Iberdomide–daratumumab doubles MRD-negative response over DVd, with more neutropenia and infection

Design

Phase 3, randomised, open-label (primary MRD analysis)

Population

420 adults with relapsed or refractory myeloma after 1–2 prior lines

Primary outcome

MRD-negative complete response (PFS pending)

Effect

41% vs 21%; difference 20.1 points (95% CI 11.5–28.6); OR 2.8

EXCALIBER-RRMM, an open-label phase 3 trial in The Lancet Oncology, randomised adults with relapsed or refractory multiple myeloma after one or two prior lines, excluding anti-CD38- and bortezomib-refractory disease, to iberdomide (an oral cereblon modulator) with daratumumab and dexamethasone, or daratumumab, bortezomib and dexamethasone (DVd).

In the first 420 patients, at a median 15.7 months, MRD-negative complete response was reached by 41% versus 21% (difference 20.1 percentage points). Grade 3–4 adverse events occurred in 92% versus 70%, including neutropenia in 84% versus 11% and infections in 39% versus 22%; serious pneumonia occurred in 18% versus 6%. Treatment-related deaths were about 1% in each arm. The trial was funded by the manufacturer.

MRD negativity is associated with longer survival in myeloma, but it is a surrogate. Progression-free survival, the trial's other primary endpoint, is being assessed in a larger cohort, and the comparator was a regimen many patients will already have moved beyond.

This is a signal of potency, not yet a reason to change regimens. Iberdomide is investigational; wait for progression-free survival and regulatory review.

• Treat this as a surrogate-endpoint result until progression-free survival reports
• Expect high rates of neutropenia and infection with iberdomide combinations
• Plan infection prophylaxis and growth factor support if using cereblon modulator combinations
• Note that iberdomide is investigational and not yet a standard option

Why it matters

A stronger cereblon modulator may deepen responses, but the infection cost is substantial.

Don't overread it

MRD negativity is a surrogate; this result does not yet show longer survival.

The statistics, in plain English

A 20-point difference in MRD-negative complete response (95% CI 11.5 to 28.6) is large and unlikely to be chance. Whether it translates into longer progression-free survival is the question the trial has not yet answered.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.