ABSTRACT
Given the limited real-world data of caplacizumab, our multicenter real-world study was designed to assess the safety and efficacy of caplacizumab in immune thrombotic thrombocytopenic pupura (iTTP), compared to historic controls. We have studied 70 patients: 23 in the caplacizumab and 47 in the historic control group. Plasma exchange was applied in all episodes except for two patients that denied plasma exchange. Rituximab as first-line treatment was more common in the caplacizumab group compared to historic control. Caplacizumab (10 mg daily) was given at a median on day 7 (1-43) from initial diagnosis for 32 (6-47) dosages. In the caplacizumab group, a median of 12 (8-23) patients required plasma exchange sessions versus 14 (6-32) in the control group. Caplacizumab administration did not produce any grade 3 complications or major hemorrhagic events. After a median of 19.0 (2.6-320) months since the iTTP diagnosis, 5 deaths occurred (4 in the control group and 1 in the caplacizumab group, p = 0.310). Caplacizumab patients achieved early platelet normalization and ADAMTS13 activity normalization at the end of treatment. Relapse was observed only in 2/23 (9%) caplacizumab patients, compared to 29/47 (62%) historic controls (p < 0.001). Overall, caplacizumab is safe and effective in treating iTTP, including cases refractory to plasma exchange, re-administration, and cases without previous plasma exchange treatment. No major hemorrhagic events were observed. Cessation of dosing guided by ADAMTS13 has ensured a low relapse rate.
ABSTRACT
BACKGROUND: Recent data suggest that novel biologic agents are associated with increased risk of thrombotic microangiopathy (TMA). Ruxolitinib, an approved treatment for graft-vs-host-disease (GVHD), has been associated with thrombocytopenia of unclear etiology. METHODS: We investigated factors and outcomes associated with transplant-associated thrombotic microangiopathy (TA-TMA) in patients with GVHD. We retrospectively enrolled consecutive allogeneic hematopoietic cell transplantation recipients with overlap or chronic GVHD at our Joint Accreditation Committee ISCT-Europe & EBMT-accredited unit (January 2016-June 2019). Ruxolitinib has been administered off-label since 2016. RESULTS: Among 160 patients with GVHD, 18 were diagnosed with TA-TMA. TA-TMA developed at a median of 150 posttransplant days (range, 98-3013). Among pre- and posttransplant factors, TA-TMA was associated only with ruxolitinib administration and severe GVHD. Interestingly, these 2 variables did not correlate with each other. In the multivariate analysis, both were independent predictors of TA-TMA. Time-dependent analysis confirmed ruxolitinib's association with TA-TMA. With a follow-up of 38.4 months (4.6-83.9) in surviving patients, 5-year overall survival was 52.9%, independently predicted by TA-TMA, severe acute GVHD, and CD34+ cells infused. Ruxolitinib was not associated with survival outcomes. CONCLUSIONS: Our data suggest that ruxolitinib and GVHD severity are associated with TA-TMA. Given the expanding use of ruxolitinib in GVHD and ongoing trials on chronic GVHD, further studies are warranted to confirm these findings.
