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SUCCESSOR-2 — Mezigdomide + carfilzomib + dexamethasone (MeziKd), relapsed/refractory multiple myeloma, ≥1 prior line

Abstract: LBA7506 · Session: Late-breaking oral abstract, Fri May 29, 2026 · Presenter: Paul G. Richardson, MD (Dana-Farber Cancer Institute, Boston) · Embargo: May 29, 2026

At a glance

  • Sponsor: Bristol Myers Squibb
  • PI / presenter: Paul G. Richardson, MD (Dana-Farber Cancer Institute)
  • NCT ID: NCT05552976
  • Phase: 2/3 (inferential, seamless), multicenter, randomized, open-label
  • Design: MeziKd (mezigdomide 1.0 mg + carfilzomib + dexamethasone) vs Kd (carfilzomib + dexamethasone)
  • N: 479 (288 MeziKd; 191 Kd)
  • Primary endpoint(s): Progression-free survival (PFS)
  • Comparator: Carfilzomib + dexamethasone (Kd)
  • Indication: Relapsed/refractory multiple myeloma (RRMM)
  • Line: Median 2 prior lines; 92.1% triple-class-exposed, 85.8% anti-CD38 refractory, 75.8% lenalidomide-refractory

Headline result

MeziKd cut the risk of disease progression or death by 52% versus Kd: median PFS 18.0 months (95% CI 14.5–22.1) vs 8.3 months (95% CI 5.6–10.7), HR 0.48, P<.0001. Overall response rate was 80.2% with MeziKd vs 53.4% with Kd, and ≥complete response was 26.7% vs 8.9%. Grade 3–4 adverse events occurred in 83.7% vs 56.5%, driven by neutropenia (61.1% vs 9.1%) and grade 3–4 infections (34.0% vs 15.6%); grade 5 infections remained infrequent in both arms (2.4% vs 1.1%). This is the first phase 3 readout for mezigdomide.

Mechanism / class

Mezigdomide is an oral cereblon E3 ligase modulator (CELMoD) that drives degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), with more potent substrate degradation than lenalidomide or pomalidomide. Carfilzomib is an irreversible proteasome inhibitor (approved in RRMM). Mezigdomide is investigational; no regulatory approval to date.

Discussant takeaway

Not reported in available coverage.

Practice-changing?

Pending. A first-in-class phase 3 win for a next-generation CELMoD with a large PFS doubling (18.0 vs 8.3 mo) and deep responses in a heavily pretreated, predominantly triple-class-exposed/anti-CD38-refractory population positions MeziKd as a potential new oral-backbone option, but practice change awaits regulatory filing/approval and OS maturity; the higher grade 3–4 hematologic and infection burden will shape positioning.

  • Other ASCO 2026 trials: (other RRMM / CELMoD / proteasome-inhibitor trials — add as filed)

Sources

  • ASCO Meeting Library (abstract LBA7506): https://meetings.asco.org/abstracts-presentations/search?q=LBA7506
  • BMS press release: https://news.bms.com/news/corporate-financial/2026/Bristol-Myers-Squibb-Announces-CELMoD-Mezigdomide-Reduces-Risk-of-Disease-Progression-or-Death-by-More-than-50-vs--Standard-of-Care-in-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx
  • OncoDaily: https://oncodaily.com/hematology/mezigdomide-successor-2-mezikd510953
  • EMJ: https://www.emjreviews.com/oncology/news/asco-2026-successor-2-advances-relapsed-myeloma-treatment/
  • AJMC: https://www.ajmc.com/view/adding-powerful-celmod-to-carfilzomib-backbone-cuts-risk-of-disease-progression-or-death-52-in-r-r-multiple-myeloma
  • CancerNetwork: https://www.cancernetwork.com/view/mezigdomide-regimen-improves-pfs-in-pretreated-r-r-multiple-myeloma
  • ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT05552976