Background Neutropaenia is reported as a complication of rituximab (RTX) therapy for B cell malignancies with an incidence of 3-27%. [1] Data in rheumatic diseases are more limited and the optimal management of these patients has not been defined.

Objectives The aims of this study were to determine the (1) incidence of rituximab-associated neutropaenia; (2) rates of infection; (3) time for recovery; (4) safety of retreatment with RTX, as a basis for management guidelines.

Methods We conducted an observational study on all patients treated with RTX in a single centre between 2003 and 2014. Each cycle consisted of 2x1000mg (with a small percentage receiving half dose if in remission), repeated either on clinical relapse or pre-emptively. RAN was defined as an absolute neutrophil count <2.0×10⁹/L occurring at least 4 weeks after RTX excluding chronic neutropaenia or alternative plausible explanation (e.g. Felty's syndrome).

Results Rituximab-associated neutropaenia was identified in 23 patients (2.5%) from a cohort of 912, and in 36 cycles (1.2%) out of 3062 administered. 20 patients were female; median (IQR) age 61 (54-68,2) years. 19 had rheumatoid arthritis (RA) (2.72% of all RA patients in this cohort), 1 SLE, 1 cryoglobulinemia, 1 Sjogren's syndrome and 1 GPA. 21 patient received concomitant methotrexate, 1 SLE patient received cyclophosphamide and 1 RA patient received hydroxychloroquine. Neutropaenia occurred at median 17 weeks (range 4-31) following RTX infusion and median 3nd cycle (range 1-9). The majority of neutropenic episodes were transient; neutrophil count was normal on the first repeat test in 24 (66.7%) of the episodes. The frequency of mild (>1.0×10⁹/L), moderate (0.5-1.0×10⁹/L) and severe (<0.5×10⁹/L) neutropaenia were 18 (50%), 6 (16.7%) and 12 (32.3%) episodes respectively. Of these, 10 infections requiring antibiotics were recorded in severe neutropenia cases, most commonly chest infection (6 also required granulocyte-colony stimulating factor (GCSF)). No case of neutropaenia >0.5 x 10⁹/L was associated with infection. Irrespective of the degree of neutropaenia, all patients responded to RTX for the original indication. 26 (72.2%) of the episodes had complete B cell depletion as assessed by highly sensitive FACS. Of the patients who were retreated with RTX 2x1000mg: 11/19 had no recurrence of neutropaenia, 8/19 had mild neutropaenia in next cycle, and 4 patients had again recurrence of mild neutropenia. All the subsequent episodes were without associated infection or requirement for GCSF.

Conclusions This is the largest cohort analysed for rituximab-associated neutropaenia. It can be concluded: (1) at <3%, it is less common in rheumatic disease than lymphoma; (2) monitoring alone is appropriate unless there is evidence of infection, when GCSF may be required; (3) the majority of the neutropenia cases recovered promptly; (4) counts >0.5 x109/L had no infections; (5) on retreatment, mild neutropaenia recurred in less than half with few consequences, with no evidence for neutropaenia becoming more severe on repeat cycles; (6) it therefore appears retreatment with monitoring is appropriate with caution only in severely neutropenic patients. The aetiology of rituximab-associated neutropaenia needs further investigation.

References

1. Tesfa D, Expert Rev. Hematol, 2011

Disclosure of Interest J. Ferreira: None declared, M. Y. Md Yusof: None declared, S. Das: None declared, E. Vital Grant/research support from: Roche and GSK., P. Emery Grant/research support from: Abbott, BMS, Pfizer, MSD and Roche., Consultant for: BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB.