Phase 3 data show benefit in a largely triple-class-exposed population previously treated with anti-CD38 monoclonal antibodies and lenalidomide.
touchHEMATOLOGY coverage from ASCO 2026
Presented during an oral abstract session at ASCO 2026, the SUCCESSOR-2 trial reported promising new data for mezigdomide, in combination with carfilzomib and dexamethasone (MeziKd) in relapsed and refractory multiple myeloma (RRMM).
Mezigdomide is a potent oral CELMoD that has been shown preclinically to promote myeloma cell death and immune stimulation, with the potential to overcome resistance to other drug classes, including IMiDs.1 Its activity has also been supported in patients with triple-class-refractory and BCMA-exposed or refractory RRMM.2
The findings add to ongoing discussion around treatment options for a growing population of patients previously exposed to anti-CD38 monoclonal antibodies and lenalidomide, who often have poorer outcomes and limited treatment options.
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“We can reasonably conclude that oral mezigdomide combined with weekly intravenous carfilzomib is a potential new standard of care for relapsed/refractory disease and, most importantly, can be easily used across diverse care settings, including community practice.” said Dr Paul Richardson, study co-principal investigator, and Professor at the Dana-Farber Cancer Institute, Boston, MA, USA.
What did the data show
SUCCESSOR-2 (NCT05552976) is a phase 3, 2-stage trial evaluating mezigdomide, carfilzomib, and dexamethasone (MeziKd) versus carfilzomib and dexamethasone (Kd) in adults with RRMM. Eligible patients had received at least 1 and up to 9 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide.
In total, 479 patients were included in the analysis: 288 received MeziKd and 191 received Kd. Median age was 68 years, and patients had received a median of 2 prior lines of therapy. Most patients were triple-class-exposed (92.1%), refractory to an anti-CD38 monoclonal antibody (85.8%), and refractory to lenalidomide (75.8%).
At a median follow-up of 10.6 months, MeziKd significantly reduced the risk of progression or death by 52% compared with Kd, with a median progression-free survival (PFS) of 18.0 versus 8.3 months, respectively (HR 0.48; 95% CI 0.36–0.63; p<0.0001). Interestingly, the PFS benefit was consistent across prespecified subgroups, including patients with different prior treatment exposures, high-risk cytogenetics, extramedullary disease, and older age.
Overall response rate was higher with MeziKd than Kd, at 80.2% versus 53.4%, as was complete response or better, at 26.7% versus 8.9%. Deaths were reported in 21.5% and 26.7% of patients, respectively, mostly due to progressive disease.
MeziKd demonstrated a predictable and manageable safety profile, with no new safety signals reported. Grade 3–4 treatment-emergent adverse events occurred in 83.7% of patients receiving MeziKd and 56.5% receiving Kd. Grade 3–4 neutropenia was the most common event, occurring in 61.1% versus 9.1% of patients, respectively, and was reported to be manageable with dose modifications and/or granulocyte colony-stimulating factor support. Grade 3–4 infections occurred in 34.0% versus 15.6% of patients, and grade 5 infections in 2.4% versus 1.1%. Most infections were not associated with grade 3–4 neutropenia, and infections were generally managed using standard clinical practice and supportive care, with limited use of immunoglobulin replacement therapy compared with Kd.
Key clinical takeaway
In SUCCESSOR-2, MeziKd showed a clinically meaningful PFS benefit versus Kd in a predominantly triple-class-exposed RRMM population, including patients refractory to anti-CD38 monoclonal antibodies and lenalidomide.
The authors state that these data support mezigdomide, an oral CELMoD, as a potential new standard of care for RRMM across multiple settings, with a manageable safety profile.
References
- Hansen JD, Correa M, Nagy MA, et al. Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma. J Med Chem. 2020 Jul 9;63(13):6648-6676
- Richardson PG, Trudel S, Popat R, et al. Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2023 Sep 14;389(11):1009-1022.
→ Abstract LBA7506: Richardson P. 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: ASCO, Chicago, IL, USA. May 29 to June 2, 2026.
This content has been developed independently by Touch Medical Media for touchONCOLOGY and 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.
Disclosures: Paul Richardson is a Consultant for Celgene/BMS, GSK, Karyopharm, Oncopeptides, Regeneron, and Sanofi. He has received grant/research support from Oncopeptides and Karyopharm.
Cite: SUCCESSOR-2: Mezigdomide combination improves progression-free survival in relapsed and refractory multiple myeloma. touchHEMATOLOGY. 17th June 2026.
