Abstract
Pomalidomide is a third-generation immunomodulatory drug (IMiD) that has taken an important place in the management of relapsed/refractory multiple myeloma (RRMM) including in patients with resistance to lenalidomide (R). Synergism of antitumor activity was obtained by combining pomalidomide with dexamethasone (Pd), proteasome inhibitors (PIs), and monoclonal antibodies directed against CD38 and SLAMF7 receptors. The dose-limiting toxicity of pomalidomide is neutropenia (4860% grade 3 for a dose of 4 mg/day). Overcoming resistance to lenalidomide is seen as a key benefit of pomalidomide in the development of triplets that can be used in 2nd and subsequent lines of RRMM treatment. In OPTIMISMM study (phase III), 70% of patients were lenalidomide resistant. Randomization was performed on VPd (bortezomib-Pd) and Vd (bortezomib, dexamethasone) therapy. Vd as control was implemented in two related phases III trials ENDEAVOR (carfilzomib, dexamethasone) and CASTOR (daratumumab-Vd). For patients with resistance to lenalidomide, the median progression-free survival (PFS) was 9.5 mon for VPd in OPTIMISMM; 9.3 mon in CASTOR (resistant to R 21%) for DVd, and 9.3 mon in ENDEAVOR (21%) for Kd - 8.6 mon. The ICARIA-MM study (phase 3; resistance to R 94%) demonstrated the benefit of incorporating isutaximab into the triplet (median PFS 11.1 and 5.9 mon for Isa-Pd and Pd respectively; p0.0001). Similar data were obtained in the ELOQUENT-3 study (phase II; resistance to R - 90%) for elotuzumab (10.3 and 4.7 mon for EPd and Pd respectively; p=0.008). In the APOLLO study (phase III; resistance - 80%), the efficacy of the triplet with daratumumab was confirmed (12.4 and 6.9 mon for DPd and Pd respectively; p = 0.0018). In the present review, the focus is on the consideration of treatment regimens that are of relevance to Russian clinical practice.