Can young children be too clean?
Before effective therapies were available, acute lymphoblastic leukemia (ALL), the most common form of leukemia in children, was almost universally fatal. While current treatments are successful in 90 percent of cases, they can have toxic and long-lasting side effects – so determining if prevention is possible is important. A major recent analysis of 30 years of ALL research in Nature Reviews Cancer proposes the answer is likely “yes.” The review suggests that ALL occurs as the result of a two-step process: first, a predisposing mutation occurs in the fetus, followed later in life by a second mutation triggered by an infection. While only one percent of children born with an ALL-related mutation go on to have the disease, those who do appear to have had little experience in early life with common infections such as the flu. This lack of immune “priming” is thought to make them more vulnerable to a genetic change following an infection later in childhood, triggering the disease. The theory, which fits with the “hygiene hypothesis,” suggests a key to prevention is “early exposure to dirt, germs and illness.”
The yearly conference of the American Society of Clinical Oncology (ASCO, estimated attendance 45,000 this year) wrapped up June 5. Among the gazillion new findings presented, here are some that dominated a good deal of the coverage:
- Merck’s immunotherapy drug, Keytruda® (pembrolizumab). Impressive Phase III data showed that, in patients with advanced squamous cell lung cancer, Keytruda + chemo resulted in a 40 percent reduction in progression and 36 percent reduction in risk of death compared to chemo alone. Another Merck Phase III trial showed patients with non-small cell lung cancer who started therapy with Keytruda lived four to eight months longer than those on standard chemo, and experienced less severe side effects.
- Loxo Oncology’s LOCO-292. In patients with cancers caused by a rare gene alteration called RET fusion, 77 percent achieved significant tumor shrinkage.
- Cancer blood test. Described in many news reports as the “holy grail of cancer research,” a new DNA-based blood test detected a number of different types of cancer much earlier than current methods, potentially allowing earlier treatment and greater chance for a cure (BTW, this is not related to the SEC’s major fraud case against Elizabeth Holmes/Theranos a few months ago). The test demonstrated detection sensitivities of 56-90 percent for colorectal, esophageal, head and neck, hepatobiliary, lung, lymphoma, multiple myeloma, ovarian and pancreatic cancers, but less than 10 percent sensitivity for low-gleason-score prostate, thyroid, uterine, melanoma and renal cancers.
- Genomic Health Oncotype Dx test. The validity of this test, used to determine if a woman with breast cancer needs chemotherapy, was confirmed in a randomized trial. Findings showed no change in survival for women the test identified as not needing and who did not receive chemotherapy.
- Bluebird’s CAR-T (chimeric antigen receptor T-cell) therapy increased progression-free survival in multiple myeloma by 11.8 months. CAR-T therapy involves individualized genetic modifications of a patient’s own T-cells, a complex process. While the results were impressive and many oncologists are enthusiastic about CAR-T therapy potential, concerns remain about its high costs and whether other, less expensive therapies can produce similar results.
- Chemo for pancreatic cancer. A randomized Phase III trial showed that, following surgical removal of pancreatic tumors, treatment with mFOLFIRINOX (a combination of four chemotherapies) extended overall survival and disease-free survival by an average of 20 and nine months, respectively, compared with the standard-of-care treatment, gemcitabine.
- Metformin – Yes, the generic drug used first line for most patients with type 2 diabetes. In a small trial (not industry sponsored) in 140 patients in Mexico, adding metformin to drugs for lung cancer with EGFR (epidermal growth factor receptor) mutations slowed disease progression and increased survival.
Possible common cold cure?
Despite our robust immune system, we fall victim to cold viruses because they have varying surface proteins. Developing immunity to one cold virus doesn’t transfer to the many others. Recently, British researchers reported positive findings of a potential, novel approach: Instead of targeting the virus, they developed a compound that inactivates an enzyme in human cells and that the viruses require for replication. In cell studies, they showed their compound, IMP-1088, successfully blocked cold viruses and some others, apparently without harming the human cells. And since the therapy doesn’t directly target the virus, chances of developing resistance are very low. Studies in animals are next and, if successful, then in humans. Ahchoo!
Eat, drink and be wary
About a year ago, MSM reported on a study about alcohol intake and cancer risk, noting that the relationship defied the often-cited “J-shaped” curve, which shows moderate drinking (no more than 1 drink/day for women, 2 for men) is associated with the lowest risk for total and cardiovascular death (the bottom of the “J”) compared to no intake (the higher, left side of the “J”) or high intakes (the much higher, right side of the “J”). Instead, for cancers of the breast and other organs, risk rose linearly from no to moderate to high intakes – there was no “J.”
Recently, a large and rigorous analysis of data from nearly 600,000 drinkers in Europe turned more conventional wisdom on its head, showing that the lowest risk of all-cause death was associated with about “one drink” per day or less, half the current U.S. Dietary Guidelines limit of two drinks per day for men. Compared to those who reported drinking about one drink per day or less, those who reported about 1-2, 2-3.5 and greater than 3.5 drinks per day had a reduced life expectancy at age 40 of about 6 months, 1–2 years and 4–5 years, respectively. Further, while overall cardiovascular disease (CVD) had a J-shaped curve, teasing out CVD subtypes showed it was driven by an inverse relation to heart attack (higher alcohol consumption = lower risk); the relationships with other coronary diseases, stroke, heart failure, hypertension and aortic aneurysm were all linear (higher alcohol consumption = greater risk). It will be interesting to see if these new findings prompt changes in future recommendations about drinking alcohol.
Sharing clinical trial data: what do participants think?
We are increasingly and broadly sharing and providing access to participant-level clinical trial data. While there are numerous scientific and ethical arguments favoring this trend, pharmaceutical sponsors and others have raised concerns, particularly about potential harm to research participants and breaches of their privacy. There is surprisingly little research on the views of participants themselves – until now. In the June 7 issue of NEJM, investigators reported results of a survey of 771 current and recent participants from diverse clinical trials, showing that few had strong concerns about data sharing risks, and most were willing to share their data for a wide variety of uses, provided adequate security safeguards were maintained.
All of Us
On a somewhat related topic, on May 6, NIH officially launched its “All of Us” Research Program, part of the Precision Medicine Initiative started in 2016. All of Us will gather data over many years from one million or more volunteering US adults 18 years and older, with the goal of accelerating research and improving health. Researchers will be able to use data from the program to learn more about how individual differences in lifestyle, environment, and biological makeup (including genetic profiles) can influence health and disease; and participants will be able to learn more about their own health. The first datasets are anticipated to be available in 2019.
Bill may require pharma companies disclose payments to patient advocacy groups
As reported in StatNews, Sen. Claire McCaskill (D-Mo.) has introduced a bill, “The Patient Advocacy Transparency Act,” intended to expand the Sunshine Act, which currently requires companies report physician payments to a federal database. If the new bill passes, reporting payments made to patient advocacy and medical professional groups also would be required.
Speaking of sunshine…while it’s well recognized exposure to the sun’s ultraviolet (UV) light can increase the risk for skin cancer, it also has benefits, such as increasing the synthesis of vitamin D and enhancing mood. Recent research reported in Cell suggests it may also improve learning and memory. While the researchers were examining neuron contents, they found an unexpected substance called urocanic acid, known to be produced on the skin in response to UV light, suggesting a “skin-brain connection.” Additional studies in mice showed that urocanic acid enhanced brain synthesis of the neurotransmitter glutamate, and was associated with improved learning and memory in standard tests. So this summer, be sure to use that sunscreen, but know that some sun exposure might make you smarter – at least, you may become more skilled at finding cheese!