Long-term efficacy and safety of 2CdA (cladribine) in extra-pulmonary adult-onset Langerhans cell histiocytosis: analysis of 23 cases from the French Histiocytosis Group and systematic literature review.

Abstract

Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete picture of the efficacy and safety of 2CdA (2-chlorodeoxyadenosine, cladribine) is lacking. We report a retrospective multicentre study of 23 adult LCH (a-LCH) patients who received single-agent 2CdA and a systematic literature review. All had previously received systemic therapy (vinblastine, n = 19). Response to 2CdA was evaluable in 22 cases. Overall response rate (ORR) was 91%. Complete response (CR) occurred in 11 cases (50%). Nine patients (39%) developed grade 3-4 neutropenia and/or severe infection. A literature review yielded 48 additional cases. A pooled analysis confirmed our findings (ORR: 88%, CR: 49%). CRs were rare with cumulative dose <50 mg/m2 . Disease progression rates were 20% and 30% at two and five years, respectively. Partial response (PR) to 2CdA was predictive of disease progression. Among eight re-treated patients, five went into CR, two in PR, and one died. Single-agent 2CdA is effective in reactivated a-LCH, including at intermediate doses. Toxicity, significant but acceptable, warrants infectious prophylaxis. Complete responders may enter prolonged remission. Further studies are needed to determine 2CdA sequencing with other agents (vinblastine, cytarabine).

• Authors: Antoine Néel, Mathieu Artifoni, Anne-Maelle Fontenoy, Benoit Tessoulin, Gwenaël Lorillon, Fleur Cohen-Aubart, Julien Haroche, Thierry Genereau, Mathilde de Menthon, Loïc Guillevin, Hélène Maillard, Jean-Emmanuel Kahn, Olivier Hermine, Carla Araujo, Claire Dromer, Denis Jullien, Mohamed Hamidou, Jean Donadieu, Abdellatif Tazi
• Journal: British journal of haematology (Br J Haematol) Vol. 189 Issue 5 Pg. 869-878 (06 2020) ISSN: 1365-2141 [Electronic] England
• PMID: 32191819 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, Systematic Review)
• Copyright: © 2020 British Society for Haematology and John Wiley & Sons Ltd.

Chemical References

• Antimetabolites
• Immunosuppressive Agents
• Cladribine

Topics

• Adult
• Age of Onset
• Aged, 80 and over
• Antimetabolites (adverse effects, therapeutic use)
• Cladribine (adverse effects, therapeutic use)
• Dose-Response Relationship, Drug
• Female
• France (epidemiology)
• Histiocytosis, Langerhans-Cell (drug therapy, mortality)
• Humans
• Immunosuppressive Agents (adverse effects, therapeutic use)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neutropenia (chemically induced)
• Proportional Hazards Models
• Remission Induction
• Retrospective Studies
• Sepsis (etiology, mortality)
• Virus Diseases (etiology)