EBMT 2022 | The value of achieving CR after alloHSCT in high-risk AML

I think the first point is that traditionally in patients who haven’t achieved a CR with induction chemotherapy being felt that they really have no effective treatment options. But in the last 15 years it’s become clear that allogeneic transplantation in fit patients who’ve failed to achieve a morphological CR after two courses of induction chemotherapy actually can be a curative strategy, and certainly superior to simply continuing with intensive chemotherapy. I think using the classical criteria for primary refractory AML, in other words failure to achieve CR morphologically after two courses of induction, essentially further intensive chemotherapy, is futile. But 25-35% of patients can survive long-term after an allograft. So I think this is very important to bear in mind for selected patients. There are clearly patients with refractory disease for whom this is not a suitable option, or not deliverable. And we also need to work as a community, I think, to identify which patients with an allograft with primary refractory AML will actually do well. Maybe it’s those with some element of chemosensitivity, or maybe this particular biological subgroup.

And I think the other area of active discussion concerning the benefit of achieving CR in the patients who are going to go to an allograft is discussing in more detail what’s a good CR. So we know that the presence of pretransplant MRD is associated with an increased relapse risk after allograft. There’s retrospective data, but there’s now prospective data from the FIGARO trial led by my colleague Sylvie Freeman and also from the Hourigan data where he didn’t use conventional MRD, but just demonstrated that the presence by NGS of molecular mutation was again associated with increased relapse which I think it’s very important because those two studies, FIGARO and the Hourigan study were actually prospective studies. Many of the data that’s quoted is retrospective study. The impact of pretransplant MRD on relapse varies wildly. And we have to be thoughtful about the importance of prospective datasets to give accurate data.

So what we know is that if you have got pretransplant MRD your relapse is higher, the question then arises, “Should you go to transplant if you’ve got pretransplant MRD?” And I think the important data from the FIGARO trial we published in JCO last year shows that although the presence of pretransplant MRD increases the relapse risk at two years from 20% to 40%, and reduces the two year overall survival from 70% to 50%, in fact a significant number of patients transplanted in morphological remission with pretransplant MRD achieve long term disease-free survival. So I don’t think there’s any evidence that if you’ve got pretransplant MRD and you’re in a morphological CR you shouldn’t proceed straight to an allograft, and there’s no evidence in my judgment that further courses of intensive chemotherapy will do any benefit. They may do harm. Clearly we need randomized studies in this area, but at the moment I think if you’ve got a pretransplant MRD your route to cure should be through a transplant and there’s a very strong case for getting on with a transplant as soon as possible. And then thinking possibly about optimizing the conditioning regimen. And so if you’ve got a patient with pretransplant MRD, you’d be favoring a myeloablative conditioning regimen over a RIC. You’d be favoring an earlier taper of immunosuppression and possibly favoring maintenance therapy.