Early-Phase Study of Iberdomide Plus Dexamethasone for Resistant Multiple Myeloma
Posted: Wednesday, September 25, 2019
Iberdomide, a new cereblon E3 ligase modulator, in combination with dexamethasone showed activity and safety in patients who had previously failed to respond to treatment for refractory or relapsed multiple myeloma. Sagar Lonial, MD, of Emory University in Atlanta, conducted the ongoing study, which was presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 8006) and published in the Journal of Clinical Oncology. Iberdomide was previously shown to overcome immunomodulatory drug resistance and demonstrated synergy with dexamethasone, daratumumab, and bortezomib.
The phase Ib/IIa multicenter, open-label, dose-escalation study enrolled 58 patients who had received a minimum of two prior regimens and had disease progression within the last 60 days of therapy. Patients were given escalating doses of iberdomide on days 1 to 21 along with 40 mg of dexamethasone on days 1, 8, 15, and 22 of the 28-day cycle.
The median age of patients in the study was 64.5 years, and the median number of five prior treatments included autologous stem cell transplant (79%), lenalidomide (100%), pomalidomide (69%), proteasome inhibitors (100%) and daratumumab (66%). The iberdomide dose ranged from 0.3 to 1.2 mg throughout the study, and patients received the therapy for a median of 12 weeks.
At the time of data presentation at the ASCO meeting, neither the maximum tolerated dose nor the recommended phase II dose was achieved. The overall response to treatment was 31%, with 16 patients achieving a partial response or better. At the time of data presentation, 19 patients had stable disease, and the disease control rate was estimated to be 88%; 20 patients remain on treatment.
Grade 3 or 4 adverse events related to treatment were noted in 72% of patients and were thought to be unrelated to the dose. Common adverse events with the investigational therapy included neutropenia (26%), thrombocytopenia (11%), and neuropathy (2%). Of the 58 patients, 3 discontinued treatment as a result of adverse events.
Disclosure: The study authors’ disclosure information may be found at coi.asco.org.
