Clofarabine monotherapy in aggressive, relapsed and refractory Langerhans cell histiocytosis

Abstract

Over 50% of patients with systemic LCH are not cured with front-line therapies, and data to guide salvage options are limited. We describe 58 patients with LCH who were treated with clofarabine. Clofarabine monotherapy was active against LCH in this cohort, including heavily pretreated patients with a systemic objective response rate of 92.6%, higher in children (93.8%) than adults (83.3%). BRAF^V600E+ variant allele frequency in peripheral blood is correlated with clinical responses. Prospective multicentre trials are warranted to determine optimal dosing, long-term efficacy, late toxicities, relative cost and patient-reported outcomes of clofarabine compared to alternative LCH salvage therapy strategies.

Keywords: Langerhans cell histiocytosis; clofarabine; myeloid neoplasia.

Figure 1.. Treatment timeline and response for relapsed and refractory LCH patients treated with clofarabine monotherapy.

Swimmer plots demonstrate responses to clofarabine monotherapy. A) LCH patients with systemic LCH lesions only. Response to therapy after each treatment regimen is indicated symbols according to the legend. B) LCH patients with CNS involvement (4 with CNS MRI changes only and 4 with clinical LCH-associated neurodegenerative disease). Responses are indicated for systemic responses (purple) and CNS responses (red). Comprehensive treatment courses and responses are shown in Supplemental Figure 1. C) Percentage of PBMC harboring the BRAF^V600E allele determined by qPCR of longitudinal samples from patients before first treatment and after completing clofarabine. Every line represents a single patient with the color of the overall line indicating the response at end of treatment: complete systemic response (green) or partial response (purple).