Clinical, radiological and molecular responses to combination chemotherapy with <scp>MAPK</scp> pathway inhibition in relapsed and refractory Langerhans cell histiocytosis
Vivekanudeep Karri, Howard Lin, Jessica Velazquez, Akanksha Batajoo, Deevyashali Parekh, Whitney Stanton, Harshal Abhyankar, Nader Kim El‐Mallawany, Jennifer E. Agrusa, Olive S. Eckstein, Nitya Gulati, Jeffrey Schwartz, Wendy Woods‐Swafford, J. Barry Boyd, Anikit Saha, Carl E. Allen, Kenneth L. McClain
Abstract
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.