CombinationTreatment SUCCESSFUL TREATMENT OF STEROID REFRACTORY CHRONIC GRAFT VS. HOST DISEASE WITH COMBINATION OF BORTEZOMIB PLUS RUXOLITINIB Panayotis Kaloyannidis, Eshrak Al Shibani, Hani Al Hashmi, Solaf Kafnar, Asraf Suhebah, John Apostolidis, Khalid Al Anezi King Fahad Specialist Hospital, Adult Hematology and Stem Cell Transplantation Department, Dammam, Saudi Arabia Background CombinationTreatment Despite the improvements on chronic graft vs host disease (cGvHD) management, it still remains the leading cause of late non-relapse mortality and also contributes in high morbidity rate and poor quality of life post allogenic stem cell transplantation. In the modern-era of GvHD treatment for steroid refractory NFKβ inhibitor (Bortezomib) and Jak-2 inhibitor (Ruxolitinib) have been approved as 2nd line treatment approach. 30% of cases still remain refractory to these novel agents. To present the clinical course and the outcome for steroid dependent cGvHD after multiple lines of treatment including Bortezomib and Ruxolitinib as single agent. Bortezomib+ Ruxolitinib+ steroid +MMF - Marked skin improvement (mRSS: 12) (fig 2) - Liver tests . 4th mo 2nd mo 1st mo Pre 8.6 92 12.8 95 10 104 14.5 131 Total bilirubin (umol/L) ALP (IU/L) 22 57 45 65 91 300 624 SGOT (IU/L) SGPT (IU/L) Aim Clinical Case Age 22 years old male Diagnosis Hepatosplenic T-cell lymphoma. Conditioning Myeloablative regimen (TBI CY) Donor Female, full matched sibling Graft source Peripheral blood stem cells GvHD prophylaxis CSP + short-term MTX Course post transplantation Engraftment day +14 Disease status: detectable disease without evidence of GvHD. Immunosuppression tapered rigorously. Disease status: complete molecular remission. induced-GvHD - Scleroderma modified-Rodnan skin score (mRSS:25).(fig. 1) - Buccal mucosal involvement. - Liver involvement(SGOT: 300 IU/L, SGPT: 624 UI/L). Calcineurin inhibitors + MMF + steroids Ruxolitinib (10mg bid) + MMF+ steroids x 2 mos Bortezomib : 1.3mg/m2(weekly x4 weeks/35 days) + MMF+ steroids Fig.1: Pre Bortezomib+Ruxolitinib Fig 2:Post 4 cycles of Bortezomib + Ruxolutinib combination After 2 months Current situation Bortezomib + Ruxolitinib + Prednisolone (70% dose reduction). MMF discontinued. Treatment for GvHD No major toxicity or neuropathy or myelotoxicity Toxicities Complete metabolic remission 100% donor chimera Last disease evaluation Treatment Two months later Comment In this extremely refractory case of cGVHD, the combination of Bortezobib & Ruxolitinib proved to be effective, demonstrating no toxicity. The inhibitory effects on lymphocytes in addition to the anti-inflammatory properties of both bortezomib and ruxolitinib, seemed to resulted in a possible synergistic effect. Future clinical trials will clarify the role of this combination in the treatment of cGvHD Initial Treatment progression