Real-world evidence is reshaping how bispecific antibodies are evaluated and utilized in relapsed/refractory multiple myeloma (R/R MM), with recent data demonstrating outcomes that more closely approximate clinical trial efficacy as treatment protocols have evolved and patient selection has been refined.
Real-World Performance Mirrors Clinical Trial Results
Initial real-world bispecific antibody data suggested modest efficacy reductions compared with clinical trial results, largely attributed to early commercial use in patients with the most aggressive disease presentations who required immediate intervention. However, subsequent real-world evidence has demonstrated outcomes that more closely approximate clinical trial efficacy, particularly as treatment protocols have been refined and patient selection has evolved.
These real-world studies importantly include patients who would not have met strict clinical trial eligibility criteria, demonstrating the broader applicability of bispecific therapies. Clinical trial populations often exclude older adults, patients with comorbidities, or those with impaired performance status, making postmarketing surveillance and registry data critical to understanding safety profiles in underrepresented subgroups such as Black, Hispanic, and older patients.
Strategic Patient Selection and Treatment Positioning
Patient selection for bispecific antibodies versus CAR T-cell therapy requires careful consideration of multiple factors, including comorbidity profiles, patient preferences regarding treatment-related risks, and disease tempo. Patients with prohibitive comorbidities for CAR T-cell therapy or those declining CAR T treatment after thorough risk-benefit discussions represent ideal candidates for bispecific antibody therapy.
For patients with rapidly progressive disease who remain CAR T candidates, bispecific antibodies serve as effective bridging therapy, with treatment choice influenced by prior therapy exposure and target antigen considerations. This broader applicability makes bispecific antibodies valuable tools for community oncologists managing complex relapsed/refractory multiple myeloma cases.
Payer Evaluation and Economic Considerations
Real-world evidence is becoming essential for payers, managed care organizations, and value-based care systems when evaluating the utility of bispecific therapies in R/R MM. While clinical trials demonstrate high response rates and progression-free survival, there is a need to validate these findings in broader, real-world populations.
Payers seek clarity on how long patients benefit from bispecifics, whether treatment-free intervals are feasible, and how these therapies compare with alternative sequencing strategies in terms of overall survival and time-to-next treatment. Cost-effectiveness plays a pivotal role in how bispecifics are positioned on formularies, with payers actively comparing the total cost of care, quality-adjusted life years, and cost-per-patient-per-month between bispecifics, CAR T-cell therapies, and conventional treatments.
Safety and Resource Utilization Assessment
Resource utilization data is needed to evaluate the broader economic impact, capturing hospital admissions, emergency visits, outpatient infusion demands, and long-term monitoring requirements such as labs and follow-up care. Safety profiles, including cytokine release syndrome, neurotoxicity, and infections, require ongoing evaluation through real-world data, especially in underrepresented patient populations.
There is growing interest in understanding whether bispecifics can serve as more cost-efficient alternatives, potentially delaying or replacing higher-cost options such as CAR T. Insights into treatment discontinuation, patient adherence, and the impact of prior BCMA-directed therapies will also shape value-based contracts and step therapy policies.
The evolving treatment landscape emphasizes the importance of individualized therapy selection based on comprehensive patient assessment. Real-world data continues to support the effectiveness of bispecific antibodies in diverse patient populations, including those with high-risk features that may have excluded them from initial clinical trials. Ultimately, robust real-world data can guide smarter reimbursement decisions, foster more equitable care access, and optimize how new therapies are integrated into treatment pathways across diverse patient populations.
