# Peripheral blood inflammatory ratios predict efficacy and toxicity of CAR-T cell immunotherapy in relapsed/refractory multiple myeloma

## TL;DR

This study shows that blood inflammatory ratios can predict how well CAR-T therapy works and how severe its side effects are in patients with multiple myeloma.

## Contribution

The study introduces a new composite index (CIPI) based on inflammatory ratios to predict CAR-T outcomes in multiple myeloma.

## Key findings

- Low baseline inflammatory ratios correlate with better CAR-T efficacy and longer progression-free survival.
- The CIPI score effectively stratifies patients into risk groups with distinct survival outcomes.
- High inflammatory ratios are linked to increased cytokine release syndrome severity and higher IL-6 and ferritin levels.

## Abstract

Despite the remarkable efficacy of chimeric antigen receptor T-cell (CAR-T) therapy in relapsed/refractory multiple myeloma (R/R MM), treatment response and toxicity exhibit considerable heterogeneity. This study aimed to evaluate the prognostic significance of baseline peripheral blood inflammatory ratios—namely, the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR)—in patients with R/R MM receiving CAR-T therapy, and to develop an integrated prognostic index based on these parameters.

We conducted a retrospective analysis of 197 R/R MM patients who received CAR-T therapy. The optimal cut-off values for NLR, MLR, and PLR were determined using receiver operating characteristic (ROC) curve analysis. Associations between these ratios and treatment efficacy, CAR transgene expansion, cytokine release syndrome (CRS), and progression-free survival (PFS) were evaluated. A composite Cellular Inflammatory Prognostic Index (CIPI) integrating NLR, MLR, and PLR was developed to assess prognostic stratification.

Optimal cut-offs for NLR, MLR, and PLR were 2.55, 0.35, and 145, respectively. Patients with low baseline inflammatory ratios exhibited significantly higher CAR transgene expansion and were associated with better treatment responses than that of patients with high baseline inflammatory ratios. The low NLR group showed a superior objective response rate (93.8% vs. 81.2%, p = 0.037) and a longer median PFS was observed in the low NLR group compared with the high NLR group (18.6 vs. 10.9 months, p = 0.0012). Elevated inflammatory ratios correlated with high peak levels of IL-6 and ferritin and an increased incidence of severe CRS (≥ grade 3). The CIPI score effectively stratified patients into low-, intermediate-, and high-risk groups with distinct PFS (median PFS: 18.9, 13.8, and 5.1 months, respectively; p < 0.0001). Multivariate analysis confirmed that the CIPI score was an independent prognostic factor for PFS, along with high tumor burden.

Baseline peripheral blood inflammatory ratios are closely associated with CAR-T cell efficacy and CRS severity in R/R MM patients receiving CAR-T therapy. The CIPI score represents a simple and reproducible prognostic biomarker that may help individualized risk stratification and inform treatment optimization in CAR-T therapy.