Expert Highlights Remaining Diagnostic Challenges With TA-TMA

Danielle Ternyila
Published: Friday, Feb 21, 2020

Sergio A. Giralt, MD, chief, Adult Bone Marrow Transplant Service, and Melvin Berlin Family Chair in Multiple Myeloma at Memorial Sloan Kettering Cancer Center

Sergio A. Giralt, MD

Although transplant-associated thrombotic microangiopathy (TA-TMA) is an entity that has been recognized for more than a decade, additional evidence has demonstrated that TA-TMA represents a spectrum of endothelial damage syndromes.

At the 2020 Transplantation & Cellular Therapy (TCT) Meetings, Sergio A. Giralt, MD, provided an overview of the ongoing challenges with prevention, diagnosis, and treatment of patients with TA-TMA.

More research, such as both retrospective and prospective studies, needs to be conducted in order to better understand how to diagnose and manage this condition, Giralt explained. Currently, there are no clear criteria for a physician to diagnose a case of TA-TMA—making this a major unmet medical need.

“We need increased awareness of TA-TMA, we need to do more prospective and retrospective studies of TA-TMA,” said Giralt. “But more importantly, as soon as drugs become available, we need to do very well-planned clinical trials looking at reverting this, particularly in patients who are at high-risk for this complication.”

There are no standard treatment strategies for TA-TMA, but complement inhibitors appear promising, he added.

Additionally, further research needs to focus on determining the right therapy for patients with regard to the onset of adverse events that patients with TA-TMA experience, as well as genomic testing to determine potential risks for developing the disease.

In an interview with OncLive during the 2020 Transplantation & Cellular Therapy Meetings, Giralt, professor of medicine at Weill Cornell Medical College, as well as chief of Adult Bone Marrow Transplant Service, and Melvin Berlin Family Chair in Multiple Myeloma, Memorial Sloan Kettering Cancer Center, discussed the diagnostic challenges of TA-TMA.

OncLive: Could you provide an overview of TA-TMA?

Giralt: TA-TMA is an entity that has been described now for more than 10 years. It comes when patients have evidence of microangiopathic anemia as determined by schistocytes in the peripheral blood, as well as increased destructions of red blood cells and decrease in platelet counts.

It is caused, we think, by the damages that high-dose chemotherapy and radiation conditioning regimens produce. We also know that it can be caused by calcineurin inhibitors, as well as viral bacterial and fungal infections.

Initially, TA-TMA was associated with devastating consequences and very high mortality rates. It was only recognized late in the setting of multi-organ failure. We now recognize that TA-TMA actually represents a spectrum of disorders that fall under the categories of endothelial damage syndromes.

What we don’t have is very clear criteria. Although there have been various criterion described in literature, TA-TMA is usually associated with 1 or more of these findings: schistocytosis, anemia, thrombocytopenia, elevated lactic acid dehydrogenase, increased platelet transfusion refractoriness—together with clinical syndromes of renal dysfunction, neurologic dysfunction, hypertension, or [idiopathic pneumonia syndrome]. There is no established treatment, although there is now evidence that complement activation may contribute to the pathogenesis of TA-TMA.

Interesting data have shown that eculizumab (Soliris), a complement inhibitor, or narsoplimab (OMS721), another complement activate inhibitor, can reverse and improve the outcomes of patients with this devastating complication.

What are the major challenges in this space?

The major challenge with TA-TMA is that we still don’t have clear diagnostic criteria. We don’t have a good biomarker. Many other entities that are not TA-TMA can look like TA-TMA. Until we have clear diagnostic criteria and a good biomarker, it will be difficult to design and conduct prospective clinical trials. Researchers are working to define clear biomarkers. We believe that markers of complement activation will help us define a group of patients with TA-TMA who may respond to complement inhibitors.

How else can we overcome these challenges?

As with everything in our field, we have to come together and do very well-designed first retrospective studies and then prospective trials to see what the spectrum of the disorders are. Personally, I believe that TA-TMA represents a variety of triggers and that TA-TMA triggered from a calcineurin inhibitor may be different than a TA-TMA triggered by a viral infection.

The treatment for both [cases] involves addressing the triggering event. However, in many cases, we have to stop the process of microangiopathic hemolytic anemia and endothelial damage. Preferably, we need to find ways of reverting the endothelial damage that triggered the procedure.

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