Dr Arnulf on Managing Tumor Burden for Improved 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 the implications for evaluating patient factors and biomarkers influencing outcomes with idecabtagene vicleucel (ide-cel; Abecma) in patients with triple-class–exposed relapsed/refractory multiple myeloma, as well as highlights the next steps for this research.

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 progression-free survival (PFS) in participants treated with ide-cel on the phase 3 KarMMa-3 trial (NCT03651128). The study focused on identifying characteristics that predict better outcomes in patients receiving this BCMA-directed CAR T-cell therapy for relapsed or refractory multiple myeloma.

The results demonstrated that the majority of patients with longer PFS achieved clearance of both involved and heterotypic serum-free light chains (sFLC) following infusion with ide-cel. Notably, patients who had longer PFS following ide-cel infusion tended to have a relatively lower tumor burden and lower levels of peripheral inflammatory markers before starting treatment. Additionally, among patients who achieved initial sFLC clearance, those with longer PFS were able to maintain this clearance for a longer duration compared to patients with shorter PFS. A higher proportion of patients with longer PFS also reached minimal residual disease (MRD) negativity at 6 months following treatment with ide-cel and maintained MRD negativity more consistently over time than those with shorter PFS.

These findings highlight the importance of managing baseline tumor burden and controlling inflammatory parameters to optimize treatment outcomes with ide-cel, Arnulf explains. The data suggest that lower tumor burden prior to infusion is associated with longer PFS, underscoring the potential benefit of performing bridging therapy to reduce tumor burden before administering ide-cel, he emphasizes. Furthermore, managing inflammatory markers and ensuring that infections are under control and inflammatory parameters are normalized before treatment are crucial steps, Arnulf adds.

Moving forward, the focus will be on refining patient selection by correcting for known prognostic factors and incorporating genetic risk assessments, Arnulf says. This approach aims to better identify patients who are most likely to benefit from ide-cel therapy, he concludes.