Post-Conference Perspectives: Advances in the Treatment of HSCT-TMA - Episode 3

Post-Transplant TMA: Survival with MASP-2 Inhibitors

Vincent T. Ho, MD: The question is in regard to the abstract that was published in the EHA [European Hematology Association Open Access Library] in 2018 by Alessandro Rambaldi, MD. This is a phase II, 3-stage study of narsoplimab in patients who had transplant-associated, post-transplant TMA [thrombotic microangiopathy]. The eligibility for this trial included patients who were at least 30 days postallogeneic transplant who developed TMA on immune suppression. These patients who were enrolled on the study had to have persistent disease after stopping their calcineurin inhibitor.

There were 3 stages. The first stage was to treat patients with 3 different dose levels of this drug for 4 weeks, and the goal of this first stage was to find the best dose. In the second stage, these patients were treated at the higher dose of narsoplimab, and they were treated as the 4 weeks or 8 weeks in the third stage. This trial is ongoing, but the interim analysis was published in the abstract form at EHA. What they found was that there was an encouraging 100-day survival as well as overall survival in this cohort. They compared this cohort with a cohort of historical controls that were case matched.

What they found was that the median survival for the patients on this trial was about 350 days compared with the historical cohort, for whom the median survival was about 21 days. They also found a significant improvement in overall survival at 100 days from the TMA diagnosis: I believe it was over 60%, compared with 20% in the historical cohort. Based on these encouraging, albeit nonrandomized data, the FDA gave the drug a breakthrough designation, and a current registration trial is under way in a multicenter study.

In terms of anticipating how narsoplimab could be used in our practice, it will depend on a number of factors. First is how safe and tolerable this drug is, and the second factor might be cost. Based on the trial data so far, this drug appears to be quite well tolerated, although there are a number of patients who have died of infections—which is probably expected for this population, based on their disease. However, if the drug is proven to be safe and effective, there should be a role for this medication in the use early on after the TMA diagnosis. One key point that I’d like to make is that with TMA, waiting for the disease to lead to renal compromise is probably too late. There’s more literature now suggesting that it is important to treat early and that it’s important to treat before the serum creatinine starts to rise. One earlier marker for severe TMA, as I mentioned before, is the presence of proteinuria. In patients who start to develop proteinuria or have elevated levels of soluble complement, C5b-9, those are the patients who should probably be treated before they actually develop renal failure or develop end-organ disease.

Transcript Edited for Clarity