Few studies have reported the associations of granulocyte colony-stimulating factor (G-CSF) with cytokine release syndrome (CRS), neurotoxic events (NEs) and efficacy after chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) multiple myeloma (MM). We present a retrospective study performed on 113 patients with R/R MM who received single anti-BCMA CAR T-cell, combined with anti-CD19 CAR T-cell or anti-CD138 CAR T-cell therapy.
Eight patients were given G-CSF after successful management of CRS, and no CRS re-occurred thereafter. Of the remaining 105 patients that were finally analyzed, 72 (68.6%) received G-CSF (G-CSF group), and 33 (31.4%) did not (non G-CSF group). We mainly analyzed the incidence and severity of CRS or NEs in two groups of patients, as well as the associations of G-CSF timing, cumulative dose and cumulative time with CRS, NEs and efficacy of CAR T-cell therapy.
Both groups of patients had similar duration of grade 3–4 neutropenia, and the incidence and severity of CRS or NEs.There were also no differences in the incidence and severity of CRS or NEs between patients with the timing of G-CSF administration ≤3 days and those >3 days after CAR T-cell infusion. The incidence of CRS was greater in patients receiving cumulative doses of G-CSF >1500 μg or cumulative time of G-CSF administration >5 days. Among patients with CRS, there was no difference in the severity of CRS between patients who used G-CSF and those who did not. The duration of CRS in anti-BCMA and anti-CD19 CAR T-cell–treated patients was prolonged after G-CSF administration. There were no significant differences in the overall response rate at 1 and 3 months between the G-CSF group and the non–G-CSF group.
Our results showed that low-dose or short-time use of G-CSF was not associated with the incidence or severity of CRS or NEs, and G-CSF administration did not influence the antitumor activity of CAR T-cell therapy.
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- A combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial.Lancet Haematol. 2019; 6: e521-e529
- Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma.N Engl J Med. 2019; 380: 1726-1737
- CAR T cell therapies for patients with multiple myeloma.Nat Rev Clin Oncol. 2021; 18: 71-84
- Cytokine storm.N Engl J Med. 2020; 383: 2255-2273
- ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells.Biol Blood Marrow Transplant. 2019; 25: 625-638
- Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia.Cancer Discov. 2018; 8: 958-971
- Toxicities of chimeric antigen receptor T cells: recognition and management.Blood. 2016; 127: 3321-3330
- Macrophage, the potential key mediator in CAR-T related CRS.Exp Hematol Oncol. 2020; 9: 15
- Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells.Nat Med. 2018; 24: 739-748
- CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade.Nat Med. 2018; 24: 731-738
- Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma.N Engl J Med. 2017; 377: 2531-2544
- GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts.Blood. 2019; 133: 697-709
- T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial.Lancet. 2015; 385: 517-528
- T Cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma.J Clin Oncol. 2018; 36: 2267-2280
- Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma.Blood Adv. 2021; 5: 143-155
- KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma.N Engl J Med. 2020; 382: 1331-1342
- G-CSF does not worsen toxicities and efficacy of CAR-T cells in refractory/relapsed B-cell lymphoma.Bone Marrow Transplant. 2020; 55: 2347-2349
- Effect of early granulocyte-colony-stimulating factor administration in the prevention of febrile neutropenia and impact on toxicity and efficacy of anti-CD19 CAR-T in patients with relapsed/refractory B-cell lymphoma.Bone Marrow Transplant. 2022; 57: 431-439
- Filgrastim associations with CAR T-cell therapy.Int J Cancer. 2021; 148: 1192-1196
- Potent anti-leukemia activities of humanized CD19-targeted chimeric antigen receptor T (CAR-T) cells in patients with relapsed/refractory acute lymphoblastic leukemia.Am J Hematol. 2018; 93: 851-858
- International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma.Lancet Oncol. 2016; 17: e328-e346
- Multiple Myeloma, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology.J Natl Compr Canc Netw. 2020; 18: 1685-1717
- Monocyte lineage-derived IL-6 does not affect chimeric antigen receptor T-cell function.Cytotherapy. 2017; 19: 867-880
- Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia.Cancer Discov. 2016; 6: 664-679
- Granulocyte-macrophage colony-stimulating factor inactivation in CAR T-cells prevents monocyte-dependent release of key cytokine release syndrome mediators.J Biol Chem. 2019; 294: 5430-5437
- Using CRISPR/Cas9 to Knock Out GM-CSF in CAR-T Cells.J Vis Exp. 2019;
- Presently available biosimilars in hematology-oncology: G-CSF.Target Oncol. 2012; 7: S29-S34
- Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-gamma.Blood. 2000; 95: 270-276
- Characterization of granulocyte colony-stimulating factor receptor expressed on human lymphocytes.Br J Haematol. 2002; 118: 296-304
- Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells.Cancer Discov. 2017; 7: 1404-1419
- Characteristics and risk factors of cytokine release syndrome in chimeric antigen receptor T cell treatment.Front Immunol. 2021; 12611366
Published online: March 11, 2023
Accepted: January 23, 2023
Received: August 18, 2022
Publication stageIn Press Corrected Proof
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