Page 179 - 2018_11-Haematologica-web

Sirolimus-calcineurin inhibitor for chronic GvHD
Biomarkers
Correlative biology studies were attempted using a pre- specified analysis of plasma B-cell activating factor (BAFF) levels determined by enyme-linked immunosorbent assay, and CD3+CD4+CD35+CD127– Treg and CD19+ B- cell enumeration in blood by flow cytometry. Data were available for 99% of patients at baseline, 86% at 60 days and 76% at 180 days after beginning study therapy. Median Treg levels (cells per microliter) in both arms were identical, 26, at baseline (P=0.96), and were lower, 18, at day 60 (P=0.87). At day 180 after starting study therapy, the median Treg number was higher in the group treated with two drugs, 21 (range, 0-68) than in the group treated with three drugs 14.5 (range, 1-239) (P=0.04), but there was no significant difference in Treg: conventional
T-cell (Tcon) ratios. Treatment success at day 180, irre- spectively of treatment arm, was associated with signifi- cantly higher median Treg levels at day 60, 21 (range, 2- 78) versus 10 (range, 1-53) among those with treatment failure (P=0.006). This trend attenuated at day 180 (20 ver- sus 16, P=0.14). Similarly, Treg:Tcon ratios at baseline and day 60 were higher among patients in whom treatment was a success than among those in whom it failed (data not shown).
B-cell numbers were not significantly different between arms, except at day 180 when the median B-cell number (cells per microliter) was higher in the two-drug arm, 148 (range, 0-1547) than in the three-drgu arm, 68 (range, 0- 1035) (P=0.045). Overall, median plasma BAFF levels were low (1.0 – 1.9 ng/mL) at all time-points, potentially
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Figure 2. Overall survival, progression-free survival, and failure-free survival. (A) Probability of overall survival by treatment arm (P=0.281). (B) Probability of progres- sion-free survival by treatment arm (P=0.142). Progression-free survival was defined as no clinical evidence of progression or relapsed disease, or any therapy used to treat persistent, progressive, or relapsed disease including withdrawal of immunosuppressive therapy or donor lymphocyte infusion. (C) Probability of failure-free survival in the (C) sirolimus + prednisone (2-drug) arm and (D) control (3-drug) arm. Failure-free survival was defined by the absence of secondary immunosuppres- sive therapy for chronic graft-versus-host disease, non-relapse mortality, and recurrent or progressive malignancy during treatment. Note: the numbers shown are estimates at each time point for each endpoint. Siro/Pred: sirolimus + prednisone; NRM: non-relapse mortality; FFS: failure-free survival.
haematologica | 2018; 103(11)
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