LCH-III (2001-2008)

LCH-III was a multicenter, prospective, open, phase-III, randomized clinical trial for patients with MS-LCH. Previously untreated patients with MS-LCH were stratified into a “high risk” and a “low risk” group, depending on presence of RO involvement at diagnosis.¹

The “high-risk” Stratum aimed to improve initial response and survival by randomized addition of intermediate-dose (500 mg/m²) intravenous methotrexate (MTX) at weeks 1, 3 and 5 to the standard arm of vinblastine and prednisolone. In both randomization arms, a second 6-week course of initial therapy was given in case of insufficient response. Both randomization arms received continuation therapy consisting of prednisolone/vinblastine pulses every 3 weeks and daily oral mercaptopurine for total treatment duration of 12 months, whereas weekly oral methotrexate was added to the experimental arm. Altogether 235 patients were randomized in the “high-risk” Stratum.

In the “low-risk” Stratum the standard combination of prednisolone/vinblastine was randomized for duration of the continuation therapy, namely total treatment duration of 6 months versus 12 months. In the “low-risk” Stratum were randomized 187 patients.

MAIN FINDINGS OF LCH-III:

• The two-drug combination prednisolone/vinblastine given for a total treatment duration of 12 months remains the standard of care for patients with high-risk LCH.
• Lack of response in high-risk LCH patients defines a small group with poor prognosis (“very-high risk”), which needs a more effective treatment
• Patients with low-risk MS-LCH benefit from a 12-month compared to 6-month treatment duration in terms of risk of disease relapse

The cumulative findings of those trials formed the current standard front-line treatment for pediatric-onset multisystem LCH.^2,3

REFERENCES:

1. Gadner H, Minkov M, Grois N, Potschger U, Thiem E, Arico M, et al. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood, 2013,  121(25):5006-14.

2. Minkov M. Multisystem Langerhans cell histiocytosis in children: current treatment and future directions. Paediatr Drugs, 2011, 13(2):75-86.

3. Minkov M. An update on the treatment of pediatric-onset Langerhans cell histiocytosis through pharmacotherapy. Expert Opin Pharmacother, 2018, 19(3):233-42.