Advances in Ph+ ALL: Evolving Therapies and Future Strategies


Hagop M. Kantarjian, MD, and Bijal D. Shah, MD, MS, delve into upcoming strategies for handling Philadelphia-chromosome positive acute lymphoblastic leukemia, considering recent breakthroughs.


Bijal D. Shah, MD, MS: Dr Kantarjian, now that we’ve discussed…the evolution of therapy in ALL [acute lymphoblastic leukemia] … with the hyper-CVAD [cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, methotrexate, cytarabine, and dexamethasone], the dose-reduced chemotherapies with the TKIs [tyrosine kinase inhibitors, the importance of blinatumomab in the management of these patients. We’ve really come a long way where we can talk about 90% survival…in adults with ALL, which I think was unheard of 10 years ago. What do you think the next 5 years have in store for us?

Hagop M. Kantarjian, MD: So I think there are 3 or 4 points we need to discuss in terms of what are the unmet needs or where we’re going get in the next 5 years. The first one is, what if I have a patient who cannot take ponatinib because of a history of cardiovascular problems? Or a patient who has started on ponatinib-blinatumomab and has a problem? So this is where I think replacing ponatinib with dasatinib or with bosutinib would be a good treatment approach. So there’s no reason why a person who has…contraindications to ponatinib would not be treated for a period of time with dasatinib-blinatumomab or bosutinib-blinatumomab…but then at some point in time, we have to carve out a period of time when they are exposed to ponatinib to suppress the T315I clone. And that period does not have to be too long. And it could be with 15 mg a day, which would be safe.

The second point is, how long do we need to treat the patients with ponatinib? And this is where we are going to try to borrow from the CML experience in terms of treatment-free remission. And what we need to do is probably use the clonoSEQ…MRD [minimal residual disease] instead of the PCR [polymerase chain reaction]. So for people who are not familiar with this, the PCR looks at the BCR-ABL RNA message and in 100,000 cells. The clonoSEQ looks at the immunoglobulin heavy chain rearrangement, and it can look at 1 million to 3 million cells. So what we decided at MD Anderson is if we get a patient to be clonoSEQ MRD negative for 5 years or more, and if those patients have [adverse] effects, we’re going to stop to see the incidence of treatment-free remission. If you borrow from the CML [chronic myeloid leukemia] experience, patients who are PCR negative for 5 years or more…there’s an experience of potential treatment-free remission rate of 85%.

And I think the third challenge is, as I pointed out…the incidence of CNS [central nervous system] leukemia and whether we need to reintroduce some form of chemotherapy as a CNS prophylaxis in addition to the 15 and 30 … So these are the 3 things that we are going to work on at MD Anderson. If you have problems with ponatinib, how can you replace it, and how do you keep it at least for a period of time? When do you consider stopping therapy? And that will depend on the clonoSEQ MRD negativity. And the third one is watching closely for CNS relapses and amending our regimens accordingly.

Bijal D. Shah, MD, MS: That’s incredible. Thank you so much, Dr Kantarjian. It’s been a pleasure talking about Philadelphia chromosome–positive ALL. It really is an exciting time.

Hagop M. Kantarjian, MD: Thank you, Dr Shah. Take care.

Transcript is AI-generated and edited for clarity and readability.

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