saying.
  • Repeat information aloud after someone gives it to you, and write down the important points. For example, before you write down an appointment, you might say, “Okay, so we’re meeting at 2:00 p.m., Monday, June 3rd, at 503 Main Street.”
  • Keep your mind active. Do crossword puzzles and word games, or go to a lecture on a subject that interests you.
  • Proofread. Double-check the things you write to make sure you’ve used the right words and spelling.
  • Train yourself to focus. We often do one thing while thinking about another, which increases our chances of forgetting something important. For example, if you keep misplacing your keys, take extra time to think about or picture what you’re doing every time you put them down. Also, say aloud to yourself, “I’m putting my keys on my dresser.” Then look at them again, and repeat: “The keys are on my dresser.” Auditory (hearing) cues give your memory an extra boost.
  • Exercise, eat well and get plenty of rest and sleep. Research shows that these things help keep your memory working at its best.
  • Tell your loved ones what you’re going through. Depending on how private a person you are, you might tell your family and friends, so that they’ll understand if you forget things you normally wouldn’t forget. They may be able to help and encourage you.
  • Speak with an oncology social worker. If living with symptoms of chemobrain makes you anxious or sad, seek help. Oncology social workers, such as those at CancerCare, can work with you to help you find ways to cope.

I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: http://www.chemotherapyadvisor.com/combating-chemobrain-keeping-your-memory-sharp/article/355759/?DCMP=ILC_CTA_patientfactsheet62614&CPN=&spMailingID=8893805&spUserID=MTEzNTY2NDIzNjk0S0&spJobID=322187237&spReportId=MzIyMTg3MjM3S0.

Chemotherapy and Neuropathy: What Can You Do?

American Society of Clinical Oncology Clinical Practice Guidelines

Bald woman chemotherapy patient white woman

What You Need to Know: Although the chemotherapy–induced peripheral neuropathies (CIPN) trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPN treatment options.

The Study: A systematic literature search identified relevant, randomized controlled trials (RCTs) for the treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life.

Details:

  • A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations.
  • Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes.
  • Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points.
  • The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms.

I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: Journal of Clinical Oncology, 18 April 2014

Chemotherapy for Breast Cancer and Aging

 woman white with wrinkles

What You Need to Know: Adjuvant chemotherapy for breast cancer is gerontogenic, defined as accelerating the pace of physiologic aging, a new study reported.

Background: Loss of organ function, characterized by an increase in cellular senescence, is one physiological part of aging. Markers of cellular senescence have been identified as leukocyte telomere length, expression of senescence-associated cytokines including interleukin-6, and expression of p16INK4a, and ARF in peripheral blood T lymphocytes (PBTLs).

The authors previously showed p16INK4a is a marker of accelerated molecular age in PBTLs associated with smoking, physical inactivity, and chronic human immunodeficiency virus infection. To date, reports have not explored how long-term effect of cytotoxic chemotherapy given with curative intent affects molecular aging.

The Study: Hanna K. Sanoff, MD, Norman E. Sharpless, MD, and Hyman B. Muss, MD, of the Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina, and their colleagues prospectively collected blood and clinical data from 33 women with stage I-III breast cancer before, immediately after, 3 months after, and 12 months after anthracycline-based chemotherapy. Blood was analyzed for markers of cellular senescence.

The Evidence: They observed increased expression of the senescence markers p16INK4a and ARF in PBLTs immediately after chemotherapy, and these remained elevated for at least 1 year after treatment. In an independent cohort of 176 breast cancer survivors, prior chemotherapy was associated with a persistent increase in p16INK4a at an average of 3.4 years after treatment. These results suggest the age-promoting effects of chemotherapy last for several years after treatment and may be permanent.

The authors concluded, “We have shown that cytotoxic chemotherapy potently induces the expression of markers of cellular senescence in the hematologic compartment in vivo, comparable with the effects of 10 to 15 years of chronologic aging in independent cohorts of healthy donors.” Further studies are underway.

I’m Dr. Michael Hunter, and I do wonder how much of this aging can be “undone” with physical activity such as exercise.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: Journal of the National Cancer Institute (2014; doi:10.1093/jnci/dju057).

Okay to Boost Aerobic Activity During Breast Cancer Chemotherapy

young woman running city park

For highly motivated women with breast cancer, exercising at levels higher than currently recommended during chemotherapy (up to 3 hours, 3 times weekly) is safe and will not interfere with the completion of chemotherapy or exacerbate symptoms, a new study suggests. In fact, this regimen could help women keep fit during chemotherapy and better manage their symptoms.

The Study: Within 1 to 2 weeks of starting chemotherapy and until 3 to 4 weeks afterward, the women performed 1 of 3 exercise regimens 3 times a week. Those in the standard-dose group (n = 96) performed 25 to 30 minutes of aerobic exercise, those in the high-dose group (n = 101) performed 50 to 60 minutes of aerobic exercise, and those in the combination group (n = 104) performed 50 to 60 minutes of aerobic exercise plus resistance exercise.

This study suggests that clinicians can recommend “higher volumes of exercise to breast cancer patients without concerns for adverse effects, provided the exercise is supervised by a qualified exercise specialist,” said lead author Kerry S. Courneya, PhD, professor and Canada research chair in physical activity and cancer at the University of Alberta in Edmonton.

Adding more aerobic exercise, as opposed to strength training, might be best. However, a critic counters:

“It didn’t seem to make a huge difference whether you were exceeding the recommendations or sticking with what is recommended, and it didn’t show a whole lot of benefit for doing strength training in addition to aerobic activity,” Dr. Ligibel told Medscape Medical News.

The Bottom Line: Check with your care providers to see if you can exercise, either vigorously or less vigorously. You may reduce fatigue, and lower your chances of heart attack, stroke, other cancers, and dementia. We are getting more and more data suggesting significant benefits associated with exercise, even if it is simply walking for 30 minutes, 5 days per week. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Lymphedema: Estimating the Risk for Patients with Breast Cancer

Breast cancer awareness
Breast cancer awareness (Photo credit: AslanMedia)

The development of breast cancer-related lymphedema is tied closely to how many nodes are removed by surgery. Radiation therapy and chemotherapy can also increase risk. A recent study from Korea (published in (check out the length of the this name!) International Journal of Radiation Oncology Biology Physics, 2013) attempted to estimate the risk of lympededema based on combinations of these treatment factors.

The Study: The authors looked at 772 patients with breast cancer. All had primary surgery with axillary node dissection from 2004 to 2009. The study looked back at these patients (retrospective analysis). Adjuvant chemotherapy was given to 677 patients. Of the 675 who got radiation therapy, 35% had a component directed at the nodes above the collarbone (supraclavicular nodes).

Results: Half of patients were followed beyond 5.1 years. The 5 year cumulative chance of getting edema was 17%. Of these 76% developed it in the first 2 years after surgery. Fully 91% of those who got it did so within 3 years.

Risk factors included number of nodes removed by the surgeon, chemotherapy use, and whether the nodes above the collarbone were treated with radiation therapy. The total number of risk factors correlated well with the incidence of lymphedema. Patients with 0 to 1 risk factors had a 5 year risk of only 3%, while those with 2 or 3 risk factors had a risk of 19% and 38%, respectively.

My take: The bad news? Any lymph node removal introduces risk. The good news? If a patient had 10 of fewer nodes removed, and no other risk factors, the 5 year risk dropped to 1.4%. For those who had fewer than 10 nodes removed but got chemotherapy, the risk was 3.8%. Fortunately today, many patients who have a limited node sampling of only 1 to 3 nodes (to help establish prognosis for invasive breast cancer) have a very low risk of significant lymphedema. The so-called sentinel node procedure has truly improved the surgical management for many patients with early breast cancer. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minutes. Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. All can be found at the Apple Ibooks store. Thank you.