Selecting a Novel Therapy for Relapsed/Refractory ALL


Max S. Topp, MD: We have an evolution here in the relapsed and refractory situation. So we have now 2 approved drugs within Europe: inotuzumab ozogamicin and blinatumomab. Both are great agents for the patients, so now we have to choose 1 of them. Which 1 are we going to use when we have a relapsed ALL [acute lymphoblastic leukemia] patient? The question really is, what is my aim? How old is the patient? What is his disease history? Is it a first relapse or second relapse, as opposed to another relapse? All these things play a role in decision making.

So it’s very clear that there’s no size that fits everyone. But I think if it is a young patient who has not seen a prior transplant, we definitely would like to get this patient to transplantation as quickly as possible, but also in a great condition. So blinatumomab, particularly if the patient has low disease burden, has a response rate of 75% to 80%, so that will be the natural choice over inotuzumab if I want to go to transplant. Why that? Because both have the same response rates, but if the goal is to go to transplant and to put the patient into remission, inotuzumab has a significant toxicity when combined with transplantation, leading to VOD [veno-occlusive disease] in these patients, which is detrimental. But blinatumomab doesn’t have that. So the choice is very clear there.

On the other hand, you have patients in this scenario who might be the exception, who arrive with very high tumor burden and hyperleukocytosis, and those patients are going to have a lower chance of getting a remission with blinatumomab mainly. So maybe inotuzumab would be better suited in those patients to reach their goal.

In the post-transplant situation—a patient had an allotransplantation and has a relapse—again it really depends on the performance status of the patient, when the relapse was, how long the transplantation was, and how the transplant was tolerated. So for anyone who has a late relapse after transplant, I would really try to get them into transplant offering between these 2 drugs, most probably blinatumomab because of what the sequence is after transplant, where inotuzumab leads to VOD in the context. So then in the elderly patient population, who are transplant ineligible, blinatumomab is…more cumbersome to use because there’s a 24-7 continuous infusion of 28 days. So for someone who’s age 75, a weekly infusion of 4 hours or 1 hour with inotuzumab is easier for this patient group.

So the sequence there would be most probably inotuzumab, and if they relapse, blinatumomab. But again, this is just a really bold statement out of context. It depends on the patients, comorbidities, and also the compliance of the patient. Also, a patient who might be 60 may want to go to a transplant, and I may think this is a great idea for this patient. And again, sequence then will be blinatumomab rather than inotuzumab.

So in summary, these 2 trials, both phase III trials that were published almost within a year of each other don’t give you a clear answer of which 1 to use. I think it has a lot to do with personal experience, and also what do you see where the patient is going? And you can’t compare them because the patient groups are very different that were selected for these clinical trials. So it is again a question of experience in that situation. But the majority of these patients will be treated at leukemia centers with doctors who have seen a certain set of ill patients in that unfortunate situation.

Transcript Edited for Clarity

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