Background/Purpose: The incidence and clinical consequences of rituximab-mediated late-onset neutropenia (LON) have been studied in various diseases, but data from Systemic Lupus Erythematosus (SLE) are limited. We studied the prevalence, consequences and predisposing factors for LON following treatment with rituximab in patients with SLE.

Methods: Ninety-two patients from the Karolinska SLE cohort treated with rituximab were enrolled in this retrospective observational study. Rituximab was given according to the lymphoma course (weekly for four weeks; 73 cycles), the arthritis course (at week 0 and 2; 94 cycles), or as a single infusion (16 cycles), with (60 cycles) or without (123 cycles) cyclophosphamide. LON was defined as an absolute neutrophil count <1,500 cells/μL, corresponding to a neutropenia of grade II–IV according to the National Cancer Institute Common Terminology Criteria for Adverse Events, occurring four weeks to two years after initiation of rituximab treatment, provided that other apparent causes were excluded. Cases of grade II-IV neutropenia occurring later than two years after treatment initiation, but during sustained B cell depletion, were also considered cases of LON.

Results: Thirty-two of 92 patients developed LON (17 patients developed grade II neutropenia, 7 developed grade III, and 8 patients developed grade IV neutropenia) after a median time of 222 days (range: 28–1990 days). Twenty-two patients were asymptomatic. Thirteen patients were admitted to the hospital (median hospital stay: 6 days; range: 1–47 days), either due to suspicion of infection, or for observation and/or treatment with Granulocyte-Colony Stimulating Factor. Three patients were hospitalised due to other causes during the incidence of LON. Ten patients presented with fever, and three of them developed critical conditions and had positive microbiological cultures (Staphylococcus aureus sepsis, Pseudomonas aeruginosa sepsis, Streptococcusfasciitis). Except for one febrile patient with grade III neutropenia, all patients with fever were treated with intravenous broad-spectrum antibiotics. The infections resolved with antibiotics; however, one patient required admission to an Intensive Care Unit. Nine patients were retreated with rituximab after the incidence of LON, and three of them developed LON following these subsequent cycles.

There was no association between neutropenia grade and severity of complications. No predictors for LON were identified among dosages of rituximab, prednisone equivalent or cyclophosphamide (concurrent or accumulated), preceding neutropenia, sex, age, and disease duration. 

Conclusion: SLE patients had a higher prevalence of rituximab-mediated LON (35%) compared with patients with lymphoma (3–27%) and rheumatoid arthritis (3%). Although this phenomenon is typically self-limiting, our results demonstrate that it is a common complication in SLE patients, which can lead to life-threatening conditions, and underscore the importance of monitoring these patients for neutrophil counts, fever and infections.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/late-onset-neutropenia-following-rituximab-treatment-in-patients-with-systemic-lupus-erythematosus/