Hispanic Patients with Philadelphia (Ph)-Like B-cell Acute Lymphoblastic Leukemia Continue to Experience Poor Outcomes, According to Expert

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There is progress being made regarding research on immunotherapies and the mutation, which adversely affects a higher number of patients in this population.

Amir Ali, PharmD, BCOP, hematology and oncology clinical pharmacist with the Norris Comprehensive Cancer Center at the University of Southern California, Los Angeles, California, speaks with Pharmacy Times at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition, taking place December 9-12, 2023, in San Diego, California. Ali will discuss how Philadelphia (Ph)-like B-cell acute lymphoblastic leukemia (ALL) is characterized, a study that looked at the disease and clinical outcomes in the higher-risk Hispanic population, and he sheds light on the need for more research.

PT Staff: What are the clinical features of Philadelphia (Ph)-like B-cell acute lymphoblastic leukemia (ALL)?

Amir Ali, PharmD, BCOP: So I always like to start off by giving a brief history about Ph-like and Philadelphia chromosome positive ALL (Ph-positive ALL) as well. So this all starts off in the 1950s at the University of Pennsylvania. This is where they discovered the Philadelphia chromosome, hence the name. And what they found with this chromosome is that it was expressed very often in chronic myelogenous leukemia (CML) cases, almost universally. And they also saw that about 30% of cases in AML express Ph chromosome positivity.

A lot of work has been done since the discovery, but what it's been associated with is poor outcomes for these patients. Luckily, we're able to now have more of a targeted approach to treating these patients. And what we see now with the advent of tyrosine kinase inhibitors (TKI), specifically those targeting BCR:ABL1 for patients, an increased survival. So we're very, very fortunate for that.

We're starting to understand a concept called Ph-like ALL, which is very similar to Ph-positivity, but we noticed 1 difference. So for Ph-like ALL, you have the 922 translocation expressing that fusion protein, but with Ph-like ALL, you actually don't see that fusion protein showing up. So very similar characteristics, but certainly slightly different. It's been noticed in about 10 to 30% of these patients expressing Ph-like ALL. So we're starting to develop a more keen understanding of the differences there.

PT Staff: What current immunotherapy options exist for patients within this high-risk subgroup?

Amir Ali, PharmD, BCOP: What we notice is that Ph-like ALL is a very heterogeneous disease. And patients certainly differ in terms of their characteristics when you go from one patient to the next. So it's important to step back and understand that it's responses really can differ per patient. But what you notice sometimes are specific genetic altercations, or mutations, associated with Ph-like ALL, and sometimes we have targetable mutations that we're able to target. If they have the ABL translocation, you're able to target that specifically with some TKIs. [There is] some preliminary small data looking at Ph-like ALL and using these TKIs, but certainly a lot of research is needed for these patients.

What we've noticed also in the realm of immunotherapy is the use of blinatumomab (Blincyto; Amgen). Certainly, there has been a lot of cases where, by using immunotherapy blinatumomab, which is a BiTE (bispecific T-cell engager) therapy that targets cluster of differentiation 3 (CD3) and CD19. In ALL cases, there's a lot of work with that agent looking at Ph-positive ALL. But more work certainly needs to be done for Ph-like ALL. So our understanding is growing slowly. But certainly, there needs to be more research that's done to look at these patients specifically in the response to immunotherapy.

Credit: AkuAku - stock.adobe.com

Credit: AkuAku - stock.adobe.com

PT Staff: Can you briefly describe this study? What results did you expect to see, and what did you observe?

Amir Ali, PharmD, BCOP: So we know that in the Hispanic population, there is certainly a high incidence of ALL, and also a high incidence of Ph-like ALL. Being at USC Keck School of Medicine, we certainly have a demographic that's very rich in Hispanic patients, and we thought it would be prudent for us to specifically look at the outcomes and clinical features of these Hispanic patients suffering from Ph-like ALL. So that was the premise of our abstract that ASH, specifically looking at our large subsets of patients suffering from Ph-like ALL and looking at their clinical features and outcomes. And we certainly have some very powerful results that we've seen, and it confirms a lot of literature out there and [that was] also being presented at previous conferences. So we're finding with our results is certainly that Ph-like ALL, specifically looking at Hispanic populations, is associated with an increased risk of relapse and a poor event-free survival as well. We are looking at specific mutational subtypes for these patients, so we can see a lot of incidents of the cytokine receptor-like factor 2 (CRLF2) mutation for these patients. And that's also indicative of poor response to therapy of these patients. So it's really confirming our understanding that these Hispanic patients are experiencing a lot of these poor outcomes, mainly because of that Ph-like mutation. So it's reinforcing the fact that more research needs to be done in this specific subtype of patients.

PT Staff: What else is necessary to understand regarding Ph-like ALL and at-risk populations? What could be the direction of future research?

Amir Ali, PharmD, BCOP: I think pharmacists play a key role in the management of Ph-like ALL patients and understanding the research out there and communicating that to providers in managing these patients. So what we noticed specifically, is again, that these patients are very heterogeneous. There are so many targetable mutations that can be seen one example being CRLF2. But few of these mutations have druggable targets, at least until we find druggable targets for them.

So we do have some TKIs for those ABL patients out there, and a small understanding of how blinatumomab plays a role in treatments of these patients, but it's up to us as providers to really push for more research to be done at this large subset of patients, because historically, there is has been an unmet need in terms of the treatments for these patients. So we continue to vouch for these patients and advocate for them to find some of these more trouble targets. I don't think we're ever going to have a future where we're actually looking at targets for each of these mutations, but at least we can work on some of these higher-risk mutations and high prevalence mutations and come up with some treatment options specifically for Ph-like ALL.

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