Therapeutic Approaches in Philadelphia-like ALL

Transcript:Mark R. Litzow, MD: Well, let’s conclude this section, and let me ask Anthony, how do you approach the patient who’s Philadelphia [Ph]-like ALL? Do you change your management at this point? Or, what, how do you handle that?

Anthony S. Stein, MD: If the patient has an ABL mutation, I would add dasatinib to the regimen, just like a Ph-positive patient. For somebody who has a JAK2 mutation, currently the data don’t show that by adding ruxolitinib to the treatment adds any benefit. I know there’s still ongoing trials but the ones that have so far been done have not shown any additional benefit.

We actually did an abstract that’s being presented at ASH [the American Society of Hematology meeting] tomorrow. We have interesting data where we’ve looked at our patients that got blinatumomab at City of Hope together with St. Jude [Children’s Research Hospital] where we looked at I think 28 samples. And out of those samples approximately half of them were Philly-like [Ph-like] patients.

And when we break it down, patients who had a CRLF2 mutation, 80% of those patients actually responded to blinatumomab. So hopefully we are planning to look at further samples to see if that stands on in a large number of patients, and then that may be an additional treatment that may be offered to Philly-like patients, at least to patients with Philly-like, or the CRLF2 mutation.

Mark R. Litzow, MD: That’s really fascinating.

Anthony S. Stein, MD: Yes.

Mark R. Litzow, MD: Jae, your perspective?

Jae Park, MD: I think these are tough patient populations because we don’t have good data to guide adding TKI [tyrosine kinase inhibitor], whether it’s going to improve the outcome of these patients, and that interests me here, the data of blinatumomab. Usually the initial induction consolidation, and the initial induction regimen approaches are the same for me. So even with that information that in the absence that usually have not been adding the TKI. Consolidation is once they do achieve remission, if they do get there, I think that’s kind of the tough question.

I think the tough part is, if they are MRD [minimal residual disease]-positive at the end of induction, I know this is going to be a high-risk patient population, I’ll try to consolidate, and getting into MRD-negative, I send these patients to transplant. If they are MRD-negative after initiating induction, they are Ph-like at the beginning, are they really high-risk patient populations? It’s a little bit challenging to decide. I think we’re beginning to get more data. Because more MRD-positive, which will be discussed later, tends to be Ph-like patients.

But if they actually do become MRD-negative, what are the prognostic implications for those patients? And do they really need to be treated as the very high risk and therefore automatically going to transplant in CR1 [first complete remission] versus observe, or whether it’s novel agents such as blinatumomab, maybe they don’t need to. I think there are all these questions arising as we are getting more information about the prognostic implication with older tradition in chemotherapy with the Ph-like with newer therapy, just like how we’re dealing with the Ph-positive disease now. Whether that’s also changed, I think it will be an interesting development.

Bijal D. Shah, MD: I’m very glad you mentioned this issue of cytoreduction, or MRD detection after induction. Because what we’ve seen in the Philadelphia-likes are two patterns of relapse. The first is the refractory patient, and these may be MRD-positive, or, just quite frankly, morphologically positive after induction or induction consolidation.

But the other pattern we’ve seen is late relapse. And what we’ve seen, at least at our center as we enroll to trials, there’s no question, we are profoundly enriching for Philadelphia-like patients when we do the sequencing. So I suspect that it’s going to be a little bit more nuanced. And these are the patients where, for example, I’ve seen shortly after maintenance, we’ve seen these relapses. There’s another peak; the peak is probably right around 3 years is what we’re seeing in this group of patients. Again, all identified retrospectively, which is the challenge. But identified as these late relapses and then we find them, the Ph-like translocations that are likely, or perhaps driving these relapses. And are those patients, and I think they are, different than the Philly-like that’s refractory right from the get-go?

Anthony S. Stein, MD: In the last Alliance study by Wendy Stock [MD] they found that patients who were Philly-like, their survival was much lower than patients who were not Philly-like.

Bijal D. Shah, MD: Do you think transplant is the right answer for that group?

Anthony S. Stein, MD: Well, that’s the question, we don’t know. By transplanting these patients, are these patients also going to have a higher relapse rate after having a transplant or not? I think at the end, this was only recently recognized. I think we have to go back into our transplant data and see how many of these patients have actually been transplanted, and has transplant improved on their survival.

Transcript edited for clarity.