TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.
This week’s topics include a look at diabetes nationally, a new treatment for celiac disease, a way forward with the most severe form of amyloidosis, and a blood test for multiple cancers.
program notes:
1:53 Plus antibody 53% response
2:50 Side effects similar between two groups
3:25 A blood test for cancer
4:25 Specificity of 99%+
5:25 Better at solid tumors
7:02 Antibodies to an enzyme
8:03 Gluten-free diet
9:01 Trends in prevalence of diabetes
10:03 Maybe even higher now
11:05 Two out of three factors weren’t controlled
12:02 End
Transcript:
Elizabeth Tracey: Is a cancer blood test coming to fruition?
Rick Lange, MD: A new treatment for celiac disease.
Elizabeth: What’s the status of diabetes nationally?
Rick: And can we treat amyloid associated with immunoglobulin?
Elizabeth: That’s what we’re talking about this week on TT HealthWatch, your weekly looking at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore based medical journalist.
Rick: I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I’m also dean of the Paul L. Foster School of Medicine.
Elizabeth: And let’s just note, just opened up a new dental school so that’s so impressive. Congratulations.
Rick: The first one in Texas in 50 years and only one of 67 in the United States. It’s a great day.
Elizabeth: Rick, in honor of that, which one of these would you like to start with?
Rick: Let’s start with the one that may be most obscure to many of our listeners, that’s this disease or entity called amyloidosis. What happens is people will begin to produce immunoglobulin, a particular type called light chain. It’s a very lethal form of amyloidosis and this light chain — it’s a misfolded protein causing amyloid protein. It gets deposited in kidneys and it gets deposited in the heart. These cells that produce the immunoglobulin are called plasma cells and these plasma cells are also very active in a disease called multiple myeloma, a type of cancer of the bone marrow. Now there are typical chemotherapeutic agents that are used to treat multiple myeloma and they are somewhat effective for amyloid, but not entirely.
So this is a new type of drug. This is an antibody, daratumumab, and this is an antibody that binds to a protein that’s on the plasma cell, called the CD38 protein. They took almost 400 individuals that had amyloidosis affecting their kidneys and their heart and they randomized them to routine chemotherapy or routine chemotherapy plus this antibody.
Routine chemotherapy, the response was 18%. When they added this antibody, it increased to 53%. By the way, at 6 months, when they looked at the cardiac and renal responses, more individuals that received the antibody responded with an improvement in their heart and kidney function than those that received routine chemotherapy.
This is an antibody that is injected subcutaneously. What we need to know is, does it improve long-term survival? So we need longer studies, but at least these end points are very encouraging.
Elizabeth: Well, having borne witness sadly to people with this condition who ultimately die of it, I’m happy to hear that there is an agent that might actually have an impact. What were the side effects of using it?
Rick: The major side effects were low white count, pneumonia, cardiac failure, and diarrhea. Now how much of those were due to the drugs and how much of those were due to the disease is very difficult to ascertain. In fact, when you compare the two groups, chemotherapy versus chemotherapy with daratumumab, the side effects were very similar between the two groups.
Elizabeth: Can we talk just for a moment about amyloidosis, just kind of in general? I was unaware previous to this article that there were several different types of it because it seems a lot more common than I think I ever knew.
Rick: There are… and again, this is one of the most lethal forms. There are other types of conditions that also cause amyloid protein to be deposited in the brain or central nervous system, in the heart, in the kidney, and in the intestines as well.
Elizabeth: Let’s just mention, of course, this is in the New England Journal of Medicine. And since we’re geeking out, why don’t we turn to Annals of Oncology? This is another study that I think is really gratifying. The search has been on for several years now to develop a blood test for cancer. We know that cancer cells are happily breaking up and shedding their DNA into the bloodstream, and so the promise of that has been tantalizing and there have been many groups who have been looking at it.
This is actually the third stage of a study that was undertaken by a multi-center group. It is called the Circulating Cell-Free Genome Atlas Study. As I said, this is the third iteration of this where they are trying to look at this clinically.
In this aspect of the study, they had 4,077 participants, 2,823 of whom had cancer and 1,254 who did not have cancer. That was confirmed at 1 year of follow-up. They were looking for this array, in fact, 12 different cancer types in a blood sample, and they were able to achieve a specificity — very impressive — of 99.5%. However, the sensitivity was only 51.5%.
The sensitivity unsurprisingly increased as the cancer progressed. As people went from stage 1 to stage 3, they had this progression and finally in stage 4 they had a sensitivity of 90.1%. So that’s pretty good, but we don’t really want to be waiting until people are stage 4 — and that is totally contrary to the promise of these tests — in order to achieve that kind of sensitivity.
Rick: You’re right. People would like a single blood test to be able to detect cancer in its early stages. And as you noted, this particular test, at least in its current iteration, is probably not that test. The sensitivity was less than 20% for picking up cancer in stage 1, which is the earliest form, which is putatively the most treatable form.
It also depends upon which type of cancer they were looking at. For example, it was better at looking at solid tumors and less able to find hematologic malignancies. It does not assess its value as a screening test. They recommend in this study that it’s not meant to replace routine screening tests we already do. It’s interesting, but there is still a lot we need to find out before we can determine whether this is actually good at predicting cancer.
Elizabeth: Still bringing it closer to fruition and I’m going to guess that we’re going to be talking about a practical test here, I’m guessing, in the next couple years. Will you take that bet?
Rick: I bet we’re not. I bet it’s still in its infancy and we are not able to detect early cancer.
Elizabeth: Okay. We’ve got a bet on then. Returning to the New England Journal of Medicine.
Rick: Elizabeth, let’s talk about celiac disease. This is a condition that affects up to 2% of the population in most countries, characterized by inflammation of the small intestine. It’s driven by people that ingest gluten, which is found in wheat and related grains, and they are genetically predisposed.
The symptoms associated with celiac disease include intestinal issues, but also includes fatigue and anemia, osteoporosis, and even autoimmune diseases. Now, the current treatment is just to avoid gluten, but that’s difficult to do. Even in those that do avoid gluten, their intestine oftentimes doesn’t recover. In fact, you can see inflammation in the intestine even when they avoid eating for 50% of individuals.
This is a study of what’s called a transglutaminase inhibitor. What the transglutaminase does is it takes the gluten, it changes it, that makes the gluten more presentable to cells that cause inflammation. So antibodies to transglutaminase are characteristic of celiac disease.
What this particular oral medication does is it inhibits that enzyme so the enzyme doesn’t break down the gluten, the gluten doesn’t attach to the cells, and in theory it could cause decreased inflammation.
They took approximately 120 patients. This was a dosing study. These are all people that had celiac disease. They gave them increasing doses of the inhibitor — it’s an oral medication — and then gave them 3 grams of gluten at the same time. Then they looked inside their intestine and what they found is that there was a marked decrease in the typical findings associated with celiac disease in individuals that got the inhibitor.
Benefits? Decreased inflammation, decreased inflammatory cells, and an improvement in their symptoms as well while still taking gluten. This is the first treatment we’ve had available aside from just avoiding gluten in your diet.
Elizabeth: Of course, this issue of celiac disease has been one that was brought to the fore, many people claiming that they have gluten sensitivities and trying to achieve a gluten-free diet. What are your thoughts about the applicability, the wide-ranging applicability, of this particular treatment?
Rick: People that have true celiac disease, you can demonstrate that by taking biopsies of the intestine to demonstrate there are changes in the intestinal architecture and also inflammatory cells. That’s exactly what these individuals had. Whether this will be beneficial in people who have gluten sensitivity is completely unknown at this time.
Elizabeth: Right, I just wonder. It seems like when there is something that’s made available that ostensibly treats a particular condition, lots of people jump on the bandwagon and want to try it.
Rick: I would reserve this in particular for those individuals who have honest to goodness celiac disease. It’s not approved by the FDA, so there is still more to be done. This is just 120 patients. For proof of concept, in terms of using an inhibitor to transglutaminase 2, pretty novel.
Elizabeth: We’ll see more. Let’s turn now to JAMA and to our giant public health issue, which is the trends in prevalence of diabetes. This study takes a look at how well are folks controlling risk factors in diabetes among U.S. adults — over essentially 20 years of data here.
They use the NHANES, National Health and Nutrition Examination Survey. Their total number of people who were included in this were 28,143. They looked at three risk factor goals: their individualized hemoglobin A1c targets, their blood pressure less than 130/80, and LDL less than 100 milligrams per deciliter. They said, well, how prevalent was diabetes way back when? What’s going on with it now? Then how well are people really controlling these three risk factors?
The bad news is that not only did diabetes prevalence increase a lot over that particular time, from 9.8% lo these many years ago, to 14.3% in the latest year 2017-2018, for which it was analyzed. I’m betting would be even a little bit higher now. Also part of the bad news, only 21.2% of these adults had achieved goals for all three of those risk factors: the hemoglobin A1c, their blood pressure, and their LDL cholesterol.
Rick: Now why this is important is because diabetes predisposes people to develop cardiovascular disease, strokes, kidney disease, and heart attacks, and other risk factors contributed to that. You’ve mentioned some of those already — that is poorly controlled diabetes, elevated cholesterol, and elevated blood pressure. You want to control all three of those.Well, the fact that only one in five individuals did that successfully is really disconcerting.
Interestingly enough, the one that improved the best was controlling your cholesterol. That’s because we now have effective medications to do that. The other two require lifestyle changes to get your hemoglobin A1c down. Not only do you have to be on the right medications, but you have to control your diet. We didn’t do a very good job of that.
Controlling blood pressure, that’s also medications and lifestyle changes as well. The fact that that didn’t get any better over the last 20 years is also concerning. So unfortunately, I think we are a society that likes to take medications and really doesn’t want to change our lifestyle.
Elizabeth: I would just note, of course, that there were Black adults and Hispanics more subject to this particular risk than were White adults, and also sorting, again, unsurprisingly, with education level.
Rick: Yes. You’re not surprised, but those minority groups frequently end up on the short end of the stick with regard to health outcomes. The other group that did particularly poor were individuals aged 18 to 44. So they weren’t taking things seriously, so we need to address all of these things.
Elizabeth: On that rather sobering note, that is the look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.
Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.