Abstract
Introduction:
Six percent of all non-Hodgkin lymphomas (NHL) cases are mantle cell lymphoma (MCL). MCL has a poor prognosis and is considered incurable with current strategies. Intensive approaches are not applicable to most these patients considering the median age at diagnosis (70 years old). Due to the molecular events that drive MCL to be a lymphoma with an aggressive and indolent behavior as well as a tendency to clonal evolution (dysfunction of cell cycle, response to cellular damage and apoptosis), we present a global therapeutic approach which includes an effective induction with a low toxic profile, as well as consolidation and maintenance with the final aim of increasing and maintaining responses.
Methods:
From December-2008 to January-2018 all MCL patients treated in first line in our center were included. The therapeutic approach was based on an induction with R-GemOx (rituximab, gemcitabine and oxaliplatin) followed by consolidation with autologous stem cell transplant or ibritumomab tiuxetan followed by rituximab maintenance (Rm) (every 2 months for 2-3 years). Since 2016, all patients with less than complete response after induction/consolidation, received Ibrutinib 560 mg daily added to Rm. Standard prognostic variables were collected at diagnosis including MIPI; the response evaluation and follow-up was made considering Cheson criteria; for toxicity assessment, we used OMS grading scales of toxicity criteria. Overall survival (OS) and progression free survival (PFS) were estimated from the beginning of the treatment with the Kaplan-Meier method.
Results:
Thirteen treatment-naïve MCL patients were included from December-2008 to January-2018. Main characteristics of patients are shown in Table 1. Briefly, this is an old high risk series with a median age at diagnosis of 71 years old and poor prognosis (31% and 69% belong to intermediate and high risk MIPI groups, respectively). Two cases were refractory to R-GemOx induction (a blastic MCL and another case with high MIPI (7.7)). Four cases relapsed between 30 and 66 months after treatment was started. All cases with CR or PR after induction (n=11; 85%), obtained a CR at the end of the maintenance. One of the refractory cases after a second line followed by rituximab and ibrutinib maintenance also reached CR. Only 2 patients died (15%): one disease progression and another non-related pulmonary thromboembolism. The median follow-up was 51 months. Four-years OS was of 83% with a median PFS of 58 months (Figure 1). R-GemOx toxicity profile was manageable: most of them grade 1-2 neutropenia (43%), vomits (100%), diarrhea (30%) and anemia (30%). Grade 3-4 toxicity was scarce (neutropenia 14% and thrombocytopenia 36%).
Conclusions:
R-GemOx followed by consolidation and Rm should was an effective approach with manageable toxicity and excellent survival considering the median age and the high MIPI risk of the series.
We plan to test this global approach in a prospective clinical trial.
No relevant conflicts of interest to declare.
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