iberdomide (CC-220) / BMS - LARVOL DELTA

Not Just Bone Deep: A Pancreatic Presentation of Myeloma – A Case Report and Review of the Literature (ACG 2025) - "Relapsing disease was diagnosed in 2024 via a pathologic right humerus fracture while on lenalidomide maintenance therapy. He received four cycles of iberdomide, daratumumab, carfilzomib, and dexamethasone (Iber-KDd) as part of a clinical trial prior to his ED visit...Prior to discharge, he started dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) with the plan to bridge to CAR-T therapy and to start palliative radiation therapy as an outpatient. This case demonstrates extramedullary involvement of relapsing multiple myeloma in the pancreatic body without physical signs or laboratory findings of obstructive jaundice...The cytoplasm is moderate in amount, eosinophilic, and finely granular, with some cells exhibiting perinuclear clearing (hof), characteristic of plasma cell differentiation. The cytomorphology raises concern for extramedullary involvement by a plasma cell neoplasm, such as multiple myeloma."

Case report • Clinical • Review • Back Pain • Genito-urinary Cancer • Hematological Malignancies • Hepatology • Multiple Myeloma • Musculoskeletal Diseases • Musculoskeletal Pain • Ovarian Cancer • Pancreatic Cancer • Plasmacytoma • Renal Cell Carcinoma • Solid Tumor

Relapsed/Refractory Indolent Lymphoma: Options Beyond Immunotherapy (SOHO 2025) - "Third-line immunotherapy-based strategies are now approved for the treatment of patients with multiple relapses, including the chimeric antigen receptor T-cell (CAR-T) constructs axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel, as well as bispecific antibodies like the anti-CD20 × CD3 agents mosunetuzumab and epcoritamab...Obinutuzumab was chosen as the companion of zanubrutinib due to the high proportion of rituximab-refractory patients enrolled in the study and was administered in both arms up to 20 infusions...Loncastuximab with Rituximab In a population of 39 advanced-stage FL patients, including 20 cases of disease relapse within 24 months since frontline treatment (POD24), the combination of the two drugs in an outpatient fixed-duration regimen produced a complete response rate of 67% after 12 weeks on-therapy, which rose to 77% within 21 weeks...Compared with existing agents targeting Ikaros/Aiolos, such as lenalidomide, avadomide, and..."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CRBN • IKZF1

Iberdomide (IBER), Daratumumab (DARA), and Dexamethasone (DEX) (IberDd) Shows Deep Antimyeloma Activity Across Molecular Patient Subsets With Transplant-Ineligible (TNE) Newly Diagnosed Multiple Myeloma (NDMM): Results From the Phase 1/2 CC-220-MM-001 Trial (SOHO 2025) - P1/2 | "Data on IberDd in patient subgroups where DARA, lenalidomide, and DEX-a current standard of care-may be less effective are lacking. IberDd markedly decreased sFLCs and led to MRD negativity across all 3 IBER doses irrespective of molecular and immune subgroups, suggesting deep and broad activity in TNE NDMM."

Clinical • P1/2 data • Hematological Malignancies • Multiple Myeloma • Oncology • SDC1 • TP53

GCK inhibition enhances iberdomide antimyeloma effects by promoting IKZF1 degradation via a CRBN-independent mechanism. (PubMed, Blood Neoplasia) - "An isogenic subline of MM.1S cells with acquired lenalidomide resistance remains sensitive to GCK inhibition-induced IKZF1/3 downregulation and cell growth inhibition. These findings underscore GCK as a promising therapeutic target for bypassing IMiD resistance in MM. Combining GCK inhibition with iberdomide could provide a novel strategy to manage relapsed or refractory patients with multidrug resistance, especially after the exhaustion of immunotherapy."

IO biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation • BCL6 • CRBN • IKZF1 • MYC

Multiple Myeloma Unpacked (ICML 2025) - P3 | "Several other phase II studies have explored the efficacy of triplet regimens incorporating Rd as a backbone, combined with agents such as elotuzumab [30], ixazomib [31], or carfilzomib [32] as well as quadruplet regimen including daratumumab and carfilzomib [33]...The landscape of induction treatment has evolved with the incorporation of the anti-CD38 monoclonal antibody daratumumab (D) into the triplet bortezomib-thalidomide-dexamethasone (VTd) and, more recently, bortezomib-lenalidomide-dexamethasone (VRd)...In transplant-ineligible patients, VRd [45], daratumumab-lenalidomide-dexamethasone (DRd) [46, 47] and daratumumab-bortezomib-melphalan-prednisone (DVMP) [48, 49] have been the standards of cares for years...The FDA approval of isatuximab-bortezomib-lenalidomide-dexamethasone (Isa-VRd), based on the results of the IMROZ study [38], which demonstrated the superiority of Isa-VRd over VRd in terms of MRD negativity and PFS, introduces a new SoC...Consequently,..."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • Smoldering Multiple Myeloma • B2M • CRBN • CTCs • XPO1

Iberdomide (IBER), Daratumumab (DARA), and Dexamethasone (DEX) (IberDd) in Transplant-Ineligible (TNE) Newly Diagnosed Multiple Myeloma (NDMM): Results From the Phase 1/2 CC-220-MM-001 Trial (SOHO 2025) - P1/2 | "Context: Lenalidomide (LEN) plus DARA and DEX is a standard of care in TNE NDMM. Preliminary data on IberDd in TNE NDMM show notable efficacy and a manageable safety profile and no new safety signals across all 3 IBER doses."

P1/2 data • Hematological Malignancies • Multiple Myeloma • Oncology

PLYCOM: A Study Evaluating the Safety and Efficacy of Multiple Treatments in Participants With Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: May 2027 ➔ Jul 2028 | Trial primary completion date: May 2027 ➔ Jul 2028

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

GOLSEEK-1: A Phase 3, Double-Blind, Randomized Study of Golcadomide+R-CHOP vs Placebo+R-CHOP in Patients With Previously Untreated, High-Risk, Large B-Cell Lymphoma (SOHO 2025) - P3 | "Introduction: Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) is standard treatment for diffuse large B-cell lymphoma (DLBCL) and is curative in 60%-70% of patients...Golcadomide+R-CHOP demonstrated tolerability and high rates of durable response in untreated aggressive B-cell lymphoma (BCL), including in HR patients in the phase 1b CC-220-DLBCL-001 study... GOLSEEK-1 is assessing the potential of golcadomide+R-CHOP to improve outcomes for patients with previously untreated HR LBCL based on promising phase 1 results. GOLSEEK-1 is actively recruiting at 309 sites in 36 countries. Acknowledgements: Presented at 2025 EHA Annual Congress; modified using BMS AI."

Clinical • P3 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • CRBN • IKZF1 • MYC

Efficacy and Safety of Iberdomide, Daratumumab, and Dexamethasone, in Transplant-Ineligible Newly Diagnosed Multiple Myeloma Patients: Initial Analysis of the GEM-IBERDARAX trial (IMS 2025) - No abstract available

Clinical • Late-breaking abstract • Hematological Malignancies • Multiple Myeloma • Transplantation

Iberdomide, daratumumab, and dexamethasone (IberDd) in transplant-ineligible/deferred (TNE) newly diagnosed multiple myeloma (NDMM): updated results from the CC-220-MM-001 trial (IMS 2025) - No abstract available

Hematological Malignancies • Multiple Myeloma • Transplantation

Study of Intravenously (IV) Infused Etentamig in Combination With an Oral Cereblon E3 Ligase Modulatory Drug (CELMoD) Agent Assessing Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=135 | Recruiting | Sponsor: TeneoOne Inc. | Trial primary completion date: Jun 2036 ➔ Mar 2036

Adverse events • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation

Targeting degradation of IKZF1 and IKZF3 through modulation of the E3 ligase substrates in the context of cellular therapies for multiple myeloma. (PubMed, Biomark Res) - "Building on the success of immunomodulatory agents, CRBN E3 ligase modulators (CELMoDs), iberdomide (CC-220) and mezigdomide (CC-92480), have been designed as promising and more selective agents. Combining CELMoDs with cellular therapies significantly improves the response rate in MM patients. In this paper, based on the literature presented at the Annual Meeting of the American Society of Hematology (ASH), the American Society of Clinical Oncology (ASCO), the International Myeloma Society (IMS), and the European Hematology Association (EHA) in the 2020-2025 timeframe, we explore the rationale and emerging evidence of combining CELMoDs with immunotherapies, and their use as a bridge to transplant or as post-ASCT maintenance therapy in MM."

Journal • Review • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation • Transplantation • CRBN • IKZF1 • IKZF3

An immunostimulatory CELMoD combination overcomes resistance to T-cell engagers caused by a high multiple myeloma burden. (PubMed, Blood) - "The addition of anti-PD1 and pomalidomide reduced the T cell exhaustion that occurs in response to TCE in high tumor burden settings. This was accompanied by more favorable T cell profiling, with limited expansion of regulatory T cells and exhaustion. In total, administering TCE following dexamethasone and iberdomide treatments provided deeper and more durable responses with reduced risk of CRS."

Journal • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • IKZF1

Iberdomide (IBER) treatment (Tx) enhances manufactured chimeric antigen receptor (CAR) T cell expansion and functionality and is immunostimulatory in patients post-CAR T cell therapy (IMS 2025) - No abstract available

CAR T-Cell Therapy • Clinical

Talquetamab in Combination With Iberdomide and Dexamethasone for Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Thomas Martin, MD | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

Novel Cereblon-Binding Immunomodulators Have Increased Potency Against Gammaherpesvirus- Associated Lymphomas In Vitro. (PubMed, J Med Virol) - "Cereblon-binding immunomodulators (CBIs), such as pomalidomide (Pom), show in vitro efficacy and clinical activity against certain of these lymphomas. Next generation CBIs, such as golcadomide (Golc) and iberdomide (Iber), have increased affinity to the primary cellular target, cereblon, making them potentially better anticancer agents...The novel CBIs had relatively little activity in Pom-resistant cell lines with low levels of cereblon, suggesting that binding to cereblon is also important for the functions of the novel CBIs. These data show that the newer CBIs are more potent and effective against PEL and BL lines than Pom, and therefore, are worth investigating clinically in patients with these tumors."

Journal • Preclinical • Burkitt Lymphoma • Epstein-Barr Virus Infections • Hematological Malignancies • Kaposi Sarcoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Solid Tumor • CD86 • CRBN • ICAM1 • IRF4

MODIFY: Isatuximab and Iberdomide as Immunotherapy for High Risk in Smouldering Myeloma (clinicaltrials.gov) - P2 | N=63 | Recruiting | Sponsor: University College, London | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2030 ➔ Nov 2032 | Trial primary completion date: Sep 2029 ➔ Nov 2032

Enrollment open • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Study of Intravenously (IV) Infused Etentamig in Combination With an Oral Cereblon E3 Ligase Modulatory Drug (CELMoD) Agent Assessing Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=135 | Recruiting | Sponsor: TeneoOne Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2036 ➔ Jan 2037 | Trial primary completion date: Mar 2036 ➔ Jun 2036

Adverse events • Enrollment open • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation

Differential substrate degradation by super-degron: EGFP in wild-type mouse cells, PD-1 requires CRBN humanization. (PubMed, iScience) - "However, using EGFP as an indicator, we found that a super-degron tag (SD) enables degradation in mouse cells when combined with iberdomide or mezigdomide. Moreover, pomalidomide that crosses the brain-blood barrier reduced PD-1 expression in the brain. These results suggest that SD and thalidomide analogs can be used for in vitro and in vivo protein knockdown in mice, although some conditional settings are required."

IO biomarker • Journal • Preclinical • CD8 • CRBN • PD-1

EXCALIBER: Open-label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P3 | N=864 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

CC-220-DLBCL-001: Study of Safety and Efficacy of Iberdomide (CC-220) and CC-99282 Combined With R-CHOP to Treat Lymphoma (clinicaltrials.gov) - P1 | N=174 | Recruiting | Sponsor: Celgene | Trial completion date: Jun 2027 ➔ Dec 2028 | Trial primary completion date: Jun 2027 ➔ Dec 2028

Trial completion date • Trial primary completion date • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

GOLSEEK-1: A PHASE 3, DOUBLE-BLIND, RANDOMIZED STUDY OF GOLCADOMIDE + R-CHOP VERSUS PLACEBO + R-CHOP IN PATIENTS WITH PREVIOUSLY UNTREATED, HIGH-RISK, LARGE B-CELL LYMPHOMA (ICML 2025) - P3 | "Introduction: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is standard treatment (Tx) for diffuse large B-cell lymphoma (DLBCL) and is curative in ≈60–70% of patients (pts)...In the phase 1b study CC-220-DLBCL-001, GOLCA + R-CHOP was well tolerated, with promising activity and combinability and high rates of durable responses irrespective of COO in pts with previously untreated aggressive BCL, including HR pts...Key secondary endpoints include PFS in non–high-grade BCL, event-free survival, independently assessed complete metabolic response, undetectable minimal residual disease by PhasED-Seq, and overall survival. This study is recruiting globally at 309 sites in 36 countries."

Clinical • P3 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • CRBN • IKZF1

Testing the Combination of Two Approved Drugs and One Experimental Drug in Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=88 | Suspended | Sponsor: Alliance for Clinical Trials in Oncology | Not yet recruiting ➔ Suspended

Trial suspension • Hematological Malignancies • Multiple Myeloma • Oncology

MINIMAL RESIDUAL DISEASE-DRIVEN STRATEGY FOLLOWING ISATUXIMAB-CARFILZOMIB-LENALIDOMIDE-DEXAMETHASONE INDUCTION IN TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: PRIMARY ENDPOINTS OF THE PHASE 3 MIDAS TRIAL (EHA 2025) - P3 | "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 before maintenance. Further follow-up, including sustained MRD negativity and PFS data, is needed to evaluate the long-term outcomes of this MRD-adapted strategy."

Minimal residual disease • P3 data • Residual disease • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

IBERDOMIDE AND DEXAMETHASONE IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA (EHA 2025) - "Background: Iberdomide (Iber) is a cereblon E3 ligase modulator (CELMoD) with more potent tumoricidal and immune-stimulatory effects compared to lenalidomide and pomalidomide...After LenDex plus daratumumab became a standard of care, the IberDex arm was closed, having enrolled 18 pts... In this frail, elderly MM cohort, IberDex showed notable and sustained efficacy, with only two progressions after nearly two years of follow-up. Toxicity was manageable, with low rates of non-hematologic AEs, and severe infections mainly occurring in older, frail patients receiving 1.6 mg."

Clinical • Anemia • Febrile Neutropenia • Geriatric Disorders • Infectious Disease • Multiple Myeloma • Neutropenia • Pneumonia • Respiratory Diseases • Targeted Protein Degradation • Thrombocytopenia • CRBN