Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma
Abstract Chimeric antigen receptor T cells (CAR T) are groundbreaking therapies but may cause significant toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias. Granulocyte colony-stimulating factor (G-CSF) is often used...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-11-01
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| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-022-00741-2 |
| _version_ | 1797984663434690560 |
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| author | Kevin Charles Miller Patrick Connor Johnson Jeremy S. Abramson Jacob D. Soumerai Andrew J. Yee Andrew R. Branagan Elizabeth K. O’Donnell Anna Saucier Caron A. Jacobson Matthew J. Frigault Noopur S. Raje |
| author_facet | Kevin Charles Miller Patrick Connor Johnson Jeremy S. Abramson Jacob D. Soumerai Andrew J. Yee Andrew R. Branagan Elizabeth K. O’Donnell Anna Saucier Caron A. Jacobson Matthew J. Frigault Noopur S. Raje |
| author_sort | Kevin Charles Miller |
| collection | DOAJ |
| description | Abstract Chimeric antigen receptor T cells (CAR T) are groundbreaking therapies but may cause significant toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias. Granulocyte colony-stimulating factor (G-CSF) is often used to mitigate neutropenia after CAR T, but there is no consensus recommended strategy due to hypothesized, but largely unknown risks of exacerbating toxicities. To investigate the impact of G-CSF, we retrospectively analyzed 197 patients treated with anti-CD19 CAR T for lymphoma and 47 patients treated with anti-BCMA CAR T for multiple myeloma. In lymphoma, 140 patients (71%) received prophylactic G-CSF before CAR T (mostly pegylated G-CSF) and were compared with 57 patients (29%) treated with G-CSF after CAR T or not exposed. Prophylactic G-CSF was associated with faster neutrophil recovery (3 vs. 4 days, P < 0.01) but did not reduce recurrent neutropenia later. Prophylactic G-CSF was associated with increased grade ≥2 CRS (HR 2.15, 95% CI 1.11–4.18, P = 0.02), but not ICANS. In multiple myeloma, prophylactic G-CSF was not used; patients were stratified by early G-CSF exposure (≤2 days vs. ≥3 days after CAR T or no exposure), with no significant difference in toxicities. Future trials should clarify the optimal G-CSF strategy to improve outcomes after CAR T. |
| first_indexed | 2024-04-11T07:06:39Z |
| format | Article |
| id | doaj.art-3228817cf75c47368f94792a61f6aa4d |
| institution | Directory Open Access Journal |
| issn | 2044-5385 |
| language | English |
| last_indexed | 2024-04-11T07:06:39Z |
| publishDate | 2022-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj.art-3228817cf75c47368f94792a61f6aa4d2022-12-22T04:38:23ZengNature Publishing GroupBlood Cancer Journal2044-53852022-11-01121011210.1038/s41408-022-00741-2Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myelomaKevin Charles Miller0Patrick Connor Johnson1Jeremy S. Abramson2Jacob D. Soumerai3Andrew J. Yee4Andrew R. Branagan5Elizabeth K. O’Donnell6Anna Saucier7Caron A. Jacobson8Matthew J. Frigault9Noopur S. Raje10Department of Medicine, Massachusetts General HospitalCenter for Lymphoma, Massachusetts General HospitalCenter for Lymphoma, Massachusetts General HospitalCenter for Lymphoma, Massachusetts General HospitalCenter for Multiple Myeloma, Massachusetts General HospitalCenter for Multiple Myeloma, Massachusetts General HospitalCenter for Multiple Myeloma, Massachusetts General HospitalTufts University School of MedicineImmune Effector Cell Therapy Program, Dana-Farber Cancer InstituteCellular Immunotherapy Program, Massachusetts General HospitalCellular Immunotherapy Program, Massachusetts General HospitalAbstract Chimeric antigen receptor T cells (CAR T) are groundbreaking therapies but may cause significant toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias. Granulocyte colony-stimulating factor (G-CSF) is often used to mitigate neutropenia after CAR T, but there is no consensus recommended strategy due to hypothesized, but largely unknown risks of exacerbating toxicities. To investigate the impact of G-CSF, we retrospectively analyzed 197 patients treated with anti-CD19 CAR T for lymphoma and 47 patients treated with anti-BCMA CAR T for multiple myeloma. In lymphoma, 140 patients (71%) received prophylactic G-CSF before CAR T (mostly pegylated G-CSF) and were compared with 57 patients (29%) treated with G-CSF after CAR T or not exposed. Prophylactic G-CSF was associated with faster neutrophil recovery (3 vs. 4 days, P < 0.01) but did not reduce recurrent neutropenia later. Prophylactic G-CSF was associated with increased grade ≥2 CRS (HR 2.15, 95% CI 1.11–4.18, P = 0.02), but not ICANS. In multiple myeloma, prophylactic G-CSF was not used; patients were stratified by early G-CSF exposure (≤2 days vs. ≥3 days after CAR T or no exposure), with no significant difference in toxicities. Future trials should clarify the optimal G-CSF strategy to improve outcomes after CAR T.https://doi.org/10.1038/s41408-022-00741-2 |
| spellingShingle | Kevin Charles Miller Patrick Connor Johnson Jeremy S. Abramson Jacob D. Soumerai Andrew J. Yee Andrew R. Branagan Elizabeth K. O’Donnell Anna Saucier Caron A. Jacobson Matthew J. Frigault Noopur S. Raje Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma Blood Cancer Journal |
| title | Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma |
| title_full | Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma |
| title_fullStr | Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma |
| title_full_unstemmed | Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma |
| title_short | Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma |
| title_sort | effect of granulocyte colony stimulating factor on toxicities after car t cell therapy for lymphoma and myeloma |
| url | https://doi.org/10.1038/s41408-022-00741-2 |
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