Cladribine therapy for systemic mastocytosis

Abstract

Patients with systemic mastocytosis (SM) can suffer from disabling symptoms related to mast cell mediator release or mast cell infiltration, requiring mast cell eradication. In the present absence of any curative therapy, a recent case report describing the efficacy of cladribine showed promising results. In a pilot study, the efficacy of cladribine (0.10-0.13 mg/kg in a 2-hour infusion, days 1-5; repeated at 4-8 weeks until 6 cycles) was studied. Ten patients with SM with severe symptoms were treated. Four patients were classified as having indolent or smoldering mastocytosis, 3 as having aggressive systemic mastocytosis, and 3 as having SM with an accompanying hematologic malignancy. Nine patients received 6 courses, 1 patient stopped because of toxicodermia. All responded concerning signs, symptoms, and mast cell parameters (serum tryptase and urinary histamine metabolite excretion), although none achieved a complete remission. Prolonged follow-up is required, as response is ongoing in most cases. One patient relapsed within 11 months and showed a second response. Side effects were mainly related to bone marrow suppression. Single-agent cladribine is an effective and relatively safe treatment for severe systemic mastocytosis. The optimal dose and schedule need to be explored.

Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth

“…Both midostaurin and cladribine (2CdA) can inhibit growth of neoplastic MC in patients with ASM or MCL (20,21,24,46,48). Previous data have shown that both drugs, when combined, exert growth-inhibitory effects on neoplastic MC in vitro (21).…”

Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management

“…Has demonstrated in vitro and in vivo activity against neoplastic MC; the published experience suggests that 2-CdA has therapeutic activity in all SM subtypes including in MCL [98][99][100][101][102][103].…”

A pilot study of nonmyeloablative allogeneic hematopoietic stem cell transplant for advanced systemic mastocytosis

“…13,14 More importantly, greater reduction in disease burden may be necessary to achieve better longterm control of mastocytosis. Newer therapeutic agents for SM including cladribine, [15][16][17] imatinib mesylate (for selected cases without c-kit codon 816 mutations [18][19][20][21][22], and novel KIT inhibitors 23 may be considered for this purpose. Indeed, a number of novel targeted agents have demonstrated promising activity in vitro and/or in vivo against the c-kit D816V mutation believed to be the pathogenic mutation in most cases of systemic mastocytosis.…”