EBMT 2025 | Rescue strategies after failure of SCT in myelofibrosis

So we had a very nice discussion about one of the most critical points. We know today that the stem cell transplantation is the only curative option we have for patients with myelofibrosis. That’s the point number one. And we know from the literature that from 10 to 30% of the patients who receive stem cell transplant can relapse. And in general, this event occurs in the first seven months after stem cell transplantation and the overall survival of this patient is about two years. So it is quite important to have a strategy. 

And the best strategy to improve survival for those patients who follow stem cell transplantation is to have a strategy of control and monitor of mutations. So it’s quite important to have an assessment, a quantification of the VAF of JAK2, CALR, and MPL. And we have to monitor our patient at the 30, 100, 180, and one year. So this is quite important because if we capture the molecular relapses, a better option for patients to achieve a new molecular response and a better survival. 

And then, of course, what can we do? We of course, for those patients with no GVHD, we can do a tapering of immunosuppressive therapy if the patient is still on this therapy. That’s the point number one. This must be very careful because GVHD may reappear. So we have to follow this patient very carefully. 

Option number two is DLI. And DLI again is a choice for those patients without GVHD. And we have to do DLI and after six weeks to monitor the patient and say if GVHD occurs, no way to a second DLI. If GVHD does not occur, we have to choose if the patient is in remission, no need of DLI. If the patient is not in remission, need of a second DLI. And in general, patients can obtain a molecular remission in 60-70% depending on the casuistic of the patients and so the DLI is effective. 

And when also this procedure is not indicated or fail, we can consider the second stem cell transplantation. And in a general BMT observation, about 30% of the patients who receive the first stem cell transplant and fail, receive the second stem cell transplant. And again, this is an option for not all patients, 30% is not all, and of course, it’s an option for patients with a good performance status. 

And then if we fail any cellular therapy, we can consider azacitidine for instance, a hypomethylating agent, or interferon that can increase the rate of GVL. And this is of course an option for some patients. 

And if all of these things fail, we have to consider to restart the JAK inhibitor, so ruxolitinib, momelotinib, or fedratinib. And we have to tailor the decision around the patient profile. So if the patient presents mainly with anemia, momelotinib is probably the best choice. If the patient presents with symptomatology and excess splenomegaly, ruxolitinib, or fedratinib would be an alternative option. 

But of course, we have many clinical trials. We are in the process to start Phase I study with mutant-specific drugs. And we are doing a Phase I study with an antibody against mutant CALR. And we will start very soon also bispecific, again with CALR. We know that, for the time being, in general, clinical trials exclude patients who receive stem cell transplantation. The only one character active is the bispecific against CALR mutated. So we have to consider this in our decision, in our model of decision.

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