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Treatment of Steroid Resistant Acute GVHD with Daclizumab and Etanercept



Treatment of Steroid Resistant Acute GVHD with Daclizumab and Etanercept



Blood 100(11): Abstract No 1633, November 16



Steroid resistant acute GVHD (aGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT) is associated with high morbidity and mortality. In the past treatment consisted mainly of a single agent anti T-cell antibody. Here we report the results of a phase II study of treatment of steroid resistant aGVHD with the humanized IL-2 receptor antibody Daclizumab in combination with the TNF-receptor fusion protein Etanercept. Methods: Treatment consisted of Daclizumab 1mg/kg given IV on days 1, 4, 8, 15, 22 and Etanercept 16mg/m2 SC on days 1, 5, 9, 13, 17. Methylprednisolon (MP) was continued with 2mg/kg/day with dose reduction starting 5 days after the initiation of Daclizumab. Partial remission was defined as 50% reduction of symtoms of aGVHD (skin involvement, diarrhea, hyperbilirubinemia) and complete remission was defined as resolution of all symptoms of aGVHD. Patients: Twelve patients (age 22-57 years) with steroid resistant aGVHD (grade 3 n=6), grade 4 n=6) after myeloablative allogeneic HSCT were treated with Daclizumab and Etanercept. Steroid resistant aGVHD was defined as progression after 3 days of MP or no response after at least 7 days of MP 2mg/kg. All patients had underlying hematologic malignancies and the donor types were HLA matched related (n=4), HLA matched unrelated (n=7), and HLA mismatched unrelated (n=1). The median time of onset of aGVHD was 35 (range 9-105) days. The median time from onset of aGVHD to the initiation of antibody treatment was 17 (range 3-34) days. Results: Treatment resulted in 6 complete and 4 partial remissions. One patient died 5 days after initiation of treatment and was not evaluated for response. One patient with aGVHD grade 4 did not respond and died due to relapse of AML. Two patients with partial remission died due to infectious complications (bacterial sepsis and aspergillosis) on days 75 and 146 after completion of antibody treatment. One partial responder progressed with chronic cutaneous GVHD while on antibody treatment that responded to rapamycin. Five of the 6 patients with complete remission are currently alive with a median follow up of 9 (range 1-16) months. One patient died due to relapse of ALL. Two patients relapsed with aGVHD after withdrawal of immunosuppression. Four patients developed chronic GVHD. Acute toxicity of treatment was minimal besides infectious complications (pulmonal aspergillosis n=5, CMV reactivation n=8, hemorrhagic cystitis n=2). One patient developed interstitial pneumonia 95 days after completion of antibody treatment. Discussion: The data demonstrate the feasibility of the combination of Daclizumab and Etanercept in treatment of steroid resistant aGVHD. Only one treatment failure has been observed and the treatment related mortality rate of 25% is in line with published results.

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Accession: 035980619

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