Acalabrutinib-Related Dermal Toxicities: A Next-Generation Diagnostic Challenge

Abstract

Abstract Introduction/Objective Bruton's tyrosine kinase (BTK) inhibitors represent an advance in treating multiple hematologic malignancies. Next-generation BTK inhibitors, acalabrutinib, have been designed to optimize BTK inhibition and decrease the potential of associated side effects. Methods/Case Report A 74-year-old male presented with generalized weakness and shortness of breath. Radiological examination revealed bilateral pleural effusions, lymphadenopathy, and hepatosplenomegaly. Evaluation of the pleural fluid showed a low-grade lymphoma. A lymph node and bone marrow biopsy revealed B-cell lymphoma with lymphoplasmacytic differentiation, with bone marrow involvement. MYD 88 mutation was identified, and it was consistent with Waldenstrom's macroglobulinemia. Acalabrutinib therapy was started, with good response. Two weeks later, he presented with two distinct rashes. 1)Blanching erythematous macules and papules coalescing to patches on the upper thighs and hypogastric region. Punch biopsy of this rash showed superficial perivascular dermatitis with predominantly T-cells and mild lobular panniculitis consistent with BTK inhibitor toxicity. 2)Red-brown erythematous plaques with induration on the central chest. The biopsy of this rash showed cutaneous involvement by the known B- cell lymphoplasmacytic lymphoma. Results (if a Case Study enter NA) NA Conclusion Cutaneous involvement by Waldenstrom Macroglobulinemia is uncommon. It can be due to 1) nonspecific rashes secondary to the hyperviscosity or cryoglobulinemia 2) cutaneous involvement by the lymphoma, called cutaneous macroglobulinosis. We present uncommon simultaneous cutaneous involvement of Waldenstrom’s Macroglobulinemia and BTK inhibitor toxicity. BTK-inhibitors-induced rashes present with a relatively non-specific and varied clinical presentation, often in chronically ill patients taking additional medications. Next-generation BTK inhibitors present a more selective binding to BTK. However, they are still associated with similar dermatological toxicities. A high index of suspicion is needed for diagnosis and treatment.