Long-lasting complete response to imatinib in a patient with systemic mastocytosis exhibiting wild type KIT

Abstract

Systemic mastocytosis (SM) is a hematopoietic disorder characterized by abnormal expansion of mast cells (MCs) in visceral organs. The skin is involved in most cases. In adult patients the transforming KIT mutation D816V is usually present and confers resistance against imatinib. Therefore, imatinib is not recommended for patients with KIT D816V+ SM. Nonetheless, imatinib may work in patients with SM lacking KIT D816V. However, little is known about long-term efficacy and safety of this drug in SM. We report on a 62-year-old female patient with indolent SM (ISM) who suffered from severe debilitating skin involvement despite therapy with anti-mediator-type drugs, psoralen and ultraviolet-A-radiation. Although multifocal MC infiltrates were detected in the bone marrow by immunohistochemistry, no KIT mutation was found by sequencing analysis. In 2003, treatment with imatinib (induction, 400 mg/day; maintenance, 200 mg/day) was initiated. During therapy, skin lesions and tryptase levels decreased. Treatment was well tolerated without any side effects. After 10 years, skin lesions have disappeared and the tryptase level is within normal range. This case-study confirms the long-term efficacy and safety of imatinib in patients with SM lacking activating KIT mutations. Imatinib should be considered in select cases of SM in whom MCs exhibit wild-type KIT.

Keywords: KIT D816V; Mastocytosis; drug safety; imatinib; long-term efficacy; tryptase.

Figure 1

Immunohistochemical detection of neoplastic mast cells in the patient’s bone marrow (BM). BM sections were examined by indirect immunohistochemistry using an antibody against KIT (upper panel) and against tryptase (lower panel). Original magnification x 60. Note the presence of multifocal, perivascular accumulations of mast cells which is a pathognomonic feature and major criterion of systemic mastocytosis (SM).

Figure 2

Facial skin lesions in patient with mastocytosis. Facial skin was examined and photographed before treatment with imatinib (left panel) and one year after therapy with imatinib (right panel). The loading dose of imatinib (5 months) was 400 mg/day, and maintenance dose 200 mg/day.