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Pomalidomide and Low-Dose Dexamethasone Following Second-Line Lenalidomide-Based Therapy in Relapsed or Refractory Multiple Myeloma

Conference Correspondent - Conference Correspondent, ASH 2016 - Multiple Myeloma

Preclinical studies have shown that lenalidomide-resistant myeloma cells remain sensitive to pomalidomide. Furthermore, subanalyses have demonstrated that pomalidomide and low-dose dexamethasone are efficacious in patients refractory to lenalidomide.

This study included adult patients with a documented diagnosis of multiple myeloma (MM), measurable disease, 2 prior lines of treatment, and progressive disease after 2 or more cycles of second-line treatment with a lenalidomide-based therapy. The primary end point was overall response rate (ORR), and secondary end points included time to response, duration of response, time to progression (TTP), progression-free survival (PFS), and overall survival (OS).

Of 51 enrolled patients, 12 (23.5%) remain on treatment and 39 (76.5%) discontinued treatment, the majority due to progressive disease. The median age was 68.0 years, and most (92.2%) patients had an Eastern Cooperative Oncology Group performance status of ≤1. All 51 patients had prior lenalidomide-based treatment; 37 (72.5%), 2 (3.9%), and 1 (2.0%) patients had prior treatment with bortezomib, carfilzomib, or ixazomib, respectively.

With a median follow-up of 13.6 months, the ORR was 29.4%, including 2% (n = 1) with complete response, 9.8% (n = 5) with very good partial response, and 17.6% (n = 9) with partial response. A total of 45.1% of patients achieved at least minimal response. Of the patients who achieved ≥ partial response, 66% have an ongoing response; median TTP in these patients was 1.9 months. One-year PFS, OS, and TTP rates were 54.6%, 88.2%, and 60.9%, respectively. Common (≥5%) grade 3/4 adverse events included anemia (25%), neutropenia (12%), thrombocytopenia (10%), fatigue (10%), and infections (19.6%; including pneumonia [7.8%]). These findings suggest that pomalidomide and low-dose dexamethasone can be used immediately following lenalidomide-based therapy to treat patients with relapsed/refractory MM. Investigations of additional biomarkers, high-risk genetic aberrations, clonal evolution, and minimal residual disease are currently underway, and may help to identify subpopulations most likely to benefit from sequential immunomodulator-containing therapies.

Siegel DS, et al. ASH 2016. Abstract 4497.

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Last modified: August 30, 2021