Dr. Richardson envisions iberdomide as a well-tolerated upfront and maintenance therapy due to its favorable safety profile. In contrast, the more potent mezigdomide is targeted for heavily pre-treated, relapsed/refractory patients, particularly those who have failed immunotherapies.
In the maintenance setting, iberdomide isn't just a marginal improvement over the standard, lenalidomide. Cross-trial data suggests it more than doubles the rate of response improvement (70% vs. 30%) while surprisingly causing fewer side effects, such as gastrointestinal issues.
Unlike therapies that can deplete the immune system, mezigdomide enhances T-cell number and function. This unique immune-enhancing property makes it a promising agent to use before, or in combination with, immunotherapies like CAR-T to overcome resistance and improve outcomes in highly refractory patients.
Dr. Richardson repeatedly emphasizes that modern clinical trial design must incorporate FDA guidance. Key elements now considered vital for approval include upfront dose optimization phases and deliberate inclusion of diverse populations, particularly African American patients, to ensure relevance and equity.
Based on findings from the DETERMINATION-1 and MIDAS trials, which questioned the overall survival benefit of early transplant, new strategies are emerging. The DETERMINATION-2 trial will use iberdomide-based therapy and defer transplant for standard-risk, MRD-negative patients, reserving it for higher-risk cases.