Hematopoietic stem cell boost for persistent neutropenia after CAR T-cell therapy: a GLA/DRST study

Author:

Gagelmann Nico1ORCID,Wulf Gerald Georg2,Duell Johannes3,Glass Bertram4,van Heteren Pearl4,von Tresckow Bastian5ORCID,Fischer Monika2,Penack Olaf6,Ayuk Francis1,Einsele Herrmann3,Holtick Udo7,Thomson Julia2,Dreger Peter8,Kröger Nicolaus1ORCID

Affiliation:

1. 1Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2. 2Hämatologie und Medizinische Onkologie, UM Göttingen, Göttingen, Germany

3. 3Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany

4. 4Klinik für Hämatologie und Stammzelltransplantation, Helios Clinic Berlin-Buch, Berlin, Germany

5. 5Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

6. 6Department of Hematology, Oncology, and Tumor Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

7. 7Department of Internal Medicine I, Leukapheresis and Stem Cell Transplant Unit, University Hospital of Cologne, Cologne, Germany

8. 8Internal Medicine V - Hematology, Oncology & Rheumatology, University Hospital Heidelberg, Heidelberg, Germany

Abstract

Abstract Hematotoxicity after chimeric antigen receptor (CAR) T-cell therapy is associated with infection and death but management remains unclear. We report results of 31 patients receiving hematopoietic stem cell boost (HSCB; 30 autologous, 1 allogeneic) for either sustained severe neutropenia of grade 4 (<0.5 × 109/L), sustained moderate neutropenia (≤1.5 × 109/L) and high risk of infection, or neutrophil count ≤2.0 × 109/L and active infection. Median time from CAR T-cell therapy to HSCB was 43 days and median absolute neutrophil count at time of HSCB was 0.2. Median duration of neutropenia before HSCB was 38 days (range, 7-151). Overall neutrophil response rate (recovery or improvement) was observed in 26 patients (84%) within a median of 9 days (95% confidence interval, 7-14). Time to response was significantly associated with the duration of prior neutropenia (P = .007). All nonresponders died within the first year after HSCB. One-year overall survival for all patients was 59% and significantly different for neutropenia (≤38 days; 85%) vs neutropenia >38 days before HSCB (44%; P = .029). In conclusion, early or prophylactic HSCB showed quick response and improved outcomes for sustained moderate to severe neutropenia after CAR-T.

Publisher

American Society of Hematology

Subject

Hematology

Reference18 articles.

1. Recent advances in CAR T-cell toxicity: mechanisms, manifestations and management;Brudno;Blood Rev,2019

2. Early and late hematologic toxicity following CD19 CAR-T cells;Fried;Bone Marrow Transplant,2019

3. Hematopoietic recovery in patients receiving chimeric antigen receptor T-cell therapy for hematologic malignancies;Jain;Blood Adv,2020

4. GLA/DRST real-world outcome analysis of CAR-T cell therapies for large B-cell lymphoma in Germany;Bethge;Blood,2022

5. CAR-HEMATOTOX: a model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma;Rejeski;Blood,2021

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