ASH Clinical News ACN_5.3_web | Page 36

On Location 2018 ASH Annual Meeting Age, Blood Type, and Rituximab Use Associated With Relapse Risk in TTP For patients with thrombotic thrombocyto- penic purpura (TTP), rituximab prevented relapse in the first year after administration, but the protective effect waned over time, according to results from a study presented at the 2018 ASH Annual Meeting. The authors, led by Lova Sun, MD, from Mas- sachusetts General Hospital, also found that younger age, prior episodes of TTP at presentation, and a non-O blood type predicted a higher risk of relapse. “Rituximab has been increasingly incorporated into the treatment of TTP, but the exact nature and duration of its impact on relapse has not yet been fully established,” Dr. Sun said during her presentation. “The goal of our study was to identify risk factors at presentation for subsequent TTP relapse and to charac- terize the impact of rituximab on relapse in the setting of increased use of this drug for TTP in the past decade or so.” The study consecutively enrolled 124 patients who presented with acute TTP at one of five academic medical centers between 2004 and 2017. The median age at presentation was 42 years (range = 31- 52 years), and most patients (104; 84%) presented with de novo disease. Of the 124 patients enrolled, 60 (48%) received rituximab, and the au- thors observed an “unsurprisingly steady increase” in the proportion of patients who were treated with rituximab during the study period. The drug was admin- istered at a median of 12 days (range = 7-24 days) after presentation. Thirty-four patients in the entire cohort (27%) experienced disease relapse at a median of 1.96 years (range = 1.05-4.07 years) after presentation. Eight patients (7.3%) died within 90 days of presentation, most frequently due to infections or cardiac arrest. Dr. Sun noted that these patients had a delay to diagnosis and start of plasma exchange therapy. The baseline characteristics between patients who did and did not receive rituximab were similar, she reported, “with the exception that patients who received rituximab had a more severe and refractory disease course, lower platelet count at day 4 [after presenta- tion], a higher reticulocyte count, and more plasma exchange procedures.” (P values for these comparisons were not reported.) In a Kaplan-Meier survival analysis, the researchers found that patients treated with rituximab had a signifi- cantly lower relapse risk at one year after presentation, compared with patients who did not receive ritux- imab (p=0.01). However, at five years of follow-up, the relapse-free survival curves converged, with no difference over time (p=0.45). The median time to relapse among all patients was 1.96 years (range = 1.08-4.06 years) and was nearly three times longer in the rituximab-treated group than the non- rituximab-treated group (3.71 years [range = 1.75-4.93 years] vs. 1.33 years [0.43-2.35 years]; p value not reported). After adjusting for follow-up time, time • presenting with TTP relapse (hazard ratio [HR] = 3.05; 95% CI 1.4-6.6; p=0.005) ASH Clinical News • non-O blood group (HR=2.11; 95% CI 1.03-4.3; p=0.041) While rituximab on the day of administra- tion was associated with a decreased relapse The First and Only Treatment for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) FROM A DEADLY DISEASE RISES A DURABLE RESPONSE INDICATION • ELZONRIS is a CD123-directed cytotoxin for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older IMPORTANT SAFETY INFORMATION Boxed WARNING: CAPILLARY LEAK SYNDROME • Capillary Leak Syndrome (CLS), which may be life-threatening or fatal, can occur in patients receiving ELZONRIS. Monitor for signs and symptoms of CLS and take actions as recommended WARNINGS AND PRECAUTIONS Capillary Leak Syndrome • ELZONRIS can cause capillary leak syndrome (CLS), which may be life-threatening or fatal if not properly managed. The overall incidence of CLS in clinical trials was 55% in patients receiving ELZONRIS, including 46% in Grades 1 or 2, 6% in Grade 3, 1% in Grade 4, and 2 fatal events. Common signs and symptoms (incidence ≥ 20%) associated with CLS that were reported during treatment with ELZONRIS include hypoalbuminemia, edema, weight gain, and hypotension • Before initiating therapy with ELZONRIS, ensure that the patient has adequate cardiac function and serum albumin is ≥ 3.2 g/dL • During treatment with ELZONRIS, ensure that serum albumin levels are ≥ 3.5 g/dL and have not been reduced by ≥ 0.5 g/dL from the albumin value measured prior to dosing initiation of the current cycle. Monitor serum albumin levels prior to the initiation of each dose or more often as indicated clinically thereafter. Additionally, assess patients for other signs or symptoms of CLS, including weight gain, new onset or worsening edema including pulmonary edema, hypotension, or hemodynamic instability • Counsel patients to seek immediate medical attention should signs or symptoms of CLS occur at any time Copyright 2019 - Stemline Therapeutics, Inc. All rights reserved. 1/2019 US-ELZ-1800028 34 • age <25 years (HR=2.94; 95% CI 1.2-7.2; p=0.018) from presentation to rituximab administra- tion, and the waning effect of rituximab over time, the researchers identified the following factors as predictors of relapse: