thalidomide

Approved therapies include immunomodulatory agents (IMiDs, such as thalidomide, lenalidomide, and pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), and monoclonal antibodies (mAb) targeting CD38 (especially daratumumab and isatuximab) and SLAMF7. The most significant differences between the guidelines occur during the induction phase, influenced by regulatory approvals in the United States and Europe. This article will focus on the changing landscape of therapies for newly diagnosed multiple myeloma (NDMM) in transplant-eligible.

P3, N=177, Active, not recruiting, University of Arkansas | Trial completion date: Aug 2025 --> Aug 2026 | Trial primary completion date: Aug 2025 --> Aug 2026

This case underscores the potential of icaritin as a therapeutic option for HCC patients with compromised health status. The combination of icaritin and thalidomide demonstrated promising efficacy in this real-world scenario. Multidisciplinary combination treatment strategies incorporating icaritin merit further exploration, given its immunomodulatory effects and favorable safety profile.

P2, N=30, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026

Among the imaginative innovations, here we discuss cereblon and thalidomide derivatives as a means of recruiting neosubstrates and their degradation, allosteric heterogeneous bifunctional drugs like PROTACs, drugging phosphatases, inducers of targeted posttranslational protein modifications, antibody-drug conjugates, exploiting membrane interactions to increase local concentration, stabilizing the folded state, and more...We discuss potential ways to target heterogeneity by predicting it. The increase in experimental and clinical data, computed (cell-type specific) interactomes, capturing transient cryptic pockets, learned drug resistance, workings of regulatory mechanisms, heterogeneity, and resistance-based cell signaling drug combinations, assisted by AI-driven reasoning and recognition, couple with creative allosteric drug discovery, charting future innovations.

P3, N=140, Recruiting, Air Force Military Medical University, China | Not yet recruiting --> Recruiting | N=70 --> 140 | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Aug 2024 --> Aug 2025

Polymorphisms in TNF, IL6, IL1β, and IFNγ genes may modulate their expression levels, potentially impacting the required dosage of thalidomide in the treatment of ENL. Our findings should be confirmed in further studies to estimate the size effect of these polymorphisms on ENL treatment with thalidomide.

The present systematic review establishes that pembrolizumab can be used as adjuvant therapy in patients with advanced renal cancer at high risk after nephrectomy. This is supported by the KEYNOTE-564 study, which concluded that it increased disease-free survival (DFS) and overall survival (OS). The use of sunitinib is discussed, since the study published in NEJM shows a modest benefit in terms of DFS, but only in an independent and blinded central review. According to the PROTECT study, pazopanib has no overall benefit. The EVEREST study showed no significant benefit over everolimus. Further studies are needed to confirm the use of axitinib, as the ATLAS trial showed statistically significant results in DFS in higher-risk population based on investigator assessment, but not based on independent central review. Therapy with 5-FU, α-IFN and IL-2, atezolizumab, sorafenib, thalidomide, nivolumab + ipilimumab should not be used in the adjuvant setting.

Therapies for ENL management, such as thalidomide, methotrexate, apremilast, minocycline and tumour necrosis factor-alpha inhibitors, hold potential. This review addresses recent advances in leprosy reaction pathogenesis and diagnostics, offering therapeutic insights and preventive strategies to mitigate their onset.

Taken together, our findings suggest that carvacrol mitigated haloperidol-induced Parkinson-like symptoms, partially through the downregulation of TNF-α and NLRP3.

P=N/A, N=20, Recruiting, Institute of Hematology & Blood Diseases Hospital, China

The cereblon (CRBN) E3 ubiquitin ligase complex is a crucial component of the UPS, particularly in modulating protein degradation in response to small-molecule modulators like thalidomide...Importantly, MORF4L1 is upregulated in multiple cancers, including HCC, suggesting a broader role in tumorigenesis. Our findings reveal MORF4L1 as a physiological CRBN substrate and highlight the therapeutic potential of targeting CRBN substrates in cancer.

P=N/A, N=55, The First Affiliated Hospital, Zhejiang University School of Medicine; The First Affiliated Hospital, Zhejiang University School of Medicine

P4, N=600, The Affiliated Hospital of Xuzhou Medical University; The Affiliated Hospital of Xuzhou Medical University

P=N/A, N=100, Not yet recruiting, Institute of Liver and Biliary Sciences, India

Nevertheless, several agents have recently emerged, including anamorelin, a ghrelin receptor agonist, growth differentiation factor 15 neutralization therapy, and melanocortin receptor antagonist, as candidates for ameliorating anorexia associated with cancer cachexia. Therefore, in this review, we outline cancer cachexia-associated anorexia and its pharmacotherapy, including corticosteroids, progesterone analogs, cannabinoids, anti-psychotics, and thalidomide which have been previously explored for their efficacy, in addition to the aforementioned novel agents, along with their mechanisms.

This study highlights THD's role in modifying the tumor microenvironment to enhance PD-1 mAb efficacy, proposing a clinically feasible approach for improving PD-1 mAb treatment outcomes.

Our results suggest that IKZF1 rs4132601 and IKZF3 rs907091 may affect response to treatment and progression in patients with MM.

Lenalidomide, a derivative of thalidomide, is a type of immunomodulatory drug (IMiD) that has been standard therapy for multiple myeloma (MM) and other hematologic malignancies for almost two decades. In addition, treatment with IMiDs is also associated with an increased risk for myelodysplastic neoplasms (MDS), squamous cell carcinoma of the skin, and, less frequently, acute lymphoblastic leukemia (ALL). We present a case of an elderly male with MM and multiple subsequent skin cancers, who presented with pancytopenia and was diagnosed with B-lymphoblastic leukemia (B-ALL) after 10 years of maintenance lenalidomide therapy.

Furthermore, High-risk patients tended to be more sensitive to thalidomide, MK-0752, and BRD-K17060750. The novel platelets-related genes signature we identified could be used for prognosis and treatment prediction in GC.

Moreover, 20a was further examined through a docking study and a 200 ns molecular dynamics simulation for its complex with VEGFR-2, along with computational ADME properties. This work suggests the high significance of compounds 20a, 7a and 28, as lead compounds for development of new effective immunomodulatory antitumor drugs.

These results were slightly better than those of thalidomide. The obtained results revealed that Compound 12 had better immunomodulatory properties than thalidomide, with stronger effects on TNF-α, NF-κB P65, VEGF and caspase-8. This work indicates that compounds 7d and 12 have interesting biological properties that should be further evaluated and modified in order to develop clinically useful thalidomide analogs.

We recently reported that increased expression of ST3GAL1 was associated with inferior PFS in patients with autologous stem-cell transplant (ASCT)-eligible newly diagnosed MM patients treated with bortezomib, thalidomide, and dexamethasone (VTd) +/- Dara as induction and consolidation within the CASSIOPEIA study. Conclusions : Within part 2 of CASSIOPEIA, increased expression of ST3GAL1 is significantly associated with inferior PFS and predicts lack of sustained MRD and disease progression in patients MRD negative (10-5) prior to the onset of maintenance therapy or observation. Our preliminary data suggest that desialylation strategies, currently in clinical development, could help achieve deep and durable remissions in MM patients receiving current Dara based quadruplet treatment approaches.

Ixazomib combined with thalidomide and dexamethasone is effective in the treatment of MM, with good short-term efficacy, survival and safety. However, its long-term efficacy needs further observation.

P2, N=100, Recruiting, Medical University of Vienna | Trial completion date: Apr 2026 --> Apr 2030 | Trial primary completion date: Apr 2026 --> Apr 2030

The original molecular glue degraders (thalidomide, lenalidomide, and pomalidomide) are known to bind to cereblon (CRBN) and alter its surface to induce recruitment, ubiquitination, and degradation of therapeutically valuable neosubstrates (IKZF1, IKZF3, and CK1α). Herein, we describe the medicinal chemistry efforts that resulted in the discovery of SJ3149 as well as other potent and selective CK1α degraders. We report kinetic profiling and parameters of CK1α degradation, ternary complex, antiproliferative effects, in vitro ADME data, and in vivo pharmacokinetic studies with demonstrated oral bioavailability.

P2, N=50, Active, not recruiting, University of Arkansas | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

Post-treatment 18F-FDG PET (Daratumumab Bortezomib Thalidomide Dexamethasone) revealed a completely reduced signal of bone lesions, suggesting a complete response, which was substantiated both clinically and biologically, with the concurrent disappearance of telangiectasia and the monoclonal component, and the normalization of the EPO level. In future, additional data will be required to confirm the added value of 18F-FDG PET with TEMPI. Nevertheless, 18F-FDG PET can be a preferred tool for the extension workup and therapeutic evaluation of TEMPI syndrome.

P=N/A, N=83, Recruiting, Hospital General de Mexico | Trial completion date: Mar 2024 --> Oct 2024

P2, N=401, Active, not recruiting, Stichting European Myeloma Network | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: May 2024 --> Jun 2025

When patients with a recurrence of AML have a history of consuming or contacting aquatic products, clinicians should be vigilant about Aeromonas veronii infection. The presence of Aeromonas veronii in peripheral blood must alert clinicians to the possibility of severe sepsis and septic shock. Early diagnosis and prompt treatment are crucial to reducing patient mortality.

P2, N=96, Recruiting, Xinqiao Hospital of Chongqing | Not yet recruiting --> Recruiting | Initiation date: Apr 2024 --> Aug 2024

A series of rigid ALK PROTACs were developed through conjugation of Ceritinib and thalidomide, orally bioavailable PROTAC 4B (F = 14.22 %) was obtained by overall optimization of molecular properties. Furthermore, 4B significantly inhibited the growth of Karpas 299 xenografts in vivo with TGI of 49.5 % and showed superior anti-proliferative activity against G1202R mutation to Ceritinib (IC50 = 52.82 nM vs IC50 = 109.5 nM). Overall, 4B is expected to be a potential treatment for ALK-driven malignancies.

P4, N=400, Not yet recruiting, Xi'an Jiaotong University Second Affiliated Hospital; Xi'an Jiaotong University Second Affiliated Hospital

P4, N=138, Recruiting, Xinhua Hospital, Shanghai Jiaotong University School of Medicine; Xinhua Hospital, Shanghai Jiaotong University School of Medicine

P4, N=100, Not yet recruiting, Huai'an First People's Hospital; Huai'an First People's Hospital

P2, N=50, Not yet recruiting, Chinese people's liberation army general hospital No.7 medical center; Chinese people's liberation army general hospital No.7 medical center

This case report delineates successful remission with upadacitinib in a child with CD refractory to infliximab, ustekinumab, adalimumab, thalidomide, and prednisone. Notably, the patient carried an ataxia telangiectasia mutated (ATM) gene mutation. These findings provide valuable evidence for PCD management and highlight the potential benefits of upadacitinib in this population.

P2, N=48, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Recruiting

The dog was treated with amputation of the penis, scrotal urethrostomy, and five adjuvant doses of doxorubicin along with thalidomide. Penile hemangiosarcoma seems to share the same aggressive behavior with other hemangiosarcomas seen in other anatomical locations. Therefore, surgery and chemotherapy may improve survival time in dogs with penile hemangiosarcoma as well.

By combining multiple ML algorithms, we developed a novel prognostic model with excellent performance in PAAD cohorts. ML also proved to be powerful for identifying biomarkers and potential targets for improved PAAD patient stratification and immunotherapy.

Cediranib and thalidomide effectively reduced tumor size over time. The accessibility of Evans Blue outside the tumor core continuously decreased over time. The vascular density was significantly decreased after treatment while the proportion of normal vessels remained unchanged over time. In contrast to histological studies, DCE-MRI did not tackle any significant change in hemodynamic parameters, in the core or margins of the tumor, whatever the parameter used or the pharmacokinetic model used. While cediranib and thalidomide were effective in decreasing the tumor size, they were ineffective in transiently increasing the delivery of agents in the core and the margins of the tumor.