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Additional Advances in aTTP Research and Clinical Trials With Spero Cataland, MD

Dr. Spero Cataland, Professor of Internal Medicine and the Benign Hematology Section Head at The Ohio State University, Wexner Medical Center, is currently serving as chair of i3 Health's free CME/NCPD activity and Hematology Fellows Lecture Series, Current Standards and New Directions in Treatment of Acquired Thrombotic Thrombocytopenic Purpura (aTTP). In this interview, Dr. Cataland provides an update on new research that has occurred in the field during the past year and shares a preview of what learners can look forward to when attending his presentation at their own institution.  

Oncology Data Advisor: Today, I have the pleasure of speaking with Dr. Spero Cataland from The Ohio State University. Dr. Cataland is currently serving as chair of i3 Health's online activity and Hematology Fellows Meeting Series on current standards and new directions in the treatment aTTP. Today, he's here to share some additional perspectives on the research that is covered in the activity. Dr. Cataland, pleasure to have you on today.

Spero Cataland, MD: Thank you very much. It's really a pleasure to be here and talk with you today and discuss what I think is a very interesting disease or collection of diseases in thrombotic microangiopathies. It's certainly something I focus on as a clinician and clinical researcher at The Ohio State University.

Oncology Data Advisor: Absolutely. To start off, would you like to introduce yourself and say a little bit about what you do?

Dr. Cataland: Sure, my name's Spero Cataland. I'm a Hematologist at the Wexner Medical Center at the Ohio State University. I'm also the Head of Benign Hematology. I have a clinical and research focus on non-malignant hematology, especially thrombotic microangiopathies such as acquired TTP, congenital TTP, and atypical hemolytic uremic syndrome (HUS).

Oncology Data Advisor: Awesome. As we mentioned, this activity from i3 Health was recorded last July, about nine months ago. Have there been any new advances in TTP treatment and management that have occurred since this was recorded?

Dr. Cataland: That's a great question. Any specific advances? Not so much, but we're moving in that direction. Since this has been recorded, there has been ongoing enrollment on two prospective studies investigating the use of caplacizumab as well as recombinant ADAMTS13 protease. These are two different studies using caplacizumab or the recombinant with a minimal plasma exchange approach. The idea is, can you treat TTP with targeted therapies, either caplacizumab or recombinant ADAMTS13, without the need for plasma exchange, without the exposure to plasma and the risks that go along with it? It's very exciting. Both of those studies are progressing nicely and accruing patients, and I think very soon we will have some very interesting data on that.

Oncology Data Advisor: That's great. In addition to these, are there any other ongoing trials or research or even just new directions in TTP that you're looking forward to seeing results of in the near future?

Dr. Cataland: I think there's kind a change in this disease from one that's an acute disorder with flares and relapse to one that is a chronic disorder that we know is associated with, unfortunately, shortened life expectancy and a greater risk for cardiovascular complications. It's these cardiovascular complications that likely lead to this shortened mortality. Efforts to improve the quality of life and the quantity of life by addressing these long-term complications are really where things are ongoing. As part of our United States Thrombotic Microangiopathy Alliance (USTMA) that I help to lead, we're focusing on those neurovascular complications in TTP, done by my colleague Shruti Chaturvedi at Johns Hopkins. We're working on cardiac complications in TTP at The Ohio State, as well looking at some of these neurocognitive functions and mood disorder issues investigated by my colleagues at the University of Minnesota. It's interesting how there's a new focus on this disorder as a chronic disease that needs long-term management and follow-up, not just the risk of relapse as has been in the past, but monitoring for these complications and trying to prevent them or ameliorate them if we can for patients.

Oncology Data Advisor It's very exciting. Would you like to tell us a little bit more about some of this research that you're personally involved in or anything that you'd like to highlight?

Dr. Cataland: There are some of things that are going to be coming out very soon, and one thing that's very exciting—not in immune-mediated TTP but in congenital TTP—is there should be a publication out very soon regarding the recombinant ADAMTS13 data in congenital TTP. I think that's very exciting. In addition to the fact that it's being studied in immune-mediated TTP makes it equally exciting—it's a new angle to approach these patients. I think some of these data I've already referred to regarding the cardiovascular complications in these patients are very interesting. A lot of the work that's going to go on is to try to understand how common they are. Right now, we just don't know how to screen for them, other than having an informed clinician who knows about them to ask about them.

I think most important is the mechanism for why these complications occur, which would then allow us to try to intervene and prevent them. Some of the cardiac data we've shown is as a small vessel disease in these patients. This is really inducible by stress on the cardiac magnetic resonance imaging (MRI) studies that we did in TTP patients. The knee jerk reaction is always to put them on aspirin, as most hematologists would say, but these complications don't seem to be mediated by thrombotic complications. It's rather a functional defect in their endothelium. So, I think it's very interesting work. It's exciting to be really looking at these patients in a different way, not just at acute episodes and not just at ADAMTS13 activity.

Oncology Data Advisor: Absolutely, thanks for sharing all of that. With all these new directions that are being explored, what are you personally most looking forward to seeing in the treatment and management of TTP in coming years?

Dr. Cataland: I think the most exciting thing is to be able to do this without plasma exchange therapy. Plasma exchange therapy has obviously been lifesaving for patients. It's very effective, but it's got its own issues—again, the need for the deep line plasma exposure, the risks of the plasma exposure. I think what we're seeing is going from the broad general approach of plasma exchange to the more specific targeted therapies of TTP and using caplacizumab or recombinant ADAMTS13, as well as any other number of approaches that are being developed in preclinical research as well as early clinical trials. I think it's very interesting and exciting to see this go from the non-specific therapy to the more specific targeted therapy to allow us to do this without plasma exchange. Ideally, hopefully at some point we can do this completely without the need for hospitalization as an outpatient, which would be better for patients.

Oncology Data Advisor: Absolutely, that'll be very exciting to see all this come into play in coming years. My final question for you is, do you have any messages or words of advice for clinicians regarding how they can best manage these complications and optimize quality of life for their patients who have experienced TTP?

Dr. Cataland: I think the best advice I give the trainees and clinicians in general is to try to keep up on some of these issues and complications that occur. Many times, you won't get the correct answer if you don't ask the correct questions. You have to understand these complications. For example, if these neurocognitive deficits tend to be short-term memory issues, you talk to the patient, and they may seem perfectly functional, but there may be deficits in their short-term memory—forgetting where they just put their keys, asking their spouse the same question two or three times that they just asked them—which is frustrating for both members in that relationship. I think understanding these complications allows you to ask more directed and targeted questions to really elicit the responses that you're looking for, helping you to probe if these complications may be there.

Oncology Data Advisor: Thank you, that's very helpful advice. Anything else you'd like to mention about current or ongoing directions in TTP research or anything else regarding this activity?

Dr. Cataland: People could certainly say, "This is a rare disease, I'm not going to see this in my career." And I would tell you, you are going to see this in your career. You're going to see this in your career because they do show up in the emergency department, but they're also living longer. We're getting fewer and fewer issues with mortality upfront, and more survivors are living longer. We're all going to have to deal with these issues. The other thing that's important is that some of these issues and treatments that we're seeing used in TTP are going to expand to other disorders, especially treatment of stroke. I think it's very exciting. You may see some of these issues indeed be applicable to other diseases as we go forward and these treatments are applied to other diseases. It's very exciting, I think.

Oncology Data Advisor: Absolutely. Well, thank you so much for coming on today to talk about all this and share this research with us. It was wonderful to hear about all this latest progress and new directions, and we're looking forward to working with you again in the future. Thank you again.

Dr. Cataland: Thanks, and take care. I appreciate it.

About Dr. Cataland

Spero Cataland, MD, is a Professor of Clinical Internal Medicine and the Director of Benign Hematology at the James Cancer Center and Wexner Medical Center of The Ohio State University. He specializes in the treatment of nonmalignant blood disorders, including platelet abnormalities, blood clotting, and bleeding disorders. Dr. Cataland is involved in numerous clinical trials studying thrombotic thrombocytopenic purpura, atypical hemolytic-uremic syndrome, and other rare blood diseases.

Transcript edited for clarity. Any views expressed are the speaker's own and do not necessarily reflect those of Oncology Data Advisor. 

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