Survival in Adults with High Risk TA-TMA - A Comparative Analysis of Narsoplimab Versus Supportive Care Open Access

• Narsoplimab-treated patients with TA-TMA had significant reductions in mortality risk in analyses using well-matched external controls

• Based on robust comparative analyses, narsoplimab is a potential option to provide significant survival benefits in patients with TA-TMA

Hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is a potentially fatal multisystem complication of hematopoietic cell transplantation (HCT) for which there is no approved treatment. In a single-arm study (NCT02222545), narsoplimab treatment for TA-TMA demonstrated a median overall survival (OS) of 274 days from date of diagnosis. Here, we compare OS observed in two cohorts treated with narsoplimab to OS in a well-matched external control to test survival benefit in patients with high-risk TA-TMA. Overall survival in patients (age ≥16 years) with high-risk TA-TMA treated with narsoplimab in a single-arm, open-label study (NCT02222545) or in the narsoplimab expanded access program (EAP; NCT04247906) was compared to OS in a control group with high-risk TA-TMA from the Kyoto Stem Cell Transplantation Group (KSCTG) registry. Narsoplimab-treated patients in the single-arm study (N=28) had a four-fold reduction in risk of mortality compared with patients from the KSCTG registry (N=111) (hazard ratio [HR] 0.25; 95% confidence interval [CI] 0.19, 0.34; P<0.0001). Similarly, in high-risk patients treated with narsoplimab in the EAP (N=49), mortality risk was significantly lower than high-risk patients from the KSCTG registry (N=121) (HR 0.38; 95% CI 0.28, 0.51; P<0.0001). When narsoplimab-treated patients from the single-arm study and the EAP (N=77) were compared with KSCTG patients, the HR for mortality was 0.28 (95% CI 0.22, 0.37; P<0.0001). In conclusion, in patients with high-risk TA-TMA, narsoplimab treatment significantly reduced mortality relative to a well-matched external control group who did not receive narsoplimab. These results support narsoplimab as a potential therapeutic option for TA-TMA.