1. 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
SGOT (IU/L)
SGPT (IU/L)
Aim
Clinical Case
Age 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