ASH 2022 | Orca-T with tacrolimus or TAC/MMF/PTCy as GvHD prophylaxis in allotransplant recipients

So there’s two really important studies that were presented at ASH this year that both are in allo-transplant, and both have different approaches to reducing the rate of graft-versus-host disease, while maintaining the curative intent of allo-transplant. The first is Orca-T with single agent tacrolimus immunosuppression. And then the other strategy is post-transplant cyclophosphamide with mycophenolate and tacrolimus as GvHD prophylaxis.

So first, we’ll talk about the study from Orca-T. Orca-T is a cellular immune therapy, which is a purified T-regulatory population, that’s polyclonal from a donor. And this is given in conjunction with allo-transplant. So this time at ASH, the efficacy data of a Phase Ib/II trial was presented by Everett Meyer. This is a follow-up from my presentation at EHA, in which we demonstrated that Orca-T is associated with a very low rate of acute severe graft-versus-host disease, of only 5%, and moderate to severe chronic graft-versus-host disease rate of only 4%.

So at ASH this year, we showed that the relapse-free survival at one year in patients who had AML, ALL, and MDS, who received Orca-T, was 81% at one year. And importantly, of the patients with acute leukemia, the relapse-free survival in patients that were in CR, but were MRD positive, that subgroup of patients, the relapse-free survival at one year was impressively 72%, in comparison to a historical control from the CIBMTR cohort, in patients that received double agent prophylaxis, of 48%. So 72% versus 48% ,patients who are MRD positive and CR. So that’s a very good rate for patients who had pretty high risk for relapse, subsequently.

In addition to that, Orca-T was well tolerated. The non-relapse mortality for the entire group was 5%. But when you look at the group of patients who received the most common conditioning regimen, which was busulfan and fludarabine and thiotepa, which is myeloablative, those patients had a non-relapse mortality of 0%. So based on these data, the FDA has supported a Phase III trial that’s currently accruing patients throughout the country.

Now, the other strategy to reduce GvH rate in allo-transplant is using post-transplant cyclophosphamide. So there was a single center Phase II trial, that presented data that used post-transplant cyclophosphamide, mycophenolate, and tacrolimus, following myeloablative conditioning regimen for transplantation.

So the rate of acute severe graft-versus-host disease was very low, 4%. And the rate of chronic graft-versus-host disease that required treatment, was also very low at 4%. Their relapse rate at two years was 25%, and their non-relapse mortality was just below 10%.

So both of these trials have demonstrated very impressive reductions in the rate of graft-versus-host disease. But these are two very different approaches, so it’s important to understand that. One approach is using single agent immunosuppression with a cellular immunotherapy. And the other approach is using triple agent immunosuppression with post-transplant cy, mycophenolate and tacrolimus.

So both will have longer term data, and then the Orca trial will have Phase III data. My anticipation is that the relapse rate with Orca-T is probably going to be lower, because you’re using only single agent prophylaxis for GvHD. That’ll maintain the graft-versus-leukemia effect as optimally as possible.

And also, with the triple agent GvH prophylaxis, you’ll probably end up seeing more medication-related toxicities, as opposed to the single agent. So it’ll be interesting to see this, and we’ll just wait for the Phase III trial to see if this assumption is correct.