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.

Case series of unique adverse events related to the use of ibrutinib in patients with B-cell malignancies—A single institution experience and a review of literature

“…By inhibiting EGFR, on the other hand, it displays proinflammatory properties, particularly on the skin, resulting in cutaneous eruptions. 12 Skin rashes are a common AE of the drug, although spongiotic dermatitis and skin rash with intramedullary fibrosis and severe arthralgia is unique to our experience. An increased incidence of skin rash with WM is not evident yet.…”

Optimising outcomes for patients with chronic lymphocytic leukaemia on ibrutinib therapy: European recommendations for clinical practice

“…In Phase III clinical trials of ibrutinib in CLL, any grade rash was reported in 8% of patients in the RESONATE study and grade ≥3 rash was reported in 3% of patients in RESONATE‐2 (Byrd et al , ; Burger et al , ). While most of the current understanding of ibrutinib‐associated rash comes from individual case reports (Mannis et al , ; Jensen et al , ), reports of larger patient groups being assessed for clinicopathological features, treatment methods and outcomes are starting to emerge (Iberri et al , ). It is the authors' experience that most patients who develop rash have prior history of hypersensitivity to other agents.…”

Ibrutinib-associated pityriasis rosea–like rash

“…One suggested mechanism of ibrutinib-induced drug eruption is through epidermal growth factor receptor (EGFR) inhibition. 9 Although ibrutinib is highly selective for Bruton tyrosine kinase, it exerts off-target effects on other kinases, such EGFR. 10 EGFR inhibitors have well-established cutaneous side effects.…”