Pomalidomide + Low-Dose Dexamethasone after Lenalidomide-Based Second-Line Treatment in Patients with RRMM: Analysis of Progression-Free Survival by Level of Disease Control
In clinical practice, lenalidomide is usually given until progressive disease in both the first and second lines of therapy, but recent studies have excluded its use in second- and third-line treatment regimens. Researchers undertook a study to evaluate the efficacy and safety of the combination of pomalidomide (POM) and low-dose dexamethasone (LD-Dex; cohort A) versus the combination of POM, daratumumab, and LD-Dex (cohort B) in patients with relapsed/refractory multiple myeloma (RRMM) who have received first- or second-line treatment with lenalidomide-based therapy.
For study inclusion, adult patients with MM had to have 2 prior lines of therapy, and progressive disease after ≥2 cycles of second-line lenalidomide-based treatment. The primary end point tested was overall response rate (ORR). Other study end points tested included time to response (TTR), progression-free survival (PFS), second primary malignancies, and biomarkers.
A total of 51 patients enrolled in cohort A. Most (88.2%) patients were refractory to prior lenalidomide therapy and 72.5% had prior bortezomib therapy. At a median follow-up of 13.6 months, cohort A showed an ORR of 29.4%, complete response of 2.0%, 9.8% very good partial response, and 17.6% partial response (PR). This cohort of patients reported a median PFS of 13.8 months, which was longer with third-line use of POM plus LD-Dex than previously reported in earlier clinical trials. The median TTR was 1.9 months, and 66% of patients had ongoing responses at 1 year. Minimal response (MR) was reached in 15.7% of patients. Patients with ≥MR had similar therapy durations as those achieving ≥PR.
The most common grade 3/4 adverse events reported were anemia (25.5%), infection (19.6%), neutropenia (11.8%), and pneumonia, thrombocytopenia, and fatigue (9.8% each). Posttreatment T-cell populations were significantly higher versus baseline (CD3+, 72.6% vs 67.8%; CD3+/CD8+, 36.9% vs 32.1%). Relative changes from baseline were significantly greater in patients with response versus patients with no treatment response (CD3+, 10.4 vs −0.8; CD3+/CD4+, 4.2 vs −3.5).
This study confirms the safety and efficacy of POM plus LD-Dex following second-line lenalidomide-based treatment failure in patients with RRMM. Immune subset analyses confirmed persistent T-cell stimulatory activity in patients who experienced failure in prior-line lenalidomide-based therapy.
Siegel D, et al. ASCO Abstract 8027.