Immunomodulatory drugs (IMiDs) like lenalidomide and pomalidomide degrade IKZF1/3 and are combined with other therapies to treat hematologic malignancies, including multiple myeloma and non-Hodgkin lymphoma. Molecular docking studies suggested that DIX-01 may form stable ternary complexes with CRBN-IKZF1 and CRBN-GSPT1, providing a structural basis for its dual-target degradation activity. Furthermore, DIX-01 significantly inhibited tumor growth in a zebrafish xenograft model transplanted with human acute myeloid leukemia cells (MV4-11), supporting its potential as a therapeutic agent for hematologic malignancies.

1 day ago

Journal

IKZF1 (IKAROS Family Zinc Finger 1) • CRBN (Cereblon) • GSPT1 (G1 To S Phase Transition 1)

lenalidomide • pomalidomide

Pomalidomide enhances CAR-T cell therapeutic efficacy and remodels immune microenvironment in lymphoid malignancies. (PubMed, Cancer Immunol Immunother)

Pomalidomide synergizes with CAR-T by directly enhancing CAR-T function (memory, cytokine/chemokine production, metabolic fitness, and reduced exhaustion) and remodeling the suppressive immune microenvironment (increased cytotoxic effectors, diminished MDSC activity). These findings provide a crucial mechanistic rationale for optimizing pomalidomide-CAR-T combinations in refractory lymphoid malignancies.

1 day ago

Journal • IO biomarker

IFNG (Interferon, gamma) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • IL2 (Interleukin 2) • CXCL11 (C-X-C Motif Chemokine Ligand 11)

pomalidomide

RVd and CyBorD therapies remodel B-cell maturation signaling and alter immune and clonal architecture in multiple myeloma. (PubMed, Cancer Biol Ther)

Although lenalidomide/bortezomib/dexamethasone (RVd) and cyclophosphamide/bortezomib/dexamethasone (CyBorD) are clinically effective, their precise impacts on PC/B-cell maturation remain unclear. RVd responders further downregulated CD56, CD269, and CD329, and increased CD243. These shared and divergent modulations elucidate the molecular underpinnings of RVd and CyBorD efficacy and inform precision regimen selection.

1 day ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • FGFR3 (Fibroblast growth factor receptor 3) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • TNFRSF17 (TNF Receptor Superfamily Member 17) • RARA (Retinoic Acid Receptor Alpha) • ABCG2 (ATP Binding Cassette Subfamily G Member 2) • PAX5 (Paired Box 5) • KLF4 (Kruppel-like factor 4) • NCAM1 (Neural cell adhesion molecule 1) • SDC1 (Syndecan 1) • CD200 (CD200 Molecule) • IRF4 (Interferon regulatory factor 4) • CD52 (CD52 Molecule) • PRDM1 (PR/SET Domain 1) • NANOG (Nanog Homeobox) • NES (Nestin) • XBP1 (X-box-binding protein 1) • CD81 (CD81 Molecule) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2) • SLAMF7 (SLAM Family Member 7) • SIGLEC9 (Sialic Acid Binding Ig Like Lectin 9)

lenalidomide • bortezomib • cyclophosphamide

Lenalidomide for Adult Histiocyte Disorders (clinicaltrials.gov)

P2, N=12, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Aug 2025 --> Feb 2026

9 days ago

Trial completion date

BRAF (B-raf proto-oncogene)

lenalidomide

10d

Evaluate the Efficacy and Safety of FB704A in Adult With Severe Asthma (clinicaltrials.gov)

P2, N=20, Recruiting, Oneness Biotech Co., Ltd. | N=40 --> 20 | Trial completion date: Sep 2025 --> May 2026 | Trial primary completion date: Sep 2025 --> Feb 2026

10 days ago

Enrollment change • Trial completion date • Trial primary completion date

14d

Updates in low/intermediate-risk MDS. (PubMed, Hematology Am Soc Hematol Educ Program)

New therapeutic options to reduce the red blood cell (RBC) transfusion burden have emerged since 2020 and include luspatercept and imetelstat. Erythropoiesis-stimulating agents and lenalidomide also address anemia and are generally recommended to start at the time of transfusion dependency, although emerging data suggest that an earlier start of these interventions might offer clinical benefits...Targeted therapy directed to the presence of an IDH1 mutation is U.S. Food and Drug Administration (FDA) approved for the rare IDH1 mutated MDS (<10% of the time) and consideration to use an IDH2 inhibitor for IDH2 mutated MDS (<5% of the time) is reasonable. Interestingly, IDH mutations seem to appear with increased frequency in older patients and in patients with underlying autoimmune/rheumatological disorders.1.

14 days ago

Review • Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)

IDH1 mutation • IDH2 mutation

lenalidomide • Reblozyl (luspatercept-aamt) • Rytelo (imetelstat)

16d

Case Report: Secondary myelodysplastic syndrome following autologous stem cell transplantation in a patient with POEMS syndrome. (PubMed, Front Immunol)

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.

16 days ago

Journal

TP53 (Tumor protein P53)

TP53 mutation

lenalidomide

17d

PROTAC-based nanoantigens promote cross-presentation and trafficking of dendritic cell vaccine for enhanced antitumor efficacy. (PubMed, J Immunother Cancer)

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.

17 days ago

Journal

CCR7 (Chemokine (C-C motif) receptor 7)

lenalidomide

17d

Pomalidomide in Treating Patients With Kaposi Sarcoma and Human Immunodeficiency Virus Infection (clinicaltrials.gov)

P2, N=26, Completed, AIDS Malignancy Consortium | Trial completion date: Jan 2026 --> Apr 2025 | Active, not recruiting --> Completed

17 days ago

Trial completion • Trial completion date

pomalidomide • thalidomide

20d

Salvage Autologous Stem Cell Transplantation Outcomes and The Use of Maintenance in Relapsed Multiple Myeloma: Real world evidence from the Canadian Myeloma Research Group Database. (PubMed, Clin Lymphoma Myeloma Leuk)

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.

20 days ago

Clinical • Journal • HEOR • Real-world evidence

SLC1A5 (Solute Carrier Family 1 Member 5)

lenalidomide

23d

Design and Synthesis of Novel Candidate CK1δ Proteolysis Targeting Chimeras (PROTACs). (PubMed, Molecules)

In the present study, we established a modular synthetic platform to systematically generate a set of PROTAC degrader candidates consisting of the CK1δ-specific inhibitor scaffold, alkyl and PEG linker motifs with various lengths, and Cereblon (CRBN)-engaging pomalidomide and thalidomide derivatives as E3 ligase binders. The most potent PROTAC P1d inhibits the phosphorylation of downstream substrates through CK1δ/ε degradation. We establish the requirement of CUL4ACRBN and the proteasome for the P1d-mediated degradation of CK1δ/ε.

23 days ago

Journal

CRBN (Cereblon)

pomalidomide • thalidomide