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Baseline Serum Inflammatory Proteins Predict Poor CAR T Outcomes in Diffuse Large B-cell Lymphoma
Rawan G Faramand1, Sae Bom Lee1, Michael D Jain1
1Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
Blood Cancer Discovery
|January 9, 2024
Summary
A simple risk score using C-reactive protein and ferritin before CAR T-cell therapy can predict outcomes for diffuse large B-cell lymphoma patients. This helps identify those at high risk for toxicities and poor survival.
Area of Science:
- Hematology
- Immunotherapy
- Oncology
Background:
- Chimeric antigen receptor (CAR) T-cell therapy has transformed treatment for relapsed/refractory hematologic malignancies.
- However, a subset of patients with diffuse large B-cell lymphoma (DLBCL) experience poor clinical outcomes and severe toxicities.
- Identifying patients at risk for adverse events and treatment failure is crucial for optimizing CAR T-cell therapy.
Purpose of the Study:
- To identify pre-treatment serum protein biomarkers associated with severe toxicities and inferior clinical responses in DLBCL patients undergoing CAR T-cell therapy.
- To develop and validate a simple risk stratification model for predicting outcomes in DLBCL patients treated with axicabtagene ciloleucel.
Main Methods:
- Serum C-reactive protein (CRP) and ferritin levels were measured before lymphodepletion in 146 DLBCL patients treated with axicabtagene ciloleucel.
- A risk stratification model was developed based on pre-lymphodepletion CRP and ferritin levels, categorizing patients into low-, intermediate-, and high-risk groups.
- The model's predictive performance for toxicities and survival was validated in two independent international cohorts.
Main Results:
- High levels of pre-lymphodepletion CRP and ferritin were associated with severe (grade ≥3) immune-mediated toxicities.
- Patients in the high-risk group exhibited inferior overall survival (OS) and progression-free survival (PFS) compared to low-risk patients.
- The risk stratification model demonstrated consistent predictive accuracy across independent validation cohorts.
Conclusions:
- Pre-lymphodepletion C-reactive protein and ferritin levels serve as valuable predictive biomarkers for outcomes in DLBCL patients receiving CAR T-cell therapy.
- A simple risk stratification model based on these readily available markers can effectively identify patients at high risk of toxicity and poor survival.
- This model can aid in patient selection and inform clinical decision-making for CAR T-cell therapy in DLBCL.
