Dasatinib Shown Effective for Treating Two Forms of Leukemia: Presented at ASH

Posted by rob on December 29, 2005 under Uncategorized | Be the First to Comment

ATLANTA, GA — December 12, 2005 — In an update of a phase 1, dose-escalating study, researchers concluded that the data supports the therapeutic potential of dasatinib in chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) patients who are imatinib-resistant or intolerant.

Results of the study were presented here on December 10th at the 47th Annual Meeting of the American Society of Hematology (ASH).

Imatinib mesylate (Gleevec) resistance in CML and Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is frequently associated with BCR-ABL mutations that interfere with the ability of imatinib to inhibit BCR-ABL overproduction.

Dasatinib (BMS-354825) is a novel, oral, multitargeted kinase inhibitor, which targets BCR-ABL and Src protein kinase. Src is a signaling protein that specializes in messages that control cell growth. The drug is 325-fold more potent than imatinib in cells transduced with normal BCR-ABL genes, and has demonstrated preclinical activity against 18 of 19 imatinib-resistant BCR-ABL mutations.

In this update by researchers from the University of California, Los Angeles (UCLA) School of Medicine, Los Angeles, California, and the University of Texas MD Anderson Cancer Center, Houston, Texas, the investigators looked at the use of dasatinib in imatinib-resistant or intolerant patients with CML in late chronic phase, accelerated phase, myeloid blast crisis, or lymphoid blast crisis/Ph+ ALL. A blast crisis is the progression of diseases to an acute advanced phase.

Charles Sawyers, MD, director of the Prostate Cancer Program Area at the UCLA Jonsson Cancer Center, and professor of medicine at UCLA School of Medicine, Los Angeles, California, presented data available for 82 patients — 40 CP, 10 AP, 22 MBC, 10 lymphoid blast crisis/Ph+ ALL.

The 40 patients in late chronic phase, with 5 years median duration of CML, were treated with 15 to 180 mg of dasatinib either once-daily QD or BID for a median of 13 months. The rate of complete hematologic response in late chronic phase patients was 93%, while major cytogenetic responses were observed in 45% and complete cytogenetic response in 35%.

In advanced disease, 44 patients have been treated with dasatinib 70 to 240 mg BID for a median of 37 months. The rate of major hematologic response is 81% in accelerated phase, 61% in myeloid blast crisis, and 70% in lymphoid blast crisis/Ph+ ALL. The complete response rate is 45% in accelerated phase, 70% in lymphoid blast crisis/Ph+ ALL, and 35% in myeloid blast crisis.

The overall rates of major cytogenetic responses and complete cytogenetic responses in advanced disease were 43% and 25%, respectively. Cytogenetic responses were seen in patients with a wide spectrum of BCR-ABL mutations, as well as in patients with minimal or no prior cytogenetic response with imatinib.

Responses were durable in late chronic and accelerated phase, but relapses have occurred in the myeloid blast crisis and blast crisis/Ph+ ALL cohorts, often due to dasatinib-resistant BCR-ABL mutations.

“We are encouraged by the results and are looking forward to seeing the results from ongoing phase 2 studies to confirm the effects of dasatinib in patients with all phases of the disease,” Dr. Sawyers said.

[Presentation title: Dasatinib (BMS-354825) in Patients With Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome- Positive Acute Lymphoblastic Leukemia (Ph + ALL) Who Are Resistant or Intolerant to Imatinib: Update of a Phase I Study. Abstract 38]

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