Zenbexus (iberdomide) / BMS - LARVOL DELTA

Iberdomide, Daratumumab, Dexamethasone (IberDd) vs Daratumumab, Bortezomib, Dexamethasone (DVd) in Patients With Relapsed/Refractory Multiple Myeloma (RRMM): Results From EXCALIBER-RRMM Phase 3 Study (IMS 2026) - P3 | "This benefit was c onsistent across prespecified subgroups, including pts refractory to lenalidomide (LEN) in last LOT, pts with renal impairment, and ≥75y of age. IberDd led to a statistically significant and clinically meaningful improvement in MRD-negative CR vs DVd, with a manageable safety profile. IberDd represents an effective tx option for pts with RRMM as early as first relapse, that can be easily administered across diverse care settings."

Clinical • Late-breaking abstract • P3 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Renal Disease

First-Year Results of Isatuximab-Iberdomide Maintenance in MRD-Positive Newly Diagnosed Multiple Myeloma Patients Included in the Phase 3 MIDAS Trial (IMS 2026) - P3 | "While daratumumab plus lenalidomide maintenance has shown efficacy in recent studies (PERSEUS, AURIGA), no data are available regarding anti-CD38 combined with a CELMoD in maintenance... MIDAS (NCT04934475) is an ongoing phase 3 trial evaluating an MRD-adapted consolidation and maintenance strategy in TE-NDMM patients treated with six cycles of isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd)... Maintenance with isatuximab plus iberdomide after Isa-KRd induction and single or tandem ASCT is feasible with a manageable safety profile. This combination induced substantial MRD conversion during the first year of maintenance in patients remaining MRD-positive after consolidation. These findings support further evaluation of anti-CD38 plus CELMoD-based maintenance strategies in high-risk NDMM patients."

Clinical • IO biomarker • Minimal residual disease • P3 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia

Multi-Center Phase II Trial of Iberdomide and SQ Daratamumab as Post-ASCT Maintenance Therapy in Pts With Multiple Myeloma (the IBEX Trial): Initial Safety Analysis and Interim Efficacy Results. (IMS 2026) - "Lenalidomide (LEN) is standard maintenance therapy. Addition of an anti-CD38 antibody such as daratumumab (DARA) increases MRD(-) responses and further improves outcomes...All pts received aspirin unless anticoagulated... Post-ASCT maintenance with IBER plus DARA is feasible and safe. Neutropenia was manageable at the doses used in IBEX. Improvements in IMWG response and MRD conversion were observed despite pre-ASCT quadruplet induction."

Clinical • P2 data • Cardiovascular • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Respiratory Diseases • Targeted Protein Degradation • CRBN

Iberdomide Hydrochloride. (PubMed, Am J Health Syst Pharm) - No abstract available

Journal

Iberdomide (CC-220) Monotherapy or in Combination with an Anti-CD20 Monoclonal Antibody As Effective Therapy in Patients with Relapsed/Refractory Lymphoma: Early Results from a Phase 1/2 Study (ASH 2022) - P1/2 | "In vitro studies suggest IBER enhances T-cell immunostimulatory and direct cytotoxic effects versus lenalidomide...Methods Pts with RR lymphomas and ≥ 2 prior lines of treatment (tx) were given escalating doses of IBER alone (cohort A: all lymphomas), or with rituximab (cohort B: all B-cell lymphomas) or obinutuzumab (cohort C: marginal zone lymphoma [MZL] or grade 1–3a follicular lymphoma [FL]) to determine maximum tolerated dose (MTD)...These data highlight the potential of CELMoD agent-based tx in pts with RR lymphoma to address unmet needs such as treating disease progression after CAR T cell tx. Study support: This study was funded by Bristol Myers Squibb."

Clinical • Combination therapy • Monotherapy • P1/2 data • Anemia • Constipation • Diffuse Large B Cell Lymphoma • Endocrine Disorders • Febrile Neutropenia • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Metabolic Disorders • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Septic Shock • Targeted Protein Degradation • Thrombocytopenia • CD4 • CRBN • IKZF1

Iberdomide plus daratumumab and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (EXCALIBER-RRMM): an open-label, randomised, controlled, phase 3 trial. (PubMed, Lancet Oncol) - P3 | "Iberdomide, daratumumab, and dexamethasone significantly improved MRD-negative complete response compared with daratumumab, bortezomib, and dexamethasone. The most common grade 3 or grade 4 adverse events were haematological events and infections, which were mostly manageable with standard supportive care. These findings support iberdomide, daratumumab, and dexamethasone as an efficacious treatment option for patients with relapsed or refractory multiple myeloma with the potential to be administered across diverse care settings. Assessment of progression-free survival, the second dual primary endpoint, is ongoing."

Journal • P3 data • CNS Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Targeted Protein Degradation • CRBN

Bristol Myers Squibb Announces First Presentation of Results for ZENBEXUS (iberdomide) in Combination with Daratumumab from Phase 3 EXCALIBER-RRMM Trial in Relapsed or Refractory Multiple Myeloma (Businesswire) - "At a median follow-up of 15.7 months in 420 evaluable patients, the study showed a statistically significant and clinically meaningful improvement in minimal residual disease (MRD)-negative complete response (CR) rate, with significantly more patients achieving an MRD-negative CR with ZDd compared to DVd (41.1% vs. 20.7% [95% CI: 11.5%–28.6%]; p<0.0001; odds ratio 2.75 [95% CI: 1.77–4.30]). The dual primary endpoints of the study are MRD-negative CR rate and progression-free survival (PFS)."

P3 data • Multiple Myeloma

Iberdomide Pairs With Isatuximab to Rescue MRD-Positive Patients After Transplant (Pharmacy Times) - "Of 219 patients who started Isa-Iber maintenance (108 in Arm C, 111 in Arm D), 203 completed the first year of treatment. Fifty-five patients converted from MRD-positive to MRD-negative at the stringent 10⁻⁶ sensitivity threshold during that single year of maintenance...Broken out by arm, MRD-negativity at 10⁻⁶ improved from 40% post-consolidation to 58% after one year of maintenance in the single-ASCT arm and from 32% to 48% in the tandem-ASCT arm. At the more commonly used 10⁻⁵ threshold, rates moved from 67% to 76% (Arm C) and from 62% to 70% (Arm D)....No unexpected toxicity signals emerged, and the profile was consistent across both transplant arms."

P3 data • Multiple Myeloma

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

Carfilzomib, Iberdomide, and Dexamethasone (KID) in Patients with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Results from a Phase 1/2 Study (IMS 2026) - P1/2 | "Introduction: Standard upfront regimens demonstrate stringent complete response (sCR) rates of 10-15% following induction, and 40% following consolidation in patients (pts) with newly diagnosed multiple myeloma (NDMM). Induction tx with KID achieved 31% sCR/CR rates post ASCT overall and 31% in the high-risk NDMM pts at interim analysis, despite short tx duration. All pts were successfully mobilized. Further studies will evaluate KID with post-ASCT iber + elranatamab consolidation followed by iber maintenance."

Clinical • P1/2 data • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Targeted Protein Degradation • Thrombocytopenia • Transplantation • CRBN

Trial in Progress: Isatuximab and Iberdomide as Immunotherapy for High-Risk Smouldering Myeloma - the UK Myeloma Research Alliance MODIFY Clinical Trial (IMS 2026) - "Patients receive isatuximab (1400 mg subcutaneous), iberdomide (Cereblon E3 ligase modulator, 1.0 mg) and dexamethasone (20 mg) for a fixed duration of 2 years (26 cycles). n/a"

Clinical • Hematological Malignancies • Multiple Myeloma • Targeted Protein Degradation • CRBN

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

Iberdomide Priming Enhances Anti-BCMA CAR-T Efficacy in Multiple Myeloma (IMS 2026) - "Here we report the first in vivo validation in NSG murine models and characterize the immunomodulatory effect of Iber+Dexamethasone (Dex) on the bone marrow (BM) of patients who progressed on anti-BCMA therapy. Iber priming prior to CAR-T manufacturing enhances in vivo anti-myeloma efficacy in NSG models, providing preclinical validation. Comprehensive BM immune profiling demonstrates dynamic remodeling by Iber+Dex in patients progressing after BCMA-directed therapy. Together, these data support Iber-based priming as a strategy to improve anti-BCMA CART efficacy and enhance subsequent T cell-directed therapies."

CAR T-Cell Therapy • Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • CD4 • CD69 • CD8 • PD-1

Matching-Adjusted Indirect Comparisons (Maics) of Iberdomide, Daratumumab (DARA), and Dexamethasone (Iberdd) Versus Regimens Containing DARA and Imids in Relapsed/Refractory Multiple Myeloma (RRMM) (IMS 2026) - "In the ongoing phase 3 randomized controlled trial EXCALIBER-RRMM, IberDd demonstrated significantly higher MRDneg CR in comparison with DARA + bortezomib + dexamethasone (DEX) (DVd) in RRMM; however, head-to-head comparative evidence versus other DARA-based standard regimens is unavailable. Two unanchored MAICs were therefore conducted to estimate the comparative efficacy of IberDd versus DARA + lenalidomide + DEX (DRd) and DARA + pomalidomide + DEX (DPd)... Across 2 independent unanchored MAICs, IberDd was associated with significantly [REDACTED] MRDneg CR rates versus commonly used DARA-based regimens in patients with RRMM after ≥1 prior line. Findings were robust across sensitivity analyses and support the clinical efficacy of IberDd, with potential implications for RRMM treatment paradigms."

Hematological Malignancies • Multiple Myeloma • IKZF1

Iberdomide Drives Effector T Cell Expansion and Increases Immune Activation in Combination with Daratumumab and Dexamethasone in the Multiple Myeloma Patients (IMS 2026) - "Recently, the phase 3 EXCALIBER-RRMM trial demonstrated superior minimal residual disease (MRD) negativity rates with Iber+Dara+Dex versus Bortezomib Dara+Dex. ber functions as the primary immunomodulatory agent driving therapeutic activity in this combination, with Dara inducing CD38+ cell depletion in NK cells and T-cells. Immunomodulatory changes observed in BM that are absent in PB with Dara addition—particularly alterations in central memory T-cells—provide compelling rationale for comprehensive BM tumor microenvironment analysis in future mechanistic studies. These findings support the biological basis for superior MRD negativity observed with triplet therapy in EXCALIBER-RRMM."

Clinical • Combination therapy • IO biomarker • Hematological Malignancies • Multiple Myeloma • Targeted Protein Degradation • CD14 • CD38 • CD69 • CD8 • CRBN

Genomic Determinants of Response to Iberdomide Combination and Monotherapy in Early Relapsed Multiple Myeloma (IMS 2026) - "Introduction: Most patients with multiple myeloma (MM) develop lenalidomide (Len) resistance at first relapse. Most will receive a second IMiD (e.g., pomalidomide; Pom) during their course...We performed whole genome sequencing (WGS) for patients on the ReKInDLE study of Iberdomide, Carfilzomib, Daratumumab, and dex (Iber-DKd; n=32) for Len-exposed early-relapsed MM, with de-escalation to Iber monotherapy after 8 cycles... CELMoDs have activity in IMiD-resistant settings but discrete resistance variants apart from CRBN mutations appear to influence response, arguing for screening in IMiD-resistant scenarios, and for earlier CELMoD integration prior to selection of universal IMiD/CELMoD resistance. Sequencing of additional cases is in progress."

Monotherapy • Hematological Malignancies • Multiple Myeloma • Targeted Protein Degradation • CRBN • DDB1 • IKZF1 • IL17RB • SDC1

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

Carfilzomib, Iberdomide, and Dexamethasone (KID) in Patients With Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Results From a Phase 1/2 Study (IMS 2026) - P1/2 | "Introduction: Standard upfront regimens demonstrate stringent complete response (sCR) rates of 10-15% following induction, and 40% following consolidation in patients (pts) with newly diagnosed multiple myeloma (NDMM). Induction tx with KID achieved 31% sCR/CR rates post ASCT overall and 31% in the high-risk NDMM pts at interim analysis, despite short tx duration. All pts were successfully mobilized. Further studies will evaluate KID with post-ASCT iber + elranatamab consolidation followed by iber maintenance."

Clinical • P1/2 data • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Targeted Protein Degradation • Thrombocytopenia • Transplantation • CRBN

Iberdomide, bortezomib, and dexamethasone (IberVd) in transplant-ineligible (TNE) newly diagnosed multiple myeloma (NDMM): Updated results from the CC-220-MM-001 trial. (ASCO 2025) - P1/2 | "Funded by Bristol Myers Squibb Clinical Trial Registration Number: NCT02773030 Background: Lenalidomide (LEN), bortezomib (BORT), and dexamethasone (DEX) are recommended for NDMM. With longer follow-up (13–25 mo), IberVd confirmed durable deep responses, with ≥ CR % rising from 56.3% to 75.0%, and an encouraging safety profile with no new signals in pts with TNE NDMM. These data support IberVd evaluation in the frontline setting."

Fatigue • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Novel Coronavirus Disease • Oncology • Pain • Pneumonia • Respiratory Diseases • Thrombocytopenia • Transplantation

A phase 2 trial of iberdomide, carfilzomib, daratumumab and dexamethasone quadruplet therapy for relapsed/refractory multiple myeloma: The rekindle study (ASH 2025) - P2 | "In this context, Iberdomide is a potent cereblon E3 ligase modulator (CELMoD)with demonstrated activity in IMiD-resistant disease (Lonial et al., Lancet Haematology. This quadruplet reinduction strategy adds another treatment alternative in the early relapsesetting (i.e., following lenalidomide resistance; 1-3 prior lines) where parenteral (SC or IV) T-cellredirecting therapies are gaining increased prominence. IberKDd is safe with a manageable toxicityprofile, and it affords the opportunity for de-escalation to oral monotherapy; decreasing the burden ofcontinuous parenteral therapy which is common in this setting of MM."

P2 data • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Myocardial Infarction • Neutropenia • Respiratory Diseases • Targeted Protein Degradation • Thrombocytopenia • CRBN

MRD-driven strategy following IsaKRD induction in transplant-eligible NDMM: Primary endpoints of the phase 3 MIDAS trial. (ASCO 2025) - P3 | "Funded by No funding sources reported Clinical Trial Registration Number: NCT04934475 Background: The phase III IFM2020-02-MIDAS study (NCT04934475) evaluated a minimal residual disease (MRD)-driven consolidation and maintenance strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD) in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM)...MRD-positive patients after induction (MRD ≥10⁻⁵) were randomized to either single ASCT plus 2 cycles of IsaKRD (Arm C) or tandem ASCT (Arm D) followed by isatuximab plus iberdomide maintenance... After 6 induction cycles with IsaKRD, in patients who achieved MRD negativity at 10⁻⁵, MRD negativity rates at 10⁻⁶ before maintenance were not significantly different between the transplant-based approach and IsaKRD consolidation alone, whereas in patients who do not achieve MRD negativity at 10-5, tandem ASCT did not significantly improve MRD negativity rates at 10⁻⁶..."

P3 data • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

All-oral triplet iberdomide, ixazomib, and dexamethasone in elderly patients with multiple myeloma at first relapse: Results of the IFM phase 2 study I2D. (ASCO 2024) - P2 | "Background: The triplet combination daratumumab, lenalidomide and dexamethasone (DRd) and bortezomib, lenalidomide and dexamethasone (VRd) are to date the standard of care for patients with transplant ineligible (TI) newly diagnosed multiple myeloma (MM)...Iberdomide is a novel oral cereblon E3 ligase modulator (CELMoD) that demonstrated promising activity in MM patients refractory to lenalidomide/pomalidomide... The oral tripletiberdomide, ixazomib and dexamethasone demonstrated a favorable efficacy / safety profile in elderly MM patients at first relapse, including in patients with lenalidomide and daratumumab refractory disease."

Clinical • P2 data • Dermatology • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Pain • Targeted Protein Degradation • Thrombocytopenia • CRBN

Iberdomide vs. Iberdomide Plus Isatuximab Maintenance Therapy Post ASCT in Newly Diagnosed Multiple Myeloma (clinicaltrials.gov) - P3 | N=411 | Active, not recruiting | Sponsor: University of Heidelberg Medical Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Iberdomide (IBER) in Combination with Dexamethasone (DEX) in Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Anti-B-Cell Maturation Antigen (BCMA)-Exposed Cohort of the CC-220-MM-001 Trial (ASH 2022) - P1b/2a, P3 | " Eligible pts had RRMM, had received ≥ 3 prior lines of therapy (including lenalidomide or pomalidomide, a PI, an anti-CD38 mAb, and an anti-BCMA therapy) and had documented progressive disease (PD) on or within 60 days of their last antimyeloma therapy (documented PD if chimeric antigen receptor [CAR] T cell therapy was the last therapy). IBER + DEX showed encouraging efficacy and safety in pts with triple-class-exposed RRMM and prior anti-BCMA therapy. The results are comparable to those from Cohort D of the same study, which is assessing IBER + DEX in pts with triple-class refractory RRMM. These findings support further development of IBER in RRMM, including in anti-BCMA-exposed pts."

Combination therapy • Anemia • Cardiovascular • Febrile Neutropenia • Hematological Malignancies • Hypertension • Immune Modulation • Immunology • Infectious Disease • Inflammation • Leukopenia • Multiple Myeloma • Neutropenia • Plasmacytoma • Pneumonia • Respiratory Diseases • Septic Shock • Targeted Protein Degradation • Thrombocytopenia • CD4 • CD8 • CRBN

SAFETY AND EFFICACY OF IBERDOMIDE-BASED QUADRUPLET FOR PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA: THE IDEAL PHASE I/II TRIAL RESULTS (EHA 2026) - P1/2 | "We conducted the IDEAL study (NCT05392946) to examine the safety and efficacy of a novel finite-duration approach in which iberdomide (CC-220) — an oral cereblon E3 ligase modulator ( ( CELMoD), with a higher affinity and specificity for cereblon than lenalidomide — was substituted for lenalidomide in the traditional quadruplet induction for patients with NDMM...Methods IDEAL is a Phase 1 (3+3 design)/ Phase 2 (single stage) trial in which Iberdomide, daratumumab, bortezomib & dexamethasone (Iber-DVd) were given for twelve 28-day cycles (C1-12) as induction followed by iberdomide monotherapy maintenance (C13-36)...Reused with permission. This abstract was accepted and previously presented at the 2026 ASCO Annual Meeting."

Clinical • P1/2 data • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Targeted Protein Degradation • Thrombocytopenia • CRBN