Table 1.
a Summary of key evidence for ruxolitinib in treatment of steroid-refractory GvHD. b. Summary of key evidence for ECP in treatment of steroid-refractory GvHD.
| Study | Trial design | Treatment | ORR %/CR% | Other results |
|---|---|---|---|---|
| a | ||||
| Acute GvHD | ||||
| Jagasia et al. [21] (n = 71) | Open-label, single-arm, multicentre phase II | Ruxolitinib + CS | 55/27 | ORR in skin, liver, and gut 61%, 27%, and 46%; median DOR at 6 mo was 345 days; 6-mo and 12-mo OS 51% and 43%; 6-mo and 12-mo NRM 44% and 53% |
| Zeiser et al. [15] (n = 309; 154 vs155) | Open-label, randomized, multicentre phase III | Ruxolitinib + CS vs best available therapy | 62 vs 39 (p < 0.001)/ 34 vs 19 ns | ORR (Day 56): 40% vs 22% (p < 0.001); median FFS 5 mo vs 1 mo: median OS 11 mo vs 6.5 mo; 6-mo NRM 36% vs 43%; 12-mo NRM 43% vs 45%; CMV infection 26% vs 21%. |
| Moiseev et al. [22] (n = 32, children and adults) | Prospective | Ruxolitinib + CS± other IS | 75/63 | Reduced ORR in grade III-IV aGvHD, liver GvHD severity, grade IV GI GvHD; OS 59%; CMV infection 59% |
| Liu et al. [23] (n = 40, haplo) | Prospective | Ruxolitinib + CS | 85/62.5 | Worse ORR and OS in liver involvement; ORR in skin, liver, and gut 83%, 48%, and 82%; 6-mo OS and TRM 57% and 33%; GvHD recurrence 26.5% |
| Zeiser et al. [24] (n = 54) | Retrospective | Ruxolitinib + CS + IS | 81.5/46 | Median time to response 1.5 weeks; 6-mo OS 79%, aGvHD recurrence in 7%; CMV infection in 33% |
| Leung et al. [25] (n = 26) | Retrospective | Ruxolitinib + CS | 86/36 | CR at 3 mo 68%; 1-yr and 2-yr OS 58% and 37% |
| Wei et al. [26] (n = 23) | Retrospective | Ruxolitinib + CS ± IS | 86.9/56.5 | ORR in skin, liver and gut 88%, 67% and 92%; 1-yr and 2-yr OS 83% and 75%; CMV reactivation in 52% |
| Gomez et al. [27] (n = 23) | Retrospective | Ruxolitinib + CS | 69.5/21.7 | ORR in skin, liver, and gut 69%, 69%, and 67%; CR in skin, liver, and gut 19%, 23%, and 19%; 6-mo OS 47% |
| Chronic GvHD | ||||
| Zeiser et al. [19] (n = 329;165 vs 164) | Open-label, randomized, multicentre phase III | Ruxolitinib + CS vs best available therapy + CS | 50/7 vs 26/3 | ORR in skin 41%, mouth 50%, upper GI 50%, lower GI 53%, joints 38%; median FFS at week 24 > 18.6 mo vs 5.7 mo (p < 0.001); 6-mo FFS 75% vs 44.5%; symptom release at week 24 24% vs 11% (p = 0.0001); 1-yr OS 81% vs 84% |
| Moiseev et al. [22] (n = 43, adults and children) | Prospective | Ruxolitinib + CS ± other IS | 81/21 | No changes in eye, lung, joint, and genitalia severity; OS 85%; NRM 7% |
| Wang et al. [28] (n = 70) | Retrospective | Ruxolitinib + CS ± other IS | 74/49 | Lower ORR in severe cGvHD; best ORR in mouth with 83%; lowest ORR in liver with 64%; 1-yr OS 66%; 1-yr NRM 20% |
| Gomez et al. [27] (n = 56) | Retrospective multicentre | Ruxolitinib + CS | 57/3.5 | ORR in skin sclerosis 56%, in lung 61.5% and gut 56%; 1-yr OS 81%; CMV infection in 20% |
| Yang et al. [29] (n = 53 children) | Retrospective | Ruxolitinib + CS | 81/28 | GvHD recurrence in 31%; 6-mo OS and EFS 100% and 97% |
| Redondo et al. [30] (n = 48) | Retrospective | Ruxolitinib + CS | 77/15 | ORR of 77% in sclerotic skin, 45% in gut, and 33% in lung disease; similar ORR in moderate and severe cGvHD of 74% and 77%; 2-yr NRM 15%; 2-yr OS 83% |
| Modi et al. [31] (n = 46) | Retrospective | Ruxolitinib + CS ± other IS | 48/10 | 12-mo ORR of skin 25%, 60% mouth, 26% eye, 10% lung and 41% joints; 1-yr FFS 54% |
| Zeiser et al. [24] (n = 41) | Retrospective, multicentre | Ruxolitinib + CS ± other IS | 85/7 | 6-mo OS 97%; CMV infection in 15% |
| Xue et al. [32] (n = 36) | Retrospective | Ruxolitinib + CS | 62/na | Significant improvement in skin, genital and oral GvHD at 3 mo, ocular GvHD at 6 mo; 1-and 2-yr OS 81% and 74%; 1-and 2-yr TRM 19% and 19% |
| Wei et al. [26] (n = 32) | Retrospective | Ruxolitinib + CS ± other IS | 78/25 | ORR for mouth 91%, eye 80%, liver 80%, lung 44%: lower ORR in severe cGvHD of 65%; 1-and 2-yr OS 81% and 73% |
| Leung et al. [25] (n = 31) | Retrospective | Ruxolitinib + CS | 86/17 | 6-mo ORR and CR 83% and 52%; 1-and 2-yr OS 94% and 81% |
| b | ||||
| Acute GvHD | ||||
| Greinix et al . [34] (n = 59) | Prospective, single-arm, phase II | ECP + CS in second-line | 70/60 | CR in skin 82%, liver 61% and gut 61%; 4-yr OS 47% (59% and 11% in ECP responders and non-responders); 4-yr TRM 36% (14% and 73% in ECP responders and non-responders) |
| Amat et al. [35] (n = 37) | Prospective, multicenter | ECP + CS in second-line | 73/40.5 | ORR in skin 71%, liver 54.5% and gut 67%; significant longer OS in CR pts (median > 47 mo vs 12 mo) |
| Jagasia et al. [36] (n = 108) | Retrospective, multicentre | ECP + CS vs Inolimomab/Etanercept + CS in second-line | 66/54 vs 32/20 (p = 0.001) | ECP as independent predictor of ORR (HR, 3.42, p = 0.007), OS (HR, 2.12, p = 0.018); ECP associated with superior OS (HR, 4.6, p = 0.016) in SR aGvHD grade II and lower NRM (HR, 0.45, p = 0.018) |
| DasGupta et al. [37] (n = 128) | Retrospective, multicentre | ECP + CS in second-line | 77/67 | 6-mo-FFTF 77%; 2-yr OS 56%; 2-yr TRM 34% |
| Worel et al. [38] (n = 99) | Retrospective, single center | ECP + CS in second-line | 75/53 | ORR in skin 80%, liver 61% and GI 75%; 1-yr and 5-yr TRM 22% and 31%; 1-yr and 5-yr OS 69% and 50% |
| Calore et al. [39] (n = 72, children) | Retrospective | ECP + CS ± other IS | 83/64 | CR in skin in 70%, liver in 84%, and gut in 71%; 5-yr OS 71% |
| Niittyvuopio et al. [40] (n = 52) | Retrospective, single center | ECP + CS in second-and third line | 62/48 | CR in skin 77%, liver 33%, and gut 34%; 1-yr OS 51% |
| Perotti et al. [41] (n = 50, children) | Retrospective, single center | ECP + CS | 68/32 | ORR in skin 83%, liver 67%, and gut 73%; 1-yr OS 64% |
| Malagola et al. [42] (n = 45) | Retrospective, multicentre | ECP + CS in second-line | Na/91 | CR in grade II 97% and grades III/IV 67% |
| Messina et al. [43] (n = 33, children) | Retrospective, single center | ECP + CS ± other IS | 75/54 | CR in skin 76%, liver 60% and gut 75%; 5-yr OS 69% |
| Chronic GvHD | ||||
| Flowers et al. [44] (n = 95; 48 vs 47) | Prospective, randomized, multicenter | ECP + CS ± other IS vs CS ± other IS | 40 vs 10 at w12 in skin (p = 0.002) | ORR in eye 30% vs 7% (p = 0.04) and mouth 53% vs 27% (p = 0.06); median % improvement of TSS at week 12 14.5% vs 8.5%, at week 24 31.4% in the ECP arm. |
| Greinix et al. [45] (n = 29) | Prospective, crossover, multicentre | ECP + CS ± other IS | 31% at w24 in skin | ORR in liver 50%, mouth 70%, and joints 36%; median % improvement of TSS at week 24 25.8% |
| Sakellari et al. [46] (n = 88) | Prospective, single center | ECP + CS | 73/40 | ORR in skin sclerosis 83%, visceral involvement 53% and lung 27%; 5-yr TRM 24%; 5-yr OS 64.5% |
| Gandelman et al. [47] (n = 77) | Prospective, multicentre | ECP + CS ± other IS | 62/14 | ORR in skin 55%; ECP responses independent of risk factors of poor outcome |
| Dignan et al. [48] (n = 82) | Retrospective, single center | ECP + CS ± other IS | 79/na | ORR in skin 92% and mouth 91% at 6 mo; 3-yr OS 69% |
| Couriel et al. [49] (n = 71) | Retrospective, single center | ECP + CS ± other IS | 61/20 | ORR in skin 57%, liver 71% and mouth 78%; 1-yr OS 53%; response to ECP and platelet count at ECP start significantly predict NRM |
| Greinix et al. [50] (n = 47) | Retrospective, single center | ECP + CS ± other IS | 83/na | CR in skin 68%, mouth 81%, and liver 68% |
ORR overall response rate, CR complete response rate, CS corticosteroids, DOR duration of response, Mo months, OS overall survival, NRM nonrelapse mortality, Ns not significant, FFS failure-free survival, CMV cytomegalovirus, IS immunosuppressants, aGvHD acute graft-versus-host disease, GI gastrointestinal, Yr year cGvHD chronic graft-versus-host disease EFS event-free survival, TRM transplant-related mortality, Na not applicable, ECP extracorporeal photopheresis, ORR overall response rate, Pts patients, HR hazard ratio, SR steroid-refractor, FFTF freedom from treatment failure, TSS total skin score.