MAPK inhibitors

Forty-four LCH patients with risk-organ involvement and ten LCH patients without risk-organ involvement were treated with vemurafenib. Of the 44 risk-organ–involved patients, 31 received vemurafenib as their original therapy and 13 received vemurafenib as treatment after disease progression. The ten risk-organ–negative patients also received vemurafenib after disease progression.[148][Level of evidence C3]

Forty-four LCH patients with risk-organ involvement and ten LCH patients without risk-organ involvement were treated with vemurafenib. Of the 44 risk-organ–involved patients, 31 received vemurafenib as their original therapy and 13 received vemurafenib as treatment after disease progression. The ten risk-organ–negative patients also received vemurafenib after disease progression.[148][Level of evidence C3]

After 8 weeks of treatment, there were 38 complete responses and 16 partial responses. Most patients were treated for 6 months.

Forty-four LCH patients with risk-organ involvement and ten LCH patients without risk-organ involvement were treated with vemurafenib. Of the 44 risk-organ–involved patients, 31 received vemurafenib as their original therapy and 13 received vemurafenib as treatment after disease progression. The ten risk-organ–negative patients also received vemurafenib after disease progression.[148][Level of evidence C3]

Thirty patients stopped taking vemurafenib; 24 of these patients subsequently relapsed: 72% of patients at 6 months and 84% of patients at 12 months off therapy.

Forty-four LCH patients with risk-organ involvement and ten LCH patients without risk-organ involvement were treated with vemurafenib. Of the 44 risk-organ–involved patients, 31 received vemurafenib as their original therapy and 13 received vemurafenib as treatment after disease progression. The ten risk-organ–negative patients also received vemurafenib after disease progression.[148][Level of evidence C3]

The relapse rate was 95% for patients with risk-organ involvement and 57% for patients without risk-organ involvement.

Forty-four LCH patients with risk-organ involvement and ten LCH patients without risk-organ involvement were treated with vemurafenib. Of the 44 risk-organ–involved patients, 31 received vemurafenib as their original therapy and 13 received vemurafenib as treatment after disease progression. The ten risk-organ–negative patients also received vemurafenib after disease progression.[148][Level of evidence C3]

Relapse was associated with the persistence of circulating BRAF-positive cells.

Forty-four LCH patients with risk-organ involvement and ten LCH patients without risk-organ involvement were treated with vemurafenib. Of the 44 risk-organ–involved patients, 31 received vemurafenib as their original therapy and 13 received vemurafenib as treatment after disease progression. The ten risk-organ–negative patients also received vemurafenib after disease progression.[148][Level of evidence C3]

The most frequent adverse effects of the drug were dermatologic. In a review of 57 patients with LCH who received vemurafenib for refractory disease, 72% of patients had cutaneous adverse events, 86% of which were grade 1 or grade 2.[149] Most patients had photosensitivity, keratosis pilaris, macular or follicular rashes, or xerosis. No skin tumors were observed.

A systematic review and meta-analysis evaluated the efficacy and safety of vemurafenib for the treatment of patients with LCH. The analysis found 416 studies, 22 of which fit the inclusion criteria. There were 104 patients with relapsed or refractory disease and 3 patients with newly diagnosed disease.[150]

A systematic review and meta-analysis evaluated the efficacy and safety of vemurafenib for the treatment of patients with LCH. The analysis found 416 studies, 22 of which fit the inclusion criteria. There were 104 patients with relapsed or refractory disease and 3 patients with newly diagnosed disease.[150]

With vemurafenib treatment, the median time to first response was 1 week and the median time to best response was 5.25 months.

A systematic review and meta-analysis evaluated the efficacy and safety of vemurafenib for the treatment of patients with LCH. The analysis found 416 studies, 22 of which fit the inclusion criteria. There were 104 patients with relapsed or refractory disease and 3 patients with newly diagnosed disease.[150]

Sixty-two patients (58%) achieved NAD status, and 36% had decreased active disease.

A systematic review and meta-analysis evaluated the efficacy and safety of vemurafenib for the treatment of patients with LCH. The analysis found 416 studies, 22 of which fit the inclusion criteria. There were 104 patients with relapsed or refractory disease and 3 patients with newly diagnosed disease.[150]

The overall response rate was 94.4%.

A systematic review and meta-analysis evaluated the efficacy and safety of vemurafenib for the treatment of patients with LCH. The analysis found 416 studies, 22 of which fit the inclusion criteria. There were 104 patients with relapsed or refractory disease and 3 patients with newly diagnosed disease.[150]

Major toxicity included rash and photosensitivity.

A systematic review and meta-analysis evaluated the efficacy and safety of vemurafenib for the treatment of patients with LCH. The analysis found 416 studies, 22 of which fit the inclusion criteria. There were 104 patients with relapsed or refractory disease and 3 patients with newly diagnosed disease.[150]

The authors concluded that vemurafenib was highly efficacious and safe to treat patients with refractory LCH, but the duration of therapy has yet to be established.

A multicenter, retrospective analysis of experiences that used various MAPK inhibitors to treat 21 pediatric patients with LCH who had failed at least one previous therapy (median, three previous therapies) demonstrated the following:[124][Level of evidence C3]

A multicenter, retrospective analysis of experiences that used various MAPK inhibitors to treat 21 pediatric patients with LCH who had failed at least one previous therapy (median, three previous therapies) demonstrated the following:[124][Level of evidence C3]

An overall response rate of 86% (complete response, 19%; partial response, 67%).

A multicenter, retrospective analysis of experiences that used various MAPK inhibitors to treat 21 pediatric patients with LCH who had failed at least one previous therapy (median, three previous therapies) demonstrated the following:[124][Level of evidence C3]

Stable disease in 10% of patients.

A multicenter, retrospective analysis of experiences that used various MAPK inhibitors to treat 21 pediatric patients with LCH who had failed at least one previous therapy (median, three previous therapies) demonstrated the following:[124][Level of evidence C3]

The most frequent toxicities were skin rashes and arthralgias. Other toxicities included neutropenia, fatigue, and uveitis.

One study compared dabrafenib alone (13 patients) with dabrafenib and trametinib (12 patients) for the treatment of patients with relapsed or progressive LCH.[151]

One study compared dabrafenib alone (13 patients) with dabrafenib and trametinib (12 patients) for the treatment of patients with relapsed or progressive LCH.[151]

With a 2-year follow-up, the responses were similar in both arms (46.2% complete response, 30.8% regressive disease, and 23.1% stable disease for dabrafenib alone vs. 33.3% complete response, 25.0% regressive disease, and 25.0% stable disease for combination therapy).

One study compared dabrafenib alone (13 patients) with dabrafenib and trametinib (12 patients) for the treatment of patients with relapsed or progressive LCH.[151]

Adverse events were also similar and included pyrexia and vomiting, cough, and increased serum creatinine.

One study compared dabrafenib alone (13 patients) with dabrafenib and trametinib (12 patients) for the treatment of patients with relapsed or progressive LCH.[151]

This study would suggest that combination therapy is not more effective in patients with LCH. However, more data are needed.