ASH 2011 Myelodysplastic Syndromes Update – Day 1 & Day 2
Published: Dec 12, 2011 6:00 pm
The American Society of Hematology (ASH) 2011 annual meeting is currently being held in San Diego. This article will summarize the myelodysplastic syndromes-related highlights from Saturday, the first full day of the conference, and Sunday, the second day of the meeting.
Saturday started off with an education session on myelodysplastic syndromes (MDS) that consisted of three talks. The program was repeated in the afternoon.
The day ended with a large poster session, during which study results from hundreds of blood disorder-related studies were displayed on big posters attached to boards throughout the exhibition hall. Many posters were accompanied by a presenter or printouts of the poster for attendees to take with them.
There were a number of posters about current MDS treatments as well as new drugs that are under development. Some of the highlights are described below.
French researchers conducted a small study to see if home administration of Vidaza (azacitidine) is possible. They argued that home administration would significantly improve the quality of life of MDS patients. They found that home administration was safe and feasible. A similar median number of cycles and treatment delays were observed between patients who received Vidaza at the hospital and those who received Vidaza at home. Side effect levels and rates of hospitalization were also similar between the two groups (abstract).
Preliminary results from a Phase 1/2 study suggest that the HDAC inhibitor panobinostat, which is being developed by Novartis, is well tolerated and shows some clinical activity in combination with Vidaza in previously untreated MDS patients. The maximum tolerated dose was 30 mg of panobinostat in combination with a 5-day Vidaza schedule of 75 mg/m2 daily (abstract).
Results of an analysis of five trials involving Revlimid (lenalidomide) for the treatment of MDS did not show any clear evidence that Revlimid is associated with an increased risk of secondary cancers in patients with lower-risk MDS with or without del(5q). According to the study authors, the rate of invasive secondary cancers among patients treated with Revlimid was what would be expected among persons in this age group (abstract). Concerns about an increased risk of secondary cancers were first raised at last year’s ASH meeting when study results showed an increased rate of secondary cancers in multiple myeloma patients who had received Revlimid as maintenance therapy (see related news).
Results of a small French study showed that Nplate (romiplostim), which is currently approved to increase platelet levels in patients with chronic immune thrombocytopenia, may be a treatment option for patients who experience low platelet counts after donor stem cell transplantation. Low platelet counts increased in all seven study participants who received Nplate therapy (abstract).
Results from a Korean analysis showed that for patients who receive Vidaza or Dacogen (decitabine) before donor stem cell transplantation, outcomes after stem cell transplantation were better for patients who started the transplant process while still responding to Vidaza or Dacogen than for patients who had progressed. These findings suggest that stem cell transplantation should be initiated while the patient is still responding to Vidaza or Dacogen therapy (abstract).
Treatment with Vidaza or Dacogen may also be a good treatment alternative for patients who are older or cannot tolerate donor stem cell transplantation. When researchers from the MD Anderson Cancer Center in Texas retrospectively compared outcomes for patients who received treatment with Vidaza or Dacogen to patients with similar characteristics who had received a stem cell transplant, they found that the median survival was 26 months for patients receiving a stem cell transplant and 25 months for patients treated with Vidaza or Dacogen. The eight-year overall survival rates were 24 percent and 23 percent, respectively (abstract).
Another analysis from the National Institutes of Health looked at the role of immunosuppressive therapy in MDS. In some types of MDS, the immune system attacks the bone marrow and prevents it from making healthy blood cells. As a result, scientists have recently proposed immunosuppressive therapy as a possible treatment for MDS. This therapy employs drugs that reduce the immune system’s response, thereby allowing the bone marrow to produce more blood cells. The analysis showed that the overall response rate to immunosuppressive therapy was 41 percent. Response rates were higher in patients younger than 60 years old and patients with lower-risk MDS. The number of immature blood cells and the duration of transfusion dependence did not affect response (abstract).
Yesterday was the second full day of the ASH annual meeting. The MDS sessions included a series of talks in the afternoon and a poster session in the evening.
The talks in the afternoon focused on treatment options for MDS patients.
Results of a Phase 1/2 extension study showed that Nplate improved platelet counts in 37 percent of lower-risk MDS patients. However, Nplate also led to an increase in immature blood cell counts and increased risk of progression to acute myeloid leukemia (AML), so the study was discontinued earlier this year (abstract).
After that, results results from a Phase 1 trial were presented showing that the investigational drug ARRY-614 has clinical activity in lower-risk, relapsed/refractory MDS patients. The goal of the study was to determine the maximum tolerated dose of ARRY-614. At the highest dose tested, 38 percent of patients showed blood cell count improvements. The most common side effects were rash and diarrhea (abstract).
In addition, results from a retrospective analysis were presented showing that Revlimid extends overall survival and is not associated with an increased risk of progression to AML in lower-risk, transfusion-dependent MDS patients with the chromosomal abnormality del(5q). The two- and five-year rates of AML progression were 7 percent and 23 percent for patients who received Revlimid, compared to 12 percent and 20 percent for patients who did not receive Revlimid. Median time to AML progression has not been reached for this patient group. The two- and five-year overall survival rates were 90 percent and 54 percent for patients who received Revlimid, compared to 74 percent and 41 percent for patients who did not receive Revlimid. Median overall survival was 5.2 years for patients who received Revlimid, compared to 3.8 years for patients who did not receive Revlimid (abstract).
The evening once again featured a poster session that included additional results from many MDS-related clinical trials. Some of the results are highlighted below.
In one study, researchers tested the combination of the HDAC inhibitor belinostat, which is being developed by the pharmaceutical company Spectrum Pharmaceuticals, in combination with Velcade (bortezomib) in patients with AML and MDS. They found that the combination was tolerated and showed modest activity. The maximum tolerated dose has not been reached yet (abstract).
In another study, researchers investigated the efficacy of Vidaza in MDS patients with the chromosomal abnormality del(5q) who had previously failed Revlimid treatment. They found that the response rates were similar to those reported in patients without the chromosomal abnormality, which led the researchers to conclude that Vidaza may be an effective salvage treatment for this patient population (abstract).
In a Phase 1 study, researchers evaluated Telintra (ezatiostat hydrochloride) in combination with Revlimid in lower-risk MDS patients with the chromosomal abnormality del(5q). Forty-three percent of patients responded at the highest dose recommended for further testing. According to the researchers, Telintra may enhance Revlimid’s efficacy and the combination was well tolerated (abstract).
In another Phase 1 trial, researchers tested quick, sequential administration of Vidaza and Revlimid because they hypothesized that this approach may be particularly useful for patients with high-risk MDS and AML. Patients received 75 mg/m2 Vidaza on days 1 to 5, followed by Revlimid starting on day 6 for five to ten days of a 28-day treatment cycle. Different Revlimid doses were tested, but the maximum tolerated dose has not been reached yet. So far, 60 percent of previously untreated patients have achieved a complete response (abstract).
Transfusion dependency may be an important factor for the prognosis of MDS patients. When European researchers retrospectively analyzed data from an MDS and AML registry, they found that patients who required more than 20 units of transfusions had the highest death rate (30 percent), compared to patients who did not need transfusions (5 percent) (abstract).
When French researchers investigated the impact of incorporating the immunosuppressive therapy agent antithymocyte globulin (ATG) into the preparative treatment for donor stem cell transplantation, they found that ATG resulted in a lower rate of acute graft-versus-host disease, a common transplant-related complication. At the same time, ATG did not negatively affect relapse rates nor survival (abstract).
- ASH 2010 Myelodysplastic Syndromes Update – Day Two
- ASH 2010 Myelodysplastic Syndromes Update – Day 3 Evening & Day 4
- ASH 2011 Myelodysplastic Syndromes Update – Day 3 & Day 4
- ASH 2011 Myelodysplastic Syndromes Update – Day 1 & Day 2
- Vidaza And Revlimid Combination Continues To Show Promise In MDS Patients (ASH 2011)