Second-line CML drug evokes faster response, fewer side effects, pivotal study finds

June 05, 2010

CHICAGO - Dasatanib, a medication currently approved as treatment for drug-resistant chronic myeloid leukemia (CML), provided patients with quicker, better responses as a first therapy than the existing front-line drug, according to researchers at The University of Texas MD Anderson Cancer Center.

The findings were presented at the 46th Annual Meeting of the American Society of Clinical Oncology today, and published in the New England Journal of Medicine. Hagop Kantarjian, M.D., professor and chair of MD Anderson's Department of Leukemia, presented the findings and is the corresponding author on the published study.

Currently, imatinib, or Gleevec ®, is the approved initial therapy for CML, which has increased the five-year survival rate for the disease from 50 percent to 90 percent, said Kantarjian. However, 30-40 percent of imatinib patients do not achieve confirmed cytogenic complete response (CCyR), or the absence of the defective chromosome that causes the disease, within a year. This benchmark is clearly associated with improvements in long-term outcome, said Kantarjian.

"Previous research conducted at MD Anderson found that more patients taking dasatinib were achieving complete responses more quickly than they do on the current standard of care," said Kantarjian. "In this pivotal Phase III study, we confirmed that dasatinib gets more patients to high-quality remission faster than imatinib, making it a superior front-line therapy. Dasatinib, on average, also has a more favorable side-effect profile."

For the multinational Phase III study, known as DASSIN (Dasatinib versus Imatinib Study In treatment-naïve CML patients), 519 newly diagnosed CML patients who had received no prior treatment were randomized to receive either dasatinib, also known as Sprycel ®, 100 milligrams once daily (259 patients), or imatinib, 400 milligrams once daily (260 patients). CCyR, confirmed on two assessments, was the study's primary endpoint. Secondary endpoints included rate of and times to CCyR and major molecular response (MMR), defined as a level of .1 percent or lower of the defective chromosome, as well as safety.

After a minimum follow-up of 12 months, the researchers found that the rates of confirmed CCyR and MMR in those taking dasatinib were 77 percent and 46 percent, respectively, compared to 66 percent and 28 percent, on the imatinib arm.

Therapy failed in nine patients (3.5 percent) in those taking imatinib, compared to five patients (1.9 percent) taking dasatanib. The dasatanib arm reported fewer side effects - nausea, vomiting, muscle inflammation, rash, fluid retention - with most other toxicities being similar in both arms.

"We've learned that in cancer therapy, it's important to use your big guns up front. We know that achieving complete cytogenetic response within a year of starting treatment is associated with more favorable long-term survival; therefore, using this second-generation drug first will likely improve outcomes for patients with chronic myeloid leukemia," said Kantarjian.

CML is caused by an abnormality known as the Philadelphia chromosome that produces an aberrant protein, Bcr-Abl, which causes the overproduction of one type of white blood cell that drives the disease. Dasatinib, a tyrosine kinase inhibitor, blocks the action of Bcr-Abl; the drug is currently approved by the U.S. Food and Drug Administration for patients who can't tolerate imatinib or whose CML resists the drug.
-end-
The study was supported by Bristol-Myers Squibb, makers of dasatinib. Kantarjian receives research funding from the company.

In addition to Kantarjian, other authors on the ASCO study include: Jorge Cortes, M.D., Department of Leukemia, MD Anderson; Neil Shah, M.D., Ph.D., San Francisco School of Medicine; Andreas Hochhaus, M.D., Universitaetsklinikum Jena; Sandip Shah, M.D., Vedanta Institute of Medical Sciences; Manuel Ayala, M.D., Centro Medico Nacional La Raza; Beatriz Moiraghi, M.D., Hospital General De Agudos J.M. Ramos; Mejia M. Brigid Bradley-Garelik, M.D, Bristol-Myers Squibb; Chao Zhu, Ph.D., Bristol-Myers Squibb, and Michele Baccarani, M.D., University of Bologna.

About M. D. Anderson

The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For six of the past eight years, including 2009, MD Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.

University of Texas M. D. Anderson Cancer Center

Related Leukemia Articles from Brightsurf:

New therapeutic approach against leukemia
Using an RNA molecule complex, researchers can prevent retention of cancer stem cell in their tumor supporting niche

Nanoparticle for overcoming leukemia treatment resistance
One of the largest problems with cancer treatment is the development of resistance to anticancer therapies.

Key gene in leukemia discovered
Acute myeloid leukemia (AML) is one of the most common forms of blood cancer among adults and is associated with a low survival rate, and leads to the inhibition of normal blood formation.

Vitamin B6, leukemia's deadly addiction
Researchers from CSHL and Memorial Sloan Kettering Cancer Center have discovered how Acute Myeloid Leukemia is addicted to vitamin B6.

Artificial intelligence tracks down leukemia
Artificial intelligence can detect one of the most common forms of blood cancer - acute myeloid leukemia -- with high reliability.

Milestone reached in new leukemia drug
Using a chemical compound called YKL-05-099, a team of cancer researchers from CSHL and the Dana Farber Institute was able to target the Salt-Inducible Kinase 3 (SIK3) pathway and extend survival in mice with MLL leukemia.

The drug combination effective against bovine leukemia
Scientists have succeeded in reducing levels of the bovine leukemia virus (BLV) in cows with severe infections by combining an immune checkpoint inhibitor and an enzyme inhibitor.

Towards a safer treatment for leukemia
An international team of researchers at VIB-KU Leuven, Belgium, the UK Dementia Institute and the Children's Cancer Institute, Australia, have found a safer treatment for a specific type of leukemia.

Research paves way for new source for leukemia drug
Chemistry researchers have patented a method for making anti-leukemia compounds that until now have only been available via an Asian tree that produces them.

An atlas of an aggressive leukemia
A team of researchers led by Bradley Bernstein at the Ludwig Center at Harvard has used single-cell technologies and machine learning to create a detailed 'atlas of cell states' for acute myeloid leukemia (AML) that could help improve treatment of the aggressive cancer.

Read More: Leukemia News and Leukemia Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.