On June 12, 2025 Bristol Myers Squibb (NYSE: BMY) reported the presentation of new data from its targeted protein degradation platform during the 2025 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress being held from June 12-15 in Milan, Italy (Press release, Bristol-Myers Squibb, JUN 12, 2025, View Source [SID1234653840]). Presentations feature updated clinical findings on the company’s investigational oral CELMoD agents mezigdomide and iberdomide in multiple myeloma, and golcadomide in non-Hodgkin lymphoma, as well as the first results evaluating the company’s first-in-class, oral BCL6 ligand-directed degrader (LDD) (BMS-986458) in non-Hodgkin lymphoma.

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The latest data presented for the three lead CELMoD agents and BCL6 LDD underscore the potential impact that these therapies may have in addressing significant unmet medical needs in hematologic malignancies. These agents are part of continuing research across targeted protein degradation at Bristol Myers Squibb, which also encompasses additional CELMoD agents, LDDs and degrader antibody conjugates (DACs) across blood cancers and solid tumors, as well as non-malignant hematologic disorders.

Protein degraders, like CELMoD agents and LDDs, are therapies designed to target and degrade specific proteins that drive diseases, including many proteins that are difficult to target through conventional small-molecule inhibitors. These innovative agents have the possibility to enhance the efficacy of existing therapies and overcome resistance in various malignancies, potentially improving patient outcomes.

"As a leader in the field of targeted protein degradation, we are committed to applying our decades of expertise to the development of these next wave of agents. The efficacy and safety data presented at the EHA (Free EHA Whitepaper) Annual Meeting this year is promising and reinforces the potential of CELMoD agents in combination with other standard treatments," said Anne Kerber, Senior Vice President, Head of Development, Hematology, Oncology and Cell Therapy for Bristol Myers Squibb. "These analyses also add to the body of evidence for these programs as we continue pivotal studies for each of the agents that we anticipate reading out in the next year and onwards."

Key targeted protein degradation data being presented by Bristol Myers Squibb at the EHA (Free EHA Whitepaper) Annual Congress include:

Mezigdomide (MEZI):

Abstract #4160130: Updated results were presented from the dose-escalation phase of the MM-002 study for the combinations of mezigdomide, dexamethasone, and bortezomib (Cohort A MeziVd; n=28), and mezigdomide, dexamethasone, and carfilzomib (Cohort C MeziKd; n=27) in patients with relapsed/refractory multiple myeloma (RRMM) who had received 2–4 prior therapies:

Overall response rate (ORR) was 75.0% for Cohort A and 85.2% for Cohort C, respectively.
Median (95% CI) duration of response (DOR) for Cohort A and Cohort C was 10.9 (8.8–18.7) and 11.9 (6.4–35.9) months, respectively.
Median (95% CI) progression-free survival (PFS) for Cohort A and Cohort C was 12.3 and 13.5 months, respectively.
Results from the dose-expansion cohort (Cohort D) of the study were also presented for the MeziVd combination (n=49) in patients with RRMM who had received 1–3 prior therapies:

ORR was 85.7%
Median (95% CI) DOR was 19.4 months (9.7-NA)
Median PFS (95% CI) was 17.5 months
The most common grade 3/4 treatment-emergent adverse event (TEAE) across arms was neutropenia and was managed with G-CSF and dose modifications.

Abstract #4160802: New data was presented evaluating mezigdomide in all-oral triplet combinations with other oral novel agents in RRMM.

Results showed that the ORR was:
50% for mezigdomide plus EZH2 inhibitor tazemetostat and dexamethasone (n=16)
35% for mezigdomide plus BET inhibitor BMS-986158 and dexamethasone (n=20)
80% for mezigdomide plus MEK inhibitor trametinib and dexamethasone (n=20)
The most frequent grade 3/4 TEAE was neutropenia, and grade 3/4 nonhematologic TEAEs were low.
A separate analysis(Abstract #4160749) showed that these combinations lead to the activation and proliferation of NK and T cells, including in patients previously treated with T cell-redirecting therapies.
Iberdomide (IBER):

Abstract #4160144: Updated results were presented from MM-001, evaluating the combination of iberdomide, bortezomib, and dexamethasone (IberVd) in patients with transplant-ineligible, newly diagnosed multiple myeloma (NDMM), confirming durable, deep responses in the study.

At a median follow-up of 25 months, the ORR in the intent-to-treat (ITT) population (n=18) was 88.9%, with 66.6% having a complete response or better.
44% of patients in CR achieved minimal residual disease (MRD) negativity at a sensitivity of 10-5.
The most common hematologic grade 3/4 TEAE was neutropenia (29.4%); 2 (11.8%) patients had grade 3/4 peripheral neuropathy. Overall, the most common grade 3/4 TEAEs were infections (47.1%).
Golcadomide (GOLCA):

Abstract #4160953: Updated results were presented from a study evaluating golcadomide with or without rituximab for the treatment of R/R follicular lymphoma (FL). Patients with R/R FL who had received ≥2 prior lines of treatment received golcadomide monotherapy in the dose-escalation part of the study (Part A), followed by golcadomide once daily at 0.2 or 0.4 mg with or without rituximab in the expansion part (Part B). Results continued to show promising efficacy with durable responses in heavily pre-treated patients with R/R FL.

In Part A, the ORR was 67%, with a complete response rate (CRR) of 42% for patients treated with golcadomide monotherapy.
In Part B, the ORR was 94% and the CRR was 63% for patients treated with golcadomide 0.4mg + rituximab. The median DOR was 4.8 months at a median follow-up of 5.75 months. Responses were consistent in patients who received prior lenalidomide-based and/or T cell-redirecting therapy.
The most common grade 3/4 treatment-related adverse events across dose levels in Part B (n=60) were neutropenia and anemia, occurring in 60% and 13% of patients, respectively. No patients discontinued therapy due to side effects related to golcadomide. Non-hematologic side effects were infrequent and mostly low-grade.
Abstract #4161005: Updated results were presented from a study evaluating golcadomide with or without rituximab for the treatment of R/R diffuse large b-cell lymphoma (DLBCL). Patients received golcadomide once daily at either 0.2 mg (n=39) or 0.4 mg (n=38). Results continued to show durable responses in heavily pre-treated patients with R/R DLBCL and a consistent safety profile.

For patients treated with golcadomide 0.4mg + rituximab, the ORR was 58% and the CRR was 44%, with a median DOR of 14.5 months. Among patients who had prior T cell–redirecting therapy, the ORR was 56%, and the CRR was 38%.
The most common grade 3/4 treatment-related adverse events across dose levels (n=77) were neutropenia and anemia, occurring in 64% and 20% of patients, respectively. Most adverse events were manageable, with discontinuation due to AE occurring in 7% of patients.
Based on the results of early studies, mezigdomide, iberdomide and golcadomide are being evaluated in multiple phase 3 studies:

SUCCESSOR-1: mezigdomide, bortezomib, and dexamethasone vs. pomalidomide, bortezomib, and dexamethasone in patients with RRMM (projected data in 2026)
SUCCESSOR-2: mezigdomide, carfilzomib, and dexamethasone vs. carfilzomib and dexamethasone in patients with RRMM (projected data in 2026)
EXCALIBER RRMM: iberdomide, daratumumab, and dexamethasone vs. daratumumab, bortezomib, and dexamethasone in patients with RRMM (projected MRD data in 2025)
EXCALIBER Maintenance: iberdomide maintenance vs. lenalidomide maintenance following autologous stem cell transplant in patients with NDMM (projected data in 2029)
GOLSEEK-1: golcadomide and R-CHOP chemotherapy vs. placebo and R-CHOP in patients with previously untreated high-risk LBCL (projected data in 2028)
GOLSEEK-4: golcadomide and rituximab vs. investigator’s choice in patients with R/R FL who received at least 1 prior systemic therapy (projected data in 2030)
BMS-986458 BCL6 LDD:

Abstract #4160340: First clinical findings were presented from the dose-escalation part of the first-in-human, multicenter, open-label study of BMS-986458 in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). Initial results evaluating 31 heavily pre-treated patients treated with BMS-986458 were promising and support continued development for the treatment of NHL.

BMS 986458 was well-tolerated, with the most common treatment-related adverse events (TRAEs) being grade 1/2 arthralgia (19.4%) and fatigue (16.1%); no grade ≥3 treatment-related cytopenias or treatment-related discontinuations were observed.
Rapid and sustained degradation of BCL6 was demonstrated in peripheral blood and in the tumor at all doses evaluated.
Antitumor activity was evident from the first dose level in DLBCL and FL patients. Among 21 efficacy-evaluable patients, the ORR was 81% (N=17), and CRR was 23.8% (N=5).