Ixazomib-induced cutaneous necrotizing vasculitis

Abstract

Ixazomib is a second-generation proteasome inhibitor that has been approved in the combination treatment of multiple myeloma and is currently under clinical investigation for the management of Waldenstrom's macroglobulinemia. While cutaneous adverse events secondary to proteasome inhibitors have been reported, the side effect profile of ixazomib remains to be documented. We report two patients, one with multiple myeloma and one with Waldenstrom's macroglobulinemia, who developed cutaneous necrotizing vasculitis after the initiation of ixazomib. Both patients exhibited no signs of systemic vasculitis and completed their anti-cancer regimens with resolution of their respective eruptions following dose reductions in ixazomib and initiation of low-dose prednisone. A collaborative effort towards the characterization of such cutaneous toxicities facilitates early intervention, maintenance of life-preserving anti-cancer therapy, and allows clinicians opportunity to better understand the pathophysiology of vasculitis. Moreover, appropriate identification and characterization of cutaneous toxicities from novel therapies allows providers to accurately identify safety concerns, treat toxicity, and improve patient quality of life.

A Rare Case of Ixazomib-Induced Cutaneous Necrotizing Vasculitis in a Patient with Relapsed Myeloma

“…In the phase III trial that led to ixazomib's approval for relapsed myeloma, 36% of the ixazomib group experienced rash (grade 1 and 2) and 21% resolved without intervention compared to 23% in the placebo group with 12% resolving without intervention [3]. Cutaneous necrotizing vasculitis is extremely rare, and its pathogenesis is unknown [7, 8].…”

“…Guidelines for ixazomib-induced cutaneous necrotizing vasculitis are currently ambiguous, and little characterization is available as it is not a commonly reported adverse event [1, 7, 8]. Recognizing cutaneous toxicities secondary to myeloma therapies is critical for early intervention [8].…”

“…Guidelines for ixazomib-induced cutaneous necrotizing vasculitis are currently ambiguous, and little characterization is available as it is not a commonly reported adverse event [1, 7, 8]. Recognizing cutaneous toxicities secondary to myeloma therapies is critical for early intervention [8]. Vasculitic skin lesions may manifest due to vasculitis also involving internal organs, requiring systemic workup to rule out other possible causes, making diagnosing cutaneous vasculitis a diagnosis of exclusion [9].…”

“…Skin biopsies demonstrated interface dermatitis, lymphocytic vasculitis, and mixed, acute, and chronic granulomatous necrotizing vasculitis involving small- and medium-sized vessels with a lot of eosinophils. Both patients received treatment for their respective diseases; however, dose reductions and low dose steroids were needed [8].…”

“…Eruption and spreading of the rash can be managed by administering a corticosteroid on nontreatment days, holding treatment for a week and reducing ixazomib dosage [8]. Topical steroids will only provide symptomatic relief, and in trials with bortezomib-induced cutaneous vasculitis, recurrence is prevented by premedication before treatments [10].…”