Newly Diagnosed Myeloma: Novel Scenario for Carfilzomib-Linked Thrombotic Microangiopathy
Posted: Thursday, April 29, 2021
Experts are still learning about the mechanism of carfilzomib‐associated thrombotic microangiopathy in patients with multiple myeloma, although those with hypertension seem to be most susceptible. Until now, the condition has been associated with relapsed or refractory rather than newly diagnosed disease. However, in the British Journal of Haematology, Kwee Yong, PhD, of University College Hospitals, London, United Kingdom, and colleagues described eight patients with newly diagnosed myeloma who experienced thrombotic microangiopathy events while receiving carfilzomib on the phase II, 281-patient CARDAMON trial. This is the largest case series in this population reported to date, noted the team.
Thrombotic microangiopathy encompasses a group of disorders characterized by occlusive microvascular thrombosis, which can cause microangiopathic hemolytic anemia, thrombocytopenia, and end‐organ damage, explained the authors. It has been associated with not only carfilzomib but the other proteasome inhibitors, bortezomib, and ixazomib.
The first three cases of thrombotic microangiopathy in newly diagnosed patients in the CARDAMON trial occurred during the maintenance of single‐agent carfilzomib. Two occurred during induction with carfilzomib given with cyclophosphamide and dexamethasone, and three occurred during carfilzomib, cyclophosphamide, and dexamethasone consolidation. At the presentation of thrombotic microangiopathy, six of the eight patients were hypertensive, noted Dr. Yong and co-investigators. Ultimately, they reported, “seven of eight had acute kidney injury, and in three, renal impairment persisted after resolution of thrombotic microangiopathy in other respects.
“We were initially surprised [that] three cases occurred during maintenance, in patients who had previously tolerated treatment well during induction and consolidation” and had a treatment break longer than 5 weeks, wrote the authors. In response, they instituted a protocol amendment: aggressive hypertension management, carfilzomib step‐up dosing (20 mg/m2 on day 1) at the start of maintenance before dose escalation to 56 mg/m2 maximum, and adding 10 mg of dexamethasone as premedication to maintenance carfilzomib infusions.
“Supportive care and avoidance of the triggering drug are the only known beneficial management approaches for drug-induced thrombotic microangiopathy,” they concluded.
Disclosure: For disclosures of the study authors, visit onlinelibrary.wiley.com.
