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J.M. Logue et al.
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Figure 3. Infections in the first 30 days after axi-cel therapy for aggressive B-cell lymphoma. (A) Rate and type of infection observed in 85 patients in the first 30 days after axi-cel infusion. (B) Infection by grade of cytokine release syndrome (CRS) or neurotoxicity. (C) Non-severe and severe infections in the first 30 days by receipt of anti-IL-6R therapy (tocilizumab) or steroid therapy. CRS: cytokine release syndrome.
given that 65.9% of the original cohort received at least 3 prior lines of therapy. However a limitation of this study is that there is no standardized schedule for bone marrow biopsies at our institution before or after treatment with axi-cel. Rather, biopsies were done at the discretion of the attending physician with the primary reason for bone marrow biopsy after axi-cel being prolonged cytopenias. Therefore, this data set may not capture all dysplasia or fibrosis events that occur pre- or post-axi-cel therapy. Ultimately, a prospective study including bone marrow biopsies would be helpful.
The mechanism for prolonged cytopenias after CAR T-cell therapy is unclear. Purine analogues such as fludara- bine are often associated with prolonged cytopenias, but responding patients generally recover lymphocyte counts and cytopenias within weeks to months after fludarabine and cyclophosphamide, even after six cycles such as is given in CLL.13,14 Fried et al. studied 38 pediatric and adult
patients after CD19 CAR T therapy for B-cell lymphomas or acute lymphoblastic leukemia (ALL) in the first 2 months after therapy and found a moderate correlation between neutrophil counts and soluble SDF-1.8 Our data suggest that although patients may have hypocellular bone marrows and severe cytopenias in the months after axi-cel, supportive care is effective as patients generally recover their counts over subsequent months.
In our cohort, 36.5% of patients were diagnosed with infections within 30 days after axi-cel, and 44.3% of patients had infections between days 31 and 360. Hill and colleagues previously reported on infections following treatment with a CD19/4-1BB/CD3z/EGFRt CAR T-cell therapy for ALL, CLL, and non-Hodgkin lymphoma on clinical trials.3 They saw that 23% of patients had infec- tions within 28 days, and 14% of patients had infections between days 29 and 90. Park and colleagues reported on infections occurring after treatment with a
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haematologica | 2021; 106(4)