Carfilzomib‐induced hemolysis is noticeably common but rarely shows features of thrombotic microangiopathy: A retrospective study

Abstract

Objective Hemolysis is a sporadically reported but potentially serious side effect of the proteasome inhibitor carfilzomib. We aimed to investigate the frequency of hemolysis in an unselected cohort. Methods We performed a retrospective, single‐center study of the incidence of hemolysis in patients treated with carfilzomib, based mainly on consecutive haptoglobin levels. The patients were diagnosed with myeloma (n = 20), AL amyloidosis (n = 3), and light‐chain deposition disease (n = 1). Carfilzomib treatment was applied after a median of 3 (range: 1‐7) therapy lines. Results Haptoglobin levels were normal/increased before, generally suppressed during, and normalized after treatment with carfilzomib. Very low haptoglobin (<0.1 g/L) implying the presence of hemolysis was observed in 16 of 24 (67%) patients during carfilzomib therapy. Hemolysis was mild in 11 of 16 (69%) affected patients, whereas 5 of 16 (31%) required transfusion. Severe hemolysis was explained by thrombotic microangiopathy (TMA) in one patient who died of the complication. Mechanisms were unclear in the remaining 15 patients. Conclusions Hemolysis was surprisingly common but mostly mild during carfilzomib treatment. However, the possibility of TMA should be kept in mind in this setting. Hypothetically, non‐TMA hemolysis could be attributed to the accumulation of globin chains due to the suppression of eukaryotic translation initiation inhibition by carfilzomib.

How I treat microangiopathic hemolytic anemia in patients with cancer

“… 25 Isolated microangiopathic hemolytic anemia, without all the features of a full-blown TMA, was observed at very high rates in carfilzomib-treated patients in a recent case series where it occurred in 16 out of 24 patients (67%). 26 In this single-center cohort, 11 out of 16 patients had mild hemolysis with haptoglobin <0.1 g/L but no transfusion requirement; 5 out of 16 required transfusion, and 1 patient had a severe and subsequently fatal TMA. 26 Cases of TMA have also been reported with the newer generation of PIs such as ixazomib.…”

“… 26 In this single-center cohort, 11 out of 16 patients had mild hemolysis with haptoglobin <0.1 g/L but no transfusion requirement; 5 out of 16 required transfusion, and 1 patient had a severe and subsequently fatal TMA. 26 Cases of TMA have also been reported with the newer generation of PIs such as ixazomib. 27 …”

Carfilzomib-induced thrombotic microangiopathy (TMA): an under-recognised spectrum of disease from microangiopathic haemolysis to subclinical TMA

“…A recent analysis by Kozlowski et al (2020) showed that haemolysis in carfilzomib-treated patients is indeed common, although often mild [ 10 ]. The rate of haemolysis reported in that study was somewhat higher, perhaps due to our use of strict multi-point criteria.…”