ASH 2024 | Immune profiling to predict response and resistance to CAR-T therapy in multiple myeloma

We are just learning about determinants of response and resistance to CAR-T therapy in myeloma. We know that antigen escape is an important mechanism, but it’s not universal. And it’s in fact restricted to only a few patients treated with anti-BCMA CAR T-cells. We know that depth of response is important, but it’s also not a determinant for long-term survival in these relapsed/refractory patients treated with CAR T-cells. And therefore, we hypothesized that looking at immune profiles before, throughout, and after CAR-T infusion could be complementary. And indeed, we found that patients’ immune status was influenced by the number of prior lines of treatment, also by staging prior to CAR-T therapy. We showed that a baseline immune score was predictive of PFS. We also showed that beyond the percentage of CAR T-cells at month 1, the CD4 to CD8 ratio, a more composite immune risk score based on CAR-T phenotypes was much more predictive of PFS. And importantly, among patients that were MRD negative at month 1, the phenotype of the CAR T-cells was able to segregate MRD negative patients with longer PFS and MRD negative patients with dismal PFS. And then we show that the infusion of CAR T-cells produces dramatic changes in the patient’s immune status during the first year after infusion, and that these changes also correlated with PFS, alluding to the possibility of immune surveillance after CAR-T infusion.

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