Rituximab in neuromyelitis optica: A review of literature

Table 2 Monitoring parameters in Neuromyelitis optica patients treated with rituximab

Ref.	Monitoring parameter/comments
Cree et al[20]	CD19 levels- when detectable, patients were re-treated. CD 19 followed bimonthly. 2 protocols-planned infusions every 6 mo or 12 mo
Jacob et al[23]	CD19 not routinely monitored. Some RTX given when B-cell counts detectable either 6 or 12 mo in intervals or when CD19+ became detectable
Bomprezzi et al[31]	Flow cytometry used to test circulating B cells. Suggest clinical relapses occurring while on RTX therapy correlate with reconstitution of circulating B cells. Correlated that even early rise in CD20+ cells correlated with radiologically proven relapses. B cells had re-sent between 2% and 12% at time of new attack. Total of 7 patients relapsed after RTX-5 had acute event when B cell counts just returned to greater than 1%, whereas 2 patients continued to relapse despite B cells being undetectable. Detected significant variability in timing of reconstitution of normal values, which implies that scheduling of doses of RTX can be adjusted accordingly
Bedi et al[24]	CD19 cell counts planned every 2-3 mo, but not collected systematically for report
Pellkofer et al[30]	Measured lymphocyte subsets by flow cytometry; B cell depletion defined as counts below 0.01 × 109 /L. B cells became undetectable in 9 out of 10 patients within 14 d after 1st dose. Time of B-cell repopulation varied. After 3 patients experienced a relapse shortly after reappearance of B cells, RTX given at fixed interval every 6 to 9 mo, which this led to improved outcomes
Javed et al[22]	“Non-responders” were defined as clinical attack < 6 mo post rituximab treatment, when B cell count was still undetectable
Gredler et al[26]	Flow cytometry used; B cells quantified using following combinations of monoclonal antibodies: CD3/19/45, 19/27/45, 19/38/45. Two patients out of 6 had relapses while B-cells were absent
Lindsey et al[32]	4 patients had relapses after more than 1 mo when peripheral B cell count “very low”. Case 1: CD19 increased to 250 cells/µL had sensory relapse, no further symptoms for 18 mo; Case 2: Had relapses with CD19 count of 0; Case 3, 4, 6 no further relapses; Case 5: CD19 1 cells/µL at 10 mo, 12 cells/µL at 13 mo and subsequent relapses; Case 7--continued to have relapses with 1 cell/µL at 7 mo, 4 cells/µL at 12 mo. Case 8: CD19 count 3 cells/µL, with continued relapses; Case 9: continued relapses with CD19 1 cells/µL
Kim et al[27]	Blood samples obtained every 6 wk in 1st year, every 8 wk in second year. Therapeutic target for CD 27+ memory B cell depletion was less than 0.05% of PBMCs. Patients received additional infusion of 375 mg/m2 if frequency of re-emerging memory CD27+ B cells in PBMCs exceeded 0.1% by flow cytometry. CD 19 B cells counts measure- less than 0.01 × 109 /L or less than 0.5% of PBMCs (considered B cell depletion in prior studies. 60%-65% relapses occurred when CD19 were depleted. Authors argue CD27+ more informative biomarker than CD19
Yang et al[28]	Goal of CD19+ B cells to less than or equal to 1%, as well as CD19 CD27 B cells to less than or equal to 0.05% of PBMCs. All with no relapses despite low doses of RTX (100 mg single infusion and follow up infusion at mean of 35 wk)
Mealy et al[29]	CD19 cell counts tested monthly, repeated dosing scheduled on detection of CD19 greater than 1% of total lymphocyte population or at regular 6 mo intervals
Farber et al[21]	Total of 23 relapses, of which 70% occurred when B cells < 1% of lymphocytes. 7 relapses (30%) occurred when B cells greater or equal to 1% of lymphocytes. CD19 > 1% was associated with higher rate of relapses

RTX: Rituximab.