Efficacy and Safety of Ruxolitinib in Steroid-Refractory/Dependent Chronic Graft-versus-Host Disease: Real-World Data and Challenges

Redondo, Sara; Esquirol, Albert; Novelli, Silvana; Caballero, A; Garrido, Ana; Oñate, Guadalupe; López, Jordi Antón; Moreno, Carol; Saavedra, Silvanna-Daniela; Granell, Miquel; Briones, Javier; Sierra, Jorge; Martino, Rodrigo; García‐Cadenas, Irene

doi:10.1016/j.jtct.2021.10.015

Cited by 12 publications

(9 citation statements)

References 24 publications

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“…The REACH studies also investigated patients with late stage and severe disease (64% stage III–IV aGvHD; 57% had severe cGvHD) [ 14 , 15 ] but the inclusion of pediatric patients (from 2 years old) and the number of patients treated in this CU program, and in other ruxolitinib real-world studies [ 29 – 31 ] have greatly expanded the ruxolitinib-treated population beyond the REACH trial populations ( ≥ 12 years old) [ 14 , 15 ]. Consistent with other CU programs [ 28 – 30 , 32 ] many patients in this study had received multiple lines of therapy and concomitant medications, which highlights the complexity of their disease. Interestingly, ruxolitinib was considered predominantly as a second- or third-line treatment option, which suggests that physicians’ have confidence in the efficacy of ruxolitinib versus investigators’ choice of treatment as demonstrated in patients with steroid-refractory aGvHD and cGvHD in the REACH studies, and its safety in vulnerable patients [ 14 , 15 ].…”

Section: Discussionsupporting

confidence: 70%

Ruxolitinib in patients with graft versus host disease (GvHD): findings from a compassionate use program

Pattipaka,

Sarp,

Nakhaei

et al. 2024

Bone Marrow Transplant

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The ruxolitinib compassionate use (CU) program offered ruxolitinib to patients ≥2 years of age with confirmed steroid-resistant acute or chronic graft-versus-host disease (aGvHD and cGvHD, respectively). Data from 1180 patients (n = 775, 370 and 35 with cGvHD, aGvHD, and non-specified GvHD, respectively) were analyzed. Most patients had severe cGvHD (56%) or stage III/IV aGvHD (70%) disease and had previously received corticosteroids ( > 80%); ruxolitinib was requested primarily as a second-/third-line option. Patients <12 and ≥12 years old most often received the recommended ruxolitinib doses (5 mg twice daily [BID] and 10 mg BID, respectively); however, 23% and 30% of ≥12 year olds with cGvHD and aGvHD, respectively, received the lower dose of 5 mg BID. Notably, corticosteroid usage decreased with ruxolitinib treatment; at the initial ruxolitinib request, 81% and 91% of patients with cGvHD and aGvHD, respectively, were receiving corticosteroids whereas at resupply, 62% and 64%, respectively, were receiving corticosteroids. Eighty two percent of evaluable patients with cGvHD had a complete or partial response to treatment and 56% of evaluable patients with aGvHD had a best response of grade 0/I. These findings demonstrate the rapid and positive effects of ruxolitinib in patients with GvHD in a real-world setting.

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Section: Discussionsupporting

confidence: 70%

Ruxolitinib in patients with graft versus host disease (GvHD): findings from a compassionate use program

Pattipaka,

Sarp,

Nakhaei

et al. 2024

Bone Marrow Transplant

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“…Organ responses and results of other prospective and retrospective studies on the use of ruxolitinib for SR acute and cGvHD are shown in Table 1a [15,19,[21][22][23][24][25][26][27][28][29][30][31][32].…”

Section: Jak-inhibition In Chronic Gvhdmentioning

confidence: 99%

Extracorporeal photopheresis in acute and chronic steroid‑refractory graft-versus-host disease: an evolving treatment landscape

2022

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Patients with steroid-refractory graft-versus-host disease (GvHD) are known to have a poor prognosis and for decades no approved drug has been available to treat this serious condition. Although ruxolitinib, a selective Janus kinase (JAK)1/2 inhibitor demonstrated significantly higher response rates in randomized trials compared to the best available therapy, and thus, is of benefit in both acute as well as chronic GvHD, there is an urgent medical need to improve results, such as durability of responses, response in eye, liver and lung manifestations and reduction of infectious complications. In this “Review” article we would like to offer strategies for improving treatment results in patients with steroid-refractory GvHD by combining ruxolitinib with extracorporeal photopheresis (ECP), a leukapheresis-based immunomodulatory treatment frequently applied in T-cell mediated immune disease including GvHD. Our article explores key published evidence supporting the clinical efficacy of both ruxolitinib and ECP in the treatment of GvHD and highlights their potentially complementary mechanisms of action.

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“…This survival outcome can be compared with the 82% 2-year OS in a recently reported phase 2, rho-associated coiled-coil–containing protein kinase-2 inhibitor trial, 21 71% 2-year OS in the follow-up study of ibrutinib, 20 76% 2-year OS in a real-world experience of ibrutinib, 25 approximately 73% 2-year OS in the phase 3 ruxolitinib study, 23 and 77% and 83% in reports of real-world experience with ruxolitinib. 26, 27 …”

Section: Discussionmentioning

confidence: 99%

Organ-specific response after low-dose interleukin-2 therapy for steroid-refractory chronic graft-versus-host disease

et al. 2022

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Despite new therapeutic options, treatment of steroid-refractory chronic graft-versus-host disease (SR-cGVHD) remains challenging as organ involvement and clinical manifestations are highly variable. In previous trials of low-dose interleukin-2 (LD IL-2), we established the safety and efficacy of LD IL-2 for treatment of SR-cGVHD. In the present report, we combined 5 phase I or II clinical trials conducted at our center to investigate organ-specific response rate, co-involvement of organs, predictors of organ-specific response and its possible association with immune response. For 105 adult patients included in this report, the overall response rate after 8 or 12 weeks LD IL-2 was 48.6% and 53.3% including late responses in patients who continued treatment for extended periods. Skin was the most frequent organ involved (84%) and the organ-specific response rate was highest in liver (66.7%) followed by GI (62.5%), skin (36.4%), joint/muscle/fascia (34.2%) and lung (19.2%). In multivariable analysis, shorter time from diagnosis of cGVHD to IL-2 initiation, shorter time from transplant to IL-2 initiation, and fewer prior therapies were associated with overall response as well as skin response. For immunologic correlates, CD4Treg:CD4Tcon ratio at one week was significantly higher in patients with overall and skin response; skin response was significantly associated with lower number of total CD3 T cells, CD4Tcon and CD8 T cells and higher number of B cells. For lung responders, terminal effector memory cell counts were lower within all T cell populations compared to non-responders. Organ-specific mechanisms of injury should be investigated and organ-specific targeted therapies need to be developed.

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Efficacy and Safety of Ruxolitinib in Steroid-Refractory/Dependent Chronic Graft-versus-Host Disease: Real-World Data and Challenges

Cited by 12 publications

References 24 publications

Ruxolitinib in patients with graft versus host disease (GvHD): findings from a compassionate use program

Ruxolitinib in patients with graft versus host disease (GvHD): findings from a compassionate use program

Extracorporeal photopheresis in acute and chronic steroid‑refractory graft-versus-host disease: an evolving treatment landscape

Organ-specific response after low-dose interleukin-2 therapy for steroid-refractory chronic graft-versus-host disease

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