Retrospective analysis of cardiovascular (CV) events following compassionate use of carfilzomib (CFZ) in patients (Pts) with relapsed and refractory multiple myeloma (RRMM).

Abstract

8595 Background: Herein, we report CV events observed in late-stage, heavily pretreated pts who received salvage CFZ under a compassionate use protocol. Methods: Pts received IV single-agent CFZ (20-45 mg/m2) over 2-30 min on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle (C) or CFZ with weekly dexamethasone (4-40 mg) during C1, along with other agents (eg, lenalidomide, thalidomide, cyclophosphamide, doxorubicin, cisplatin, vorinostat) during C2 and beyond. CV events were grouped according to preferred terms. Serious CV events were defined as those that required hospitalization. B-type natriuretic peptide (BNP) values were measured at baseline; peak values were recorded during C1. Results: 143 pts (median age, 61 years old; 70% were male) received treatment. Prior to enrollment, pts received a median of 7 prior lines of therapy (range, 2-15), including doxorubicin (range, 0-360 mg/m2). Most pts (92%) had prior autologous stem cell transplants (ASCT), with 74% receiving ≥2 ASCT (range, 0-5). Pts received CFZ for a median of 2C (range, 1-36). Of pts with available BNP values at baseline and during C1 (n=69; 48.3%), the median peak BNP increase from baseline was 407 pg/ml (P<0.001). 27 pts (18.9%) experienced a serious CV event, 21 (77.7%) of which had preexisting CV risk factors. Of these 27 pts, 11 pts (7.7%) developed CHF or worsening of existing CHF (confirmed by echocardiogram [ECHO] ≤1 month from diagnosis), and 13 (9.1%) required hospitalization for hypotension (n=6), arrhythmia (n=2), hypertension (n=2), pulmonary edema (n=1), pulmonary embolism (n=1), or pulmonary hypertension (n=1). Additionally, 3 pts (2.1%) experienced cardiopulmonary arrest. Of the 11 CHF pts, 10 had a baseline ECHO (recorded ≤6 months before study); left ventricular ejection fraction decreased from a median of 55% (pretreatment) to 33% (posttreatment). Conclusions: Late-line, heavily pretreated pts with RRMM occasionally experienced CV events following administration of CFZ with or without other antimyeloma agents. Given the number of confounding factors and the uncontrolled nature of these data, causality for these CV events could not be definitively determined.