Clinical outcomes of patients with FLT3-ITD-mutated R/R AML undergoing HSCT after quizartinib or salvage chemo

Dr Siddhartha Ganguly - The University of Kansas Health System, Kansas City, USA

This afternoon I’m going to present a post-hoc analysis of clinical characteristics and outcomes of patients in the QUANTUM-R trial that was presented last year by Dr Jorge Cortes, those patients that underwent subsequent haematopoietic stem cell transplantation. These patients are all FLT3-ITD mutated relapsed/refractory and, as you understand, FLT3-ITD positive relapsed/refractory patients with acute myeloid leukaemia have a very poor and dismal prognosis and options for therapy are limited.

Quizartinib is a potent and oral very selective FLT3 inhibitor and that was used compared to the salvage chemotherapy in the QUANTUM-R trial. That was presented last year by Dr Jorge Cortes where it was shown that the quizartinib arm had median survival of around 6.7 months compared to salvage chemotherapy where the median survival was in the range of 4.2 months. That was statistically significant.

Several patients from that trial were allowed to undergo haematopoietic stem cell transplantation according to the physician’s discretion. Patients that were on the Q arm, they were also allowed to restart either continuation, maintenance, consolidation of quizertinib post-transplantation. So there are 245 patients in the quizertinib arm and 122 patients in the salvage chemotherapy arm. 78 patients from the quizertinib underwent allogeneic stem cell transplantation without any additional AML therapy compared to only 14 patients in the salvage chemotherapy arm. So the transplantation rate was much higher in the quizertinib arm, approximately 34-35%, compared to the salvage chemotherapy that was only 11%. So the question is why patients are getting more transplantation in the quizertinib arm. Of course the transplantation was per physician discretion but when I looked into that data it seemed that the composite complete remission rate was much higher in the quizertinib arm. The duration of the CRC was longer in the quizertinib arm and also there were very fewer early deaths in the quizertinib arm, giving the transplant physician a chance to take the patients who achieved CRC, a longer duration of CRC, and still alive within the first 30-60 days giving a window of opportunity to take them to the allogeneic stem cell transplantation. Of course there are many other variables and post-hoc analysis does not have granular data but it seems that is the reason why patients receive more transplant in the quizertinib arm.

Now, after the transplantation patients who received transplantation, their survival was around 12 months compared to the patients that did not undergo transplantation and the survival advantage was statistically significant. No matter how they went to the transplant, whether they went through the quizertinib arm or the salvage chemotherapy arm, as long as patients were getting transplant they were reaping the benefit of the survival advantage.

Now, interestingly, those patients who received quizertinib went into a complete remission then underwent allogeneic transplantation and then started back on quizertinib maintenance, their median survival was in the range of 27 months so that’s phenomenal in patients that have got not much therapy options and very poor long-term prognosis.

So a paradigm is emerging in patients that have FLT3-ITD mutated relapsed/refractory AML. If we can use a strong potent FLT3 inhibitor and put them into complete remission and take them to the transplant and post-transplantation start back on the inhibitor, maybe that’s one of the ways to overcome this very difficult to treat AML population. Now, we do not have the granular details of all the post-transplantation patients because it was a post-hoc analysis but we are trying to reach out to CIBMTR to gather those data and hopefully, maybe next year, we’ll have some more data and we might be able to come back with another abstract or put that in our manuscript.

The implications of my abstract would be if we do see patients with relapsed/refractory AML and FLT3-ITD mutations we should strongly consider adding a FLT3 inhibitor, a strong, potent selective FLT3 inhibitor, and there are several in the market and I’m not going to compare one against the other, but put them on a FLT3 inhibitor in the induction regimen, take them to transplantation and then as soon as the counts recover and the patients tolerate, put them on a FLT3 inhibitor as a maintenance. That’s what the science will be in future.