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    DRUG:

    lenalidomide

    i
    Other names: IMiD3, CDC 5013, CC-5013, CDC-501, CDC-5013, IMiD-1, IMiD-3, ENMD-0997, CC 5013, CDC 5013, ENMD 0997
    Company:
    Generic mfg.
    Drug class:
    TNFα inhibitor, IL-6 inhibitor, IL-12 inhibitor
    Related drugs:
    1d
    Targeting Ikaros and Aiolos: Next-Generation Cereblon E3 Ligase Modulators in MM. (PubMed, Eur J Haematol)
    With frontline therapeutic strategies increasingly employing quadruplet induction regimens and prolonged lenalidomide maintenance, resistance to traditional IMiDs has become more prevalent, creating an urgent need for next-generation cereblon E3 ligase modulators (CELMoDs) capable of overcoming IMiD refractoriness and enhancing the immunologic microenvironment. Iberdomide (CC-220) and mezigdomide (CC-92480) are rationally engineered CELMoDs designed to achieve deeper degradation of Ikaros (IKZF1) and Aiolos (IKZF3), restore cereblon-mediated activity, and potentiate immune effector responses...We examine how their pharmacodynamic properties differ from classical IMiDs, their relevance in triple-class and penta-refractory MM, and their integration into emerging combination strategies with monoclonal antibodies and T-cell-redirecting immunotherapies. Special emphasis is placed on ongoing and future trials that may refine their therapeutic positioning, alongside a critical appraisal of the limitations and future directions of this rapidly advancing drug class.
    Review • Journal
    |
    IKZF1 (IKAROS Family Zinc Finger 1) • CRBN (Cereblon) • IKZF3 (IKAROS Family Zinc Finger 3)
    |
    lenalidomide • iberdomide (CC-220) • mezigdomide (CC-92480)
    1d
    Dose Finding Study of Ibrutinib Plus Lenalidomide / Rituximab in Relapsed or Refractory Mantle Cell Lymphoma (clinicaltrials.gov)
    P1, N=27, Active, not recruiting, Hackensack Meridian Health | Trial completion date: Oct 2025 --> Jul 2026
    Trial completion date
    |
    Imbruvica (ibrutinib) • Rituxan (rituximab) • lenalidomide
    3d
    Belantamab Mafodotin and Lenalidomide for the Treatment of Multiple Myeloma in Patients With Minimal Residual Disease Positive After Stem Cell Transplant (clinicaltrials.gov)
    P2, N=4, Active, not recruiting, Roswell Park Cancer Institute | Suspended --> Active, not recruiting | N=20 --> 4
    Enrollment closed • Enrollment change • Minimal residual disease
    |
    lenalidomide • Blenrep (belantamab mafodotin-blmf)
    4d
    Celestimo: A Study Evaluating the Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide With a US Extension of Mosunetuzumab in Combination With Lenalidomide in Participants With Follicular Lymphoma (clinicaltrials.gov)
    P3, N=478, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Jan 2026 --> May 2026
    Trial primary completion date
    |
    CD20 (Membrane Spanning 4-Domains A1)
    |
    Rituxan (rituximab) • lenalidomide • Lunsumio (mosunetuzumab-axgb)
    4d
    PLUTO: Combining Latency Reversing Agents to Address the HIV Reservoir (clinicaltrials.gov)
    P1/2, N=30, Not yet recruiting, Erasmus Medical Center
    New P1/2 trial
    |
    CD4 (CD4 Molecule)
    |
    lenalidomide
    4d
    Combination Treatment Therapy Approaches for the Treatment of High-Risk Multiple Myeloma, REACH Trial (clinicaltrials.gov)
    P2, N=17, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting | N=75 --> 17
    Enrollment closed • Enrollment change
    |
    TP53 (Tumor protein P53)
    |
    TP53 mutation
    |
    lenalidomide • carfilzomib • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • Hemady (dexamethasone tablets) • dexamethasone injection
    5d
    GMMG-HD7: Trial on the Effect of Isatuximab to Lenalidomide/Bortezomib/Dexamethasone (RVd) Induction and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma (GMMG HD7) (clinicaltrials.gov)
    P3, N=662, Active, not recruiting, University of Heidelberg Medical Center | Trial completion date: Mar 2027 --> Jun 2028 | Trial primary completion date: May 2025 --> Jun 2028
    Trial completion date • Trial primary completion date
    |
    lenalidomide • bortezomib • doxorubicin hydrochloride • cyclophosphamide • dexamethasone • Sarclisa (isatuximab-irfc) • dexamethasone injection
    5d
    GLOBRYTE: A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma (clinicaltrials.gov)
    P3, N=182, Recruiting, Hoffmann-La Roche | Trial completion date: Sep 2027 --> Mar 2028 | Trial primary completion date: Feb 2027 --> Aug 2027
    Trial completion date • Trial primary completion date
    |
    CCND1 (Cyclin D1)
    |
    Chr t(11;14)
    |
    Rituxan (rituximab) • lenalidomide • Gazyva (obinutuzumab) • bendamustine • Actemra IV (tocilizumab) • Columvi (glofitamab-gxbm)
    7d
    SIDNEY: A Novel Vaccine (EO2463) as Monotherapy and in Combination, for Treatment of Patients With Indolent Non-Hodgkin Lymphoma (clinicaltrials.gov)
    P1/2, N=80, Recruiting, Enterome | N=60 --> 80 | Trial completion date: May 2032 --> May 2034 | Trial primary completion date: May 2026 --> May 2029
    Enrollment change • Trial completion date • Trial primary completion date
    |
    Rituxan (rituximab) • lenalidomide • EO2463
    8d
    A Prospective, Single-Arm, Multicenter Study on the Efficacy and Safety of Lisaftoclax Combined with Rituximab and Lenalidomide Regimen in the Treatment of Previously Untreated Elderly Patients with Mantle Cell Lymphoma (ChiCTR2500115112)
    P=N/A, N=40, Not yet recruiting, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University; Jiangsu Province Hospital, The First Affiliated Hospital of Na
    New trial
    |
    Rituxan (rituximab) • lenalidomide • lisaftoclax (APG-2575)
    8d
    A multicenter prospective randomized controlled study of quadruplet regimen in newly diagnosed transplant-ineligible high-risk multiple myeloma patients (ChiCTR2600116772)
    P4, N=117, Not yet recruiting, Peking Union Medical College Hospital; Peking Union Medical College Hospital
    New P4 trial
    |
    TP53 (Tumor protein P53)
    |
    TP53 mutation
    |
    lenalidomide • bortezomib • Sarclisa (isatuximab-irfc)
    8d
    Iberdomide Maintenance Versus Lenalidomide Maintenance Therapy Following Autologous Stem Cell Transplant in Participants with NDMM (ChiCTR2600117745)
    P3, N=1216, Recruiting, Peking University People's Hospital; Peking University People's Hospital
    New P3 trial
    |
    lenalidomide • iberdomide (CC-220)