Advances in Care for Patients With Myelodysplastic Syndromes
ORLANDO, Fla.—A number of recent advances have been made that will improve the care of patients with myelodysplastic syndromes (MDS), including new developments in prognosis, the use of allogeneic transplantation, and endpoints in the management of patients with MDS. The findings were presented by three researchers during an education program presented at the 52nd American Society of Hematology Meeting and Exposition.
The development of several new scoring models that can predict the likely prognosis of MDS in patients is among the most promising of the advancements. During a presentation about these breakthrough classification systems for patients with MDS, Guillermo Garcia-Manero, MD, of MD Anderson Cancer Center in Houston, Texas, highlighted the positive impact these resources will have on identifying each patient's individual expectation for survival based on sets of specific criteria.
The ability to categorize patients by their predicted prognosis will significantly improve clinician-patient communication and allow patients to better understand and prepare for their most likely disease outcome, according to Dr. Garcia-Manero. In addition, clinicians will be better able to align patients with the optimal treatment method. Among the new scoring models are the IPSS, Global MDS, and WPSS scoring models. New classifications in the IWG-IPSS effort will also be presented at the Edinburgh 2011 MDS Meeting and will include data on over 8,000 patients from approximately 16 centers.
Optimal patient selection and the timing of allogeneic transplant are critical to improving outcomes in patients with MDS, according to research presented during a discussion called “How Does Allogeneic Transplant Fit Into Current MDS Therapy?” by Corey Cutler, MD, MPH, FRCPC, of the Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
Since MDS is the third most common indication for allogeneic transplant, it would appear that nearly all patients should receive a transplant, according to Dr. Cutler. However, clinicians should look to new data and eliminate biases such as selecting their best patient for treatment or assuming that low or intermediate-risk patients do not need immediate transplants.
For example, new data indicates that patients with low survival would benefit from earlier transplants. Patients with low levels of serum ferritin, a substance that correlates with liver iron content in MDS/AML, would also benefit from earlier transplant. Individual genes are another strong predictor of outcome in patients with MDS, and the presence of a single gene can add significant prognostic information, added Dr. Cutler. The IPSS model is a useful starting point for transplant referral.
The likelihood of a patient's response to 5-Azacytidine should also be used to determine the decision to transplant. Research with hypomethylating agents indicates that low-dose 5-Azacytidine after transplant will decrease the relapse rate in patients who receive the therapy. Future research should examine the role of pre-emptive/prophylactic DLI studies and vaccination, and optimal conditioning in these patients should be further studied, he added.
Clinicians should become familiar with how to best use new therapies for MDS in order to achieve optimal dosing and schedules and therefore improve patient outcomes, according to a talk presented by William Blum, MD, of the Ohio State University Comprehensive Cancer Center, Columbus, Ohio. Although the therapies—including azacitidine, decitabine, and lenalidomide—are old news, we need to evaluate if we are using these drugs in the optimal way and whether we really need to administer the drugs the same way, according to Dr. Blum.
In 2010, finding the best treatment for MDS patients means selecting the therapy that is best suited for the individual; improving overall survival and controlling symptoms; and selecting a treatment based on risk factors. Research has indicated that supportive care or ATG should be used in low-risk patients; ATG should be considered in patients with intermediate risk, EPO level greater than 500, younger patients, and HLA-DR15; and azacitidine, decitabine, and transplantation should be considered in high-risk patients.
Past studies have found that the use of AZA in high-risk patients at a dose of 75 mg/m2/d SC x 7d every 28d is more effective than another method (CR 17%, PR 12% with AZA compared to CR 8%, PR 4% with CCR [P = 0.001]). There was a 51% improved survival with AZA at 2 years. In another study of the use of supportive care versus decitabine in which response assessment was studied over 2 cycles, decitabine had a superior response but overall survival did not improve. The ADOPT trial demonstrated that 82% of study responders showed improvement when they used decitabine over 2 cycles.
Research on patients who use lenalidomide has shown that 84% of patients require dose reductions after 3 weeks of using the drug and are able to restart treatment in 3 weeks, stated Dr. Blum. The rate of cytogenetic CR was more effective in a 10 mg dose (25%) than a 5 mg dose (11%).
Clinicians should follow new guidelines on dosing, scheduling, and timing of therapy in order to achieve the best patient outcomes. To improve results with these therapies further, patients with MDS should be considered at younger ages for transplant, and clinicians should consider referring patients to have predictive markers investigated, Dr. Blum concluded.
Off Label Use: decitabine, clofarabine, and azacitidine in AML.