Pomalyst Plus Low-Dose Dexamethasone Is Active In High-Risk Relapsed Myeloma Patients (IMW 2013)
Published: Apr 10, 2013 5:44 pm
A sub-analysis of recent Phase 2 clinical trial results indicates that Pomalyst in combination with low-dose dexamethasone is effective and safe in multiple myeloma patients with high-risk chromosomal abnormalities who did not respond to prior therapy.
The findings were presented by Dr. Paul Richardson of the Dana-Farber Cancer Institute in Boston at the International Myeloma Workshop (IMW) in Kyoto, Japan, this past Sunday.
In the new analysis, high-risk patients were defined as those with a deletion in chromosome 17 (del17p) or the translocation t(4;14).
Although the response rates were lower and survival times shorter in high-risk patients than in standard-risk patients, Dr. Richardson nevertheless thinks that Pomalyst (pomalidomide) in combination with low-dose dexamethasone (Decadron) is a reasonable treatment option for high-risk patients who do not respond to prior therapy.
“Three-drug regimens, such as Pomalyst-Velcade-dexamethasone or Kyprolis-Pomalyst-dexamethasone, are preferred [in this patient population], but Pomalyst-dexamethasone is clearly active in itself as well,” he said.
Results similar to those from the new analysis also are available for Kyprolis. They indicate that relapsed patients with high-risk disease respond just as well to Kyprolis as other patients. In addition, the response and survival results seen with single-agent Kyprolis in high-risk relapsed patients appear to be slightly more favorable than those seen with the Pomalyst/low-dose dexamethasone combination.
Chromosomal abnormalities are the result of structural changes in the chromosomes of a patient’s myeloma cells. These changes may occur through deletions, insertions, duplications, or movement (“translocation”) of chromosomal regions.
Previous studies have shown that myeloma patients who possess the chromosomal abnormalities known as t(4;14) and del17p have poorer survival outcomes than patients who do not have these abnormalities. Patients with either of these chromosomal abnormalities are considered to have high-risk disease (see related Beacon news 1 and 2).
Pomalyst (pomalidomide) was approved earlier this year by the U.S. Food and Drug Administration (FDA) for the for the treatment of multiple myeloma patients who have received at least two prior therapies including Revlimid (lenalidomide) and Velcade (bortezomib) and have demonstrated disease progression on or within 60 days of completion of the last therapy (see related Beacon news).
Pomalyst’s FDA approval was based on data from the Phase 2 “MM-002” clinical trial of Pomalyst with or without low-dose dexamethasone in relapsed and refractory myeloma patients.
Updated results from this study were presented at the American Society of Hematology (ASH) meeting in December (see related Beacon news). They showed that the combination of Pomalyst and low-dose dexamethasone had an overall response rate of 34 percent in myeloma patients with a median of five previous lines of therapy. Median progression-free survival in these patients was 4.6 months and median overall survival was 16.5 months.
In the current sub-analysis, investigators assessed the efficacy and safety of Pomalyst plus low-dose dexamethasone in a subset of patients from the MM-002 study who had high-risk chromosomal abnormalities, compared to the efficacy and safety in patients with standard-risk disease.
Overall, 30 patients from the original study were categorized as high-risk patients and 57 as standard-risk patients. The median patient age was the same for high-risk and standard-risk patients (64 years). Both patient groups had received a median of five prior therapies.
The overall response rate was 23 percent for patients with high-risk disease, compared to 40 percent for those with standard-risk disease.
Patients with high-risk disease responded more quickly (1.2 months) than patients with standard-risk disease (1.9 months). However, the duration of response was noticeably shorter in patients with high-risk disease (4.9 months), compared to patients with standard-risk disease (10.1 months).
The median progression-free survival was 3.1 months for patients with high-risk disease and 5.5 months for those with standard-risk disease.
The difference in overall survival was more notable, with a median overall survival of 13.2 months for patients with high-risk disease, and 21.7 months for those with standard-risk disease.
However, none of the differences between the two groups were statistically significant.
Patients with high-risk disease showed higher rates of severe blood-related side effects than patients with standard-risk disease: low white blood cell counts (48 percent versus 40 percent) and low platelet counts (31 percent versus 16 percent). Severe, non-blood-related side effects, on the other hand, seemed to be higher in standard-risk patients: pneumonia (28 percent versus 21 percent) and fatigue (18 percent versus 10 percent).
To place the efficacy results from the new study in perspective, one can compare them to those from a Phase 2 trial that investigated treatment with single-agent Kyprolis in a group of patients very similar to those in the Pomalyst/low-dose dexamethasone trial (see the Kyprolis study in Blood [pdf] and the related Beacon news article).
In the case of single-agent Kyprolis, the overall response rate in high-risk relapsed myeloma patients was 30 percent, the median duration of response was 6.9 months, and the median progression-free survival was 3.6 months. (Overall survival results were not published.)
For more information about the new Pomalyst/low-dose dexamethasone analysis, please see Dr. Richardson’s presentation slides, which he has made available for download and viewing as a courtesy to The Beacon’s readers.
- Kyprolis Shows Good Response Rates In Heavily Pretreated High-Risk Myeloma Patients
- Additional Analyses Of Pomalyst Plus Low-Dose Dexamethasone Studies Presented At ASH 2013
- Pomalyst-Based Combination Regimens Presented At ASH 2013
- High-Risk Myeloma Patients With Trisomies May Not Be High Risk After All
- Researchers Publish Final Results Of Pomalyst Trial That Led To Approval In Europe