This phase 3 RCT (EXCALIBER-RRMM) compared iberdomide + daratumumab + dexamethasone (Iber-Dara-Dex) vs. daratumumab + bortezomib + dexamethasone (DVd) in adults with relapsed/refractory multiple myeloma (1–2 prior lines) over a median 15.7 months of follow-up, with MRD-negative complete response and progression-free survival as dual primary endpoints.
MRD-negative complete response was achieved in 41% (85/207) with Iber-Dara-Dex vs. 21% (44/213) with DVd (stratified difference 20.1%, 95% CI 11.5–28.6, p<0.0001; OR 2.8, 95% CI 1.8–4.3); however, progression-free survival data are not yet mature.
Progression-free survival (the second co-primary endpoint) remains immature and pending; the open-label design introduces potential bias; and patients with anti-CD38- or bortezomib-refractory disease were excluded, limiting generalizability to heavily pre-treated or refractory populations.
Iberdomide + daratumumab + dexamethasone roughly doubles the rate of MRD-negative complete response versus the DVd standard in 1–2 prior line RRMM, but clinicians should anticipate substantially higher rates of grade 3–4 neutropenia (84% vs. 11%) and serious infections including pneumonia (18% vs. 6%), requiring proactive monitoring and supportive care.
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