Efficacy and safety of vemurafenib in Langerhans cell histiocytosis (LCH): A systematic review and meta-analysis

Abstract

Almost half of the patients with Langerhans cell histiocytosis (LCH) are refractory to primary induction chemotherapy or undergo reactivation. The ideal treatment modality for refractory/relapsed LCH is yet not evidenced. This review aimed to determine the efficacy and safety of vemurafenib (a BRAF pathway inhibitor) in LCH, particularly the refractory/relapsed cases. The literature search was conducted using PubMed, Embase, CENTRAL, and abstracts published in the SIOP meetings. Studies that described the outcome of patients of LCH being treated with vemurafenib, alone or in combination, were included. A total of 416 studies were screened, and after applying exclusion criteria, 22 studies (n = 107) were included in the final analysis. The first-line therapy was prednisolone plus vinblastine for most patients (n = 92, 86%), and vemurafenib was started upfront in 3 patients (3%). The median time to first clinical response with vemurafenib was one week. The median time to best response was 5.25 months. Out of 107 patients, 62 patients (58%) had ultimately no active disease (NAD) while 39 (36%) had active disease better (ADB), making the overall response rate (ORR) of 101/107, ie, 94.4% (CI 0.88; 0.98). The main adverse effects of vemurafenib were rash or photosensitivity (47%) and other cutaneous adverse events (15%). Vemurafenib is highly efficacious and safe in the treatment of refractory LCH; however, the timing of its commencement and duration of therapy is yet to be established. Larger prospective collaborative trials are needed to answer the appropriate treatment duration and effective maintenance therapy approach.

Keywords:

• Vemurafenib
• efficacy
• LCH
• Langerhans cell histiocytosis

Acknowledgments

We thank all the patients, surrogates, and researchers involved in the studies.

Contributors

DM, AKG and JPM designed the study. DM and JPM extracted the studies. AKG helped when there was any discrepancy in the interpretation of studies and outcomes. DM, JPM and PH wrote the manuscript. PH did the statistical analysis. PH, PT, and RS supervised the whole review and manuscript writing. Finally, all the authors reviewed and approved the manuscript

Disclosure statement

No potential conflict of interest was reported by the author(s).

Funding

The author(s) reported there is no funding associated with the work featured in this article.