MeziKd nearly doubled progression-free survival over Kd alone in the first randomized phase 3 trial of mezigdomide, supporting a potential new option at first relapse
“The battle against myeloma is a marathon, so we need as many treatment options as possible, especially when these include novel agents with unique mechanisms of action”
touchHEMATOLOGY coverage from EHA 2026
Abstract LB5004: Dimopoulos MA, Schjesvold F, Fu C, et al. MEZIGDOMIDE, CARFILZOMIB, AND DEXAMETHASONE (MEZIKD) VS CARFILZOMIB AND DEXAMETHASONE (KD) IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): RESULTS FROM THE PHASE 3 SUCCESSOR-2 TRIAL. Presented at: EHA 2026, Stockholm, Sweden. June 11–14th, 2026.
Late-breaking results from the phase 3 SUCCESSOR-2 trial (NCT05552976), presented at the European Hematology Association (EHA) 2026 Congress, show that adding mezigdomide to carfilzomib and dexamethasone (MeziKd) significantly improves outcomes in relapsed/refractory Multiple myeloma, particularly in patients previously exposed to lenalidomide and anti-CD38 therapy.
MeziKd nearly doubled progression-free survival versus Kd alone, with a median PFS of 18.0 months (95% CI, 14.5–22.1) versus 8.3 months (95% CI, 5.6–10.7) (HR, 0.48; 95% CI, 0.36–0.63; P<0.0001). Responses were also deeper, with an overall response rate of 80.2% versus 53.4%, and complete response or better in 26.7% versus 8.9%. Notably, the benefit was maintained across high-risk subgroups, including patients with high-risk cytogenetics, extramedullary disease, and those aged ≥75 years.
Grade 3–4 adverse events were more frequent with MeziKd (83.7% vs 56.5%), particularly neutropenia (61.1% vs 9.1%) and infections (34.0% vs 15.6%), but were considered manageable. “The main toxicity is neutropenia, but this is something we are very familiar with managing in hematology,” said Prof Meletios Dimopoulos (Professor and Chairman, Department of Clinical Therapeutics at Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens).
As the first randomized phase 3 study of mezigdomide, SUCCESSOR-2 strengthens the case for CELMoD-based strategies in earlier relapse and positions MeziKd as a potential new option for patients with increasingly limited therapeutic choices. Speaking after his presentation, Prof Dimopoulos provides further insight into the study and where he sees the regimen fitting into the evolving treatment landscape.
Could you summarize the unique mechanism of action of mezigdomide?
Mezigdomide binds to cereblon very tightly, and this has as a consequence direct myeloma cell kill, but also beneficial activity on T cells and NK cells by reducing T-cell exhaustion. T-cell exhaustion is very important because it has been seen with all T-cell redirecting therapies. Mezigdomide gives us the opportunity to administer this agent in patients who have experienced T-cell exhaustion, not only to achieve an anti-myeloma effect, but also to potentially reverse this exhaustion and allow us to administer T-cell redirecting agents again in the future.
Were there any patient populations where the magnitude of benefit particularly stood out?
We were very happy to see that this combination was active in patients with high-risk cytogenetics, but also in patients with plasmacytomas. We know that plasmacytomas, especially extramedullary plasmacytomas, but also paraskeletal plasmacytomas, are usually hard to treat, even with CAR-T cells and bispecific antibodies. So we saw very interesting activity in this setting.
Where do you see MeziKd fitting into the treatment sequence?
I believe mezigdomide with carfilzomib and dexamethasone can be used as early as second-line treatment, but also later in the course of the disease, depending on the clinical condition of the patient and the treatment setting. It is an outpatient regimen. We do not expect to see opportunistic severe infections that require hospitalization, so it is a very practical regimen that could be used across many relapsed myeloma settings.
This content has been developed independently by Touch Medical Media for touchHEMATOLOGY. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media. This article was created by the editorial team utilizing AI as an editorial tool (ChatGPT 5.5 [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
Cite: SUCCESSOR-2 positions MeziKd as a potential new option in lenalidomide- and anti-CD38-exposed RRMM. touchHEMATOLOGY. 1st July 2026.
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