Multiple Myeloma

Thus, NK cells can naturally work in tandem with anti-MM therapies and be strategically modulated for improved anti-MM effect. This review article describes immunotypic and phenotypic differences in NK cells along with the functional changes in homeostatic and malignant states and provides expert insights on strategies to harness the potential of NK cells for improving outcomes in MM.

In vitro we have shown that the addition of TGF-β1 antibody or CD38 antibody can effectively inhibit the proportion of CD38high Tregs. This study describes the characteristics of DHMM based on bicentric data, which is helpful to better provide theoretical support for the treatment of DHMM.

Subtype Classification: The DNN model excelled in classifying multiple myeloma, MGUS, and light-chain myeloma, demonstrating sensitivity and specificity above 90% across all subtypes. AI models based on routine laboratory results significantly enhance the precision of diagnosing and classifying plasma cell dyscrasias, presenting a promising avenue for early detection and individualized treatment strategies.

Moreover, Pin1 inhibition combined with Pyk2 inhibition decreases myeloma burden both in vitro and in vivo. Altogether, our findings reveal the tumor-promoting role of Pin1 in MM and provide evidence that targeting Pin1 could be a therapeutic strategy for MM.

Translationally, dual pharmacological inhibition of NAT10 and XPO1 sensitizes MM cells to BTZ treatment in both cell lines and in a xenograft mouse model of MM. Thus, our study elucidates previously unrecognized role of ac4C modification of XPO1 mRNA in the chemoresistance of MM and provides a potential option for clinical management of R/R MM patients in the clinic.

Berberine is also being used as a popular weight losing compound, because it is much cheaper and available without a prescription than the semaglutide containing weight losing drugs (Wegovy and Ozempic). In contrast to Berberine, semaglutide had no effects on myofibril assembly in culture assays for both cardiac and skeletal muscle cells. We postulate that analyses of cultured embryonic cardiac and skeletal muscle cells will provide a preclinical assay for the testing of novel cancer drugs with improved outcomes for patients, an important goal for cancer therapeutics.

Targeting CLK2 shows antitumor effects on MM partially through inhibiting SRSF phosphorylation and inducing NMD of RAE1. Therefore, targeting the CLK2/SRSFs/RAE1 axis could be a potential therapeutic strategy for MM.

P=N/A, N=2990, Recruiting, Zhujiang Hospital

P1, N=24, Not yet recruiting, Wuhan Union Hospital, China

Additionally, molecule A7 reversed growth factor IL-6 induced MM cell proliferation, improved the antiproliferative activity of Ixazomib and increased the apoptotic rate of MM cells treated with Ixazomib. Collectively, potent SIRT3 inhibitors with MM cell differentiation potency were developed for the cancer therapy used alone or in combination.

DSF alone overcomes CFZ resistance through lipid peroxidation elevation and acts synergistically with CFZ in CFZ-resistant MM cell lines. Our results suggest that DSF is a promising anti-myeloma agent for overcoming CFZ resistance in MM through ferroptosisinduction.

P1/2, N=90, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

In addition, CD4+ and CD8+ T cells more frequently expressed TIGIT and CD137, suggesting that CD112/TIGIT and CD137L/CD137 interactions may suppress T-cell activity against CD34+ MM cells. Furthermore, our finding of higher FcRH5 expression on CD34+ MM cells is encouraging for future research into the efficacy of FcRH5-targeted therapy in MM.

PMs were re-mobilized with plerixafor (n = 24, 39.3%) or non-plerixafor-based regimens (n = 37, 60.7%)...The median OS was 41.1 months for PM and 41.2 months for non-PM patients (p = 0.86). These data suggest that salvage mobilization is effective and does not affect overall outcomes after a second auto-HCT.

Here, we review FoxO1's roles across B cell and myeloid malignancies, namely acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt lymphoma (BL), Hodgkin lymphoma (HL), and multiple myeloma (MM). We also discuss preclinical evidence for FoxO1 targeting by currently available inhibitors (AS1708727, AS1842856, cpd10).

Therefore, IGF2BP1 acts as a post-transcriptional enhancer of CDC5L in an m6A-dependent manner to promote the proliferation of MM cells with 1q+. Our work identified a novel IGF2BP1-CDC5L axis and provided new insight into developing targeted therapeutics for MM patients with 1q+.

The journal is issuing this Expression of Concern because the results of the experiment as presented cannot be confirmed. The authors do not agree with the expression of concern.

P=N/A, N=88, Recruiting, Rajshekhar Chakraborty, MD | Trial completion date: Sep 2024 --> Nov 2025 | Trial primary completion date: Sep 2024 --> Nov 2025

In this study, 3 pre-analytical components were assessed for the VENTANA Kappa and Lambda Dual ISH mRNA Probe Cocktail Assay. There are many acceptable tissue thickness, fixation, and decalcification options that are compatible with this assay.

P=N/A, N=50, Recruiting, The First Affiliated Hospital of Soochow University

P2, N=146, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2025 --> Feb 2025 | Trial primary completion date: Dec 2025 --> Feb 2025

P2, N=30, Not yet recruiting, Fondazione EMN Italy Onlus

P1, N=9, Terminated, Cartesian Therapeutics | Active, not recruiting --> Terminated; Phase 1 enrollment completed. Further clinical development terminated.

P1, N=10, Terminated, Washington University School of Medicine | N=36 --> 10 | Recruiting --> Terminated; Drug formulation changed, opening new trial

P1, N=20, Completed, Noah Merin | Active, not recruiting --> Completed | N=30 --> 20 | Trial completion date: Nov 2031 --> Nov 2024

P=N/A, N=0, Not yet recruiting, Peking University Shenzhen Hospital; PEKING UNIVERSITY SHENZHEN HOSPITAL

P=N/A, N=90, Completed, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Institute of Hematology

P=N/A, N=30, Not yet recruiting, ganzhou people's hospital; ganzhou people's hospital

P2, N=150, Completed, Peter MacCallum Cancer Centre, Australia | Unknown status --> Completed

P1, N=9, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=30 --> 9

P1/2, N=82, Recruiting, Sanofi | Not yet recruiting --> Recruiting | Phase classification: P1 --> P1/2

P2, N=215, Recruiting, Memorial Sloan Kettering Cancer Center

After four cycles of cyclophosphamide, bortezomib, and dexamethasone therapy, he achieved a partial response, followed by complete hematologic response (CR) post eight cycles of lenalidomide, dexamethasone, and bortezomib therapy...Following failure of >4 lines of therapy, he received chimeric antigen receptor T (CAR-T) cell therapy (ciltacabtagene autoleucel) for salvage...This case report highlights MM management complexities in CHIP presence, suggesting potential utility of HSCT and CAR-T cell therapy. Prospective studies are necessary to evaluate the safety and efficacy of these therapies in myeloma patients with concurrent CHIP, aiming to optimize treatment strategies and improve outcomes in this challenging clinical context.

P=N/A, N=141, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=70 --> 141

P3, N=660, Completed, Fondazione EMN Italy Onlus | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Jul 2024

P1/2, N=80, Recruiting, AstraZeneca | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Mar 2026 --> Dec 2026

P3, N=520, Not yet recruiting, GlaxoSmithKline

Our findings provide a comprehensive immune landscape of MM and its precursors, offering insights into therapeutic strategies. Enhancing neutrophil and NK cell cytotoxicity, tumor antigen presentation, and CD8+ T cell versatility in precursor stages may prevent MM progression.

MALAT1 silencing may repress CXCL12 induction on MM cell proliferation, invasion, and homing behavior by inhibiting CXCR4. MALAT1 may be a promising target for MM treatment.

Thrombocytopenia was associated with the activity of NDMM and predicted prognosis in NDMM. When combined with high CRP levels, thrombocytopenia serves as a new indicator of poor prognosis in these patients.

P1, N=7, Completed, Pfizer | Active, not recruiting --> Completed

Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.