Hagop M. Kantarjian

Hagop M. Kantarjian, MD, professor, and chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center, and the Samsung Distinguished Leukemia Chair in Cancer Medicine, discusses what experts should know regarding ponatinib (Iclusig; Takeda) and blinatumomab (Blincyto; Amgen) in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).

According to data discussed during the Tenth Annual Meeting of the Society of Hematologic Oncology, the combination induced deep responses and durable remissions in patients with Ph+ acute ALL.

Kantarjian notes how these findings may influence the future of this space as research pushes towards treating patients with non-chemotherapy regimens without the need of transplant, and with the use of ponatinib and blinatumomab.

Ponatinib has shown significant activity in Philadelphia-positive ALL. When we use it at only 30 mg in combination with blinatumomab, we're getting fantastic results. I think in Philadelphia positive ALL, the tradition has been to use intensive chemotherapy with the BCR-ABL tyrosine kinase inhibitor and then move the patients to transplant, what we find is with ponatinib and blinatumomab, we're inducing the best molecular responses we've ever seen and we're reporting an estimated 3-year survival of 95% without the transplant.

This is a major inflection point in the treatment of Philadelphia-positive ALL where we are advocating for a shift in the treatment from the combination of intensive chemotherapy TKI [tyrosine kinase inhibitor] and transplant to non-chemotherapy regimens without the need of transplant, and by using 2 targeted therapies, ponatinib and blinatumomab.

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Hagop M. Kantarjian, MD, discusses what experts should know regarding ponatinib and blinatumomab in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Ponatinib and Blinatumomab Demonstrates Durable Responses in PH+ ALL

Hagop M. Kantarjian, MD, professor, and chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center, and the Samsung Distinguished Leukemia Chair in Cancer Medicine, discusses the impact of prominent treatments in acute lymphoblastic leukemia (ALL).

Kantarhijan highlights how the space for treating patients with ALL has moved away from chemotherapy to more targeted therapies, like the Bcr-Abl kinase inhibitor ponatinib (Iclusig), and combination therapies with chemotherapy. He also discusses the potential devoplpment of therapies that are tri-speicfic T-cell engagers allowing for more robust targeting of biomarkers CD19, CD20, and CD22.

 New generations of Bcr-Abl kinase inhibitors like ponatinib, are showing very promising results in combinations with antibodies like blinatumomab. The antibody cocktails with chemotherapy in pre-BALL are very promising. I'm also interested in the potential development of tri-specific T-cell engagers, instead of bi- specific T cell engagers, meaning that you get the CD3 cells to target CD19 or CD22. So instead of bytes, it will be Trites, where the molecule can target CD19 and CD20 or CD19 and CD22. The same applies for the CAR T-cells, as the CAR T-cells can target more than 1 cluster designation, meaning they could be designed to target both CD19 and CD22, or CD19 and CD20.

I think the tri-specific T cell engagers and the CAR T-cells having more than 1 leukemia target are going to be the future "nuclear bombs" against ALL. They will selectively kill the leukemia without the need for maybe intensive chemotherapy, and they should be very effective if they are well designed.

Hagop M. Kantarjian, MD, discusses the impact of prominent treatments in acute lymphoblastic leukemia.



The Impact of Prominent Treatments in ALL

Hagop M. Kantarjian, MD, professor, department of Leukemia, division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses how the treatment landscape of acute lymphocytic leukemia (ALL) compares to what it used to be.

The ongoing paradigm shift in the treatment of ALL can be credited to the introduction of the BCR-ABL tyrosine kinase inhibitors as well as new antibodies targeting CD19, CD20 and CD22. Agents like ponatinib (Iclusig), blinatumomab (Blincyto), inotuzumab ozogamicin (Besponsa) have also yielded positive results in regard to survival and rates of remission within this patient population.

Kantarjian hopes that by combining these agents with one another or with chemotherapy will better the cure rate of patients with Philadelphia chromosome-positive ALL and pre B-cell ALL.

 In acute lymphocytic leukemia, I think there's now a paradigm shift in the cytopathic approaches. This is because we started introducing targeted therapies like the BCR-ABL tyrosine kinase inhibitors in Philadelphia-positive acute lymphocytic leukemia, as well as introducing the antibodies targeting CD19 and CD22.

n Philadelphia-positive acute lymphocytic leukemia, using the third generation TKIs like ponatinib in combination with blinatumomab, which is a CD19 bispecific T-cell engager, we found that we can induce almost all patients in remission. The estimated 2 year survival is over 90%, and we are not needing to send the patients to transplant. We have shifted from a combination of intensive chemotherapy with first and second generation TKIs and relying on allogeneic transplantation to a strategy that has no chemotherapy, no need for transplant, and a very high cure potential.

In pre B-cell acute lymphocytic leukemia, we introduced both blinatumomab and inotuzumab into the frontline therapy with less chemotherapy. We again found that almost all patients achieved a complete remission, and at 3 to 4 years, their estimated survival is over 80%, which is the first time that we've seen such survivor rates at MD Anderson. I'm hoping that 5 years from now, there's going to be a therapeutic revolution in ALL instead of giving 3 years of intensive chemotherapy in adults and older patients. I hope for a cure rate of 40- 50% so we will be able to give the newer regimens and double the cure rate to levels which are similar to childhood ALL.

Hagop M. Kantarjian, MD, discusses how the treatment landscape of acute lymphocytic leukemia compares to what it used to be.

Hagop M. Kantarjian | Authors

Articles

Ponatinib and Blinatumomab Demonstrates Durable Responses in PH+ ALL

The Impact of Prominent Treatments in ALL

Evolving Treatment Landscape of Acute Lymphocytic Leukemia