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-StaffordJaime 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
- single cell
- oxidative stress
- locally advanced
- pi k akt
- cell therapy
- acute lymphoblastic leukemia
- acute myeloid leukemia
- randomized controlled trial
- diffuse large b cell lymphoma
- squamous cell carcinoma
- type diabetes
- clinical trial
- stem cells
- risk assessment
- adipose tissue
- rectal cancer
- chemotherapy induced
- insulin resistance
- multiple myeloma
- skeletal muscle
- hodgkin lymphoma
- wound healing