Page 136 - 2022_01-Haematologica-web

Y. Zaimoku et al.
sion cohort did not reach the 3-month evaluation after a hematologic response and was excluded from the statisti- cal analysis.
Data on PNH clones were not available for 23 subjects: 19 in the IST plus eltrombopag group were not analyzable as their ANC were too low, at a median (IQR) of 0 (0- 0.01)×109/L; for the other four treated with IST plus mycophenolate mofetil, PNH clone information was miss- ing. Thrombopoietin levels were quantified in 140 of the 176 patients treated with IST plus eltrombopag; we used serum samples instead of plasma in nine patients, as levels of thrombopoietin in serum and plasma obtained at the same time were equivalent (in 15 patients with AA; corre- lation coefficient of 0.95; Wilcoxon signed rank test, P=0.26) (Online Supplementary Figure S2).
The clinical characteristics of the patients are summa- rized in Table 1. The 176 patients treated with IST plus eltrombopag showed significantly higher ARC and lower platelet counts compared to the 240 patients treated with IST alone; age, sex, ANC, ALC and the prevalence of PNH clones were well balanced between the two groups. The IST plus eltrombopag group had significantly higher over- all and complete response rates than did the group treated with IST alone: overall response of 82% (144 of 176) versus 62% (149 of 240, P<0.0001) and complete response of 39% (69 of 176) versus 13% (32 of 240, P<0.0001), as pre- viously published.4 There were no significant differences in the response rates across the cohorts in the IST plus eltrombopag group and across the non-eltrombopag regi- mens, except for the absence of complete response in 35 patients treated with standard IST plus sirolimus (Online Supplementary Figure S1).
Correlates of overall response
Patients who responded to IST plus eltrombopag, as compared to those who did not, showed significantly higher ARC (median [IQR], 21 [10-36]×109/L vs. 9 [7- 22]×109/L, P=0.00090), higher ANC (0.33 [0.14- 0.53]×109/L vs. 0.06 [0.01-0.25]×109/L, P=0.00027) and a tendency to higher ALC (1.29 [0.99-1.65]×109/L vs. 1.00
[0.59-1.46]×109/L, P=0.079) before therapy, similar to the group treated with IST alone (Figure 1; Table 2). Plasma thrombopoietin levels were significantly elevated in non- responders to IST plus eltrombopag (3,000 [2,610-3,430] ng/mL vs. 2,540 [2,200-2,950] ng/mL, P=0.0037), as report- ed by others for IST alone.16 Age, sex, platelet counts or the presence of PNH clones did not correlate significantly with overall response to IST with or without eltrom- bopag. Multivariate logistic regression analysis revealed that ARC and ALC were independent predictors of overall response among all the 416 patients, consistent with the findings of a previous study;12 ARC and thrombopoietin were retained in the final model of 176 patients in the IST
Table 1. Patients’ characteristics at baseline.

Age, years Median (IQR) Range
Sex Male
Female
Blood count, ×109/L ARC
ANC ALC Platelets
TPO, pg/mL*
PNH clone† ≥1%
<1%
IST+EPAG (n=176)
32 (19-55) 3-82
87 (49%) 89 (51%)
18.8 (8.7-34.4) 0.28 (0.078-0.51) 1.26 (0.93-1.61) 8.0 (4.8-11.3)
2610 (2220-3080)
60 (38%) 97 (62%)
144 (82%) 69 (39%)
IST alone (n=240) P 30 (18-53) 0.47
2-82
141 (59%) 0.073 99 (41%)
14.3 (4.9-30.7)
0.30 (0.11-0.50) 0.36 1.28 (0.90-1.66) 0.89
9.0 (6.0-13) 0.031 NA
90 (38%) 1 146 (62%)
0.0086
Response at 6 months Overall response Complete response
149 (62%) 32 (13%)
<0.0001
<0.0001
Data are n (%) or median (interquartile range) unless otherwise noted. IST: immuno- suppressive therapy; EPAG: eltrombopag; IQR: interquartile range; ARC: absolute retic- ulocyte count; ANC: absolute neutrophil count; ALC: absolute lymphocyte count; TPO: thrombopoietin; PNH: paroxysmal nocturnal hemoglobinuria; NA: not assessed. *TPO was studied in 140 patients treated with IST+EPAG. †The PNH clone was not tested in 19 and four patients treated with IST plus EPAG and IST alone, respectively.
Figure 1. Pretreatment blood counts and overall response. Absolute reticulocyte count, absolute neutrophil count, absolute lymphocyte count and plasma throm- bopoietin level at baseline were compared between patients who achieved a response and those who did not at 6 months according to whether they were treated with immunosuppressive therapy plus eltrombopag or immunosuppressive therapy alone. ARC: absolute reticulocyte count; ANC: absolute neutrophil count; ALC: absolute lymphocyte count; TPO: thrombopoietin; NR: no response; OR: overall response; IST: immunosuppressive therapy; EPAG: eltrombopag.
128
haematologica | 2022; 107(1)