Exploring Chemotherapy-Free Treatment for Patients With Philadelphia-Positive ALL

At the 2023 Lymphoma, Leukemia & Myeloma Congress in New York, New York, Elias Jabbour, MD, MD Anderson Cancer Center, Houston, Texas, discusses possibilities for chemotherapy-free treatment of patients with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). 

Transcript:

Hello, my name is Elias Jabbour from Houston, and I'm very happy to be here in New York at the Lymphoma, Leukemia, and Myeloma Congress. My talk this morning was about chemotherapy-free [treatment] in [Philadelphia-positive] ALL.

We have made much progress. Historically, [these patients had] a very poor outcome, and then we had transplant offered to Philadelphia-positive ALL. With that, we had a survival of 35%. Then, we had a [tyrosine kinase inhibitor] (TKI) added to intensive chemotherapy. We have a long-term follow-up of imatinib and dasatinib in combination with the hyper-CVAD [where the survival] at 5 years is 45%.

Why the outcome is not so great is because [patients] are still relapsing, and the relapse is driven by the acquisition of a certain mutation called T315I, [which is known] to cause resistance to imatinib or dasatinib. Therefore, we moved one step higher by evaluating ponatinib. Ponatinib is a very potent TKI that can suppress the emergence of the 359 mutation. We combined hyper-CVAD with ponatinib and have [current] long-term follow-up where the survival is 75% in the long run. 

But then the question is, can we remove the chemotherapy and use ponatinib? Immune therapy [has been shown] to be effective in a refractory setting in Philadelphia-positive ALL, as well as Philadelphia-negative ALL. We [then] combined blinatumomab and the TKI target approach.

Several trials were completed. The first one was reported by the Italian group where they showed [data] that dasatinib followed by [blinatumomab] had a very good response rate of 60%, and a survival rate at 4 years of 78%. At MD Anderson, we elected to use ponatinib and blinatumomab because ponatinib is more effective in combination with [blinatumomab.] We can do better at 3-year overall survival of 90%, which is excellent.

Now the question is, is this curative for everybody? I think for most patients, one problem that remains is the CNS disease. Right now, we are implementing a lot of intrathecal chemotherapy, but we may still need some chemotherapy for a minority of patients. That remains to be seen. 

But I can say that the combination of blinatumomab and the TKI ponatinib, [which is] a chemotherapy-free, is quite successful and [has an] impressive safety profile, and that hopefully will become standard of care. Thank you.

Source:

Jabbour E. Can We Eliminate Chemotherapy in Ph+ ALL? Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-21, 2023. New York, NY