P2, N=0, Withdrawn, Memorial Sloan Kettering Cancer Center | N=27 --> 0 | Trial completion date: Aug 2028 --> Mar 2026 | Recruiting --> Withdrawn | Trial primary completion date: Aug 2028 --> Mar 2026
23 hours ago
Enrollment change • Trial completion date • Trial withdrawal • Trial primary completion date
Beyond protein degradation, the diverse biological activities of thalidomide are discussed, including modulation of cytokines, angiogenesis, and immune signaling pathways. Collectively, thalidomide exemplifies how mechanistic insight, synthetic innovation and careful risk-benefit evaluation can transform a once-discarded molecule into a cornerstone of contemporary drug design.
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.
Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment.
Immunomodulatory imide drugs (IMiDs) like lenalidomide and pomalidomide are effective in treating multiple myeloma (MM) but pose hematotoxicity risks by degrading neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). Moreover, we have identified a CRBN ligand that mitigates these safety liabilities and can be effectively incorporated into PROTACs. This advancement provides a promising path toward safer preclinical development of PROTACs, especially as the field expands into chronic disease treatments beyond oncology.
14 days ago
Journal
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IKZF1 (IKAROS Family Zinc Finger 1) • CRBN (Cereblon) • IKZF3 (IKAROS Family Zinc Finger 3)