P07: Results From the Cc-220-Mm-001 Dose-Expansion Phase of Iberdomide Plus Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma

Donk, Niels W.C.J. van de; Popat, Rakesh; Hulin, Cyrille; Jagannath, Sundar; Oriol, Albert; Richardson, PG; Facon, T.; Weisel, Katja; Larsen, Jeremy T.; Minnema, M.; Abdallah, Al Ola; Badros, Ashraf; Knop, Stefan; Stadtmauer, Edward A.; Chen, M; Nguyen, Tiffany; Amin, Alpesh; Peluso, Teresa; Lonial, Sagar

doi:10.1097/01.hs9.0000829600.37424.88

Cited by 5 publications

(2 citation statements)

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“…Specifically, the IberDd cohort exhibited a CBR of 47% and a DCR of 88%, and the IberVD cohort demonstrated a CBR of 65% and a DCR of 85%, emphasizing the efficacy of this treatment approach [54]. The analysis revealed diverse temporal outcomes, with mDoR ranging from non-reported to 8.3 months, mPFS spanning 2.8 to 3.7 months, and mOS exhibiting varied survival outcomes across evaluated cohorts in RRMM treatments [55][56].…”

Section: Clinical Trialsmentioning

confidence: 92%

A Review of the Immunomodulatory Activity of Novel Drug Iberdomide (CC-220) for Multiple Myeloma

Cardenas,

Cosio,

Cua

et al. 2023

Int. J. Res. Publ. Rev.

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Iberdomide (CC-220) is a novel immunomodulatory drug currently under investigation for the treatment of multiple myeloma (MM), demonstrating potential therapeutic efficacy in clinical trials. It is a cereblon E3 ligase modulator (CELMoD) that functions by stimulating the ubiquitination and proteasome-dependent degradation of the Ikaros and Aiolos proteins, which leads to tumoricidal and immunomodulatory action in myeloma cells. Preclinical studies demonstrate Iberdomide's potent anti-myeloma and immunomodulatory activities, surpassing established immunomodulatory drugs (IMiDs) like Lenalidomide and Pomalidomide. Iberdomide's enhanced cereblon binding affinity suggests superior efficacy in degrading key transcription factors crucial for MM cell survival. Initial clinical trial data indicate favorable safety profiles and promising efficacy, particularly in combination regimens. Preclinical and initial clinical data suggest its potential to overcome immunomodulatory drug resistance and enhance the immune-mediated killing of MM cells. Ongoing Phase 3 trials and additional studies will be crucial for evaluating long-term efficacy, safety, and optimal dosage, positioning Iberdomide as a transformative agent in refractory and relapsed MM scenarios.

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Section: Clinical Trialsmentioning

confidence: 92%

A Review of the Immunomodulatory Activity of Novel Drug Iberdomide (CC-220) for Multiple Myeloma

Cardenas,

Cosio,

Cua

et al. 2023

Int. J. Res. Publ. Rev.

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“…In the phase 1/2 CC-220-MM-001 study (NCT02773030), iberdomide in combination with dexamethasone was evaluated [ 91 ]. Almost all of the 107 enrolled patients were triple refractory (refractory to IMID, PI and anti-CD38 monoclonal antibody), 25% had an extramedullary disease, and 30% had high-risk cytogenetics.…”

Section: Cereblon E3 Ligase Modulators (Celmods)mentioning

confidence: 99%

CRL4CRBN E3 Ligase Complex as a Therapeutic Target in Multiple Myeloma

Barankiewicz

Salomon-Perzyński

Misiewicz-Krzemińska

et al. 2022

Cancers

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Multiple myeloma (MM) is the second most common hematological malignancy with a recurrent clinical course. The introduction of immunomodulatory drugs (IMiDs) was one of the milestones in MM therapy leading to a significant improvement in patients’ prognosis. Currently, IMiDs are the backbone of MM therapy in newly diagnosed and relapsed/refractory settings. It is now known that IMiDs exert their anti-myeloma activity mainly by binding cereblon (CRBN), the substrate receptor protein of the CRL4 E3 ubiquitin ligase (CRL4CRBN) complex. By binding CRBN, IMiDs alter its substrate specificity, leading to ubiquitination and proteasomal degradation of proteins essential for MM cell survival. Following the success of IMiDs, it is not surprising that the possibility of using the CRL4CRBN complex’s activity to treat MM is being further explored. In this review, we summarize the current state of knowledge about novel players in the MM therapeutic landscape, namely the CRBN E3 ligase modulators (CELMoDs), the next generation of IMiDs with broader biological activity. In addition, we discuss a new strategy of tailored proteolysis called proteolysis targeting chimeras (PROTACs) using the CRL4CRBN to degrade typically undruggable proteins, which may have relevance for the treatment of MM and other malignancies in the future.

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No needles needed: All-oral therapy options for relapsed and refractory multiple myeloma

et al. 2023

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P07: Results From the Cc-220-Mm-001 Dose-Expansion Phase of Iberdomide Plus Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma

Cited by 5 publications

References 0 publications

A Review of the Immunomodulatory Activity of Novel Drug Iberdomide (CC-220) for Multiple Myeloma

A Review of the Immunomodulatory Activity of Novel Drug Iberdomide (CC-220) for Multiple Myeloma

CRL4CRBN E3 Ligase Complex as a Therapeutic Target in Multiple Myeloma

No needles needed: All-oral therapy options for relapsed and refractory multiple myeloma

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