The impact of granulocyte colony stimulating factor on patients receiving chimeric antigen receptor <scp>T</scp>‐cell therapy

Barreto, Jason N.; Bansal, Radhika; Hathcock, Matthew; Doleski, Corina J; Hayne, Justin; Truong, Tuan; Nedved, Adrienne; Ansell, Stephen M.; Bennani, N. Nora; Paludo, Jonas; Villasboas, José C.; Lin, Yi; Johnston, Patrick B.

doi:10.1002/ajh.26313

Cited by 17 publications

(27 citation statements)

References 9 publications

(11 reference statements)

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“…Several retrospective studies have explored the effects of G-CSF on outcomes after CAR T in lymphoma. A group from Mayo Clinic compared 35 patients who received G-CSF after CAR T to 35 patients who did not—with no signal of increased severity of CRS or ICANS, and shorter duration of neutropenia with post-CAR T G-CSF [ 27 ]. Another study compared 42 patients who received G-CSF five days after CAR T to 28 G-CSF non-exposed patients, and found no difference in CRS or ICANS [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%

Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma

et al. 2022

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“…There were some concerns that G-CSF might affect CAR T-cell response or worsen CRS or ICANS via the activation of myeloid-related cytokines [77,78]. Overall, the data on the G-CSF are still conflicting, and some studies did not support this concern or suggested that G-CSF administration after the acute phase of CAR T-cell may shorten the duration of neutropenia and decrease the risk of infection in CAR T-cell recipients [79][80][81][82]. However, the finite role and effect of G-CSF require further studies.…”

Section: Antibacterial Prophylaxis: As Risk Of Bacterial Infectionmentioning

confidence: 99%

Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy

Wudhikarn

Perales

2022

Bone Marrow Transplant

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CD19-targeted chimeric antigen receptor (CAR) T-cell becomes a breakthrough therapy providing excellent remission rates and durable disease control for patients with relapsed/refractory (R/R) hematologic malignancies. However, CAR T-cells have several potential side effects including cytokine release syndrome, neurotoxicities, cytopenia, and hypogammaglobulinemia. Infection has been increasingly recognized as a complication of CAR T-cell therapy. Several factors predispose CAR T-cell recipients to infection. Fortunately, although studies show a high incidence of infection post-CAR T-cells, most infections are manageable. In contrast to patients who undergo hematopoietic stem cell transplant, less is known about post-CAR T-cell immune reconstitution. Therefore, evidence regarding antimicrobial prophylaxis and vaccination strategies in these patients is more limited. As CAR T-cell therapy becomes the standard treatment for R/R B lymphoid malignancies, we should expect a larger impact of infections in these patients and the need for increased clinical attention. Studies exploring infection and immune reconstitution after CAR T-cell therapy are clinically relevant and will provide us with a better understanding of the dynamics of immune function after CAR T-cell therapy including insights into appropriate strategies for prophylaxis and treatment of infections in these patients. In this review, we describe infections in recipients of CAR T-cells, and discuss risk factors and potential mitigation strategies.

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“…The incidence, severity, and duration of ICANS and utilization of tocilizumab and corticosteroids were similar between the two groups. 5…”

Section: To the Editormentioning

confidence: 99%

“…The incidence, severity, and duration of ICANS and utilization of tocilizumab and corticosteroids were similar between the two groups. 5 The immune impact of G-CSF on the repertoire and function of T cells have been explored previously. Earlier studies had demonstrated the impact of G-CSF-mobilized allografts on altering T-cell alloreactivity.…”

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confidence: 99%

Granulocyte Colony-Stimulating Factor Usage in Recipients of Chimeric Antigen Receptor T-Cell Immunotherapy

Abid

2022

JCO

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The recent ASCO guidelines on managing immunerelated adverse events in patients treated with chimeric antigen receptor (CAR) T-cell therapy recommended the use of growth factors for various indications. Specifically, the multidisciplinary team recommended routine growth factors to hasten neutrophil recovery for Common Terminology Criteria for Adverse Events (CTCAE) grades 3 and 4 neutropenia, defined as absolute neutrophil count (ANC) between 500/mm 3 and 1,000/mm 3 and , 500/mm 3 , respectively. Additionally, a recommendation was made that granulocyte colonystimulating factor (G-CSF) should be considered in patients after cytokine release syndrome (CRS) with . 7 days of neutropenia. 1Early on-target-off-tumor toxicities after CAR T-cell infusion, particularly CRS, is a direct result of in vivo T-cell expansion and production of T-cell effector cytokines including interleukin-6 (IL-6), interferon gamma, and granulocyte monocyte colony-stimulating factor (GM-CSF). Preclinical data had earlier demonstrated that IL-6 is produced predominantly by monocytes and macrophages. 2 G-CSF leads to the proliferation and differentiation of myeloid precursors and promotes antigen-presenting cell function that could exacerbate the incidence and/or severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). 3 The clinical data on the utilization of growth factors in CAR-T setting are limited and conflicting. We presented the differing data in our recent comprehensive review. 4

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The impact of granulocyte colony stimulating factor on patients receiving chimeric antigen receptor T‐cell therapy

Cited by 17 publications

References 9 publications

Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma

Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma

Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy

Granulocyte Colony-Stimulating Factor Usage in Recipients of Chimeric Antigen Receptor T-Cell Immunotherapy

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