Efficacy of the GemOx‐R regimen leads to the identification of Oxaliplatin as a highly effective drug against Mantle Cell Lymphoma

• Published in: British journal of haematology Vol. 174; no. 6; pp. 899 - 910
• Main Authors: Obrador‐Hevia, Antònia, Serra‐Sitjar, Margalida, Rodríguez, José, Belayachi, Lamiae, Bento, Leyre, García‐Recio, Marta, Sánchez, Jose María, Villalonga, Priam, Gutiérrez, Antonio, Fernández de Mattos, Silvia
• Format: Journal Article
• Language: English
• Published: England 01.09.2016
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis - drug effects; Cell Cycle - drug effects; Cell Line; Cell Survival - drug effects; cisplatin; cytarabine; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Drug Resistance, Neoplasm; Drug Synergism; Female; GemOx‐R; Humans; Lymphoma, Mantle-Cell - diagnosis; Lymphoma, Mantle-Cell - drug therapy; Lymphoma, Mantle-Cell - mortality; Male; mantle cell lymphoma; Middle Aged; Neoplasm Staging; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - pharmacology; Organoplatinum Compounds - therapeutic use; oxaliplatin; Recurrence; Retreatment; Retrospective Studies; Rituximab - administration & dosage; Salvage Therapy; Treatment Outcome; cytarabine; mantle cell lymphoma; oxaliplatin; GemOx-R; cisplatin
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.14141

Summary Mantle Cell Lymphoma (MCL) is an aggressive lymphoma subtype that accounts for 6–8% of non‐Hodgkin lymphomas. The disease is mostly incurable and characterized by a continuous pattern of relapse. Major changes have recently been implemented in the management of MCL, but continuous relapses still mark this disease as a challenge for clinicians. We previously reported the efficacy of GemOx‐R (Gemcitabine, Oxaliplatin and Rituximab) in patients with refractory and relapsing MCL. We present results for a larger series with longer follow‐up and including high‐risk frontline patients, showing an overall response rate of 83%. The efficacy of each component of GemOx‐R was evaluated in a panel of MCL cell lines. Also, patient‐derived primary cells were used in ex vivo experiments. The results show that oxaliplatin has a profound effect on cellular viability and is the most effective drug within this regimen. We further present synergistic efficacy of oxaliplatin combined with cytarabine in MCL cells. Interestingly, this synergistic effect was not seen when cisplatin and cytarabine were combined, indicating that among the platinum‐derived agents oxaliplatin may be the preferred approach. Taken together our findings suggest that oxaliplatin alone or combined with cytarabine could constitute an alternative backbone for MCL regimens.