Off and On Again Story of Ponatinib in CML

Michael Deininger, MD, PhD


December 20, 2013

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Hello. I am Dr. Michael Deininger, Professor and Division Chief of Hematology and Hematologic Malignancies at the University of Utah School of Medicine in Salt Lake City, Utah, and the Huntsman Cancer Institute. Welcome to this edition of Medscape Oncology Insights. Today I would like to discuss several key studies in chronic myeloid leukemia as presented at the 55th annual meeting of the American Society of Hematology (ASH)

I would like to cover 3 topics. The first is the PACE trial,[1] the ponatinib phase 2 trial and what is going to happen with ponatinib. The second is an update of phase 3 studies[2,3] comparing imatinib vs the second-generation tyrosine kinase inhibitors (TKIs). The third topic is the other extreme of the spectrum: the imatinib discontinuation studies called STIM1[4] and STIM2.[5]

PACE: In Step for Solid, Durable Responses

The PACE trial is a phase 2 trial that was conducted in more than 400 patients with refractory chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), broadly stratifying patients into 3 groups: chronic phase, accelerated phase, and blast crisis phase plus Ph+ ALL. Patients were further stratified according to whether they had the T315I mutation.

The update of this study with considerable follow-up showed that responses in chronic phase continue to be very solid, with approximately 50% major cytogenetic responses in patients without the T315I mutation and in roughly 70% of patients with the T315I mutation. These responses typically are durable, and so the overall survival and progression-free survival in the chronic-phase cohort is very good and very promising.

Patients in accelerated phase, as we might expect, did slightly worse compared with those in chronic phase, and we see more relapses in this patient cohort. Unfortunately, in blast crisis and Ph+ ALL, the results are not as good, and most patients in this cohort will have a relapse of their disease within 12 months.


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