Presentation (CTI)

OBJECTIVES: EU Joint Clinical Assessment (JCA) requires early development of evidence-based PICO scenarios that reflect rapidly evolving treatment landscape. In TCE-expanding treatment options, emerging biomarkers, and shifting treatment sequencing create substantial challenges for defining relevant populations and comparators. We evaluated the use of the Real-Time AI-Assisted Systematic Literature Review (REAL-SLR) platform to support transparent, continuously updated PICO mapping for JCA planning.
METHODS: A PRISMA-compliant, continuously updated REAL-SLR was conducted using the multiple myeloma database. Interventional trials in RRMM identified through publications and conference abstracts were mapped according to prior drug class exposure, refractoriness, risk, line of therapy, interventions, comparators, and outcomes. Regulatory documents, European/USA guidelines and health technology assessments (HTAs) supplemented evidence mapping. Structured evidence maps were used to identify potential JCA-relevant PICO scenarios in TCE RRMM.
RESULTS: As of 12 June 2026, the REAL-SLR included 440 studies, of which 213 evaluated TCE populations and 45 investigated EMA-approved therapies. Evidence mapping identified seven base-case PICO scenarios comprising 19 potential comparators across seven clinically relevant subpopulations defined LOT (1-2, 3, or ≥4 prior LOTs), prior BCMA-targeted/CAR-T eligibility, and refractoriness. Among the 19 comparators, only 10 were supported by pivotal trial evidence in TCE populations. Accounting for country-specific comparator landscapes in the UK and Germany expanded the number of relevant PICOs to thirteen. Continuous evidence monitoring identified pivotal bispecific antibody trials supporting migration of BCMA-directed therapies into earlier treatment lines, suggesting prior BCMA exposure may become a key population-defining characteristic in future JCA assessments.
CONCLUSIONS: Treatment sequencing changes and geographic variation in comparator use can substantially alter JCA-relevant PICOs in TCE-RRMM. Living evidence approaches may identify comparator shifts before formal HTA assessment, reduce evidence-generation risk, and improve JCA preparedness in rapidly evolving oncology indications.