Efficacy of emicizumab therapy in two adult patients with type 3 von Willebrand disease.

Type 3 von Willebrand disease (T3VWD) is a rare inherited bleeding disorder caused by the absence of von Willebrand factor (VWF). The traditional treatment for T3VWD has been VWF concentrates, but their effectiveness may be limited due to the development of alloantibodies. Emicizumab, a bispecific mAb, has shown promise in treating hemophilia A and is being studied as prophylaxis for T3VWD. In this case series, two patients with T3VWD received emicizumab prophylaxis and experienced a significant reduction in bleeding episodes and improved quality of life with fewer healthcare encounters. Although breakthrough bleeding was rare, one patient experienced a terminal intracranial bleed. Despite limited clinical experience with emicizumab in T3VWD, these cases suggest that emicizumab may be a valuable prophylactic option for patients with T3VWD. Further research is needed to determine the long-term efficacy and safety profile of emicizumab and optimal therapy for breakthrough bleeds in this patient population.

Allogeneic Hematopoietic Cell Transplantation with Non-Myeloablative Conditioning and Post-Transplant Cyclophosphamide Prophylaxis in Patients with Reduced Systolic Function.

Post-transplantation cyclophosphamide (PTCy) has become standard of care for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic cell transplantation (alloHCT), allowing for expanded donor options. However, there is scant literature examining outcomes of patients with reduced systolic function receiving PTCy. The present study aimed to describe our experience in performing alloHCT in patients with reduced systolic function, including their nonrelapse mortality (NRM), overall survival (OS), and cumulative incidence of early cardiac events (ECEs). We performed a retrospective descriptive analysis using the Johns Hopkins Hematologic Malignancy database. From 2017 through 2021, 1118 consecutive patients underwent alloHCT with nonmyeloablative (NMA) conditioning and PTCy. Forty-three of those patients had a pretransplantation left ventricular ejection fraction (LVEF) ≤45% measured by transthoracic echocardiography. Patients whose LVEF improved on treatment prior to transplantation were also included. These 2 cohorts were stratified into 2 groups-heart failure with reduced ejection fraction (HFrEF) and heart failure with recovered ejection fraction (HFrecEF)-and subgroup analyses compared NRM, OS, and cumulative incidence of ECEs, including arrhythmia, coronary artery disease, reduction in LVEF, and pericardial effusion, within 100 days post-transplantation. The median LVEF was 40% to 45% (range, 30% to 45%) for the 31 patients undergoing transplantation with HFrEF and 35% to 40% (range, 20% to 45%) for the 12 patients with HFrecEF. The NRM for all 43 patients was 16% (95% confidence interval [CI], 5% to 27%) at 100 days and 23% (95% CI, 11% to 36%) at 2 years. The NRM was 23% (95% CI, 8% to 38%) at 100 days and 26% (95% CI, 10% to 42%) at 2 years for the HFrEF cohort and 0 at 100 days and 18% (95% CI, 0 to 41%) at 2 years for the HFrecEf cohort. The OS at 3 years was 41% (95% CI, 26% to 62%), 40% (95% CI, 25% to 65%) and 38% (95% CI, 14% to 100%) in the combined, HFrEF, and HFrecEF cohorts, respectively. The cumulative incidence of any ECE was 37.2% (95% CI, 22% to 51.9%), including 39% of HFrEF subjects and 33% of HFrecEF subjects. Grade ≥3 toxicities were seen in 56% of patients. Reduced ejection fraction was the most common ECE. One death was attributable to a cardiac etiology. Cardiac toxicities seemed to be more frequent and severe in patients with a history of systolic dysfunction, but this did not lead to worse survival outcomes. This study adds to and extends the existing literature supporting the use of NMA conditioning and PTCy in patients with systolic dysfunction.