Bertrand Arnulf, MD, PhD, discusses the importance of managing tumor burden for improved outcomes with ide-cel in relapsed/refractory multiple myeloma.

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.

, 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.

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Bertrand Arnulf, MD, PhD, discusses patient factors and pharmacodynamic biomarkers impacting survival outcomes with ide-cel in multiple myeloma.

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

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.

 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.

Bertrand Arnulf, MD, PhD, discusses patient factors and pharmacodynamic biomarkers that impact survival outcomes with ide-cel in multiple myeloma.

Bertrand Arnulf, MD, PhD

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Dr Arnulf on Managing Tumor Burden for Improved PFS With Ide-Cel in R/R Myeloma

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