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| Item Type: | Article |
|---|---|
| Title: | The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL |
| Creators Name: | Rejeski, K., Perez, A., Iacoboni, G., Penack, O., Bücklein, V., Jentzsch, L., Mougiakakos, D., Johnson, G., Arciola, B., Carpio, C., Blumenberg, V., Hoster, E., Bullinger, L., Locke, F.L., von Bergwelt-Baildon, M., Mackensen, A., Bethge, W., Barba, P., Jain, M.D. and Subklewe, M. |
| Abstract: | BACKGROUND: CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) represents a promising treatment modality for an increasing number of B-cell malignancies. However, prolonged cytopenias and infections substantially contribute to the toxicity burden of CAR-T. The recently developed CAR-HEMATOTOX (HT) score-composed of five pre-lymphodepletion variables (eg, absolute neutrophil count, platelet count, hemoglobin, C-reactive protein, ferritin)-enables risk stratification of hematological toxicity. METHODS: In this multicenter retrospective analysis, we characterized early infection events (days 0-90) and clinical outcomes in 248 patients receiving standard-of-care CD19 CAR-T for relapsed/refractory large B-cell lymphoma. This included a derivation cohort (cohort A, 179 patients) and a second independent validation cohort (cohort B, 69 patients). Cumulative incidence curves were calculated for all-grade, grade ≥3, and specific infection subtypes. Clinical outcomes were studied via Kaplan-Meier estimates. RESULTS: In a multivariate analysis adjusted for other baseline features, the HT score identified patients at high risk for severe infections (adjusted HR 6.4, 95% CI 3.1 to 13.1). HT(high) patients more frequently developed severe infections (40% vs 8%, p<0.0001)-particularly severe bacterial infections (27% vs 0.9%, p<0.0001). Additionally, multivariate analysis of post-CAR-T factors revealed that infection risk was increased by prolonged neutropenia (≥14 days) and corticosteroid use (≥9 days), and decreased with fluoroquinolone prophylaxis. Antibacterial prophylaxis significantly reduced the likelihood of severe bacterial infections in HT(high) (16% vs 46%, p<0.001), but not HT(low) patients (0% vs 2%, p=n.s.). Collectively, HT(high) patients experienced worse median progression-free (3.4 vs 12.6 months) and overall survival (9.1 months vs not-reached), and were hospitalized longer (median 20 vs 16 days). Severe infections represented the most common cause of non-relapse mortality after CAR-T and were associated with poor survival outcomes. A trend toward increased non-relapse mortality in HT(high) patients was observed (8.0% vs 3.7%, p=0.09). CONCLUSIONS: These data demonstrate the utility of the HT score to risk-stratify patients for infectious complications and poor survival outcomes prior to CD19 CAR-T. High-risk patients likely benefit from anti-infective prophylaxis and should be closely monitored for potential infections and relapse. |
| Keywords: | Adoptive Immunotherapy, CD19 Antigens, Chimeric Antigen Receptors, Diffuse Large B-Cell Lymphoma, Disease Progression, Local Neoplasm Recurrence, Retrospective Studies |
| Source: | Journal for ImmunoTherapy of Cancer |
| ISSN: | 2051-1426 |
| Publisher: | BMJ Publishing Group |
| Volume: | 10 |
| Number: | 5 |
| Page Range: | e004475 |
| Date: | 17 May 2022 |
| Official Publication: | https://doi.org/10.1136/jitc-2021-004475 |
| PubMed: | View item in PubMed |
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