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Pomalidomide Plus Low-Dose Dexamethasone Improves Survival vs High-Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma

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Key Points

  • Pomalidomide plus low-dose dexamethasone improved disease-free survival, overall survival, and response rate compared with high-dose dexamethasone in patients with advanced relapsed/refractory multiple myeloma.
  • Progression-free benefit was observed in numerous subgroups irrespective of previous treatment.

Pomalidomide (Pomalyst) alone has shown limited efficacy in relapsed multiple myeloma, but synergistic effects have been noted when it is combined with dexamethasone. In a phase III trial (MM-003) reported in The Lancet Oncology, Jesus San Miguel, MD, of Universidad de Salamanca, and colleagues found that the combination of pomalidomide plus low-dose dexamethasone was associated with significantly prolonged progression-free survival and overall survival compared with high-dose dexamethasone in patients with refractory or relapsed and refractory multiple myeloma.

Study Details

In this multinational open-label trial, 455 patients with refractory or relapsed and refractory multiple myeloma were randomly assigned 2:1 to receive 28-day cycles of oral pomalidomide (4 mg/d on days 1–21) plus low-dose dexamethasone (40 mg/d on days 1, 8, 15, and 22) (n = 302) or high-dose dexamethasone (40 mg/d on days 1–4, 9–12, and 17–20) (n = 153) until disease progression or unacceptable toxicity. For patients to be eligible, they had to have received at least two previous treatments of bortezomib (Velcade) and lenalidomide (Revlimid) that failed. The primary endpoint was progression-free survival.

Progression-Free Survival Outcomes

After a median follow-up of 10.0 months, median progression-free survival was 4.0 months with pomalidomide plus low-dose dexamethasone vs 1.9 months with high-dose dexamethasone (hazard ratio [HR] = 0.48, P < .0001). Median progression-free survival was significantly longer with pomalidomide plus low-dose dexamethasone irrespective of previous treatment in subgroup analyses, including in patients refractory to lenalidomide (3.9 vs 1.9 months, P < .0001), refractory to both bortezomib and lenalidomide (3.7 vs 2.0 months, P < .0001), intolerant of bortezomib (4.0 vs 2.0 months, P = .0073), with lenalidomide as their last treatment (4.6 vs 1.9 months, P < .0001), and with bortezomib as their last treatment (3.8 vs 1.9 months, P < .0001).

Overall Survival Outcomes

Median overall survival was significantly longer in the pomalidomide plus low-dose dexamethasone group (12.7 vs 8.1 months, HR = 0.74, P = .0285), including in patients refractory to lenalidomide (12.7 vs 8.0 months, P = .0234) and patients with lenalidomide as their last therapy (12.3 vs 7.3 months, = .0097). Nonsignificant increases were observed in patients refractory to both lenalidomide and bortezomib (11.1 vs 7.7 months, P = .0957), intolerant of bortezomib (15.5 months vs 8.6 months, P = .1405), or with bortezomib as their last treatment (13.1 vs 12.3 months, P = .5457). A total of 76 patients (50%) in the high-dose dexamethasone group had received pomalidomide at a median follow-up of 10.0 months.

The overall response rate was 31% in the pomalidomide plus low-dose dexamethasone group vs 10% in the high-dose dexamethasone group (odds ratio = 4.22, P < .0001).

Toxicity

The most common grade 3 or 4 hematologic adverse events in the pomalidomide vs high-dose dexamethasone groups were neutropenia (48% vs 16%), anemia (33% vs 37%), and thrombocytopenia (22% vs 26%). Grade 3 or 4 nonhematologic adverse events included pneumonia (13% vs 8%), bone pain (7% vs 5%), and fatigue (5% vs 6%); grade 3 or higher febrile neutropenia occurred in 10% vs < 1% of patients.

In the pomalidomide plus low-dose dexamethasone group, 67% of patients required pomalidomide dose interruptions and 27% required pomalidomide dose reductions. In the high-dose dexamethasone group, 28% had dose interruptions and 32% had dose reductions. Discontinuation of treatment due to treatment-related adverse events occurred in 4% vs 6% of patients. Treatment-related adverse events led to death in 4% and 5% of patients.

The investigators concluded: “Studies of different combinations including pomalidomide in patients with refractory or relapsed and refractory multiple myeloma have shown promising results, and the enhanced effects with pomalidomide combinations should be further investigated. Based on these findings and the results of previous trials, pomalidomide plus low-dose dexamethasone could be a new treatment option for patients with advanced refractory or relapsed and refractory multiple myeloma.”

The study was funded by Celgene Corporation.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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