The MDS Beacon™

Results from several important studies about myelodysplastic syndromes (MDS) were presented at the annual American Society of Clinical Oncology (ASCO) annual meeting June 4 to 8. No MDS sessions were held on the first or last day of the conference. Presentations from June 5 and 6 are summarized below, and presentations from June 7 will be summarized in a later Beacon article.

Saturday, June 5

During a poster session held on Saturday morning, researchers presented 16 MDS studies in the format of posters. Boards throughout the hall were filled with posters that each summarized a study. For some of the posters, a researcher was present to answer questions.

In one poster, results were presented from a Phase 3 trial, which studied the frequency, timing, and management of side effects caused by Revlimid (lenalidomide). The rates of serious side effects were high (94 percent of patients on 10 mg Revlimid, 90 percent on 5 mg Revlimid, and 43 percent on placebo), but manageable. Low white blood cell counts and low platelet counts were common in the first two cycles of treatment and then decreased with further treatment.

The researchers concluded that patients should begin Revlimid treatment at 10 mg based on comparable side effects for the two dosing groups but higher response rates in the 10 mg group. Side effects should be managed by dose reductions and supportive care or discontinuation of therapy, if necessary.

Another poster presented results from a collection of studies that compared outcomes in MDS patients who were treated with Dacogen (decitabine) or Vidaza (azacitidine). With both drugs, the longer a patient received treatment, the more likely they were to respond. Patients receiving Dacogen were more likely to have hemoglobin and platelet responses as compared to patients on Vidaza. White blood cell responses were similar for both treatment groups.

Sunday, June 6

Meeting attendees learned about MDS during an education session on Sunday afternoon.

First, Dr. Guillermo Garcia-Manero of the M.D. Anderson Cancer Center spoke about prognosic models for MDS. “This is really one of the most important issues when approaching a patient with myelodysplastic syndromes,” said Dr. Garcia-Manero.

He discussed the classifications that are currently most used in an attempt to predict a patient’s prognosis: FAB, WHO, and IPSS.

“When these classifications were developed, it was not clear whether they had good prognostic models,” said Dr. Garcia-Manero.

He went on to further explain that he prefers the IPSS model because of its simplicity, but that the IPSS model is not good for patients with low-risk MDS and that it underestimates the prognostic impact of chromosomal abnormalities.

Dr. Garcia-Manero then discussed the WPSS Model, which he suggested has limited use at least in North America, and the Global MDS Model, which can be used to determine survival and rate of transformation to acute myeloid leukemia.

According to the Global MDS Model, the following characteristics are the most important for determining survival: abnormal chromosomes, age, hemoglobin count, platelet count, and percentage of blasts.

Dr. Garcia-Manero then explained that there is very active research in the area of finding genetic mutations linked to prognosis of MDS patients. Identifying these mutations should allow physicians to improve the prognostic systems. However, he said, “The search for genetic mutations has not been very fruitful.”

He concluded by saying that an international effort to revise the IPSS score is ongoing using data from about 6,000 patients.

Then Dr. David Steensma of the Dana-Farber Cancer Institute spoke about treatments for MDS beyond supportive care. He said that only in the last five years have many advances been made in the treatment of MDS.

Dr. Steensma explained that Vidaza is the first treatment shown to improve life expectancy as compared to conventional care. It extends survival by nine months.

“That’s fantastic. That’s a great result because it’s the first time that anyone has shown that active therapy can potentially modify the disease and improve survival,” said Dr. Steensma, “but we still have a long way to go.”

He then presented data showing that the dosing of Vidaza has a significant impact on response. Patients receiving Vidaza for 7 days, either 7 days in a row or 5 days one week and then 2 days the following week, had a significantly higher response rate than patients receiving Vidaza for just 5 days (57 percent vs. 68 percent vs. 41 percent).

“We should make our best effort to give a patient Vidaza for 7 days. If they have to come back in the next week, then so be it.”

Unfortunately, Dacogen did not show a similar survival advantage when studied.

Likewise, Dr. Steensma also said, “As an overall strategy, [stem cell transplantation] has not been shown to extend survival.”

Researchers are interested in determining whether Revlimid, which is approved for low-risk patients who are transfusion dependent and have del-5q syndrome, can be used for other MDS patients, such as high-risk patients and patients with multiple chromosomal abnormalities. There does appear to be some activity in these groups.

Erythropoiesis-stimulating agents, although often considered supportive care, may also affect the disease. Several retrospective studies have shown that MDS patients who received erythropoietin had superior survival.

Dr. Steensma also highlighted a Phase 2 study of Campath (alemtuzumab), in which participants were very carefully selected, leading to good response rates.

“If you very carefully select patients, immunosuppressive therapy may have a very important role in MDS, but it is just so difficult to know how to pick those patients,” concluded Dr. Steensma.

Dr. Steensma also discussed a number of ongoing clinical trials, including trials looking at Vidaza therapy after chemotherapy to maintain a complete response, histone deacetylases, and Nplate (romiplostim) in low-risk patients.