Al-Ola A Abdallah, Associate Professor at the University of Kansas Medical Center, shared on X:
“EXCALIBER‑RRMM: Iberdomide/ Daratumimab/Dex FDA approval!
Just FYI: this is from BMS News.
EXCALIBER‑RRMM is a randomized phase 3 trial comparing: IberDd vs DVd A total of 939 patients were randomized.
The trial used a two-stage design: Stage 1 evaluated iberdomide at 1.0, 1.3 and 1.6 mg. The selected dose was 1 mg orally on days 1–21 of each 28-day cycle. Dual primary endpoints: MRD-negative CR and PFS.
The approval analysis included the first 420 patients:
- IberDd: 207
- DVd: 213
- Median follow-up: 16 months
MRD-negative CR at any time:
- IberDd: 41%
- DVd: 21%
- P<0.0001
The main toxicity was myelosuppression:
- Neutropenia: 90.2%
- Grade 3: 30.9%
- Grade 4: 53.4%
- Febrile neutropenia: 5.4%
Infections occurred in 78.9%, including serious infections in 40% and fatal infections in 2%.
Other important safety findings with IberDd:
- Pneumonia: 34%
- VTE despite prophylaxis: 6.4%
- Arterial thrombosis: 3.4%
- Second primary malignancies: 6.9%
- Treatment discontinuation from adverse reactions: 7.8%
Important limitation: PFS, OS, ORR, duration of response, sustained MRD negativity and quality-of-life results have not yet been fully reported. The trial remains ongoing, and the published manuscript currently available describes the study design – not the complete results.
Some conclusions:
- The first FDA-approved CELMoD
- The first RRMM approval based on MRD-negative CR
- A new oral treatment backbone potentially available as early as first relapse
Longer follow-up will determine whether deeper MRD responses translate into improved PFS and OS. A major milestone for targeted protein degradation!
Thromoembolism in Iberdomise arm: 6.4%
Comparing AEs in both groups! Showing Pneumonia was common in the Iberdomise arm! Though questions if hypogammaglobunemia and neutropenia likely to occur at the Iberdomide arm!!
Rate and severity of infection at the Iberdomide arm:
Fatal adverse reactions occurred in 10 of approximately 204 patients of Iber/Dara/Dex (4.9%):
- Sepsis: 3 patients (1.5%)
- Listeria encephalitis: 1
- Influenza: 1
- Lung adenocarcinoma: 1
- Cardiac arrest: 1
- Large-intestinal perforation: 1
- Metabolic acidosis: 1
- Respiratory failure: 1
Fatal infections overall occurred in approximately 2%.
Second primary malignancies
At 16 months:
- IberDd: 6.9%
- DVd: 4.9%
In the IberDd arm: Second primary malignancies classified as serious adverse reactions: 5.9%. One fatal case of lung adenocarcinoma was reported.”
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