(OA-63) Efficacy and Safety of Iberdomide, Daratumumab, and Dexamethasone, in Transplant-Ineligible Newly Diagnosed Multiple Myeloma Patients: Initial Analysis of the GEM-IBERDARAX trial

In elderly transplant-ineligible newly diagnosed multiple myeloma (TIE NDMM) patients, daratumumab, lenalidomide, and dexamethasone (DRd) is a standard of care. Iberdomide, an oral novel CELMoD, has shown promising efficacy. The Spanish Myeloma Group (GEM) planned a multicenter phase II clinical trial to evaluate Iberdomide plus dexamethasone (Iberdex) alone (cohort 1-previously reported), or in combination with daratumumab (cohort 2) in TIE NDMM patients. The study aimed to include ≥30% of frail patients.  This abstract focuses on the cohort 2.



Methods: Cohort 2 (Iberdaradex) included TIE NDMM patients treated with iberdomide (1.6 mg orally on days 1–21, q4w; reduced to 1 mg after protocol amendment), weekly dexamehasone (40 mg or 20 mg if ≥75 years), and daratumumab (1800 mg, per standard schedule), until progression, toxicity, or death. An interim analysis was planned after all patients completed 6 cycles. Primary endpoint: overall response rate (ORR), and complete response (CR). Secondary endpoints: safety, minimal residual disease (MRD) by next-generation flow (sensitivity ≥10^-5), progression-free (PFS) and overall survival (OS). Frailty was assessed using the IFM frailty score.


Results:

77 patients were enrolled in the cohort 2. Median age was 77 (67-88) and 51.9% were female. ISS III 28.6%. 23 patients (31.1%) were fit, and 51 (68.9%) frail, of whom 30 (58.8%) were ultra frail.

After 6 cycles, in the efficacy-evaluable population (n=73), 91.8% of patients responded, 20.5% achieved CR or better and 75.3% VGPR or better. MRD negativity was observed in 20 patients (27.3%).  Overall, and after a median follow-up of 11.1 months (3.5-29.2), best ORR was 93.1%, CR or better was 34.2% and VGPR or better was 83.5%. No response differences based on frailty.

Safety analysis included the first 6 cycles. Iberdomide was started at 1.6 mg in 55 patients (71.4%), at 1.3 mg in 1 patient, and at 1 mg in 21 patients (27.2%). Most frequent AEs were neutropenia (any grade: 74.0%, and G3-4: 67.5%, only 5.2% febrile neutropenia) and infections (48.1% and G3-4: 16.9%), mainly respiratory (39%, G3-4: 9.1%, pneumonia 5.2%). Skin rash occurred in 23.4% (G3-4 in 2 patients) and fatigue in 16.9% (G3-4 in 3).

At data cut-off, 3 patients had progressed at 4.7, 8.9 and 13.7 months, 6-month PFS: 92.2% and 12-m PFS: 80.8%. Five deaths occurred within the first 6 months: 2 from pneumonia, 1 biliary sepsis, 1 sudden death and 1 status epilepticus- all ultra frail, and all but one had started at 1.6 mg iberdomide. Six-m OS: 93.5% and 12-m OS: 81.1%.  



Conclusions: This initial analysis demonstrates that Iberdaradex is effective in TIE NDMM patients, and it is remarkable that most of this population was frail or ultra frail. The VGPR and CR or better rates of 83.5% and 34.2% are encouraging. The safety profile after 6 cycles was acceptable and manageable in this particularly frail population.