Mezigdomide, Carfilzomib, and Dexamethasone (MeziKd) Vs Carfilzomib and Dexamethasone (Kd) In Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Phase 3 Successor-2 Trial

Presenter: Prof. Dr. Meletios Dimopoulos

• Patients with RRMM increasingly have prior anti‑CD38 monoclonal antibody and lenalidomide exposure, limiting treatment options.
• In the phase 3 SUCCESSOR‑2 trial, MeziKd was compared with Kd. Mezigdomide (a cereblon E3 ligase modulator) dose 1.0 mg was selected.
• Among 479 patients, mPFS improved to 18.0 months (95% confidence interval 14.5–22.1) vs 8.3 months (5.6–10.7; HR 0.48; P<0.0001).
• ORR was 80.2% vs 53.4%, ≥CR 26.7% vs 8.9%.
• Grade 3–4 AE were 83.7% vs 56.5%, including neutropenia (61.1% vs 9.1%) and infections (34.0% vs 15.6%).
• MeziKd demonstrated a significant and clinically meaningful efficacy advantage over Kd, supporting its use as a potential new standard of care in RRMM.

Teclistamab Improves Depth of Response and PFS Versus Lenalidomide-Dexamethasone in High-Risk Smoldering Multiple Myeloma: Results From The Phase 2 ImmunoPRISM Trial

Presenter: Omar Nadeem

• Teclistamab, a BCMA-targeting bispecific antibody, was evaluated vs lenalidomide–dexamethasone (Rd) in high-risk smoldering multiple myeloma (HR‑SMM) in the phase 2 ImmunoPRISM trial.
• CR/sCR was observed in 73% with teclistamab vs 0% with Rd, and ≥VGPR 87% vs 14% (P<0.001).
• MRD negativity (10⁻⁵) occurred in 81% vs 0%.
• At 23.4 months, 2‑year PFS was 92% vs 51% (P=0.007).
• Grade ≥3 AE included neutropenia (36% vs 79%) and infections (20% vs 21.4%), with mainly low‑grade CRS (71.1%).
• Teclistamab significantly improved depth of response, MRD negativity and PFS compared with Rd in HR-SMM.

MajesTEC-9: A Phase 3 Study of Teclistamab Monotherapy Vs Pomalidomide/Bortezomib/Dexamethasone or Carfilzomib/Dexamethasone (PVd/Kd) in Patients (PTS) with Relapsed Refractory Multiple Myeloma (RRMM)

Presenter: Cyrille Touzeau

• Teclistamab, a BCMA×CD3 bispecific antibody, was evaluated as monotherapy vs PVd/Kd in the phase 3 MajesTEC‑9 trial in RRMM with 1–3 prior lines.
• The study included 593 patients (median age 70 yrs; 80% lenalidomide‑refractory; 85% anti‑CD38‑refractory).
• Teclistamab significantly improved PFS (median not reached vs 8.2 months; HR 0.29; P<0.0001) and 18‑month PFS rates (69.8% vs 26.9%).
• OS was also improved (HR 0.60; P=0.0020).
• ≥CR rates were markedly higher 65.9% vs 16.8%.
• Grade 3–4 adverse events (84.9% vs 76.3%) and infections (41.6% vs 29.0%) were increased, with manageable cytokine release syndrome (66.0%).
• Teclistamab monotherapy significantly improved PFS and OS with deeper responses compared to standard of care in RRMM.

Phase 3, Randomized Study of Talquetamab (TAL) plus Daratumumab (DARA) ± pomalidomide (POM) Vs Dara Plus POM and Dexamethasone (DPd) In Relapsed/Refractory Multiple Myeloma (RRMM): MonumenTAL-3

Presenter: Peter Voorhees

• Tal a GPRC5D×CD3 bispecific antibody combined with D ± P was compared with DPd in the phase 3 MonumenTAL‑3 trial in RRMM.
• Among 864 patients, PFS significantly improved for Tal‑DP (HR 0.28) and Tal‑D (0.33) vs DPd (P<0.0001), with 24‑month PFS rates 81.3%, 77.6%, vs 51.2%.
• ORR were 88.2%, 88.5%, vs 77.6%, and ≥CR 71.1%, 69.0%, vs 34.5%.
• Grade 3–4 AE were frequent but manageable, including cytopenias and infections, with mostly low‑grade CRS.
• Tal‑DP and Tal‑D showed strong PFS benefit vs DPd, meaningful OS gains, and similar/lower ≥3 infections. Tal was well‑tolerated with low discontinuation. Tal‑DP had higher efficacy but more cytopenias vs Tal‑D.
• Tal-D ± Pom represents a new standard of care for RRMM as early as 2L across all practice settings.

Safety and Efficacy of Iberdomide-Based Quadruplet  for Patients with Newly Diagnosed Multiple Myeloma: The Ideal Phase I/II Trial Results

Presenter: Dr. Prashant Kapoor

• Iberdomide, a cereblon E3 ligase modulator (CELMoD), combined with daratumumab, bortezomib, and dexamethasone (Iber‑DVd), was evaluated in NDMM in the phase I/II IDEAL trial.
• Among 44 patients at the recommended phase 2 dose (0.75 mg), overall response rate was 100%, with ≥CR rates 36.4% during induction and 52.3% overall.
• MRD negativity (10⁻⁵) was 29.5% during induction and 47.7% overall. At 18.3 months follow‑up, 12‑ and 18‑month PFS rates were 91% and 88%.
• Grade 3/4 toxicities included neutropenia (41%/16%) and infections (11.4%/2.3%), demonstrating manageable safety and deep responses.
• Iber‑DVd demonstrates high efficacy with deep and durable responses, including substantial minimal residual disease negativity, in NDMM.

31^st European Hematology Association Congress (EHA 2026),11^th –14^th, 2026, Stockholm, Sweden.