After induction therapy with the lenalidomide-dexamethasone (RD) regimen, ASCT is performed and partial remission is achieved. The pathogenesis of secondary MDS in POEMS syndrome is discussed from three aspects: cytotoxic therapy, genetic predisposition, and SARS-CoV-2 infection. This case underscores the importance of prolonged surveillance for secondary myeloid neoplasms (sMN) in POEMS patients and suggests that early genomic profiling and individualized treatment may improve outcomes.
Together, we established a proof of concept for PROTAC in the DC vaccine design by linking E3 ligase to a protein model antigen, which can be readily replaced with other identified pathogenic antigens to elicit robust cytotoxic immune responses against tumors or viral diseases, and thus has serious implications in the clinics.
While novel agents continue to expand treatment options, ASCT2 remains a viable therapeutic strategy in appropriately selected patients, especially those with durable responses to prior therapy.
We previously reported that a high Kyn/Trp ratio was associated with poor prognosis in lenalidomide-treated refractory/relapsed MM patients and that IDO expression in stromal cells was upregulated by co-culture with MM cells...These results suggest that the JAK-STAT1-NF-κB-IRF1 signaling pathway may be involved in IDO upregulation. JAK inhibitors may improve the TME in MM and positively influence immunotherapy outcomes.
9 days ago
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • IDO1 (Indoleamine 2,3-dioxygenase 1) • STAT1 (Signal Transducer And Activator Of Transcription 1)
This study identifies a novel signaling cascade whereby TMZ-resistant GBM secretes COL6A1 to activate an IKZF1-UBD axis in ECs, disrupting blood vessel integrity and facilitating MDM infiltration. Our findings delineate the pivotal mechanism by which tumor cells engage ECs to drive MDM infiltration - a linchpin part of the positive-feedback loop that couples TMZ resistance to MDM influx. Targeting IKZF1 with LEN represents a promising strategy for restoring endothelial barrier function, reducing MDM infiltration, and enhancing chemosensitivity in GBM.
9 days ago
Journal
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IKZF1 (IKAROS Family Zinc Finger 1) • CHD1 (Chromodomain Helicase DNA Binding Protein 1) • COL6A1 (Collagen Type VI Alpha 1 Chain) • CLDN5 (Claudin 5) • ITGB1 (Integrin Subunit Beta 1)
We report on a series of three patients diagnosed with secondary acute lymphoblastic leukemia (sALL) following treatment for multiple myeloma (MM) where serial, commercially available, next-generation sequencing (NGS) based tracking of measurable residual disease (MRD) using the clonoSEQ assay provided valuable clinical insight. Each of the patients in this series had been treated for their MM with regimens that had included autologous stem cell transplantation following high dose melphalan chemotherapy and had been on maintenance treatment with the immunomodulatory drug lenalidomide for at least one year.
Stratifying patients with MM based on myeloma cell maturity provides meaningful information for choosing the best treatment strategy and improving patient outcomes.
Golcadomide exhibited rapid, deep, and sustained degradation of transcription factors IKZF1 and IKZF3, surpassing the anti-tumor activity of the IMiD® agent lenalidomide in preclinical models. Pharmacological and CRISPR screening further revealed genes and pathways underlying golcadomide's antitumor efficacy. These findings supported golcadomide as a promising drug candidate for DLBCL, providing a strong rationale for future golcadomide-based regimens.
1 month ago
Journal
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IKZF1 (IKAROS Family Zinc Finger 1) • CRBN (Cereblon) • IKZF3 (IKAROS Family Zinc Finger 3)
At the patient's request, six cycles of systemic chemotherapy with daratumumab, lenalidomide, and dexamethasone (DRd) were administered, leading to further shrinkage without complete response. This rare case of solitary plasmacytoma showed residual disease post definitive radiotherapy. In those residual tumors, close long-term monitoring is crucial.