carfilzomib

Treatment with the KXD regimen (carfilzomib, cyclophosphamide, dexamethasone) resulted in transient disease stabilization for approximately two months, followed by further progression. In addition, infiltration of CD138-positive plasma cell-like tumor cells with λ light chain restriction was observed in the gastric lamina propria, consistent with extramedullary disease (EMD). The final diagnosis was relapsed MM complicated by sPCL, gastric mucosal extramedullary plasmacytic infiltration, and synchronous moderately differentiated intramucosal papillary adenocarcinoma.

P1/2, N=246, Recruiting, BeOne Medicines | Active, not recruiting --> Recruiting

P1, N=15, Recruiting, City of Hope Medical Center | Trial completion date: Mar 2026 --> Nov 2026 | Trial primary completion date: Mar 2026 --> Nov 2026

Our findings highlight ABCB1 promoter hypomethylation as a potential epigenetic driver of CFZ resistance in MM. These results underscore the clinical relevance of epigenetic regulation in drug resistance and the potential of targeting DNA methylation as a therapeutic strategy to overcome resistance in MM.

In vivo experiments confirmed that WYC-209 potentiated the antitumor efficacy of CFZ by upregulating ZMYND8, thereby ameliorating tumor burden in NSG mice. These findings establish that targeting ZMYND8 with the novel retinoid WYC-209 potently enhances the efficacy of CFZ and holds translational promise for improving clinical outcomes in patients with MM.

P1/2, N=246, Active, not recruiting, BeOne Medicines | Recruiting --> Active, not recruiting

P1, N=59, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=90 --> 59

Post-ASCT2 maintenance, particularly with lenalidomide or carfilzomib-based regimens, significantly prolonged disease control in randomized and real-world studies. In the modern treatment landscape, second or salvage autologous transplantation remains a valid, safe, and effective strategy for carefully selected patients with relapsed multiple myeloma, particularly those with chemosensitive disease and prolonged initial remissions. ASCT2 should be integrated in a risk-adapted manner alongside maintenance therapy and emerging immunotherapies, serving as a durable consolidation or bridging approach rather than routine therapy for all relapsed patients.

P2, N=60, Recruiting, Amsterdam UMC, location VUmc | Not yet recruiting --> Recruiting

IDE emerges as a novel biomarker and therapeutic vulnerability in MM. This study demonstrates the relevance of IDE inhibitors as boosters of PIs to better treat patients with resistant MM.

P1/2, N=62, Not yet recruiting, Natalie Callander

P3, N=525, Active, not recruiting, Bristol-Myers Squibb | Trial primary completion date: Feb 2026 --> Jul 2026