A team of European researchers has pub­lished results of a major clinical trial investi­gat­ing the efficacy and safety of Pomalyst (poma­lido­mide, Imnovid) and dexa­metha­sone in multiple myeloma patients who have had many prior ther­apies.

Results of the trial, known as the STRATUS (MM-010) study, have pre­vi­ously been presented at several major medical meetings. This is the first time, how­ever, that the results have been summarized in a journal article.

The new efficacy and safety results are in line with previously published results of other trials testing the combination of Pomalyst and (lower-dose) dexa­metha­sone in heavily pretreated myeloma patients.

Patients in the STRATUS trial, which was conducted in Europe, had a median of five previous treatment regimens. All patients had previously been treated with Revlimid (lenalidomide) and Velcade (bortezomib), and half had also been treated with thalidomide.

A third of the trial participants responded to treatment with the Pomalyst-dexamethasone combination. An additional 50 percent of the patients achieved stable disease for at least a short period of time.

Across all patients in the study, median progression-free survival was 4.6 months, and median overall sur­vival was one year from the start of treatment.

The most common serious (grade 3 or 4) side effects were related to reduced blood counts. Half the patients in the trial experienced significant neutropenia, a third experienced significant anemia, and a quarter experienced significant thrombocytopenia (low platelet levels).

“This study confirms previous analyses demonstrating that the combination of pomalidomide and low-dose dexamethasone is a safe and effective treatment for patients with relapsed and/or refractory multiple mye­loma who have exhausted currently available treatment options,” the study authors write in the conclu­sion to their article.

Design Of The Trial

The STRATUS (MM-010) single-arm Phase 3 clinical trial included 682 patients from 91 treatment centers in 19 countries in Europe. Patients were recruited for the trial from November 2012 to December 2014.

To participate in the study, patients were required to have had at least 2 prior lines of treatment. These treat­ments must have included both Revlimid and Velcade, either separately or in combination one another, and either melphalan (Alkeran) or cyclophosphamide (Cytoxan).

The median age of the trial participants was 66 years, and they had been diagnosed a median of 5.3 years prior to entering the trial.

Patients in the study were heavily pretreated; they had received a median of five prior treatment regimens. By design, all patients were previously treated with Revlimid and with Velcade. Two thirds of the trial participants had undergone a stem cell transplant. One half of the patients had been previously treated with thalidomide.

Almost all of the patients were refractory (resistant) to Revlimid (96 percent), and a large majority were refractory to Velcade (84 percent) and to both Revlimid and Velcade (80 percent).

Trial participants received 4 mg of Pomalyst on days 1 to 21 of a 28-day treatment cycle, plus 40 mg of dexa­metha­sone (20 mg for patients over the age of 75 years) on days 1, 8, 15, and 22. This treatment regimen was continued until the patient's disease progressed, or the patient was no longer able to tolerate the treatment.

Results in the new study are based on an analysis carried out after a median follow-up time of 16.8 months.

Efficacy And Safety Results

Overall, 33 percent of patients responded to the Pomalyst-dexamethasone therapy, with 1 percent achieving a complete response, 8 percent a very good partial response, and 24 percent a partial response. An addi­tional 50 percent of patients achieved stable disease.

The median duration of response was 7.4 months.

The median progression-free survival was 4.6 months, and the median overall survival was 11.9 months.

The authors note that response rates and survival outcomes were similar for patients who were refractory to Revlimid, refractory to Velcade, and refractory to both Revlimid and Velcade. This is not particularly sur­pris­ing, however, given the significant overlap between these three groups of patients.

What is somewhat surprising about the results, though, is that the overall response rate and median pro­gression-free survival were slightly lower in patients who had three prior lines of therapy or less, compared to patients who had more than three prior lines of therapy. These differences in response rates and survival, however, were not statistically significant. (The response rates were 28 percent and 34 percent, respectively, and he progression-free survival results were 3.9 months and 4.6 months, respectively.)

Low blood counts were the most common side effect of any severity, and also the most common severe (grade 3 or 4) side effect. Significant neutropenia, anemia, and thrombocytopenia were seen in one half, one third, and one quarter of the patients, respectively.

Other common side effects of any degree occurring in at least 15 percent of the trial participants were: fatigue (29 percent), fever (29 percent), constipation (23 percent), weakness (asthenia) (23 percent), cough (20 per­cent), diarrhea (17 percent), shortness of breath (17 percent), pneumonia (16 percent), and fluid accumu­la­tion (peripheral edema) (16 percent).

There were 15 patient deaths due to side effects recorded during the study (2 percent). All but two of these deaths were due to pneumonia.

Overall, side effects led to reductions in the Pomalyst dose in 22 percent of patients, treatment interruptions in 66 percent of patients, and treatment discontinuation in 6 percent of patients.

The median duration of treatment during the study was 4.9 months, and the median Pomalyst dose intensity (actual amount of Pomalyst taken divided by planned amount of Pomalyst) was 90 percent.

For more information, please see Dimopoulos, M.A., et al., "Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma," in Blood, May 25, 2016 (abstract). Background information about the STRATUS study and results of the study also are available in abstracts 4225 and 1834 from the American Society of Hematology 2015 annual meeting.