Presentation (CTI)

OBJECTIVES: To analyse Phase 2/3 trials-in-progress in RRMM relative to current treatment guidelines, identifying where emerging evidence may drive change.
METHODS: Active/recruiting industry-sponsored Phase 2/3 RRMM trials were identified April 21, 2026 from ClinicalTrials.gov and EU-CTIS. Trials were screened for eligibility and data extracted by one reviewer. Included trials were categorised by class, target, and patient eligibility criteria. Guideline-recommended interventions were identified and trial criteria relating to prior LoT compared with guideline positioning (EHA-EMN,2025; NCCN v5.2026). Interventions not yet included in guidelines were identified and trial LoT criteria assessed.
RESULTS: 33 trials assessing 17 different therapies were identified, with bispecific antibodies (n=12) most represented. Other trials-in-progress investigated CAR T-cell therapies (n=6), antibody-drug conjugates (ADC; n=4), cereblon E3 ligase modulatory drugs (CELMoD; n=3), trispecific antibodies (n=3), anti-CD38 monoclonal antibodies (n=2), B-cell lymphoma-2 inhibitors (n=2), and small molecules (n=1). Ongoing trials for the bispecific antibodies teclistamab, elranatamab, linvoseltamab, and talquetamab are mostly exploring treatment from first relapse, either as monotherapy or combination therapy, typically ahead of guideline positioning (monotherapy: 4 line [L]+ [EHA-EMN]; 5L+ [NCCN]; exception: teclistamab+daratumumab: 2L+ [trial eligibility aligned with NCCN-recommendation]). Trials investigating CAR-T therapies typically fell within the recommended LoT (ciltacabtagene autoleucel: 2L+, idecabtagene vicleucel: 3L+), with trials investigating the ADC belantamab mafodotin also consistent with the EHA-EMN’s 2L+ and NCCN’s 3L+ recommendations. Fifteen trials are investigating therapies without RRMM marketing authorisation, of which 66.7% (n=10) enrolled patients from first relapse.
CONCLUSIONS: The RRMM pipeline reflects systematic earlier-line migration of immunotherapy, particularly bispecific antibodies, from late-salvage to early-relapse positioning. Simultaneously, novel classes (CELMoD) and targets (p300/CBP inhibitors) are advancing through development, with most studies enrolling patients from first relapse. It is anticipated that many more options will be imminently available to patients early in their treatment journey, allowing individualisation of treatment in this rare and heterogeneous disease.