P801: baseline and early post-infusion biomarkers associated with optimal response to idecabtagene vicleucel (ide-cel) in the karmma-3 study of triple-class–exposed relapsed and refractory multiple myeloma

Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: Ide-cel, a B-cell maturation antigen (BCMA) chimeric antigen receptor T cell therapy, significantly improved median progression-free survival (PFS) and overall response rate (ORR) versus standard regimens in patients with triple-class–exposed (TCE) relapsed and refractory multiple myeloma (RRMM) in the KarMMa-3 study (NCT03651128; Rodríguez-Otero et al. NEJM 2023). Previous analyses in KarMMa (Munshi et al. NEJM 2021) of patients with later-line (4L+) TCE RRMM identified low baseline levels and complete clearance of soluble BCMA (sBCMA, a measure of tumor burden) and early minimal residual disease (MRD) negativity as correlates of durable response to ide-cel. Aims: The current analysis explored the association between biomarkers and efficacy or severity of inflammatory adverse events of ide-cel in KarMMa-3. Methods: sBCMA levels were measured in blood samples collected from patients in KarMMa-3 at baseline and at regular intervals from treatment initiation until confirmed progression. MRD status was assessed in bone marrow aspirate (clonoSeq®; 10-5 sensitivity) at 6 and 12 months post infusion and reported in all patients, regardless of response. Biomarker analyses were based on patients who received ide-cel or ≥1 dose of standard regimen. Post hoc analyses assessed correlations between biomarkers and efficacy endpoints or cytokine release syndrome (CRS) and investigator-identified neurotoxicity (iiNT); associations of interest were identified using a ranked sum test and nominal P value <0.05. Results: Lower baseline sBCMA levels were associated with higher ORR (< partial response [PR] vs ≥PR) in both treatment arms (ide-cel, P=0.0223; standard regimens, P=0.0395), indicating this may be agnostic of the BCMA-directed modality. Lower baseline sBCMA was also associated with higher complete response (CR) rate (More