Minimal Residual Disease–Guided Intermittent Dosing in Patients With Cancer: Successful Treatment of Chemoresistant Anaplastic Large Cell Lymphoma Using Intermittent Lorlatinib Dosing

Authors

POKORNÁ Petra KLEMENT Giannoula Lakka VAŠÍKOVÁ Alžběta KANDEROVÁ Veronika JEŽOVÁ Marta NOSKOVÁ Kristýna MÚDRY Peter KÝR Michal MERTA Tomáš BAJČIOVÁ Viera KŘENOVÁ Zdenka PÁLOVÁ Hana ZDRAŽILOVÁ DUBSKÁ Lenka SLABÝ Ondřej VALÍK Dalibor ŠTĚRBA Jaroslav

Year of publication 2022
Type Article in Periodical
Magazine / Source JCO PRECISION ONCOLOGY
MU Faculty or unit

Faculty of Medicine

Citation
Web https://ascopubs.org/doi/full/10.1200/PO.21.00525
Doi http://dx.doi.org/10.1200/PO.21.00525
Keywords intermitent dosing lorlatinib; chemoresistant lymphoma; minimal disseminated disease; pediatric oncology
Description With the emergence of targeted therapies, the traditional maximum tolerated dosing where toxicities guide the treatment dose is no longer relevant. Especially in the case of tyrosine kinase inhibitors (TKIs), where higher doses lead to therapeutic resistance due to ligand or receptor upregulation and where off-target toxicities plague any increase of dose. In the case of TKIs, where the most effective dose is at the bottom of a U-shaped curve, therapy should be guided by biomarkers, or by minimal residual disease. We present a case of relapsed chemotherapy-refractory ALK-positive anaplastic large cell lymphoma treated with lorlatinib, where we used frequent minimal disseminated disease monitoring to guide the length of on/off therapy periods during intermitted dosing in order to prevent treatment resistance.

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