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DRUG CLASS:

IL-6 inhibitor

1d
The mitochondrial protease ClpP is a promising target for multiple myeloma treatment. (PubMed, Biochem Pharmacol)
Notably, 7b also showed efficacy against drug-resistant MM cell lines, including bortezomib- and lenalidomide-resistant cells. In vivo, 7b also exhibited remarkable anti-MM activity with tolerable side effects. In conclusion, targeting ClpP represents a promising therapeutic strategy for MM, with 7b serving as a potent anti-MM agent, especially for relapsed and refractory MM.
Journal
|
CLPP (Caseinolytic Mitochondrial Matrix Peptidase Proteolytic Subunit)
|
lenalidomide • bortezomib
4d
SBRT Plus Lenalidomide for Solitary Plasmacytoma: Phase II Trial (clinicaltrials.gov)
P2, N=41, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University
New P2 trial
|
lenalidomide
6d
MCL R2: R-CHOP + R-HAD Vs R-CHOP Followed by Maintenance Lenalidomide + Rituximab Vs Rituximab for Older Patients with MCL (clinicaltrials.gov)
P3, N=623, Completed, The Lymphoma Academic Research Organisation | Active, not recruiting --> Completed | Trial completion date: Aug 2025 --> Jan 2025
Trial completion • Trial completion date
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lenalidomide • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Rituxan Hycela (rituximab/hyaluronidase)
7d
Trial completion • Enrollment change
|
lenalidomide
7d
A Research Study of How the Medicine Ziltivekimab Works in the Body of Chinese Men and Women With Kidney Disease and Inflammation (clinicaltrials.gov)
P1, N=24, Completed, Novo Nordisk A/S | Active, not recruiting --> Completed | Trial completion date: May 2024 --> Sep 2024
Trial completion • Trial completion date
|
CRP (C-reactive protein)
10d
Bortezomib, Lenalidomide and Dexamethasone Combination Therapy in Patients With Newly Diagnosed Multiple Myeloma (clinicaltrials.gov)
P1/2, N=68, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025
Trial completion date
|
lenalidomide • bortezomib • dexamethasone
12d
SOHO State of the Art Updates and Next Questions | Novel Immunotherapy Combinations for the Treatment of Indolent B-Cell Lymphoma. (PubMed, Clin Lymphoma Myeloma Leuk)
While lenalidomide-based immunotherapy remains the standard of care for relapsed iNHL, its frontline use is limited, due to nonsuperiority as compared to CIT...We also summarize the activity in iNHL of agents targeting antigens other than CD20 (including CD19 and CD79b), and novel immunotherapies and cellular therapies (including NK-cell based treatments). The therapeutic landscape of iNHL is soon to significantly change.
Review • Journal
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CD79B (CD79b Molecule)
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lenalidomide • Lunsumio (mosunetuzumab-axgb)
13d
Haploinsufficiency of miR-143 and miR-145 reveal targetable dependencies in resistant del(5q) myelodysplastic neoplasm. (PubMed, Leukemia)
Resistant del(5q) MDS-L cells, as well as primary MDS marrow cells, are also sensitive to targeting of IGF-1R-related dependencies in del(5q) MDS, which include the Abl and MAPK signaling pathways. This work thus provides potential new therapeutic avenues for lenalidomide-resistant del(5q) MDS.
Journal
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TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1) • MIR143 (MicroRNA 143) • CSNK1A1 (Casein Kinase 1 Alpha 1) • MIR145 (MicroRNA 145)
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TP53 mutation • Chr del(5q)
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lenalidomide
18d
A Case of Myeloproliferative Neoplasm with Eosinophilia Associated with PCM1-JAK2 Rearrangement. (PubMed, Case Rep Oncol)
The response of disease to ruxolitinib may be transient and it may only serve as a temporary treatment prior to transplantation. The patient achieved complete hematologic remission and molecular response during the long-term follow-up; however, a complete molecular remission was not attained. The underlying mechanism of lenalidomide in these diseases necessitates further comprehensive investigation through fundamental research and clinical trials.
Journal
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JAK2 (Janus kinase 2) • PCM1 (Pericentriolar Material 1)
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JAK2 rearrangement
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lenalidomide • Jakafi (ruxolitinib)
18d
Tetrandrine induces cell cycle arrest in cutaneous melanoma cells by inhibiting IL-6/CDC42 signaling. (PubMed, Arch Dermatol Res)
Tetrandrine suppressed CM cell growth by triggering G0/G1 cell cycle arrest via IL-6/CDC42 inhibition. Tetrandrine should be a promising compound for CM treatment.
Journal
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CCND1 (Cyclin D1) • IL6 (Interleukin 6) • CDC42 (Cell Division Cycle 42)
|
CBT-1 (tetrandrine)
19d
DarPAL: Daratumumab and Pomalidomide in Previously Treated Patients With AL Amyloidosis (clinicaltrials.gov)
P2, N=27, Terminated, Fondazione IRCCS Policlinico San Matteo di Pavia | N=40 --> 27 | Active, not recruiting --> Terminated; low patient enrollment rate
Enrollment change • Trial termination
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pomalidomide • Darzalex Faspro (daratumumab and hyaluronidase-fihj)
20d
Lenalidomide Combined With G-CHOP in the Treatment of Newly Diagnosed DLBCL With FL (clinicaltrials.gov)
P2, N=38, Recruiting, The First Affiliated Hospital of Xiamen University | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Aug 2025 --> Aug 2027
Trial completion date • Trial primary completion date
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lenalidomide
20d
Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis (clinicaltrials.gov)
P2/3, N=2310, Recruiting, CSL Behring | Trial completion date: Dec 2028 --> Aug 2029 | Trial primary completion date: Dec 2028 --> Aug 2029
Trial completion date • Trial primary completion date
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CRP (C-reactive protein)
25d
RECLAIM: Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine (clinicaltrials.gov)
P2/3, N=460, Active, not recruiting, University Health Network, Toronto | Suspended --> Active, not recruiting | Trial completion date: Dec 2026 --> Mar 2025 | Trial primary completion date: May 2026 --> Mar 2025
Enrollment closed • Trial completion date • Trial primary completion date
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Eyevinal (ibudilast)
30d
Treatment of dexamethasone and lenalidomide-resistant multiple myeloma via RAD51 degradation using PROTAC and synergistic effects with chemotherapy. (PubMed, J Physiol Pharmacol)
Resistant cell lines were established by exposing human B lymphoblast cell lines, MM.1S and MM.1R, to increasing doses of lenalidomide or pomalidomide. The inhibition of RAD51 combined with cisplatin therapy can maximize the treatment efficacy of MM patients resistant to dexamethasone and lenalidomide. Nevertheless, further research will be needed to explore the clinical applications of these findings.
Journal
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RAD51 (RAD51 Homolog A)
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cisplatin • lenalidomide • dexamethasone • pomalidomide
1m
Influence of Cytogenetics on the Outcome of Patients With High-Risk Myelodysplastic Syndrome Including Deletion 5q Treated With Azacitidine With or Without Lenalidomide. (PubMed, Genes Chromosomes Cancer)
In summary, this study in homogenously treated MDS patients with different abnormalities of 5q demonstrates the influence of cytogenetics on treatment results. Trial Registration: EudraCT number: 2011-001639-21; ClinicalTrials.gov identifier: NCT01556477.
Clinical • Journal
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TP53 (Tumor protein P53)
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Chr del(5q)
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lenalidomide • azacitidine
1m
Evaluation of Clinical Characteristics and Prognostic Factors of Early Progressive Disease (EPD) in Newly Diagnosed Multiple Myeloma Patients: Real-World Data of the Greek Myeloma Study Group. (PubMed, Clin Lymphoma Myeloma Leuk)
In real-world, EPD is observed in more than one-fifth of patients, and it remains an unmet clinical need. Daratumumab-based therapies and ASCT significantly reduce the probability of EPD, while R2-ISS could serve as a useful prognostic tool for recognizing this population and guide therapeutic decisions.
Journal • Real-world evidence
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B2M (Beta-2-microglobulin)
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lenalidomide • Darzalex (daratumumab)
1m
Original vs. Generic Plerixafor for the Mobilization of Stem Cells in Multiple Myeloma Patients. (PubMed, Indian J Hematol Blood Transfus)
Plerixafor was administered as a just-in-time approach with granulocyte-colony stimulating factor (G-CSF) alone or with cyclophosphamide (Cy) + G-CSF mobilization...There was no statistically significant difference between the two groups in terms of age, gender, RT history, previous lines of treatment, pretransplant lenalidomide cycles (p = 0.778, 0.165, 0.520, 0.094, 0.530, respectively)...This study demonstrates the comparable efficacy of generic plerixafor in myeloma patients, suggesting that it can be a cost-effective alternative with a similar safety profile. These findings contribute to the body of evidence on the use of generic plerixafor in specific patient cohorts, emphasizing its efficacy and safety for ASCT in a sole multiple myeloma patient cohort.
Journal
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CD34 (CD34 molecule)
|
lenalidomide • cyclophosphamide • plerixafor
1m
Trial completion date • Trial primary completion date
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Eylea (aflibercept intravitreal)
1m
Targeting Ikaros and Aiolos with pomalidomide fails to reactivate or induce apoptosis of the latent HIV reservoir. (PubMed, J Virol)
In this study, we investigated the effects of pomalidomide, an immunomodulatory imide drug that induces the degradation of Ikaros and Aiolos, on HIV latency reversal and death of infected cells. Using CD4+ T cells from people living with HIV on suppressive antiretroviral therapy, as well as an in vitro model of productive HIV infection, we found that pomalidomide induced T cell activation and expression of stress proteins but no evidence of latency reversal or selective death of infected cells.
Journal • IO biomarker
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IKZF1 (IKAROS Family Zinc Finger 1) • CD4 (CD4 Molecule) • PVR (PVR Cell Adhesion Molecule)
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pomalidomide
1m
Topical transdermal administration of lenalidomide nanosuspensions-based hydrogels against melanoma: In vitro and in vivo studies. (PubMed, Int J Pharm X)
Transdermal administration of Len-NBHs represents a promising adjuvant therapy for the treatment of malignant melanoma. Preoperative administration of Len-NBHs can inhibit the outward spread of melanoma, reduce tumor size, thereby decreasing the surgical excision area and improving patient survival rates and prognosis.
Preclinical • Journal • IO biomarker
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CD93 (CD93 Molecule)
|
lenalidomide
1m
Siltuximab in Large Granular Lymphocytic Leukemia (LGLL) (clinicaltrials.gov)
P1, N=6, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: May 2027 --> Nov 2027 | Trial primary completion date: May 2027 --> Nov 2026
Trial completion date • Trial primary completion date
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CD8 (cluster of differentiation 8) • B3GAT1 (Beta-1,3-Glucuronyltransferase 1)
|
Sylvant (siltuximab)
1m
Siltuximab in Large Granular Lymphocytic Leukemia (LGLL) (clinicaltrials.gov)
P1, N=6, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jan 2025 --> May 2027 | Trial primary completion date: Jan 2025 --> May 2027
Trial completion date • Trial primary completion date
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CD8 (cluster of differentiation 8) • B3GAT1 (Beta-1,3-Glucuronyltransferase 1)
|
Sylvant (siltuximab)
1m
Targeting ABCD1-ACOX1-MET/IGF1R axis suppresses multiple myeloma. (PubMed, Leukemia)
Conversely, inhibition of VLCFA degradation via suppression of peroxisomal acyl-CoA oxidase 1 (ACOX1) increased the cytotoxicity of bortezomib, its next-generation analog, carfilzomib, and the immunomodulatory agent lenalidomide. Mechanistically, inhibition of ACOX1 promoted the accumulation of VLCFA-containing cerebrosides, altered MET and IGF1R interaction with a cerebroside analog, and selectively inhibited the association of these kinases with the plasma membrane signaling platforms, importantly, without disrupting the platforms' integrity. Our study revealed a specific metabolic vulnerability of MM cells and identified a targetable axis linking VLCFA metabolism to the regulation of MET and IGF1R activity.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • ACOX1 (Acyl-CoA Oxidase 1)
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lenalidomide • bortezomib • carfilzomib
1m
IELSG40: Clarithromycin + Lenalidomide Combination: a Full Oral Treatment for Patients With Relapsed/Refractory Extranodal Marginal Zone Lymphoma (clinicaltrials.gov)
P2, N=44, Completed, International Extranodal Lymphoma Study Group (IELSG) | Active, not recruiting --> Completed | Trial completion date: Nov 2029 --> Dec 2024
Trial completion • Trial completion date
|
lenalidomide
1m
The histone demethylase KDM5C enhances the sensitivity of acute myeloid leukemia cells to lenalidomide by stabilizing cereblon. (PubMed, Cell Mol Biol Lett)
This study provides a possible strategy for a combination treatment with MLN4924 and Len for leukemia.
Journal
|
IKZF1 (IKAROS Family Zinc Finger 1) • CRBN (Cereblon) • IKZF3 (IKAROS Family Zinc Finger 3) • KDM5C (Lysine Demethylase 5C)
|
lenalidomide • pevonedistat (MLN4924)
1m
New P1 trial
1m
Study to Evaluate the Role of Siltuximab in Treatment of Cytokine Release Syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity (ICANS) Related to CAR-T Cell Therapy (clinicaltrials.gov)
P2, N=30, Recruiting, University of Alabama at Birmingham | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2026
Trial completion date • Trial primary completion date
|
Sylvant (siltuximab)
1m
IFM-CRd: Front-line Therapy with Carfilzomib, Lenalidomide, and Dexamethasone Induction (clinicaltrials.gov)
P2, N=46, Completed, University Hospital, Toulouse | Unknown status --> Completed
Trial completion
|
lenalidomide • cyclophosphamide • carfilzomib • dexamethasone
1m
Clinical Multicenter Study of Tocilizumab in the Treatment of sJIA-MAS (ChiCTR2300070171)
P=N/A, N=90, Recruiting, Children's Hospital, Zhejiang University School of Medicine; Children's Hospital, Zhejiang University School of Medicine | Not yet recruiting --> Recruiting
Enrollment open
|
CRP (C-reactive protein)
|
Actemra IV (tocilizumab) • cyclosporine
1m
Trial completion
|
CD20 (Membrane Spanning 4-Domains A1)
|
lenalidomide
1m
RECLAIM: Recovering from COVID-19 Lingering Symptoms Adaptive Integrative Medicine (clinicaltrials.gov)
P2/3, N=460, Suspended, University Health Network, Toronto | N=1000 --> 460 | Recruiting --> Suspended
Enrollment change • Trial suspension
|
Eyevinal (ibudilast)
2ms
ATLAS: Trial of Carfilzomib, Lenalidomide, Dexamethasone Versus Lenalidomide Alone After Stem-cell Transplant for Multiple Myeloma (clinicaltrials.gov)
P3, N=180, Active, not recruiting, University of Chicago | Trial primary completion date: Nov 2024 --> Nov 2025
Trial primary completion date
|
lenalidomide • carfilzomib • dexamethasone
2ms
Evaluating the impact of CRBN mutations on response to immunomodulatory drugs and novel CRBN-binding agents in myeloma. (PubMed, Blood)
Previous data suggests almost one third of myeloma patients acquire mutations in the key IMiD effector cereblon by the time they are pomalidomide refractory. Dynamic modelling based on a newly generated crystal structure of the DDB1/CRBN/lenalidomide complex, with greater resolution than those published to date, helped to understand the impact of these mutations. These results have important implications for the interpretation of CRBN sequencing results from patients for future therapy decisions, particularly differentiating those who may, despite relapsing on IMiDs with CRBN mutations, have the potential to still benefit from the use of CELMoD agents.
Journal
|
CRBN (Cereblon) • DDB1 (Damage Specific DNA Binding Protein 1)
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lenalidomide • pomalidomide
2ms
Osteosarcoma biomarker analysis and drug targeting prediction based on pyroptosis-related genes. (PubMed, Medicine (Baltimore))
Our findings suggest potential mechanisms of action for 22 pyroptosis-related genes in osteosarcoma and preliminarily predicted that the occurrence of osteosarcoma is closely related to pyroptosis, apoptosis, and immune regulation. Predicted Triethyl phosphate, Plinabulin, Siltuximab as potential osteosarcoma treatments.
Journal
|
TP53 (Tumor protein P53) • IL6 (Interleukin 6) • CASP3 (Caspase 3) • CASP8 (Caspase 8) • IL18 (Interleukin 18) • IL1A (Interleukin 1, alpha) • IL1B (Interleukin 1, beta)
|
plinabulin (BPI 2358) • Sylvant (siltuximab)
2ms
Dual targeting PD-L1 and 4-1BB to overcome dendritic cell-mediated lenalidomide resistance in follicular lymphoma. (PubMed, Signal Transduct Target Ther)
We conducted the first trial of immunotherapy rituximab plus lenalidomide in newly diagnosed FL in China (NCT03715309). Collectively, PU.1 is essential in immunomodulatory effect of FL through PD-1/PD-L1- and 4-1BB/4-1BBL-mediated microenvironmental modulation. Dual targeting PD-L1 and 4-1BB could be an alternative immunotherapeutic strategy in the chemo-free era of FL treatment.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-1 (Programmed cell death 1)
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PD-L1 expression
|
Rituxan (rituximab) • lenalidomide
2ms
New trial
2ms
New P4 trial
|
dexamethasone • pomalidomide
2ms
Large clones of Clonal Hematopoiesis affect outcome in Mantle Cell Lymphoma: Results from The FIL MCL0208 Clinical Trial. (PubMed, Blood Adv)
Here, we report a comprehensive NGS-based analysis of the M-CH mutational landscape at baseline and follow-up in patients enrolled in the Fondazione Italiana Linfomi (FIL) MCL0208 phase 3 trial (NCT02354313), evaluating lenalidomide maintenance versus observation after chemoimmunotherapy and autologous stem cell transplantation (ASCT) in untreated young MCL patients...Moreover, large M-CH clones showed longer time to hematologic recovery after ASCT compared to the remaining cohort (p=0.026). In conclusion, we showed for the first time that large CH clones might associate with unfavorable clinical impact in MCL patients.
Journal • IO biomarker
|
DNMT3A (DNA methyltransferase 1)
|
lenalidomide
2ms
Design, synthesis and biological evaluation of bisnoralcohol derivatives as novel IRF4 inhibitors for the treatment of multiple myeloma. (PubMed, Eur J Med Chem)
In vivo, SH514 effectively inhibited the proliferation of MM tumors, showing much better antitumor efficacy than the clinical drug lenalidomide, and exhibited no significant toxicity. Thus, these IRF4 inhibitors could serve as promising leads for the development of novel anti-multiple myeloma agents.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • IRF4 (Interferon regulatory factor 4) • PRDM1 (PR/SET Domain 1) • CDK1 (Cyclin-dependent kinase 1) • CANX (Calnexin) • CCNB1 (Cyclin B1) • E2F5 (E2F Transcription Factor 5)
|
CCND1 expression • IRF4 expression
|
lenalidomide
2ms
spiriTED: A Study to Investigate Efficacy and Safety of TOUR006 in Participants 18 to 80 Years of Age With Thyroid Eye Disease (clinicaltrials.gov)
P2, N=81, Recruiting, Tourmaline Bio, Inc. | Trial completion date: Feb 2026 --> Nov 2026 | Trial primary completion date: Feb 2025 --> Nov 2025
Trial completion date • Trial primary completion date