Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

In preclinical studies, oral azacitidine (CC-486), a hypomethylating agent, has been shown to have a direct anti-MM effect and in vitro anti-MM synergism when combined with lenalidomide (LEN). We present a phase 1b, single center, 3 × 3 dose escalation study with planned expansion at maximum tolerated dose (MTD), which assessed the safety and efficacy of combining CC-486 with LEN (25 mg d1-21/28) and dexamethasone (DEX) (40 mg weekly) in patients with relapsed/refractory MM who had previously failed LEN. Twenty-four patients were enrolled. The MTD of CC-486 was 150 mg d1-21; recommended expansion dose was 100 mg d1-21. Adverse events were predictable and manageable. ORR was 37.5%; clinical benefit rate was 50%. Median OS was 10.3 m; median PFS was 2.6 m. Correlative proteomics demonstrated that higher MM tumor cell cereblon expression (pretreatment, C1D5) was associated with superior PFS/OS. CC-486, LEN and DEX produced meaningful clinical responses in heavily treated LEN refractory MM patients. Proteomics may have utility in predicting clinical outcomes.

Original publication




Journal article


Leuk lymphoma

Publication Date





2143 - 2151


Relapsed/refractory myeloma, cereblon, lenalidomide, oral azacitidine, proteomics, Adaptor Proteins, Signal Transducing, Administration, Oral, Aged, Aged, 80 and over, Antimetabolites, Antineoplastic, Antineoplastic Combined Chemotherapy Protocols, Azacitidine, DNA Methylation, Dexamethasone, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Resistance, Neoplasm, Epigenesis, Genetic, Female, Gene Expression Regulation, Neoplastic, Humans, Lenalidomide, Male, Maximum Tolerated Dose, Middle Aged, Multiple Myeloma, Neoplasm Recurrence, Local, Prognosis, Progression-Free Survival, Proteomics, Ubiquitin-Protein Ligases