Ibrutinib-Associated Skin Toxicity: A Case of Maculopapular Rash in a 79-Year Old Caucasian Male Patient with Relapsed Waldenstrom's Macroglobulinemia and Review of the Literature

Abstract

Waldenstrom's macroglobulinamia (WM) is a rare malignant lymphoproliferative disorder, characterized by monoclonal IgM paraproteinemia and neoplastic proliferation of malignant lymphoplasmacytoid cells in the bone marrow. Traditionally, WM has been treated with modalities similar to those used in the management of other indolent lymphomas. Just recently, based on impressive clinical trial results in heavily pretreated WM patients, a new Bruton Tyrosine Kinase-inhibitor, Ibrutinib, has been approved for the treatment of this disorder. As the use of Ibrutinib in WM outside clinical trials is still limited, only few clinical reports illustrating treatment side effects are currently available. Here we review the current literature specific on Ibrutinib-associated rash in hematologic patients, and report on an elderly patient with WM, who developed a red maculopapular non-pruritic rash 12 weeks after starting Ibrutinib therapy. Without modifications of the ongoing Ibrutinib schedule, the rash regressed within two weeks of treatment with topical steroid-containing dermatological compounds.

Keywords: Waldenstrom's macroglobulinamia; adverse effects; ibrutinib; minireview; rash.

Figure 1.

Pruritic rash in Waldenstrom's patient developed 12 weeks after beginning Ibrutinib therapy. A) Upper back; B) back thighs and calves; C and D) close-up of rash papules seen in panels A and B.

Figure 2.

A slightly spongiotic reaction with predominantly perivascular infiltrates of lymphocytes and eosinophils with a negative reaction for fungi were seen in the histopathological examination of the punch biopsy of the skin (A: Hematoxylin Eosin, x200; B: Periodic Acid-Schiff, x200).

Figure 3.

An overview of rash onset from previously published studies and case reports regarding Ibrutinib-associated rashes in CML, CLL and MCL patients. References refer to reference list.