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.
