Thrombotic microangiopathy during carfilzomib use: case series in Singapore

Chen, Y; Ooi, Melissa; Lim, Soh Fong; Lin, Andrew; Lee, J; Nagarajan, Chandramouli; Phipps, Colin; Lee, Y S; Grigoropoulos, Nicholas F.; Lao, Zhentang; Surendran, Shilpa; Teh, Evelyn M.; Goh, Yeow Tee; Chng, Wee Joo; Gopalakrishnan, Sathish

doi:10.1038/bcj.2016.62

Cited by 30 publications

(29 citation statements)

References 12 publications

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“…8,9,11 However, CFZ-induced TMA was self-limiting after drug termination in other cases. 5,7,9,10 Fatal outcomes (as in our patient) were also observed, 6,9 demonstrating the severity of this complication.…”

Section: Discussionsupporting

confidence: 69%

“…12 This is in contrast to profound anemia in previously reported patients with CFZ-induced TMA. 7,[9][10][11] 4,[6][7][8][9][10][11] and ruled out thrombotic thrombocytopenic purpura (TTP). G6PD deficiency is not prevalent in Scandinavia (<0.5%) 15 and was not considered as possible hemolysis mechanism in our cohort.…”

Section: Discussionmentioning

confidence: 99%

“…8 Innate susceptibility can be conditioned by ethnicity, as suggested by the occurrence of TMA in as many as 4 of 24 patients (17%) treated with CFZ in Singapore. 10 Different genetic profiles in terms of complement mutations have been reported in Chinese patients with TMA, compared with European and Japanese patients. 17 The hypothesis of complement pathway involvement in the pathogenesis of CFZ-induced TMA was supported by effectiveness of a complement monoclonal antibody, eculizumab, in four reported patients with this condition.…”

Section: Discussionmentioning

confidence: 99%

“…(MAHA) as the hallmark of thrombotic microangiopathy (TMA) has been described in single patients treated with CFZ [4][5][6][7] and in case series, [8][9][10][11] the latter also including patients treated with bortezomib. 9 Besides MAHA, CFZ-induced TMA presented commonly with renal failure and hypertension in addition to thrombocytopenia.…”

mentioning

confidence: 99%

“…9 Besides MAHA, CFZ-induced TMA presented commonly with renal failure and hypertension in addition to thrombocytopenia. [4][5][6][7][8][9][10][11] Recently, mostly well-compensated hemolysis was observed in 8 of 10 patients treated with CFZ in a single center. 12 The most sensitive and specific hemolysis parameter is a decreased plasma level of the heme scavenger protein haptoglobin (Hp).…”

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confidence: 99%

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

Kozlowski

Behnam

Uggla

et al. 2020

European J of Haematology

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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.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Kozlowski

Behnam

Uggla

et al. 2020

European J of Haematology

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Carfilzomib‐Induced Thrombotic Microangiopathy—Two Case Reports

Attucci,

Pilerci,

Messeri

et al. 2024

Cancer Reports

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BackgroundThrombotic microangiopathy (TMA) is a pathological syndrome characterized by a combination of three key features: microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and organ damage, primarily affecting the kidneys. There are several drugs known to have a definite or probable causal association with TMA, and carfilzomib, a second‐generation irreversible proteasome inhibitor (PI), approved for the treatment of multiple myeloma (MM), is one of them. In the medical literature, there have been a growing number of reports describing this serious adverse event occurring in MM patients. The precise mechanisms underlying the development of PI‐induced TMA are not yet fully understood. Significant improvements in both renal and hematological aspects have been documented following the administration of eculizumab.Recent FindingsIn this report, we present two cases of MM patients who developed TMA while undergoing carfilzomib therapy. These cases were successfully treated at the Haematology Unit, Careggi Hospital in Florence. In our cases as well, the introduction of eculizumab resulted in rapid enhancements in renal function and platelet count, ultimately leading to the discontinuation of hemodialysis after 4 and 2 weeks, respectively.Discussion and ConclusionWe assessed 91 patients who received carfilzomib‐based therapies at our Haematology Department, during which we identified two cases of DITMA (2.2% incidence). Additionally, we conducted a literature review and discovered a total of 75 documented cases of carfilzomib‐induced TMA. Our experience aligns with the cases reported in literature: this adverse event can manifest at any point during treatment, regardless of the specific drug combinations used alongside carfilzomib. The initial and most crucial step in its management involves discontinuing carfilzomib therapy; therefore, recognizing TMA in a timely manner is of utmost importance. Eculizumab could play a role in improving and expediting the resolution of this potentially fatal adverse event, but further studies are needed.In a MM patient receiving carfilzomib, presenting with anemia, thrombocytopenia, and impaired renal function, a carfilzomib‐induced TMA should be suspected in order to discontinue the causative agent.

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