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P.A. Carpenter et al.
evant, we compared the proportion of patients with com- plete response/very good partial response who otherwise satisfied the 2-year treatment success definition. By this measure, the 29.4% (95% CI: 19.0-41.7%) in the two- drug arm did not differ from the 22.4% (95% CI: 12.5- 35.3%) in the three-drug arm (P=0.37).
To address whether certain categories of chronic GvHD responded differently in the study arms overall, in univari- ate analysis, we compared subjects with mild, moderate and severe chronic GvHD, and de novo, quiescent onset and progressive chronic GvHD. There were no statistical- ly significant differences between these groups in terms of the odds of treatment success at 6 months or 2 years. Similarly, no particular individual organ involvement was more likely to be associated with treatment success using either treatment regimen.
The overall survival rate at 2 years was 81.5% in the group treated with two drugs versus 74% in the group treated with three drugs (P=0.28) (Figure 2A). Progression- free survival rates were 78.6% with two drugs versus 67.3% with three drugs (P=0.14) (Figure 2B) and the 2- year failure-free survival rates were 48.6% with two drugs versus 46.2% with three drugs (P=0.78) (Figure 2C,D). The cumulative incidence of relapse (10.1% versus 14.9%,
Table 1. Demographic and hematopoietic cell transplant characteristics.
P=0.40), non-relapse mortality (5.6% versus 11.1%, P=0.26), and the cumulative incidence of secondary immunosuppressive therapy (38.5% versus 29.4%, P=0.22) were not different between the groups treated with two or three drugs. By 2 years, 13 deaths had occurred in the two-drug arm and 16 in the three-drug arm (Online Supplementary Table S1). Almost one-third of deaths were due to GvHD (30.8% in the prednisone/sirolimus group versus 31.3% in the pred- nisone/sirolimus/CNI group). Recurrent or progressive malignancy was the primary cause of death in 30.8% of the prednisone/sirolimus group versus 12.5% in the pred- nisone/sirolimus/CNI group (P=0.36). There were two deaths (15.4%) primarily from infection in the two-drug arm and three (18.8%) in the three-drug arm.
Curves depicting cumulative incidence of discontinuation of systemic immunosuppressive therapy by 2 years over- lapped, with the values at 2 years being 23.2% in the two- drug arm and 20% in the three-drug arm (P=0.71) (Figure 3). Mean (standard deviation) daily glucocorticoid doses (mg/kg) at baseline were 0.9 (0.4) for the group given pred- nisone/sirolimus versus 0.8 (0.2) for the group given pred- nisone/sirolimus/CNI (P=0.13). From baseline to 1 year the mean (standard deviation) daily dose reduction was 0.7 mg/kg (0.3) for the prednisone/sirolimus group and 0.5 mg/kg (0.5) for the prednisone/sirolimus/CNI group.
Gender Female Male
Ethnicity
Hispanic or Latino
Not Hispanic or Latino Unknown/not answered
Race
White
Non-white Unknown/not answered
Age, years Median <20
≥20
Primary disease Acute leukemia Chronic leukemia MDS/MPS Lymphoma Other
Disease stage Early Intermediate High risk
Stem cell type
Bone marrow (BM)
Peripheral blood stem cells (PBSC) Cord blood
Donor source (for BM/PBSC) Related
Unrelated
Type of conditioning regimen Myeloablative
Non-myeloablative or reduced intensity
24 (33.3) 48 (66.7)
8 (11.1) 63 (87.5) 1 (1.4)
54 (75.0) 13 (18.1) 5 (6.9)
50.2
5 (6.9) 67 (92.1)
47 (65.3) 7 (9.7) 12 (16.7) 5 (6.9) 1 (1.4)
46 (63.9) 11 (15.3) 15 (20.8)
5 (6.9) 64 (88.9) 3 (4.2)
29 (42.0)
40 (58.0)
47 (65.3) 25 (34.7)
33 (50.0) 33 (50.0)
0 (0.0) 59 (89.4) 7 (10.6)
57 (86.4) 9 (13.6) 0 (0.0)
54.7
2 (3.0) 64 (97.0)
25 (37.9) 8 (12.1) 9 (13.6) 17 (25.8) 7 (10.6)
27 (40.9) 21 (31.8) 18 (27.3)
5 (7.6) 60 (90.9) 1 (1.5)
38 (58.5)
27 (41.5)
29 (43.9) 37 (56.1)
continued from the previous column
GvHD prophylaxis after transplant CNI + methotrexate ± other CNI + MMF
CNI + MMF ± Other CNI+MMF+ATG
CNI + sirolimus
CNI + corticosteroids CNI only
Other regimen
Donor age, years Mean (SD) Median
Donor age, years <20
20-40 41-60 >60
Donor gender Female Male Unknown
Donor recipient gender mismatch Female-female
Female-male
Male-female
Male-male
Two drugs
N=72(%) N=66(%)
Two drugs Three drugs N=72(%) N=66(%)
Three drugs
44 (61.0) 9 (12.5) 5 (6.9) 0 (0.0) 3 (4.2) 2 (2.8) 5 (6.9) 4 (5.6)
38.5 (12.9) 38.8
3 (4.8) 31 (50.0) 24 (38.7) 4 (6.5)
35 (48.6) 37 (51.4) 0 (0.0)
14 (19.4) 21 (29.2) 10 (13.9) 27 (37.5)
22 (33.3) 15 (22.7) 7 (10.6) 1 (1.5) 5 (7.6) 0 (0.0) 5 (7.6) 11 (16.7)
44.4 (15.2) 47.0
4 (6.6) 21 (34.4) 27 (44.3) 9 (14.8)
26 (39.4) 38 (57.6) 2 (3.0)
10 (15.6) 16 (25.0) 21 (32.8) 17 (26.6)
Two drugs: prednisone/sirolimus, Three drug: prednisone/sirolimus/calcineurin-inhibitor; MDS/MPS: myelodysplastic syndrome/myeloproliferative syndrome; BM: bone marrow; PBSC: peripheral blood stem cells; CNI: calcineurin inhibitor; MMF: mycophenolate mofetil; ATG: anti- thymocyte globulin; GvHD: graft-versus-host disease; SD: standard deviation.
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haematologica | 2018; 103(11)