Treatment-emergent grade ≥ 3 events, serious adverse events (AEs) leading to carfilzomib discontinuation, and deaths were more frequent in the weekly carfilzomib arm compared to the twice weekly arm.r There was no increased risk of cardiac failure seen with weekly dosing.
AEs occurred in 227 (95%) of 238 patients in the once weekly group and 229 (97%) of 235 patients in the twice weekly group (see Table 3 below). Treatment emergent grade ≥ 3 AEs were seen in 68% of patients in the once weekly group and 62% in the twice weekly group. Frequent grade ≥ 3 events included anaemia, pneumonia, thrombocytopenia, neutropenia and hypertension. Specific toxicities of interest are seen in Table 4 below, including acute renal failure, cardiac failure and pulmonary hypertension.
Treatment related AEs leading to discontinuation of carfilzomib occurred in 19 (8%) of patients in the once weekly arm and 11 (5%) in the twice weekly arm. The most common AE leading to carfilzomib discontinuation in the study was acute kidney injury, which occurred in 4 patients in each arm. 15% of patients in the once weekly group and 12% of patients in the twice weekly group discontinued dexamethasone due to an AE. Treatment related deaths occurred in five (2%) patients in the once weekly group and two (1%) in the twice weekly group.r
A meta-analysis indicates higher than expected rates of cardiovascular events associated with carfilzomib exposure. These include hypertension (12.2%), heart failure (4.1%) and ischaemic heart disease 1.8%. Dyspnoea (not necessarily cardiac in aetiology) - is also seen at a high frequency (23.9%).r
Table 3 and 4 Adverse events (ARROW study)r
© Lancet 2018