mezigdomide (CC-92480) / BMS - LARVOL DELTA

Mezigdomide (CC-92480) Following Idecabtagene Vicleucel (Ide-Cel) in Relapsed/Refractory Multiple Myeloma Is Safe and Leads to Deepening of Responses (IMS 2026) - "This study is the first demonstrating that sequential mezigdomide following ide-cel is feasible. Mezigdomide is safe in the post CAR-T setting and shows preliminary efficacy in patients who have residual myeloma, supporting the hypothesis that mezigdomide augments CAR-T cell response via enhanced residual CAR-T efficacy and/or direct CELMoD anti-myeloma activity."

Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia

Phase I/II Study of Mezigdomide and Elranatamab for Relapsed/Refractory Multiple Myeloma Patients (MELT-MM): Updated Results From Part 1 (IMS 2026) - P1/2 | "Eligible patients had R/R MM after ≥2 prior lines including a proteasome inhibitor and lenalidomide, were anti-BCMA–naïve, ECOG PS ≤2, with measurable disease. Mezigdomide plus elranatamab demonstrates profound and rapid antimyeloma activity with a manageable safety profile. Both 0.3 mg and 0.6 mg were selected as RP2Ds. Part 2 will proceed as a 1:1 randomized expansion (Arm A 0.3 mg vs."

Clinical • P1/2 data • Acute Kidney Injury • Cytomegalovirus Infection • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Nephrology • Neutropenia • Renal Disease • Thrombocytopenia • IKZF1 • PD-1 • TIGIT

Elranatamab-bcmm (Elrexfio) plus mezigdomide produced preliminary response signals in patients with relapsed/refractory multiple myeloma, according to results from the phase 1b portion of the MELT-MM trial (NCT06645678) presented at the 23rd Annual International Myeloma Society (IMS) Meeting & Exposition. (Cancer Network) - "At a data cutoff of July 31, 2026, and a median follow-up of 13.7 months (range, 8.6-19.3) from cycle 0, day 1, all 13 evaluable patients achieved a response for an overall response rate (ORR) of 100%, including a stringent complete response (sCR) in 12 patients (92.3%) and a very good partial response in 1 patient (7.7%). The median time to response was 17 days (range, 11-45), and the median time to best response was 5.6 months (range, 3.3-5.9). Responses were consistent across the mezigdomide 0.3-mg (n = 7) and 0.6-mg (n = 6) dose cohorts and across subgroups, including patients with prior T-cell engager exposure, triple-class–refractory disease, penta-refractory disease, and soft tissue extramedullary disease, all of which had a 100% ORR....Patient-sample analyses supported the biological rationale for the combination."

P1 data • Multiple Myeloma

Characterization of the IKZF1 Interactome in Multiple Myeloma and Its Modulation by CELMoDs (IMS 2026) - " IKZF1 interactors were identified using TurboID proximity labeling in MM.1S cells expressing IKZF1-TurboID or nuclear (NLS-)TurboID controls, followed by mezigdomide treatment with proteasome inhibitor, streptavidin enrichment, and LC-MS analysis... This study provides the first comprehensive map of the IKZF1 interactome in MM, integrating proximity labeling and functional genomics. We reveal extensive, MM-specific IKZF1 interactions and a network of NF-κB regulators associated with IKZF1, suggesting crosstalk between IKZF1 regulation and NF-κB signaling under CELMoD treatment. These findings may inform strategies to overcome drug resistance."

IO biomarker • Hematological Malignancies • Inflammation • Multiple Myeloma • CCND2 • CD40 • CRBN • DDB1 • IKZF1 • IKZF3 • IL17RB • MCL1 • NFKBIE • PRDM1 • RELA • TNFA • TNFAIP3

Whole Proteome Analysis of Multiple Myeloma Patient Samples Provides New Insights into IMiD/CELMoD Resistance (IMS 2026) - " We analysed proteomic changes associated with relapse on lenalidomide (Len) therapy using paired baseline and relapse CD138+ samples from patients enrolled in the Myeloma XI trial. In a separate analysis we explored degradation profiles in patient MM cells (CD138+ samples from IMiD sensitive and resistant patients) treated ex vivo with IMiDs/CELMoDs (Len 10uM, pomalidomide [Pom] 10uM, iberdomide [Iber] 1uM and/or mezigdomide [Mezi] 1uM vs DMSO control over 4h)... Exploring the whole proteome of primary patient samples enhances our understanding of mechanisms of resistance and has highlighted potential novel therapeutic targets in IMiD resistance such as CTAG1B/CTAG1A, for which TCR engineered T cells have been studied in solid tumours."

Clinical • Hematological Malignancies • Multiple Myeloma • Solid Tumor • CDC37 • CHAF1B • CRBN • CTAG1A • CTAG1B • DHFR • IKZF1 • NCAPD2 • SDC1

Trial in Progress: Phase 1 Trial of Arlocabtagene Autoleucel (Arlo-Cel) Plus Mezigdomide (MEZI) or Elranatamab (ELRA) in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM) (IMS 2026) - P1 | "This trial will evaluate arlo-cel combinations, including with MEZI and ELRA maintenance, in RRMM."

Clinical • P1 data • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • IKZF1

Selinexor, Mezigdomide, and Dexamethasone in Relapsed/Refractory Multiple Myeloma (RRMM) Patients (Pts) Relapsing / Ineligible for T-Cell-Redirecting Therapy (TCRT): STOMP Phase 1 Preliminary Results (IMS 2026) - P1/2 | "Three pts relapsed after TCRT (3 cilta-cel; 2 talquetamab; 1 IGM-2644) and 4 after belantamab mafodotin, with 3 pts refractory to B-cell maturation antigen–targeted therapy. For the SMd all-oral combination, TEAEs were consistent with AE profiles for S and M, and no new safety signals were detected. The DLT of G4 neutropenia was manageable with filgrastim and dose reduction. Across all dose levels SMd showed efficacy in pts with heavily pretreated RRMM in whom TCRT had failed or who could not receive TCRT."

Clinical • IO biomarker • P1 data • Cardiovascular • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukopenia • Multiple Myeloma • Neutropenia • Targeted Protein Degradation • Thrombocytopenia • CCR7 • CRBN • TIGIT • XPO1

Monocytic Myeloid-Derived Suppressor Cells in Multiple Myeloma: Roles of Soluble Factors, Tumor-Derived Exosomes, and Modulation by Imids and Celmods (IMS 2026) - "lenalidomide and pomalidomide reduced CCL5 and MIF in myeloma cells, downregulated CCR5 in PBMCs, and induced IRF-8. Next-generation cereblon E3 ligase modulators, especially iberdomide and mezigdomide, were more potent, suppressing M-MDSC induction at nanomolar concentrations, reducing CCL5 expression, enhancing ISG15 and other interferon-related signatures in CD33-positive myeloid cells, and modulating gene expression patterns and decreasing IL-10 and MIF in myeloma cells... This reframes MM immune escape as an active, targetable process. Targeting CCL5, MIF, IL-10, exosomal miR-106a-5p/miR-146a-5p, or downstream pathways may restore anti-myeloma immunity."

IO biomarker • Myeloid-derived suppressor cells • Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation • CCL5 • CD14 • CD33 • CRBN • IDO1 • IL10 • IL6 • IRF8 • ISG15 • MIF • MIR106A • MIR146A • MYD88 • NDUFA2 • PD-L1 • TNFA

Mezigdomide, Carfilzomib, and Dexamethasone (Mezikd) vs Carfilzomib and Dexamethasone (Kd) in Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Phase 3 SUCCESSOR-2 Trial (IMS 2026) - P3 | "Introduction: Patients (pts) entering second-line treatment (tx) are increasingly anti-CD38 mAb- and lenalidomide (LEN)-exposed, limiting tx options...Median (range) age was 68 (30–85) y with 25.1% of pts ≥75 y; median (range) number of prior LOTs was 2 (1–9); 92.1% of pts were triple-class-exposed, with 85.8% refractory to an anti-CD38 mAb and 75.8% to LEN; 37.2% were exposed to pomalidomide and 7.3% to anti-BCMA tx... MeziKd showed a clinically meaningful PFS benefit as early as first relapse in predominantly triple-class-exposed, anti-CD38 mAb- and LEN-refractory pts, a population with significant unmet need. These data support Mezi, a potent oral tx with a predictable and manageable safety profile, as a readily accessible potential new standard of care for RRMM across multiple settings."

P3 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • IKZF1

Inobrodib Treatment Synergises with Imids to Epigenetically Downregulate IRF4 Expression in Drug-Resistant Myeloma (IMS 2026) - "Standard-of-care immunomodulatory drugs (IMiDs), e.g. pomalidomide (Pom), target the TFs IKZF1/3 to the E3 ubiquitin ligase CRBN for degradation, resulting in IRF4 downregulation...The P300/CBP inhibitor Inobrodib (Ino), in combination with Pom and dexamethasone, is currently showing promise in phase IIa clinical trials for RRMM...Ino-resistant cells displayed tolerance to both Pom and the CELMoD mezigdomide, and Pom-resistant cells were tolerant to Ino... Our findings implicate epigenetic rewiring of IRF4 expression as a common mechanism of resistance to Ino and IMiDs. However, combined treatment with Pom and Ino is able to downregulate IRF4 expression in resistant cells, depending on the presence of functional CRBN. Therapeutically, this indicates that addition of Ino to Pom treatment may help resensitise IMiD-resistant RRMM patients."

Hematological Malignancies • Multiple Myeloma • Targeted Protein Degradation • ANXA5 • CRBN • IKZF1 • IRF4

Health-Related Quality of Life with Mezigdomide, Carfilzomib, and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Phase 3 SUCCESSOR-2 Trial (IMS 2026) - P3 | "Introduction: Interim results from the phase 3 SUCCESSOR-2 study showed that adding mezigdomide (Mezi) to carfilzomib-dexamethasone (Kd) significantly prolonged progression-free survival (PFS) versus Kd alone in patients (pts) with relapsed/refractory multiple myeloma (RRMM) previously treated with anti-CD38 monoclonal antibodies (mAbs) and lenalidomide (LEN). Adding Mezi to Kd in pts with RRMM did not meaningfully compromise pt-reported global QoL, physical or role functioning, pain, fatigue, disease symptoms, or perceived treatment side effects. Together with the reported PFS benefit, these findings support MeziKd as improving disease control without a broad HRQoL trade-off."

Clinical • HEOR • P3 data • Hematological Malignancies • Multiple Myeloma

Characterization of Hematologic Adverse Events and Infections with Mezigdomide, Carfilzomib, and Dexamethasone (Mezikd) in Relapsed/Refractory Multiple Myeloma (RRMM): Phase 3 SUCCESSOR-2 Trial (IMS 2026) - P3 | "Introduction: In the phase 3 SUCCESSOR-2 trial (NCT05552976), MeziKd improved progression-free survival vs Kd (median 18.0 vs 8.3 months) in patients (pts) with RRMM previously treated with anti-CD38 monoclonal antibodies (mAbs) and lenalidomide (LEN). In SUCCESSOR-2, increased neutropenia, thrombocytopenia, and infections observed with MeziKd vs Kd were manageable with standard clinical practice (dose modifications, G-CSF, infection prophylaxis), with low Mezi discontinuation due to these AEs. G-CSF for Gr 3/4 neutropenia was an effective strategy to maintain treatment. MeziKd represents a clinically feasible outpatient treatment option for anti-CD38 mAb- and LEN-exposed RRMM."

Adverse events • P3 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia

Characterization of the IKZF1 Interactome in Multiple Myeloma and Its Modulation by CELMoDs (IMS 2026) - " IKZF1 interactors were identified using TurboID proximity labeling in MM.1S cells expressing IKZF1-TurboID or nuclear (NLS-)TurboID controls, followed by mezigdomide treatment with proteasome inhibitor, streptavidin enrichment, and LC-MS analysis... This study provides the first comprehensive map of the IKZF1 interactome in MM, integrating proximity labeling and functional genomics. We reveal extensive, MM-specific IKZF1 interactions and a network of NF-κB regulators associated with IKZF1, suggesting crosstalk between IKZF1 regulation and NF-κB signaling under CELMoD treatment. These findings may inform strategies to overcome drug resistance."

IO biomarker • Hematological Malignancies • Inflammation • Multiple Myeloma • CCND2 • CD40 • CRBN • DDB1 • IKZF1 • IKZF3 • IL17RB • MCL1 • NFKBIE • PRDM1 • RELA • TNFA • TNFAIP3

Whole Proteome Analysis of Multiple Myeloma Patient Samples Provides New Insights Into IMiD/CELMoD Resistance (IMS 2026) - " We analysed proteomic changes associated with relapse on lenalidomide (Len) therapy using paired baseline and relapse CD138+ samples from patients enrolled in the Myeloma XI trial. In a separate analysis we explored degradation profiles in patient MM cells (CD138+ samples from IMiD sensitive and resistant patients) treated ex vivo with IMiDs/CELMoDs (Len 10uM, pomalidomide [Pom] 10uM, iberdomide [Iber] 1uM and/or mezigdomide [Mezi] 1uM vs DMSO control over 4h)... Exploring the whole proteome of primary patient samples enhances our understanding of mechanisms of resistance and has highlighted potential novel therapeutic targets in IMiD resistance such as CTAG1B/CTAG1A, for which TCR engineered T cells have been studied in solid tumours."

Clinical • Hematological Malignancies • Multiple Myeloma • Solid Tumor • CDC37 • CHAF1B • CRBN • CTAG1A • CTAG1B • DHFR • IKZF1 • NCAPD2 • SDC1

Mezigdomide Plus Elranatamab Produces Significant Response in Early MELT-MM Analysis (Pharmacy Times) - "All 13 evaluable patients responded, and 12 achieved CR or better. Among 8 patients with stringent CR and available minimal residual disease (MRD) results, 7 (87.5%) achieved MRD negativity. The median time to first response was 17 days, and median progression-free survival was not reached after a median follow-up of 10 months."

P1/2 data • Multiple Myeloma

Mezigdomide, Carfilzomib, and Dexamethasone vs Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Results From the Phase 3 SUCCESSOR-2 Trial (SOHO 2026) - P3 | "Context: More patients with MM entering second-line treatment are anti-CD38 monoclonal antibody (mAb)– and lenalidomide-exposed, limiting treatment options. MeziKd showed clinically meaningful PFS benefit with a predictable and manageable safety profile in predominantly triple-class-exposed anti-CD38 mAb– and lenalidomide-refractory patients. These data support MeziKd as a readily accessible, potential new standard of care for RRMM."

P3 data • Hematological Malignancies • Multiple Myeloma • Oncology • CRBN • IKZF1

Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma. (PubMed, N Engl J Med) - P1/2 | "The all-oral combination of mezigdomide plus dexamethasone showed promising efficacy in patients with heavily pretreated multiple myeloma, with treatment-related adverse events consisting mainly of myelotoxic effects. (Funded by Celgene, a Bristol-Myers Squibb Company; CC-92480-MM-001 ClinicalTrials.gov number, NCT03374085; EudraCT number, 2017-001236-19.)."

Journal • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Plasmacytoma • Targeted Protein Degradation • CRBN

Mezigdomide (MEZI), tazemetostat (TAZ), and dexamethasone (DEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): preliminary results from the CA057-003 trial (IMW 2024) - P1/2 | "The third agent in each combination intervenes on a key oncogenic pathway upregulated in RRMM: 1) EZH2 inhibitor TAZ for PRC2 complex dysregulation; 2) BET inhibitor BMS-986158 for CKS1B (on chromosome 1q) amplification; 3) or MEK inhibitor trametinib for RAS-RAF-MEK-ERK activation. MEZI+TAZ+DEX showed promising preliminary efficacy and safety in pts with RRMM, with no new safety concerns."

Clinical • Anemia • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Plasmacytoma • Pulmonary Disease • Septic Shock • CKS1B • IKZF1

Phase 1 study of ktx-1001, a first-in-class oral MMSET/NSD2 inhibitor, demonstrates clinical activity in relapsed/refractory multiple myeloma (ASH 2025) - P1 | "Preclinically, KTX-1001synergistically inhibited cell viability in MM cell lines when combined with a proteasome inhibitor (PI),immunomodulatory drug (IMiD), or cereblon E3 ligase modulator (CELMoD™). Pairedbone marrow samples further confirmed on-target PD effects, with a marked reduction in H3K36me2levels in MM cells at Cycle 2 Day 1 with observed anti-MM effect of reduced proliferation of MM cells withconcomitant increased proliferation in immune cells in pts achieving clinical benefit. ConclusionsKTX-1001 is a novel agent showing tolerable safety profile in RRMM and demonstrating promising singleagent activity in heavily pretreated, triple class refractory RRMM including those with high-risk features.KTX is currently evaluated in ongoing study in combination with carfilzomib and the investigationalCELMoD™ mezigdomide in t(4; 14) RRMM pts."

Clinical • IO biomarker • P1 data • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Targeted Protein Degradation • Thrombocytopenia • CRBN • NSD2

Mezigdomide (MEZI) Plus Dexamethasone (DEX) and Daratumumab (DARA) or Elotuzumab (ELO) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from the CC-92480-MM-002 Trial (ASH 2023) - P1/2 | "Intravenous (IV; 16 mg/kg) or subcutaneous (1800 mg) DARA was given weekly (C1–2), then biweekly (C3–6), and monthly (≥ C7) for subcohorts B1 and B3, and weekly (C1–3) then on D1 of each 21-D (C4–8) or 28-D (≥ C9) cycle for subcohort B2; with weekly oral/IV DEX (40 mg; 20 mg > 75 y or body mass index < 18.5 kg/m2). MeziDd showed promising efficacy and a manageable safety profile in pts with RRMM and 2–4 prior lines of therapy, as did MeziEd in pts with prior anti-CD38 mAb therapy. The immune activity of MEZI was consistent with previous preclinical reports. Improved safety and efficacy may be achieved by schedule and dose adjustments."

Clinical • Cardiovascular • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Plasmacytoma • Pulmonary Embolism • Respiratory Diseases • Targeted Protein Degradation • Thrombocytopenia • CRBN

A phase 3, two-stage, randomized study of mezigdomide, carfilzomib, and dexamethasone (MeziKd) versus carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM): SUCCESSOR-2. (ASCO 2023) - P3 | "MeziKd has shown potent synergistic antiproliferative activity in MM cell lines resistant to lenalidomide (LEN), and in a phase 1/2 study showed promising preliminary efficacy and safety in RRMM...Tx in the Kd arm consists of 28-D cycles with 20 mg/m2 IV CFZ on D1 and 2 of C1, then 56 mg/m2 on D8, 9, 15, and 16 of C1, and on D1, 2, 8, 9, 15, and 16 of ≥ C2; and 20 mg oral/IV DEX (10 mg optional in certain pt groups) on D1, 2, 8, 9, 15, 16, 22, and 23...Enrollment began in October 2022 and is ongoing. Clinical trial information: NCT05552976."

Clinical • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation • CRBN • IKZF1

ISABELA: A phase 2 study of isatuximab, belantamab mafodotin, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma. (ASCO 2026) - P2 | " ISABELA is an investigator-initiated study (NCT05922501) enrolling up to 50 patients (pts) with RRMM who have received at least 1 prior line of therapy including lenalidomide and a proteasome inhibitor...Prior therapies included pom (59%), bortezomib (82%), carfilzomib (41%), ixazomib (35%), CD38 antibody (59%) [daratumumab, 59%; isa 12%], and auto SCT (24%). Prior exposure to newer therapies included drugs that target BCMA (24%) [teclistamab 6%, elranatamab 18%, CAR T-cells 12%]; GPRC5D (12%) [talquetamab]; and cereblon (29%) [mezigdomide, 29%; cemsidomide, 12%]... This is the first report in RRMM for the combination of belamaf with a CD38 monoclonal antibody. The ISABELA regimen shows promising preliminary activity in RRMM with an ORR of 86% and 16-month PFS of 73%, including quad-class-exposed pts treated with anti-BCMA therapy, with manageable, reversible AEs."

P2 data • Cardiovascular • Hematological Malignancies • Hypertension • Infectious Disease • Multiple Myeloma • Neutropenia • Ophthalmology • Plasmacytoma • Thrombocytopenia • CRBN

Mezigdomide (MEZI) in Novel-Novel Combinations for Relapsed or Refractory Multiple Myeloma (RRMM): Preliminary Results from the CA057-003 Trial (ASH 2024) - P1/2 | "The CA057-003 phase 1/2 trial (NCT05372354) is evaluating all-oral, novel-novel targeted triplet combination regimens using a MEZI plus dexamethasone (DEX) (MEZId) backbone in patients (pts) with RRMM. The third agent in each combination intervenes on a key oncogenic pathway identified by The Myeloma Genome Project to be upregulated in RRMM : the EZH2 inhibitor tazemetostat (TAZ) for PRC2 complex dysregulation, the BET inhibitor BMS-986158 for CKS1b (located on Chr 1q) amplification, and the MEK inhibitor trametinib (TRAM) for RAS-RAF-MEK-ERK activation...These results provide a rationale for further exploration of these novel all-oral combinations. Accrual continues and updated results will be presented at the meeting."

IO biomarker • Multiple Myeloma • Neutropenia • Plasmacytoma • CKS1B • IKZF1

Mezigdomide, carfilzomib, and dexamethasone versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma (SUCCESSOR-2): a phase 3, open-label, randomised controlled trial. (PubMed, Lancet) - P3 | "Mezigdomide-carfilzomib-dexamethasone provided a significant PFS benefit compared with carfilzomib-dexamethasone alone, with higher rates of grade 3 or 4 adverse events, including infections, which were mostly manageable with standard clinical practice and supportive care. These findings support mezigdomide-carfilzomib-dexamethasone as a clinically meaningful treatment option as early as first relapse in predominantly triple-class-exposed, anti-CD38 antibody-refractory and lenalidomide-refractory patients, a growing population with substantial unmet need."

Journal • P3 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Targeted Protein Degradation • CRBN • IKZF1

Early deep response to cilta-cel as 2nd CAR T-Cell therapy after CELMoD-based bridging for advanced multiple myeloma. (PubMed, Ann Hematol) - "We report on a 58-year-old male with high-risk IgA kappa multiple myeloma who was heavily pretreated and received idecabtagene vicleucel as sixth-line therapy, achieving a deep response lasting for approximately one year. Following disease progression, the patient received bridging therapy with mezigdomide,carfilzomib, and dexamethasone, followed by a second BCMA-directed CAR T-cell infusion using ciltacabtagene autoleucel...Bridging therapy and the use of an alternative CAR T-cell construct may further improve outcomes. Prospective studies are needed to define optimal patient selection and treatment sequencing in this setting."

IO biomarker • Journal • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology