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Combining Venetoclax and TKI in Ph-Positive Advanced Myeloid Leukemias

By: Sarah Campen, PharmD
Posted: Friday, May 8, 2020

The combination of venetoclax and a tyrosine kinase inhibitor (TKI) may improve outcomes in some patients with aggressive Philadelphia chromosome (Ph)-positive advanced myeloid leukemias—including chronic myeloid leukemia (CML) in myeloid blast phase and acute myeloid leukemia (AML)—according to a retrospective study published in Acta Haematologica.

“Patients with CML in myeloid blast phase may stand to benefit particularly from this combination due to BCR-ABL1 being the predominant driver,” stated Nicholas J. Short, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues.

The researchers focused on nine patients with CML in myeloid blast phase and seven patients with Philadelphia chromosome–positive AML who received venetoclax combined with TKI-based regimens at their institution. The patients included in the study had a median of five prior therapy cycles; nine patients had received decitabine-based regimens, and seven had received intensive chemotherapy-based regimens.

Of 15 evaluable patients, the overall response rate was 60%: 1 complete remission, 6 complete remissions with incomplete hematologic recovery, 1 morphologic leukemia-free state, and 1 partial response. The overall response rate was higher in patients with CML in myeloid blast phase than in those with Philadelphia chromosome–positive AML (75% vs. 43%, respectively), and the median overall survival was 10.9 months and 2.0 months, respectively. The authors noted that achieving a complete response or complete response with incomplete hematologic recovery was associated with higher baseline Philadelphia chromosome–positive metaphases and BCR-ABL1 polymerase chain reaction when compared with nonresponders.

“This is the first report of clinical activity of this rational combination in a retrospective cohort of patients,” noted the investigators. They believe that further evaluation of such combination regimens is warranted in these poor-risk populations.

Disclosure: For full disclosures of the study authors, visit karger.com.



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