Treatment of Langerhans Cell Histiocytosis Clinical Practice Guidelines (NCCN, 2021)

National Comprehensive Cancer Network

These are some of the highlights of the guidelines without analysis or commentary. For more information, go directly to the guidelines by clicking the link in the reference.

December 01, 2021

Guidelines for the treatment of Langerhans cell histiocytosis (LCH) were published in November 2021 by the National Comprehensive Cancer Network (NCCN) in Journal of the National Comprehensive Cancer Network.[1]

Decisions regarding treatment of LCH should be based on the site(s) involved and the extent of disease.

Treatment of Unifocal/Single-System Disease Not Involving Critical Organ

For patients with single-system disease not involving a critical organ (eg, central nervous system [CNS], liver, spleen, or heart), treatment is limited to local therapy and observation (watch-and-wait).

For patients with isolated bone lesions, limited curettage is recommended, but complete resection of bone lesions is not. Steroid injection may facilitate subsequent healing. For some patients with limited disease sites, radiation therapy (RT) may be used (eg, in cases of impending neurologic dysfunction and high surgical risk). Watch-and-wait is also reasonable for asymptomatic and isolated bone lesions.

For patients with single-system isolated skin disease, topical therapies (eg, psoralen with ultraviolet A and narrow-band ultraviolet B or, possibly, nitrogen mustard or steroids) may be used. Surgery is appropriate only for solitary skin lesions and only if it will not cause disfigurement. Systemic therapy may be used for symptomatic disease. Watch-and-wait is also an option.

Treatment of Multifocal/Multisystem Disease or Unifocal Disease Involving Critical Organ

Systemic therapy is often required, but in the absence of symptoms or impending organ dysfunction, watch-and-wait may be considered.

Treatment of pulmonary LCH should include smoking cessation. Watch-and-wait is an option, particularly if symptoms are absent or minor. Systemic therapy can be considered for symptomatic or progressive pulmonary LCH and for disease persisting despite smoking cessation. High-dose prednisone can be effective. Lung transplant should be considered only for highly refractory and severe disease.

Some evidence supports bisphosphonates (eg, zoledronic acid or pamidronate) for multifocal bone disease; in the absence of a response, other systemic therapies may be considered. RT can be considered for persistent disease at limited sites after systemic therapy. Indomethacin has been a successful alternative for some patients with primary and recurrent bone LCH.

Systemic Therapy

Systemic therapy is standard for multisystem/multifocal LCH, but treatment responses tend to be less robust in adults than in children. Potential options include vinblastine plus prednisone (preferred for pediatric LCH); cytarabine; cladribine; clofarabine; methotrexate; and cytarabine combined with methotrexate or intravenous immunoglobulin (IVIg) or vincristine.

Multifocal skin-involved LCH may respond to general systemic therapy for multisystem LCH, but some evidence supports use of specific options, including hydroxyurea with or without oral methotrexate and oral methotrexate combined with prednisone. Immunomodulating agents may also be used.

Targeted Therapies

Targeted therapies that may be used to treat LCH include BRAF inhibitors (eg, vemurafenib and dabrafenib; the latter may be better tolerated) and MEK inhibitors (eg, cobimetinib and trametinib).

In select cases of LCH with CSF-1R mutations and rearrangements involving RET and ALK, other kinase inhibitors may be considered. NTRK fusions can occur; thus, TRK inhibitors (eg, larotrectinib and entrectinib) may be used if indicated. Sirolimus and everolimus can be effective for PIK3CA-mutated LCH.

Treatment of Relapsed/Refractory Disease

For relapsed and refractory LCH, a systemic therapy regimen other than the first-line regimen may be considered. However, if the duration of response to the first-line regimen was greater than 1 year, repetition of that regimen may also be considered.

For more information, please go to Langerhans Cell Histiocytosis.

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