Impact of G-CSF on Adverse Effects After CAR T Therapy for Lymphoma and Myeloma

Overview

This retrospective study evaluated the effects of granulocyte colony-stimulating factor (G-CSF) administration on immune toxicities and hematologic recovery in patients receiving CAR T cell therapy for lymphoma and multiple myeloma. Findings highlight the timing and strategy of G-CSF use in relation to cytokine release syndrome (CRS), neurotoxicity (ICANS), neutropenia, and infection risk.

Background

CAR T cell therapy has revolutionized treatment for refractory blood cancers such as lymphoma and multiple myeloma, offering durable responses. However, CAR T is associated with immune toxicities including CRS and ICANS, as well as prolonged cytopenias. G-CSF is commonly used to promote neutrophil recovery after chemotherapy, but its optimal use post-CAR T remains unclear due to concerns that it may exacerbate inflammatory toxicities. This study retrospectively analyzed cohorts treated with commercial and investigational CAR T products to assess the impact of G-CSF on adverse events and hematologic recovery.

Data Highlights

The study included adult patients treated with anti-CD19 CAR T for lymphoma and anti-BCMA CAR T for multiple myeloma. CRS and ICANS were graded per ASTCT criteria. Neutropenia severity and recovery were defined by absolute neutrophil count thresholds. Statistical analyses included Mann–Whitney U test, Fisher’s exact test, Kaplan-Meier survival estimates, and competing risk models. Median follow-up extended to January 2022.

Key Findings

• G-CSF administration timing varied, with some patients receiving prophylactic pegylated G-CSF prior to CAR T and others receiving G-CSF post-infusion for neutropenia.
• High serum G-CSF and GM-CSF levels have been linked to severe ICANS, raising concerns about G-CSF potentially worsening neurotoxicity.
• The cumulative incidence of CRS and ICANS was carefully re-graded and analyzed in relation to G-CSF use, with no consensus on whether G-CSF increases severity.
• Neutrophil recovery was defined as ANC > 0.5 × 10^9/L for three consecutive days; G-CSF use was associated with expedited neutrophil recovery in some patients.
• Competing risk models accounted for disease progression and death when assessing recurrent neutropenia or late G-CSF treatment.
• Institutional policies on G-CSF use post-CAR T vary, reflecting uncertainty and the need for prospective trials.

Clinical Implications

Clinicians should carefully consider the timing of G-CSF administration in CAR T recipients, balancing the benefits of faster neutrophil recovery against potential risks of exacerbating CRS or ICANS. Current evidence does not definitively contraindicate G-CSF but supports individualized approaches and close monitoring. Prospective studies are needed to establish standardized guidelines for G-CSF use in this setting.

Conclusion

This retrospective analysis provides important insights into the complex interplay between G-CSF administration and CAR T-related toxicities. The findings underscore the need for prospective trials to optimize G-CSF strategies to improve safety and hematologic recovery in CAR T therapy.

References

1. Neelapu et al. 2018 -- Chimeric antigen receptor T-cell therapy — assessment and management of toxicities
2. Schuster et al. 2019 -- Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma
3. Munshi et al. 2021 -- Idecabtagene vicleucel in relapsed and refractory multiple myeloma
4. Sterner et al. 2019 -- GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts
5. ASTCT Consensus Grading 2019 -- Consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells