C5 inhibition allows continued antineoplastic therapy in cancer- and chemotherapy-associated thrombotic microangiopathy

Peering into the darkness of drug-induced thrombotic microangiopathy: complement, are you in there?

“…Although most of the current literature on eculizumab therapy for gemcitabine-induced TMA is limited to observational studies or case reports, the data support a more formal investigation into the efficacy of complement blockade for gemcitabine-induced TMAs and other DI-TMAs. Rapid hematologic responses and kidney recovery after eculizumab therapy for DI-TMAs are consistently reported in the available literature, however many patients did not receive eculizumab until several weeks into their TMA course (3,(10)(11)(12)(13)(14)(15). In the cohort of 12 patients described by Grall and colleagues, the median time between TMA diagnosis and eculizumab therapy initiation was 15 days with a range of 4-44 days (3).…”

“…Not only is this crucial from a DI-TMA therapy standpoint, but our experience with calcineurin inhibitors in TA-TMA patients is that they can be safely continued in many patients (along with appropriate complement-blocking therapy for TA-TMA) (8). Shah et al recently reported that 5/7 patients with DI-TMAs from chemotherapy were able to continue chemotherapy safely with concurrent C5 inhibition (15). The combination of an effective therapy for DI-TMA and the ability to continue chemotherapy/immunomodulating therapies would have a profound impact on the clinical management of these patients and must be further studied.…”

“…In this issue of the Journal of Gastrointestinal Oncology, Van den Eeckhaut et al describe their successful experience with using the C5 inhibitor, eculizumab, to treat gemcitabine-induced TMA in a patient with pancreatic adenocarcinoma (9). Gemcitabine is a well-known instigator of TMA and the report by Van den Eeckhaut and colleagues adds to growing literature describing the successful use of eculizumab in gemcitabine-induced TMA (3,(9)(10)(11)(12)(13)(14)(15). Grall et al described 12 patients with gemcitabine-induced TMA who were treated with eculizumab and reported a complete hematological remission in 83% of patients and a higher glomerular filtration rate in eculizumab-treated patients at follow up compared to historical controls (3).…”