Dr Arnulf on Patient Factors and Biomarkers Impacting PFS With Ide-Cel in R/R Myeloma

Bertrand Arnulf, MD, PhD, Department of Hematology and Immunology, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, discusses patient factors and pharmacodynamic biomarkers that may impact progression-free survival (PFS) outcomes following treatment with idecabtagene vicleucel (ide-cel; Abecma) in patients with multiple myeloma, as identified in an analysis of the phase 3 KarMMa-3 trial (NCT03651128).

The KarMMa-3 trial evaluated the efficacy of this BCMA-directed CAR T-cell therapy, vs the standard of care (SOC) in patients with triple-class–exposed relapsed/refractory multiple myeloma. The study demonstrated that ide-cel provided a superior PFS benefit compared with standard therapies; this advantage was also consistent across various high-risk patient subgroups. Notably, previous analyses indicated that lower levels of baseline soluble BCMA (sBCMA), a measure of tumor burden, and lower basal inflammatory markers were correlated with responses to ide-cel.

At the 2024 EHA Hybrid Congress data were presented from an analysis of pre- and post-treatment patient factors and pharmacodynamic biomarkers associated with longer PFS in the treated population from KarMMa-3. Results showed that the majority of patients with longer PFS achieved clearance of both involved and heterotypic serum free light chains (sFLC) following ide-cel infusion, Arnulf reports. Among those who achieved initial sFLC clearance, patients with longer PFS maintained such clearance for a longer duration vs those with shorter PFS. In turn, this suggests more durable engraftment of ide-cel and improved tumor control, he explains. Additionally, high rates of minimal residual disease (MRD) negativity were strongly associated with longer PFS, Arnulf states. A higher proportion of patients with longer PFS reached MRD negativity at 6 months following treatment with ide-cel; these patients also experienced a higher rate of sustained MRD negativity compared to those with shorter PFS.

Additionally, the study found that lower baseline levels of B2-microglobulin, lactate dehydrogenase, C-reactive protein, and ferritin at the time of lymphodepletion were associated with longer PFS, Arnulf says. This suggests that patients with lower tumor burden and reduced peripheral inflammatory markers before treatment are more likely to achieve optimal responses to ide-cel. Furthermore, lower levels of inflammatory cytokines such as TNF-alpha and IL-10 on the day of ide-cel infusion were also linked to longer PFS, he adds. These findings emphasize the importance of managing baseline tumor burden and inflammatory markers before CAR T-cell infusion to achieve optimal therapeutic outcomes, Arnulf concludes.