Clinical, radiological and molecular responses to combination chemotherapy with MAPK pathway inhibition in relapsed and refractory Langerhans cell histiocytosis.
Vivekanudeep KarriHoward LinJessica VelazquezAkanksha BatajooDeevyashali ParekhWhitney StantonHarshal AbhyankarNader K El-MallawanyJennifer AgrusaOlive S EcksteinNitya GulatiJeffrey SchwartzWendy Woods-SwaffordJaime BoydAnikit SahaCarl E AllenKenneth L McClainPublished in: British journal of haematology (2024)
Optimal therapeutic approaches for advanced Langerhans cell histiocytosis (LCH) are not known. We assessed the safety and efficacy of combined chemotherapy with MAPK pathway inhibition in 10 patients with refractory systemic disease and/or LCH-associated neurodegeneration. Overall response rate was 9/10 (90%) for the entire cohort: 5/5 (100%) for patients with systemic disease and 6/7 (86%) for patients with central nervous system disease. BRAFV600E+ peripheral blood fraction decreased in 5/6 (83%). Toxicities included fever, skin rash, myalgias, neuropathy, cytopenias and hypocalcaemia. Prospective trials are required to optimize combination strategies, determine potential to achieve cure and compare outcomes to chemotherapy or MAPK inhibitor monotherapy.
Keyphrases
- signaling pathway
- peripheral blood
- locally advanced
- oxidative stress
- single cell
- acute lymphoblastic leukemia
- acute myeloid leukemia
- squamous cell carcinoma
- multiple myeloma
- risk assessment
- diffuse large b cell lymphoma
- randomized controlled trial
- radiation therapy
- soft tissue
- cell proliferation
- bone marrow
- weight loss
- open label
- chemotherapy induced
- study protocol
- human health