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Karyotype in Myelodysplastic Syndrome Does Not Influence Efficacy of Azacitidine: Presented at MDS

By Alison Palkhivala

FLORENCE, ITALY -- May 22, 2007 -- The DNA methyltransferase inhibitor azacitidine appears to be effective in patients with myelodysplastic syndrome (MDS), regardless of their chromosome karyotype.

This feature distinguishes azacitidine from lenalidomide, which is most effective in patients with a 5q deletion chromosomal abnormality.

"We've been treating patients with MDS for nearly 10 years with azacitidine, long before it came to market, and we've accumulated [data on] well over 200 patients that we've treated," says coauthor and presenter Richard K. Shadduck, MD, director, Western Pennsylvania Cancer Institute, Pittsburgh, Pennsylvania, United States.

The notion that therapies for MDS may have different efficacies in patients belonging to different cytogenetic subgroups has come about with the discovery that lenalidomide appears to be most effective in patients with 5q chromosomal abnormalities, says Shadduck. "We looked at the question as to whether or not chromosome changes would [also] predict whether or not patients would respond to [azacitidine] therapy."

Dr. Shadduck and his colleagues evaluated 80 MDS patients who were treated with azacitidine and who had their response to treatment evaluated using the International Working Group (IWG) criteria. They also determined each patient's chromosome karyotype using routine chromosomal analysis. The 25 patients who received at least 2 cycles of azacitidine were considered evaluable for response.

Dr. Shadduck presented the findings of this analysis in a poster here on May 18^th at the 9^th International Symposium on Myelodysplastic Syndromes (MDS).

Ten of the 25 evaluable patients (40%) had a complete cytogenetic response to azacitidine. Among these 10 patients, 70% had an IWG response.

Overall, 39 patients had normal karyotypes while 41 had an abnormal karyotypes. Overall response rate in those with a normal karyotype was 64%, compared with an ORR of 48% in those with an abnormal karyotype. These 2 ORRs were not statistically significantly different (P =.24).

Among the 26 patients with a simple abnormal karyotype (defined as 2 or fewer abnormalities), 38% responded to azacitidine, compared with a 66% response rate among patients with a complex abnormal karyotype (3 or more abnormalities). Again, these 2 response rates did not differ with regard to statistical significance (P =.15).

Mean onset of response was 2.9 cycles, and mean response duration was 12.1 cycles. Neither onset of response nor duration of response differed based on karyotype.

"Others have suggested that patients with the 7q- or -7 abnormality would respond better [to azacitidine], but we don't find that," said Dr. Shadduck. Researchers previously have theorized that patients with low-grade chromosome changes would have better responses to azacitidine, and that patients with complex chromosome changes, similar to those seen in patients with acute myeloid leukaemia, would have poor responses to azacitidine. However, this study did not confirm these hypotheses, Dr. Shadduck said.

"What it means to me is I don't have to select groups to treat with azacitidine," he said. "I just treat all comers who need therapy because of transfusion requirements. All groups respond the same: low risk, high risk, good chromosomes, bad chromosomes. It's about a 45% response rate right across the board."


[Presentation title: Karyotype Does Not Predict Response to Azacitidine in Patients With Myelodysplastic Syndrome. Poster P150]

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