LCH-III
The Histiocyte Society's third international trial showed that treating multisystem Langerhans cell histiocytosis for a full year, rather than six months, roughly halves the chance of the disease coming back, while adding methotrexate added nothing but toxicity.
Overview
International randomised trial (Gadner et al., Blood 2013), more than 400 patients randomised. In risk-organ-positive disease, adding methotrexate to vinblastine and prednisone did not change response, survival or reactivation; but 12 months of therapy gave 5-year survival of 84% against 62% and 69% in the identically stratified predecessor trials LCH-I and LCH-II, and reduced 5-year reactivation to 27% from 55% and 44%. In risk-organ-negative disease, 12 months of vinblastine-prednisone lowered 5-year reactivation to 37% versus 54% with 6 months (P = 0.03). One year of vinblastine-prednisone became the international standard and the backbone of LCH-IV, which tests further prolongation and the addition of 6-mercaptopurine. The trial predates the discovery that most LCH carries BRAF V600E or other MAPK mutations, which now drive targeted therapy for refractory disease.
- 37 vs 54 out of 100 reached this endpoint at 5 years with 12 months vinblastine-prednisone compared with 6 months vinblastine-prednisone; 17 fewer per 100.
- On this measure the first group did worse, not better.
- The p-value (0.03) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
- 27 vs 55 out of 100 reached this endpoint at 5 years with LCH-III compared with LCH-I (historical, 6 months); 28 fewer per 100.
- On this measure the first group did worse, not better.
- Other groups: LCH-II (historical, 6 months) 44 of 100.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- These results apply to the people the trial enrolled: Multisystem Langerhans cell histiocytosis in children: risk-organ-positive patients randomised to vinblastine-prednisone with or without methotrexate (12 months total); risk-organ-negative responders randomised to 6 vs 12 months of vinblastine-prednisone. People in a different situation may not see the same effect.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
376 participants enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| 5-year reactivation rate, risk-organ-negativeprimary | 12 months vinblastine-prednisone | — | 37% | — | 0.03 | link |
| 6 months vinblastine-prednisone | — | 54% | ||||
| 5-year reactivation rate, risk-organ-positive (both arms, 12 months) | LCH-III | — | 27% | — | — | link |
| LCH-I (historical, 6 months) | — | 55% | ||||
| LCH-II (historical, 6 months) | — | 44% |
Pages like this
not linked directly; found by shared links- TrialFIREFLY-1
Shares BRAF, RAS / RAF / MEK / ERK (MAPK) and the tags nci-coverage, paediatric.
- TrialTADPOLE (CDRB436G2201)
Shares BRAF, RAS / RAF / MEK / ERK (MAPK) and the tags nci-coverage, paediatric.
- CancerErdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms
Shares Histiocyte Society, Langerhans cell histiocytosis (LCH), BRAF, RAS / RAF / MEK / ERK (MAPK) and the tags nci-coverage, histiocytosis.
- InstitutionACCELERATE
Shares the tags nci-coverage, paediatric.
- InstitutionInnovative Therapies for Children with Cancer (ITCC)
Shares the tags nci-coverage, paediatric.
- CancerPaediatric low-grade glioma
Shares Vinblastine, BRAF, RAS / RAF / MEK / ERK (MAPK) and the tags nci-coverage, paediatric.
- CancerCraniopharyngioma
Shares BRAF, RAS / RAF / MEK / ERK (MAPK) and the tags nci-coverage, paediatric.
- TrialInter-B-NHL Ritux 2010
Shares Methotrexate and the tags nci-coverage, paediatric.