Additional Analyses Of Pomalyst Plus Low-Dose Dexamethasone Studies Presented At ASH 2013
Published: Jan 6, 2014 5:22 pm
More than twenty presentations about studies involving Pomalyst were presented at this year’s meeting of the American Society of Hematology (ASH), which took place last month.
Several of these presentations were about the Phase 3 clinical trial that found Pomalyst (pomalidomide, Imnovid) plus low-dose dexamethasone (Decadron) significantly improved overall survival of relapsed and refractory myeloma patients compared to high-dose dexamethasone alone (see related Beacon news). This is the study that led to the approval of pomalidomide in Europe, where it is marketed under the brand name Imnovid (see related Beacon news).
Two of these ASH presentations discussed the final analysis of the Phase 3 study. The others analyzed the findings of this study or Phase 2 studies of Pomalyst plus dexamethasone based on patient characteristics, including older age, chromosomal abnormalities, or prior therapies.
Many of the other presentations were about studies of Pomalyst and dexamethasone in combination with a third drug, such as Velcade (bortezomib), Kyprolis (carfilzomib), Doxil (doxorubicin liposomal), cyclophosphamide (Cytoxan), or clarithromycin (Biaxin).
There were also several preclinical studies of Pomalyst that were presented at the meeting. A list of all Pomalyst-related abstracts from the ASH meeting can be found here.
This ASH update will summarize the findings from the presentations about Pomalyst plus dexamethasone for the treatment of relapsed and refractory multiple myeloma. A separate article will summarize findings from the Pomalyst-based three-drug combinations.
A key finding of the studies discussed below is that Pomalyst appears to be more effective in certain relapsed myeloma patients than previously thought. In particular, myeloma patients with the del(17p) chromosomal abnormality, which generally is a marker of harder-to-treat (“higher-risk”) disease, responded as well to Pomalyst as patients without any higher-risk chromosomal abnormalities.
Updated Results For Pomalyst Plus Low-Dose Dexamethasone Versus High-Dose Dexamethasone
During ASH, Dr. Meletios Dimopoulos from Alexandria Hospital in Athens (abstract) and Dr. Jesús San Miguel from the University Hospital in Salamanca, Spain (abstract), both presented final results from the Phase 3 study comparing treatment with Pomalyst plus low-dose dexamethasone to treatment with high-dose dexamethasone alone.
The study included 455 heavily pretreated multiple myeloma patients. Two-thirds of the patients were treated with 4 mg of Pomalyst on days 1 to 21 plus low-dose dexamethasone (40 mg on days 1, 8, 15, and 22) of a 28-day cycle, while the remaining third received high-dose dexamethasone (40 mg on days 1 to 4, 9 to12, and 17 to 20) without any Pomalyst.
The median age was 64 years for those who received Pomalyst plus low-dose dexamethasone and 65 years for those who received high-dose dexamethasone alone. Patients in both treatment groups had received a median of five prior lines of therapy. All had received prior Revlimid (lenalidomide) and prior Velcade therapy, 75 percent were refractory to both Revlimid and Velcade therapy, and 70 percent had undergone stem cell transplantation.
The median follow-up time was 15.4 months.
The overall response rate was significantly higher for patients receiving Pomalyst plus low-dose dexamethasone compared to patients receiving high-dose dexamethasone. Among the patients treated with Pomalyst, 32 percent responded, with 1 percent achieving a complete response, 6 percent a very good partial response, and 25 percent a partial response. Among those treated with high-dose dexamethasone, 11 percent responded, with 1 percent achieving a very good partial response, and 10 percent a partial response.
The median duration of response was 7.5 months for those treated with Pomalyst plus low-dose dexamethasone and 5.1 months for those treated with high-dose dexamethasone.
Further analyses of the results showed that outcomes were better with Pomalyst plus low-dose dexamethasone treatment, compared to dexamethasone alone, regardless of prior treatment history. In addition, time-to-progression while on Pomalyst treatment (4.6 months) was similar to time-to-progression on their last prior therapy 4.4 months).
The results showed that Pomalyst plus dexamethasone improved progression-free and overall survival. The median progression-free survival was 4.0 months for those treated with Pomalyst and 1.9 months for those treated with dexamethasone alone. Similarly, the median overall survival was 13.1 months for those treated with Pomalyst and 8.1 months for those treated with dexamethasone alone.
Pomalyst Plus Low-Dose Dexamethasone For High-Risk Myeloma
Dr. Dimopoulos and, in a separate presentation, Dr. Xavier Leleu from the Hopital Claude Huriez in Lille, France (abstract), also presented results demonstrating the efficacy of Pomalyst plus low-dose dexamethasone in patients with the high-risk chromosomal abnormalities del(17p) and t(4;14).
In particular, they showed that Pomalyst and low-dose dexamethasone appeared to have almost the same efficacy in patients with the del(17p) chromosomal abnormality as in patients without either the t(4:14) or del(17p) abnormality.
In the Phase 3 study discussed by Dr. Dimopoulos, the median progression-free survival of patients treated with Pomalyst and low-dose dexamethasone was 4.2 months for patients without either of the two high-risk abnormalities, 4.6 months for patients with the del(17p) abnormality, and 2.8 months for patients with the t(4;14) abnormality.
The median overall survival of patients treated with Pomalyst and low-dose dexamethasone was 14.0 months for patients without either of the two high-risk abnormalities, 12.6 months for patients with the del(17p) abnormality, and 7.5 months for patients with the t(4;14) abnormality.
Results from the multicenter Phase 2 trial that Dr. Leleu presented showed similar findings. The study included 50 relapsed and refractory multiple myeloma patients who had del(17p) and/or t(4;14). The median patient age was 63 years, and the patients had received a median of three prior lines of therapy.
The overall response rate was 22 percent; 32 percent for patients with del(17p) and 16 percent for patients with t(4;14). The median time-to-progression was 2.9 months: 7.3 months for del(17p) and 2.8 months for t(4;14). The median overall survival was 12 months: 12 months for del(17p) and 9.2 months for t(4;14).
Taken together, the findings from these two studies indicate that Pomalyst is more effective for myeloma patients with the del(17p) chromosomal abnormality than was previously realized.
Pomalyst Plus Low-Dose Dexamethasone For Older Myeloma Patients
Another analysis of the Phase 3 study showed that Pomalyst plus low-dose dexamethasone is beneficial for relapsed and refractory myeloma patients over the age of 65 years (abstract; full poster [PDF]).
The results for patients over the age of 65 were similar to those for patients aged 65 or younger; patients who received Pomalyst plus low-dose dexamethasone had higher response rates and longer progression-free and overall survival than patients who received high-dose dexamethasone.
According to the investigators, their findings support considering Pomalyst plus low-dose dexamethasone as a standard treatment option for relapsed and refractory myeloma patients regardless of age.
Effect Of Prior Revlimid Or Thalidomide Therapy On Pomalyst Therapy
This is an important issue because Pomalyst is in the same general class of drugs – known as immunomodulatory agents – as Revlimid and thalidomide. Typically, myeloma specialists do not expect a drug to be as effective in patients previously treated with other drugs in the same class.
Among the 208 patients included in the Phase 2 study, the median number of prior therapies was three; 91 percent had previously been treated with Revlimid or thalidomide, and 39 percent had received Revlimid or thalidomide as their last treatment prior to Pomalyst therapy.
The results show that patients whose last line of therapy contained Revlimid or thalidomide were less likely to respond to Pomalyst (29 percent response rate compared to 44 percent for those who did not receive either of these drugs in their last line of therapy). Their median duration of treatment was also shorter (5.7 months versus 7.3 months).
Among those previously treated with Revlimid or thalidomide at any point, those who had a shorter duration of Revlimid or thalidomide treatment and those who had more time between Revlimid/thalidomide treatment and start of Pomalyst treatment were more likely to respond to Pomalyst.
- Pomalyst-Based Combination Regimens Presented At ASH 2013
- Researchers Publish Final Results Of Pomalyst Trial That Led To Approval In Europe
- French Study Provides Further Insights Into Pomalyst’s Efficacy, Safety, And Dosing
- Pomalyst Approved In Canada For Relapsed And Refractory Multiple Myeloma
- Extended Use Of Revlimid Plus Dexamethasone Delays Progression Of Relapsed / Refractory Myeloma