Lower levels of inflammatory markers and tumour burden is linked to improvements in PFS with Ide-Cel in R/R multiple myeloma

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Published: 24 Jun 2024
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Prof Bertrand Arnulf - Hôpital Saint-Louis, Paris, France

Prof Bertrand Arnulf speaks to ecancer about his study, KarMMa-3.

The trial analysis identified factors linked to longer progression-free survival in multiple myeloma patients treated with idecabtagene vicleucel (ide-cel), a BCMA CAR T cell therapy.

Patients with longer PFS had lower baseline tumour burden and inflammatory markers.

Achieving and sustaining serum free light chain (sFLC) clearance post-infusion, along with higher and prolonged minimal residual disease (MRD) negativity, were strongly associated with longer PFS.

These findings emphasise the importance of managing baseline tumour burden and achieving early and sustained MRD negativity for optimal response to ide-cel therapy.

Lower levels of inflammatory markers and tumour burden is linked to improvements in PFS with Ide-Cel in R/R multiple myeloma

Prof Bertrand Arnulf - Hôpital Saint-Louis, Paris, France

Today at EHA I will present a poster regarding trying to identify prognostic factors associated with PFS in patients from the KarMMa-3 study which is evaluating Ide-Cel versus standard of care in patients with multiple myeloma in relapse after 2-4 prior lines of treatment.

These are 250 patients treated with Ide-Cel and the median PFS of these patients is 15.7 months. We tried to identify biomarkers associated with a longer PFS, a longer PFS defined by more than the median PFS and those without long PFS. So, first of all, it has been already shown that inflammatory cytokines before apheresis is associated with a lower response rate.  First we showed that at the day of infusion the tumour burden as measured by soluble BCMA and also inflammatory cytokines like TNF-α or IL-10 are associated with a lower PFS.

What we found also is that the PFS is associated with tumour burden, soluble BCMA levels, but also an inflammatory state at baseline at the moment of lymphodepletion. So a high level of CRP, a high level of ferritin and also a high level of β-2 microglobulin and LDH reflecting the tumour burden.

So what we found also is that the PFS is correlated with the level of response. We have a better PFS in patients reaching CR and when we look at MRD we have also a difference between patients reaching MRD and having a longer PFS. MRD 10-5 is 87% in patients with long PFS as compared to 14% in patients with lower PFS. When we look at MRD 10-6 it was also different, almost 70% of patients with long PFS as compared to 14% of patients with a shorter PFS.

What we also found is that the PFS is also correlated with the peak of CAR T-cell expansion but conversely there was no association between the persistence of CAR T-cell and the duration of response.

So those results show that to reach a longer PFS patients have to be in a lower tumour burden without any inflammatory state and also post-infusion they have to reach a deep response and MRD negativity measured at six months. It is also true in patients with sustained MRD negativity more than 8 months.

What is next for this study?

The next step for the study is trying to understand the relationship between CAR T exposure and response and duration of response to better select patients. Because we need to have biomarkers to identify patients who will have a long PFS as compared to patients who relapse early.