Pomalyst Combo Appears Effective in Multiple Myeloma Patients Refractory to Revlimid, Trial Reports

Multiple myeloma patients who failed to respond to treatment with oral Revlimid (lenalidomide) may benefit from by being treated soon afterward with oral Pomalyst (pomalidomide) and low-dose dexamethasone, results of a Phase 2 clinical trial in a first patient group suggest.

An overall response “was achieved by 32·1% of patients, with a majority … having disease control and no patients experiencing clinical relapse,” its researchers said.

The study, ”Pomalidomide plus low-dose dexamethasone in relapsed refractory multiple myeloma after lenalidomide treatment failure” was published in the British Journal of Haematology.

Celgene’s Revlimid is approved as a first therapy in multiple myeloma. However, most patients relapse regardless of the front-line regimen used, and doctors consider it essential to target relapses at the earliest stage.

Pomalyst (also by Celgene) plus low-dose dexamethasone is a standard treatment regimen for relapsed/refractory multiple myeloma (RRMM). It is approved in both the U.S. and EU (where Pomalyst is sold as Imnovid) for patients who have previously received two or more therapies, including Revlimid and a proteasome inhibitor. In Europe, the proteasome inhibitor used is  Velcade (bortezomib, by Takeda Oncology).

Pomalyst has shown efficacy in patients not responding to Revlimid, and in Revlimid-resistant cell lines and animal models. Although both are immunomodulatory agents, their antitumor and immune stimulating properties are different.

The open-label, international MM-014 Phase 2 trial (NCT01946477) is assessing the safety and effectiveness of treatment with Pomalyst and low-dose dexamethasone, with or without Janssen’s Darzalex (daratumumab), in up to 188 multiple myeloma patients whose disease progressed after at least two prior regimens, with the most recent being a Revlimid-based treatment. (In the U.S., the study noted, a triple combination of Pomalyst, low-dose dexamethasone, and Darzalex is also approved for advanced, pre-treated multiple myeloma patients.)

The first group, called cohort A, consisted of 56 patients, 57.1% males with a median age of 68. None had been previously treated with Darzalex.

All had been treated with Revlimid over a median period of 23.6 months shortly before enrolling. The majority (87.5%) failed to respond (refractory), with the remaining patients (12.5%) experiencing a relapse. Forty-one (73.2%) had been treated with a proteasome inhibitor and 39 (69.6%) with Velcade.

Among them, a majority (64.3%) underwent a stem cell transplant, as did 61.5% of those who had been treated earlier with Velcade.

Patients were given 4 mg of Pomalyst twice and 40 mg of dexamethasone (or 20 mg for those older than 75) four times in 28-day cycles. Both therapies were administered orally.

The study’s main objective is overall response rate. Secondary objectives include safety, overall survival, and the median time without cancer progression, or progression-free survival (PFS).

The median duration of Pomalyst treatment was 5.1 months across the total group, 10.8 months in the eight patients achieving minimal response, and 12.7 months in the 18 participants with partial response or better.

At a median follow-up time of 24.1 months, the overall response rate was 32.1% in the total population, and 28.2% in the sub-group that had been treated with Velcade. The lowest rate (25%) was seen in the subgroup of patients without a prior stem cell transplant.

Median PFS was more than one year — 12.2 months — in the total group and 7.9 months in patients previously on Velcade. Longer periods with no cancer progression were seen in patients with minimal response (13.9 months) and with partial response or better (28.5 months). Two patients (3.6%) experienced a complete response, meaning no signs of cancer after treatment.

Median overall survival was 41.7 months across the group and 38.6 months in participants who had taken Velcade.

“These findings indicate that sustained treatment with pomalidomide [Pomalyst] may improve long-term patient outcomes,” the researchers wrote.

Treatment was well-tolerated. The most common severe or life-threatening side effects were anemia (25% of patients), pneumonia (14.3%), and fatigue (also in 14.3%).

Overall, “pomalidomide plus low-dose dexamethasone is safe and effective as third-line therapy in patients with RRMM in whom lenalidomide [Revlimid]-based treatment failed, a clinically relevant patient population with poor representation in clinical trials,” they added.

“These results support not only earlier sequencing of pomalidomide-based therapy after patients become refractory to lenalidomide, but also the continued use and investigation of pomalidomide based regimens that incorporate agents with complementary mechanisms of action in this patient population,” the researchers said.

Early results in a second patient group previously treated with Darzalex suggest that such a triple combination — Pomalyst, low-dose dexamethasone, and Darzalex — is active and safe, they added.